An e-p facility for Europe. Weak interactions in e-p physics

International Nuclear Information System (INIS)

Turlay, R.

1979-01-01

We first present the recent development on an e-p collider in Europe occuring in the last year. Then a review of physics motivations for an e-p ring is discussed and developed with the latest work presented at the meeting on 'Study for an e-p Facility for Europe' held at Hamburg on April 2-3, 1979

A Bayesian decision approach to rainfall thresholds based flood warning

Directory of Open Access Journals (Sweden)

M. L. V. Martina

2006-01-01

Full Text Available Operational real time flood forecasting systems generally require a hydrological model to run in real time as well as a series of hydro-informatics tools to transform the flood forecast into relatively simple and clear messages to the decision makers involved in flood defense. The scope of this paper is to set forth the possibility of providing flood warnings at given river sections based on the direct comparison of the quantitative precipitation forecast with critical rainfall threshold values, without the need of an on-line real time forecasting system. This approach leads to an extremely simplified alert system to be used by non technical stakeholders and could also be used to supplement the traditional flood forecasting systems in case of system failures. The critical rainfall threshold values, incorporating the soil moisture initial conditions, result from statistical analyses using long hydrological time series combined with a Bayesian utility function minimization. In the paper, results of an application of the proposed methodology to the Sieve river, a tributary of the Arno river in Italy, are given to exemplify its practical applicability.

Gendered differences in the perceived risks and benefits of oral PrEP among HIV-serodiscordant couples in Kenya.

Science.gov (United States)

Carroll, Jennifer J; Ngure, Kenneth; Heffron, Renee; Curran, Kathryn; Mugo, Nelly R; Baeten, Jared M

2016-08-01

Pre-exposure prophylaxis (PrEP) is effective for preventing HIV among HIV-serodiscordant heterosexual couples. Gender roles may influence perceived personal and social risks related to HIV-prevention behaviors and may affect use of PrEP. In this study, interviews and focus groups were conducted with 68 individuals from 34 mutually disclosed serodiscordant heterosexual partnerships in Thika, Kenya. Sociocultural factors that affect adherence to PrEP were explored using grounded analysis. Three factors were identified, which shape perceptions of PrEP: gendered power dynamics and control over decision-making in the household; conflicts between risk-reduction strategies and male sexual desire; culture-bound definitions of women's work. Adherence to PrEP in the Partners PrEP Study was high; however, participants articulated conflicting interests related to PrEP in connection with traditional gender roles. The successful delivery of PrEP will require understanding of key social factors, particularly related to gender and dyadic dynamics around HIV serostatus.

Vacuolar Localization of Endoproteinases EP(1) and EP(2) in Barley Mesophyll Cells.

Science.gov (United States)

Thayer, S S; Huffaker, R C

1984-05-01

The localization of two previously characterized endoproteinases (EP(1) and EP(2)) that comprise more than 95% of the protease activity in primary Hordeum vulgare L. var Numar leaves was determined. Intact vacuoles released from washed mesophyll protoplasts by gentle osmotic shock and increase in pH, were purified by flotation through a four-step Ficoll gradient. These vacuoles contained endoproteinases that rapidly degraded purified barley ribulose-1,5-bisphosphate carboxylase (RuBPCase) substrate. Breakdown products and extent of digestion of RuBPCase were determined using 12% polyacrylamide-sodium dodecyl sulfate gels. Coomassie brilliant blue- or silver-stained gels were scanned, and the peaks were integrated to provide quantitative information. The characteristics of the vacuolar endoproteinases (e.g. sensitivity to various inhibitors and activators, and the molecular weights of the breakdown products, i.e. peptide maps) closely resembled those of purified EP(1) and partially purified EP(2). It is therefore concluded that EP(1) and EP(2) are localized in the vacuoles of mesophyll cells.

PrEP (Pre-Exposure Prophylaxis) 101

Science.gov (United States)

... than 70%. Your risk of getting HIV from sex can be even lower if you combine PrEP with condoms and other prevention methods. Download PrEP 101 Consumer Info Sheet Vital Signs Fact Sheet on Daily Pill Can Prevent HIV (PrEP) Expand All Collapse All Video Introductions to PrEP What is PrEP? A Brief ...

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

Science.gov (United States)

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.

The decision-making threshold and the factors that affect it: A qualitative study of patients' decision-making in knee replacement surgery.

Science.gov (United States)

Barlow, T; Scott, P; Thomson, L; Griffin, D; Realpe, A

2018-03-01

Osteoarthritis is a significant cause of burden to the ageing population and knee replacement is a common operation for treatment of end-stage disease. We aimed to explore these factors to help understand patients' decision-making, which is critical in informing patient-centred care. These can be used to enhance decision-making and dialogue between clinicians and patients, allowing a more informed choice. The study consisted of two focus groups, in a patient cohort after total knee replacement followed by more in-depth interviews to further test and explore themes from the focus groups, in patients in either the deliberation stage or the decision-making stage. Using qualitative research methods (iterative thematic analysis) reviewing decision-making and deliberation phases of making informed choices we found nine key themes that emerged from the study groups. An awareness of the deliberation phase, the factors that influence it, the stress associated with it, preferred models of care, and the influence of the decision-making threshold will aid useful communication between doctors and patients. Copyright © 2017 John Wiley & Sons, Ltd.

The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus

Science.gov (United States)

Rojas, Asheebo; Gueorguieva, Paoula; Lelutiu, Nadia; Quan, Yi; Shaw, Renee; Dingledine, Raymond

2014-01-01

Prostaglandin E2 (PGE2) regulates membrane excitability, synaptic transmission, plasticity, and neuronal survival. The consequences of PGE2 release following seizures has been the subject of much study. Here we demonstrate that the prostaglandin E2 receptor 1 (EP1, or Ptger1) modulates native kainate receptors, a family of ionotropic glutamate receptors widely expressed throughout the central nervous system. Global ablation of the EP1 gene in mice (EP1-KO) had no effect on seizure threshold after kainate injection but reduced the likelihood to enter status epilepticus. EP1-KO mice that did experience typical status epilepticus had reduced hippocampal neurodegeneration and a blunted inflammatory response. Further studies with native prostanoid and kainate receptors in cultured cortical neurons, as well as with recombinant prostanoid and kainate receptors expressed in Xenopus oocytes, demonstrated that EP1 receptor activation potentiates heteromeric but not homomeric kainate receptors via a second messenger cascade involving phospholipase C, calcium and protein kinase C. Three critical GluK5 C-terminal serines underlie the potentiation of the GluK2/GluK5 receptor by EP1 activation. Taken together, these results indicate that EP1 receptor activation during seizures, through a protein kinase C pathway, increases the probability of kainic acid induced status epilepticus, and independently promotes hippocampal neurodegeneration and a broad inflammatory response. PMID:24952362

Integration of ecological-biological thresholds in conservation decision making.

Science.gov (United States)

Mavrommati, Georgia; Bithas, Kostas; Borsuk, Mark E; Howarth, Richard B

2016-12-01

In the Anthropocene, coupled human and natural systems dominate and only a few natural systems remain relatively unaffected by human influence. On the one hand, conservation criteria based on areas of minimal human impact are not relevant to much of the biosphere. On the other hand, conservation criteria based on economic factors are problematic with respect to their ability to arrive at operational indicators of well-being that can be applied in practice over multiple generations. Coupled human and natural systems are subject to economic development which, under current management structures, tends to affect natural systems and cross planetary boundaries. Hence, designing and applying conservation criteria applicable in real-world systems where human and natural systems need to interact and sustainably coexist is essential. By recognizing the criticality of satisfying basic needs as well as the great uncertainty over the needs and preferences of future generations, we sought to incorporate conservation criteria based on minimal human impact into economic evaluation. These criteria require the conservation of environmental conditions such that the opportunity for intergenerational welfare optimization is maintained. Toward this end, we propose the integration of ecological-biological thresholds into decision making and use as an example the planetary-boundaries approach. Both conservation scientists and economists must be involved in defining operational ecological-biological thresholds that can be incorporated into economic thinking and reflect the objectives of conservation, sustainability, and intergenerational welfare optimization. © 2016 Society for Conservation Biology.

EP BICYCLE POOL - VIGNETTES 2002

CERN Multimedia

EP-SMI Help Desk

2002-01-01

The vignettes (insurance certificates) for 2002 become obligatory from 1 June. If you have a bicycle from the EP Pool, please bring it to the EP-SMI Help Desk (Building 124) on any working day up to 31 May between 8h.30 - 12h.00 or 13h.30 - 17h.30. EP-SMI Help Desk

Hydrodynamic impacts on biogenic stabilisation and the fate of extracellular polymeric substances (EPS) in mixed sediment bedforms.

Science.gov (United States)

Hope, J. A.; Aspden, R.; Schindler, R.; Parsons, D. R.; Ye, L.; Baas, J.; Paterson, D. M.

2014-12-01

The stability and morphology of bedforms have traditionally been treated as a function of mean flow velocity/non-dimensional bed shear stress and sediment particle size, despite the known influence of key biological components such as extracellular polymeric substances (EPS). EPS is produced by microbial communities and can increase erosion thresholds by more than 300%. However, the mechanisms behind the influence of EPS on sediment transport and bedform dynamics is poorly understood, as is the fate of EPS and exchange of EPS between the sediment bed and water column during ripple formation. The exchange of EPS between the sediment bed and water column is dynamic, with important implications for a range of physical and geochemical processes, with the spatio-temporal variation in EPS content, from source to eventual fate, being extremely important for determining the behaviour and natural variability of sedimentary systems. This paper reports on a series of flume experiments where a tripartite mixture of sand, clay and model EPS (xanthan gum) was used to create a sediment substrate, which was subject to a unidirectional current (0.8 ms-1 for 10.5 hrs, n=6). For each run the spatio-temporal changes in concentration, distribution, and effect of EPS, on the evolving bed of mixed sediment was monitored throughout, with complete 3D bed morphology scans also acquired at ~360 s intervals. The various substrate mixtures produced bedforms varying from ripples to dunes and biochemical analysis of EPS concentration across the formed bedforms, suggest EPS is winnowed from the sediment - water interface, particularly at the bedform crests. The depth of winnowing in each run was found to be related to the bedform size, with variation in the stoss, crest and trough of the bedforms identified. The loss of EPS was also significantly correlated with the depth to which clay was winnowed, presumably due to a close association between the clay mineral and EPS fractions. The paper will

Network meta-analysis of diagnostic test accuracy studies identifies and ranks the optimal diagnostic tests and thresholds for health care policy and decision-making.

Science.gov (United States)

Owen, Rhiannon K; Cooper, Nicola J; Quinn, Terence J; Lees, Rosalind; Sutton, Alex J

2018-07-01

Network meta-analyses (NMA) have extensively been used to compare the effectiveness of multiple interventions for health care policy and decision-making. However, methods for evaluating the performance of multiple diagnostic tests are less established. In a decision-making context, we are often interested in comparing and ranking the performance of multiple diagnostic tests, at varying levels of test thresholds, in one simultaneous analysis. Motivated by an example of cognitive impairment diagnosis following stroke, we synthesized data from 13 studies assessing the efficiency of two diagnostic tests: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), at two test thresholds: MMSE accounting for the correlations between multiple test accuracy measures from the same study. We developed and successfully fitted a model comparing multiple tests/threshold combinations while imposing threshold constraints. Using this model, we found that MoCA at threshold decision making. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

PrEP Whores and HIV Prevention: The Queer Communication of HIV Pre-Exposure Prophylaxis (PrEP).

Science.gov (United States)

Spieldenner, Andrew

2016-12-01

HIV pre-exposure prophylaxis (PrEP) has been introduced as another biomedical tool in HIV prevention. Whereas other such tools-including post-exposure prophylaxis (PEP) and interruption of perinatal transmission-have been embraced by those impacted by HIV, PrEP has been met with more conflict, especially within the gay community and HIV organizations. The "PrEP whore" has come to designate the social value and personal practices of those taking PrEP. This study examines the "PrEP whore" discourse by using queer theory and quare theory. Within these theoretical vantage points, the study explicates four discursive areas: slut shaming, dirty/clean binaries, mourning the loss of condoms, and reclaiming the inner whore. The study illuminates possible discursive strategies that lie outside of the domains of public health and within the individual and community.

Factors influencing access to education, decision making, and receipt of preferred dialysis modality in unplanned dialysis start patients

DEFF Research Database (Denmark)

Machowska, Anna; Alscher, Mark Dominik; Vanga, Satyanarayana Reddy

2016-01-01

for patients receiving education, making a decision, and receiving their preferred modality choice in UPS patients following a UPS educational program (UPS-EP). Methods: The Offering Patients Therapy Options in Unplanned Start (OPTiONS) study examined the impact of the implementation of a specific UPS......-EP, including decision support tools and pathway improvement on dialysis modality choice. Linear regression models were used to examine the factors predicting three key steps: referral and receipt of UPS-EP, modality decision making, and actual delivery of preferred modality choice. A simple economic assessment...... was performed to examine the potential benefit of implementing UPS-EP in terms of dialysis costs. Results: The majority of UPS patients could receive UPS-EP (214/270 patients) and were able to make a decision (177/214), although not all patients received their preferred choice (159/177). Regression analysis...

Easy-access Services in Low-threshold Opiate Agonist Maintenance

DEFF Research Database (Denmark)

Hesse, Morten; Pedersen, Mads Uffe

2007-01-01

Background: There is currently evidence that methadone and buprenorphine maintenance is effective in reducing substance abuse. However, it is not known whether psychosocial support improves the outcome of methadone maintenance in the absence of control measures, such as regular urine testing....... Materials and Methods: In a prospective observational study, the effectiveness of standard psychosocial support [SPS] was compared with enhanced psychosocial support [EPS]. EPS included intensive case management and drop-in centres. Subjects were administered the Addiction Severity Index before and after...... in the control group. Change in psychiatric and social problems were associated with the absence of no-shows. Discussion: Enhanced psychosocial support appeared to be effective at reducing problems associated with drug use in a low-threshold buprenorphine or methadone maintenance setting without substantial...

Using natural range of variation to set decision thresholds: a case study for great plains grasslands

Science.gov (United States)

Symstad, Amy J.; Jonas, Jayne L.; Edited by Guntenspergen, Glenn R.

2014-01-01

Natural range of variation (NRV) may be used to establish decision thresholds or action assessment points when ecological thresholds are either unknown or do not exist for attributes of interest in a managed ecosystem. The process for estimating NRV involves identifying spatial and temporal scales that adequately capture the heterogeneity of the ecosystem; compiling data for the attributes of interest via study of historic records, analysis and interpretation of proxy records, modeling, space-for-time substitutions, or analysis of long-term monitoring data; and quantifying the NRV from those data. At least 19 National Park Service (NPS) units in North America’s Great Plains are monitoring plant species richness and evenness as indicators of vegetation integrity in native grasslands, but little information on natural, temporal variability of these indicators is available. In this case study, we use six long-term vegetation monitoring datasets to quantify the temporal variability of these attributes in reference conditions for a variety of Great Plains grassland types, and then illustrate the implications of using different NRVs based on these quantities for setting management decision thresholds. Temporal variability of richness (as measured by the coefficient of variation, CV) is fairly consistent across the wide variety of conditions occurring in Colorado shortgrass prairie to Minnesota tallgrass sand savanna (CV 0.20–0.45) and generally less than that of production at the same sites. Temporal variability of evenness spans a greater range of CV than richness, and it is greater than that of production in some sites but less in other sites. This natural temporal variability may mask undesirable changes in Great Plains grasslands vegetation. Consequently, we suggest that managers consider using a relatively narrow NRV (interquartile range of all richness or evenness values observed in reference conditions) for designating a surveillance threshold, at which

New developments on the e-p instability at the Los Alamos Proton Storage Ring

International Nuclear Information System (INIS)

Macek, R.J.; Browman, A.; Fitzgerald, D.H.; McCrady, R.; Plum, M.; Spickermann, T.

2001-01-01

New results are reported from an R and D program aimed greater understanding and control of the e-p instability observed at the Los Alamos Proton Storage Rings (PSR). Numerous characteristics of the electron cloud for both stable and unstable beams in PSR were measured with ANL electron analyzers and various collection plates. Strong suppression of the electron flux density by TiN coating of the vacuum chamber in a straight section was also observed, thereby confirming an essential role for secondary emission at the walls. Landau Damping by a variety of techniques including higher rf voltage, transverse coupling, multipole fields in the lattice, and the use of inductive inserts has been effective in controlling the e-p instability. By these methods, the instability threshold has been raised significantly to 9.7 micro Coulombs per stored pulse. (author)

Production of extracellular polymeric substances (EPS) by Serratia sp.1 using wastewater sludge as raw material and flocculation activity of the EPS produced.

Science.gov (United States)

Bezawada, J; Hoang, N V; More, T T; Yan, S; Tyagi, N; Tyagi, R D; Surampalli, R Y

2013-10-15

Growth profile and extracellular polymeric substances (EPS) production of Serratia sp.1 was studied in shake flask fermentation for 72 h using wastewater sludge as raw material. Maximum cell concentration of 6.7 × 10(9) cfu/mL was obtained at 48 h fermentation time. EPS dry weight, flocculation activity and dewaterability of different EPS (tightly bound or TB-EPS, loosely bound or LB-EPS and broth-EPS or B-EPS) were also measured. The highest concentration of LB-EPS (2.45 g/L) and TB-EPS (0.99 g/L) were attained at 48 h of fermentation. Maximum flocculation activity and dewaterability (ΔCST) of TB-EPS (76.4%, 14.5s and 76.5%, 15.5s), LB-EPS (67.8%, 8.1s and 64.7%, 7.6s) and broth EPS (61%, 6.1s and 70.4%, 6.8s) were obtained at 36 and 48 h of growth. Higher flocculation activity and dewaterability were achieved with TB-EPS than with the two other EPS. Characterization of TB-EPS and LB-EPS was done in terms of their protein and carbohydrate content. Protein content was much higher in TB-EPS where as carbohydrate content was only slightly higher in TB-EPS than LB-EPS. Morphology of the Serratia strain after fermentation in sludge and TSB was observed under a scanning electron microscope and the cell size was found to be bigger in the sludge medium than the TSB medium. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cost-effectiveness thresholds: pros and cons.

Science.gov (United States)

Bertram, Melanie Y; Lauer, Jeremy A; De Joncheere, Kees; Edejer, Tessa; Hutubessy, Raymond; Kieny, Marie-Paule; Hill, Suzanne R

2016-12-01

Cost-effectiveness analysis is used to compare the costs and outcomes of alternative policy options. Each resulting cost-effectiveness ratio represents the magnitude of additional health gained per additional unit of resources spent. Cost-effectiveness thresholds allow cost-effectiveness ratios that represent good or very good value for money to be identified. In 2001, the World Health Organization's Commission on Macroeconomics in Health suggested cost-effectiveness thresholds based on multiples of a country's per-capita gross domestic product (GDP). In some contexts, in choosing which health interventions to fund and which not to fund, these thresholds have been used as decision rules. However, experience with the use of such GDP-based thresholds in decision-making processes at country level shows them to lack country specificity and this - in addition to uncertainty in the modelled cost-effectiveness ratios - can lead to the wrong decision on how to spend health-care resources. Cost-effectiveness information should be used alongside other considerations - e.g. budget impact and feasibility considerations - in a transparent decision-making process, rather than in isolation based on a single threshold value. Although cost-effectiveness ratios are undoubtedly informative in assessing value for money, countries should be encouraged to develop a context-specific process for decision-making that is supported by legislation, has stakeholder buy-in, for example the involvement of civil society organizations and patient groups, and is transparent, consistent and fair.

Cost–effectiveness thresholds: pros and cons

Science.gov (United States)

Lauer, Jeremy A; De Joncheere, Kees; Edejer, Tessa; Hutubessy, Raymond; Kieny, Marie-Paule; Hill, Suzanne R

2016-01-01

Abstract Cost–effectiveness analysis is used to compare the costs and outcomes of alternative policy options. Each resulting cost–effectiveness ratio represents the magnitude of additional health gained per additional unit of resources spent. Cost–effectiveness thresholds allow cost–effectiveness ratios that represent good or very good value for money to be identified. In 2001, the World Health Organization’s Commission on Macroeconomics in Health suggested cost–effectiveness thresholds based on multiples of a country’s per-capita gross domestic product (GDP). In some contexts, in choosing which health interventions to fund and which not to fund, these thresholds have been used as decision rules. However, experience with the use of such GDP-based thresholds in decision-making processes at country level shows them to lack country specificity and this – in addition to uncertainty in the modelled cost–effectiveness ratios – can lead to the wrong decision on how to spend health-care resources. Cost–effectiveness information should be used alongside other considerations – e.g. budget impact and feasibility considerations – in a transparent decision-making process, rather than in isolation based on a single threshold value. Although cost–effectiveness ratios are undoubtedly informative in assessing value for money, countries should be encouraged to develop a context-specific process for decision-making that is supported by legislation, has stakeholder buy-in, for example the involvement of civil society organizations and patient groups, and is transparent, consistent and fair. PMID:27994285

Measurement of Beauty Photoproduction near Threshold using Di-electron Events with the H1 Detector at HERA

CERN Document Server

Aaron, F.D.; Andreev, V.; Backovic, S.; Baghdasaryan, A.; Baghdasaryan, S.; Barrelet, E.; Bartel, W.; Begzsuren, K.; Belousov, A.; Belov, P.; Bizot, J.C.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Britzger, D.; Bruncko, D.; Bunyatyan, A.; Bylinkin, A.; Bystritskaya, L.; Campbell, A.J.; Cantun Avila, K.B.; Ceccopieri, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Contreras, J.G.; Coughlan, J.A.; Cvach, J.; Dainton, J.B.; Daum, K.; Delcourt, B.; Delvax, J.; De Wolf, E.A.; Diaconu, C.; Dobre, M.; Dodonov, V.; Dossanov, A.; Dubak, A.; Eckerlin, G.; Egli, S.; Eliseev, A.; Elsen, E.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Fischer, D.J.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, S.; Glazov, A.; Goerlich, L.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Grebenyuk, A.; Greenshaw, T.; Grindhammer, G.; Habib, S.; Haidt, D.; Henderson, R.C.W.; Hennekemper, E.; Henschel, H.; Herbst, M.; Herrera, G.; Hildebrandt, M.; Hiller, K.H.; Hoffmann, D.; Horisberger, R.; Hreus, T.; Huber, F.; Jacquet, M.; Janssen, X.; Jonsson, L.; Jung, A.W.; Jung, H.; Kapichine, M.; Kenyon, I.R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Kogler, R.; Kostka, P.; Kramer, M.; Kretzschmar, J.; Kruger, K.; Landon, M.P.J.; Lange, W.; Lastovicka-Medin, G.; Laycock, P.; Lebedev, A.; Lendermann, V.; Levonian, S.; Lipka, K.; List, B.; List, J.; Lobodzinski, B.; Lopez-Fernandez, R.; Lubimov, V.; Malinovski, E.; Martyn, H.U.; Maxfield, S.J.; Mehta, A.; Meyer, A.B.; Meyer, H.; Meyer, J.; Mikocki, S.; Milcewicz-Mika, I.; Moreau, F.; Morozov, A.; Morris, J.V.; Muller, K.; Naumann, Th.; Newman, P.R.; Niebuhr, C.; Nikitin, D.; Nowak, G.; Nowak, K.; Olivier, B.; Olsson, J.E.; Ozerov, D.; Pahl, P.; Palichik, V.; Pandurovic, M.; Pascaud, C.; Patel, G.D.; Perez, E.; Petrukhin, A.; Picuric, I.; Pirumov, H.; Pitzl, D.; Placakyte, R.; Pokorny, B.; Polifka, R.; Povh, B.; Radescu, V.; Raicevic, N.; Ravdandorj, T.; Reimer, P.; Rizvi, E.; Robmann, P.; Roosen, R.; Rostovtsev, A.; Rotaru, M.; Ruiz Tabasco, J.E.; Rusakov, S.; Salek, D.; Sankey, D.P.C.; Sauter, M.; Sauvan, E.; Schmitt, S.; Schoeffel, L.; Schoning, A.; Schultz-Coulon, H.C.; Sefkow, F.; Shtarkov, L.N.; Shushkevich, S.; Sloan, T.; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, A.; Staykova, Z.; Steder, M.; Stella, B.; Stoicea, G.; Straumann, U.; Sykora, T.; Thompson, P.D.; Tran, T.H.; Traynor, D.; Truol, P.; Tsakov, I.; Tseepeldorj, B.; Turnau, J.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Vazdik, Y.; Wegener, D.; Wunsch, E.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhokin, A.; Zlebcik, R.; Zohrabyan, H.; Zomer, F.

2012-10-03

The cross section for ep -> e b\\bar{b} X in photoproduction is measured with the H1 detector at the ep-collider HERA. The decay channel b\\bar{b} -> ee X' is selected by identifying the semi-electronic decays of the b-quarks. The total production cross section is measured in the kinematic range given by the photon virtuality Q^2 down to the threshold. The results are compared to next-to-leading-order QCD predictions.

Fosforihapon epäpuhtauksien uuttaminen

OpenAIRE

Sengström, Heli

2012-01-01

Fosforihappoa tuotetaan yleisesti sekä märkäprosessilla että termisellä prosessilla. Märkäprosessilla tuotettuun fosforihappoon jää erilaisia epäpuhtauksia, joita ei happoa käytettäessä saisi olla. Yleisimmät epäpuhtaudet ovat erilaiset fluoridit, kloridit ja metallit. Tämän opinnäytetyön tavoitteena oli selvittää, kuinka hyvin nämä epäpuhtaudet saadaan poistettua uuttamalla happoa liuottimella, jossa on 80 % tributyylifosfaattia (TBP) ja 20 % ExxsolTM D80 -laimenninta. Työn kokeellisessa ...

Thresholds for decision-making: informing the cost-effectiveness and affordability of rotavirus vaccines in Malaysia.

Science.gov (United States)

Loganathan, Tharani; Ng, Chiu-Wan; Lee, Way-Seah; Hutubessy, Raymond C W; Verguet, Stéphane; Jit, Mark

2018-03-01

Cost-effectiveness thresholds (CETs) based on the Commission on Macroeconomics and Health (CMH) are extensively used in low- and middle-income countries (LMICs) lacking locally defined CETs. These thresholds were originally intended for global and regional prioritization, and do not reflect local context or affordability at the national level, so their value for informing resource allocation decisions has been questioned. Using these thresholds, rotavirus vaccines are widely regarded as cost-effective interventions in LMICs. However, high vaccine prices remain a barrier towards vaccine introduction. This study aims to evaluate the cost-effectiveness, affordability and threshold price of universal rotavirus vaccination at various CETs in Malaysia. Cost-effectiveness of Rotarix and RotaTeq were evaluated using a multi-cohort model. Pan American Health Organization Revolving Fund's vaccine prices were used as tender price, while the recommended retail price for Malaysia was used as market price. We estimate threshold prices defined as prices at which vaccination becomes cost-effective, at various CETs reflecting economic theories of human capital, societal willingness-to-pay and marginal productivity. A budget impact analysis compared programmatic costs with the healthcare budget. At tender prices, both vaccines were cost-saving. At market prices, cost-effectiveness differed with thresholds used. At market price, using 'CMH thresholds', Rotarix programmes were cost-effective and RotaTeq were not cost-effective from the healthcare provider's perspective, while both vaccines were cost-effective from the societal perspective. Using other CETs, both vaccines were not cost-effective at market price, from the healthcare provider's and societal perspectives. At tender and cost-effective prices, rotavirus vaccination cost ∼1 and 3% of the public health budget, respectively. Using locally defined thresholds, rotavirus vaccination is cost-effective at vaccine prices in line

Prostaglandin E2 EP2 and EP4 receptor activation mediates cAMP-dependent hyperpolarization and exocytosis of renin in juxtaglomerular cells

DEFF Research Database (Denmark)

Friis, Ulla Glenert; Stubbe, Jane; Uhrenholt, Torben Rene

2005-01-01

/l), AE1-259-01 (1 nmol/l), EP4-selective agonist AE1-329 (1 nmol/l), and IP agonist iloprost (1 micromol/l) significantly increased C(m) mediated by PKA. The EP4 antagonist AE3-208 (10 nmol/l) blocked the effect of EP4 agonist but did not alter the response to PGE(2). Application of both EP4 antagonist....... The membrane potential hyperpolarized significantly after PGE(2), butaprost, AE1-329 and AE1-259 and outward current was augmented in a PKA-dependent fashion. PGE(2)-stimulated outward current, but not C(m) change, was abolished by the BK(Ca) channel inhibitor iberiotoxin (300 nmol/l). EP2 and EP4 m......RNA was detected in sampled JG cells, and the preglomerular and glomerular vasculature was immunopositive for EP4. Thus IP, EP2, and EP4 receptors are associated with JG cells, and their activation leads to rapid PKA-mediated exocytotic fusion and release of renin granules....

Reduction in growth threshold for pulmonary metastases: an opportunity for volumetry and its impact on treatment decisions.

Science.gov (United States)

Vogel, M N; Schmücker, S; Maksimovic, O; Hartmann, J; Claussen, C D; Horger, M

2012-07-01

This study compares tumour response assessment by automated CT volumetry and standard manual measurements regarding the impact on treatment decisions and patient outcome. 58 consecutive patients with 203 pulmonary metastases undergoing baseline and follow-up multirow detector CT (MDCT) under chemotherapy were assessed for response to chemotherapy. Tumour burden of pulmonary target lesions was quantified in three ways: (1) following response evaluation criteria in solid tumours (RECIST); (2) following the volume equivalents of RECIST (i.e. with a threshold of -65/+73%); and (3) using calculated limits for stable disease (SD). For volumetry, calculated limits had been set at ±38% prior to the study by repeated quantification of nodules scanned twice. Results were compared using non-weighted κ-values and were evaluated for their impact on treatment decisions and patient outcome. In 15 (17%) of the 58 patients, the results of response assessment were inconsistent with 1 of the 3 methods, which would have had an impact on treatment decisions in 8 (13%). Patient outcome regarding therapy response could be verified in 5 (33%) of the 15 patients with inconsistent measurement results and was consistent with both RECIST and volumetry in 1, with calculated limits in 3 and with none in 1. Diagnosis as to the overall response was consistent with RECIST in six patients, with volumetry in six and with calculated limits in eight cases. There is an impact of different methods for therapy response assessment on treatment decisions. A reduction of threshold for SD to ±30-40% of volume change seems reasonable when using volumetry.

Co-decision in the European Parliament: Comparing Rationalist and Constructivist Explanations of the Returns Directive

Directory of Open Access Journals (Sweden)

Ariadna Ripoll Servent

2011-02-01

Full Text Available This study uses rationalist and constructivist explanations of co-decision in the European Parliament (EP. It seeks to understand the change in the policy preferences of the EP during negotiations on the ‘Returns’ directive – dealing with the voluntary or compulsory return of irregular immigrants. This article shows that the introduction of co-decision contributed considerably to the EP’s change of stance on immigration policies. A long-standing advocate of civil liberties in the Area of Freedom, Security and Justice (AFSJ, the EP was expected to raise the standards of protection for third-country nationals. In view of the inability of the EP to construct a more liberal policy, the study uses two institutionalist approaches to understand why the EP was unsuccessful in raising the standards. Therefore, the approaches aim at identifying the logics and layers of change. The empirical application of the models highlights the necessity to integrate rationalist and constructivist understandings of co-decision in order to understand motivations for policy change. Synergies in the direction of change also point to the importance of institutional motivations, in order to understand major changes in the policy preferences of the EP.

Home-based pre-exposure prophylaxis (PrEP services for gay and bisexual men: An opportunity to address barriers to PrEP uptake and persistence.

Directory of Open Access Journals (Sweden)

Steven A John

Full Text Available Gay, bisexual, and other men who have sex with men (GBM are disproportionately affected by the HIV epidemic. Despite the promise of pre-exposure prophylaxis (PrEP in reducing HIV transmission risk, barriers for uptake and persistence exist. We sought to identify whether GBM in a nationwide cohort who have not yet initiated PrEP (n = 906 would prefer to get PrEP-related care from a primary care provider (PCP compared to a specialist clinic or provider. We then sought to identify their level of interest and factors associated with preference for using home-based PrEP services (i.e., HB-PrEP, defined to participants as conducting HIV/STI self-testing from home with PrEP prescription mailing after an initial in-person clinic visit. We examined the associations of demographics, sexual HIV transmission risk, concern about frequent medical checkups associated with PrEP, health care access, and PrEP intentions with preferences for healthcare provider type and HB-PrEP. Concern about frequent medical checkups were associated with preferring a PCP for PrEP-related care, but men who perceived a barrier to bringing up the topic of PrEP with a doctor preferred a specialist clinic or provider more than a PCP. HB-PrEP was more appealing for younger men and those engaged in sexual HIV transmission risk, suggesting HB-PrEP could help reach GBM most vulnerable to HIV and in need of PrEP. HB-PrEP expansion has potential to increase PrEP uptake and persistence among GBM, particularly for men with barriers to clinic-based care and higher intentions to initiate PrEP. Clinical guidelines regarding HB-PrEP are needed to expand its use.

Development of the nuclear weapons complex EP architecture

Energy Technology Data Exchange (ETDEWEB)

Murray, C.; Halbleib, L.

1996-07-01

The Nuclear Weapons Guidance Team is an interagency committee led by Earl Whiteman, DOE that chartered the generation of EP40100, Concurrent Qualification and its successor EP401099, Concurrent Engineering and Qualification. As this new philosophy of concurrent operations has evolved and as implementation has been initiated, conflicts and insufficiencies in the remaining Engineering Procedures (EPs) have become more apparent. At the Guidance Team meeting in November 1995, this issue was explored and several approaches were considered. It was concluded at this meeting, that a smaller set of interagency EPs described in a hierarchical system could provide the necessary interagency direction to support complex-wide implementation. This set consolidates many existing EP processes where consistency and commonality are critical to success of the extended enterprise. The Guidance Team subsequently chartered an interagency team to initiate development activity associated with the envisioned new EP set. This team had participation from seven Nuclear Weapons Complex (NWC) sites as well as DOE/AL and DP-14 (team members are acknowledged later in this report). Per the Guidance Team, this team, referred to as the Architecture Subcommittee, was to map out and define an EP Architecture for the interagency EPs, make recommendations regarding a more agile process for EP approval and suggest an aggressive timeline to develop the combined EPs. The Architecture Subcommittee was asked to brief their output at the February Guidance Team meeting. This SAND report documents the results of the Architecture Subcommittee`s recommendations.

Factors influencing access to education, decision making, and receipt of preferred dialysis modality in unplanned dialysis start patients.

Science.gov (United States)

Machowska, Anna; Alscher, Mark Dominik; Reddy Vanga, Satyanarayana; Koch, Michael; Aarup, Michael; Qureshi, Abdul Rashid; Lindholm, Bengt; Rutherford, Peter A

2016-01-01

Unplanned dialysis start (UPS) leads to worse clinical outcomes than planned start, and only a minority of patients ever receive education on this topic and are able to make a modality choice, particularly for home dialysis. This study aimed to determine the predictive factors for patients receiving education, making a decision, and receiving their preferred modality choice in UPS patients following a UPS educational program (UPS-EP). The Offering Patients Therapy Options in Unplanned Start (OPTiONS) study examined the impact of the implementation of a specific UPS-EP, including decision support tools and pathway improvement on dialysis modality choice. Linear regression models were used to examine the factors predicting three key steps: referral and receipt of UPS-EP, modality decision making, and actual delivery of preferred modality choice. A simple economic assessment was performed to examine the potential benefit of implementing UPS-EP in terms of dialysis costs. The majority of UPS patients could receive UPS-EP (214/270 patients) and were able to make a decision (177/214), although not all patients received their preferred choice (159/177). Regression analysis demonstrated that the initial dialysis modality was a predictive factor for referral and receipt of UPS-EP and modality decision making. In contrast, age was a predictor for referral and receipt of UPS-EP only, and comorbidity was not a predictor for any step, except for myocardial infarction, which was a weak predictor for lower likelihood of receiving preferred modality. Country practices predicted UPS-EP receipt and decision making. Economic analysis demonstrated the potential benefit of UPS-EP implementation because dialysis modality costs were associated with modality distribution driven by patient preference. Education and decision support can allow UPS patients to understand their options and choose dialysis modality, and attention needs to be focused on ensuring equity of access to educational

Decision of pedagogical tasks as mean of forming of pedagogical position of students of higher education physical establishments

Directory of Open Access Journals (Sweden)

Stepanchenko N.I.

2012-08-01

Full Text Available In the article one of terms of forming of pedagogical position for the students of higher education physical establishments - decision of educational-pedagogical situations (EPS is examined. Monitoring of progress from pedagogical disciplines confronted with the results of experiment on determination of levels of decision of EPS by students is conducted. It is set that the traditional model of studies provides the high level of capture students theoretical knowledge, but does not influence on forming of them pedagogical position. Most students were shown by the medium-and-low levels of formed of abilities to decide EPS. It is set that the traditional model of teaching provides the high level of capture students theoretical knowledge's, but substantially does not influence on forming of their pedagogical position. Basic difficulties are certain at a decision the students of EPS, which allow to define the basic going near development of methodical accompaniment of EPS, which must include: educational material which is based on integration of pedagogical and sporting preparation with support on context approach; algorithm of decision of tasks; questions of cognitive character.

Using Critical Thresholds to Customize Climate Projections of Extreme Events to User Needs and Support Decisions

Science.gov (United States)

Garfin, G. M.; Petersen, A.; Shafer, M.; MacClune, K.; Hayhoe, K.; Riley, R.; Nasser, E.; Kos, L.; Allan, C.; Stults, M.; LeRoy, S. R.

2016-12-01

Many communities in the United States are already vulnerable to extreme events; many of these vulnerabilities are likely to increase with climate change. In order to promote the development of effective community responses to climate change, we tested a participatory process for developing usable climate science, in which our project team worked with decision-makers to identify extreme event parameters and critical thresholds associated with policy development and adaptation actions. Our hypothesis is that conveying climate science and data through user-defined parameters and thresholds will help develop capacity to streamline the use of climate projections in developing strategies and actions, and motivate participation by a variety of preparedness planners. Our team collaborated with urban decision-makers, in departments that included resilience, planning, public works, public health, emergency management, and others, in four cities in the semi-arid south-central plains and intermountain areas of Colorado, New Mexico, Oklahoma, and Texas. Through an iterative process, we homed in on both simple and hybrid indicators for which we could develop credible city-specific projections, to stimulate discussion about adaptation actions; throughout the process, we communicated information about confidence and uncertainty, in order to develop a blend of historic and projected climate data, as appropriate, depending on levels of uncertainty. Our collaborations have resulted in (a) the identification of more than 50 unique indicators and thresholds across the four communities, (b) the development of adaptation action strategies in each community, and (c) the implementation of actions, ranging from a climate leadership training program for city staff members, to a rainwater capture project to improve responses to expected increases in both stormwater runoff and water capture for drought episodes.

Dynamic Mechanical Properties of PMN/CNFs/EP Composites

International Nuclear Information System (INIS)

Shi Minxian; Huang Zhixiong; Qin Yan

2011-01-01

In this research, piezoelectric ceramic PMN(lead magnesium niobate-lead zirconate-lead titanate)/carbon nano-fibers(CNFs)/epoxy resin(EP) ccomposites were prepared and the dynamic mechanical properties and damping mechanism of PMN/CNFs/EP composites were investigated. The addition of CNFs into PMN/EP composite results in decrease of volume resistivity of the composite. When the concentration of CNFs is 0.6% weight of epoxy resin the volume resistivity of PMN/CNFs/EP composite is about 10 8 Ω·m. Dynamic mechanical analysis indicates that the loss factor, loss area, and damping temperature range of PMN/CNFs/EP composites increase with the CNFs content increasing till to 0.6% of weight of epoxy resin. When the CNFs content is more than 0.6% the damping properties of composites decrease oppositely. In PMN/CNFs/EP composites, the CNFs content 0.6% and the volume resistivity of PMN/CNFs/EP composites about 10 8 Ω·m just satisfy the practicing condition of piezo-damping, so the composites show optimal damping property.

Selected engineering properties and applications of EPS geofoam

Science.gov (United States)

Elragi, Ahmed Fouad

Expanded polystyrene (EPS) geofoam is a lightweight material that has been used in engineering applications since at least the 1950s. Its density is about a hundredth of that of soil. It has good thermal insulation properties with stiffness and compression strength comparable to medium clay. It is utilized in reducing settlement below embankments, sound and vibration damping, reducing lateral pressure on substructures, reducing stresses on rigid buried conduits and related applications. This study starts with an overview on EPS geofoam. EPS manufacturing processes are described followed by a review of engineering properties found in previous research work done so far. Standards and design manuals applicable to EPS are presented. Selected EPS geofoam-engineering applications are discussed with examples. State-of-the-art of experimental work is done on different sizes of EPS specimens under different loading rates for better understanding of the behavior of the material. The effects of creep, sample size, strain rate and cyclic loading on the stress strain response are studied. Equations for the initial modulus and the strength of the material under compression for different strain rates are presented. The initial modulus and Poisson's ratio are discussed in detail. Sample size effect on creep behavior is examined. Three EPS projects are shown in this study. The creep behavior of the largest EPS geofoam embankment fill is shown. Results from laboratory tests, mathematical modeling and field records are compared to each other. Field records of a geofoam-stabilized slope are compared to finite difference analysis results. Lateral stress reduction on an EPS backfill retaining structure is analyzed. The study ends with a discussion on two promising properties of EPS geofoam. These are the damping ability and the compressibility of this material. Finite element analysis, finite difference analysis and lab results are included in this discussion. The discussion with the

Highlights from e-EPS: Jean-Michel Raimond wins EPS Edison-Volta Prize 2014

CERN Multimedia

Martina Knoop, e-EPS News

2014-01-01

e-EPS News is a monthly addition to the CERN Bulletin line-up, showcasing articles from e-EPS – the European Physical Society newsletter – as part of a collaboration between the two publications.   The European Physical Society has the pleasure to announce that the 2014 EPS Edison-Volta Prize is awarded to Jean-Michel Raimond for “seminal contribution to physics (that) have paved the way for novel explorations of quantum mechanics and have opened new routes in quantum information processing”. J.-M. Raimond’s PhD thesis was supervised by Serge Haroche at the École Normale Supérieure in Paris, France, in the early 1980′s, and together S. Haroche, M. Brune and J.-M. Raimond have built an extremely successful research group since then. J.-M. Raimond has made seminal contributions to the development of cavity QED experiments, in particular involving circular Rydberg atoms interacting with very high-Q superc...

A maladaptive role for EP4 receptors in mouse mesangial cells.

Directory of Open Access Journals (Sweden)

Guang-xia Yang

Full Text Available Roles of the prostaglandin E2 E-prostanoid 4 receptor (EP4 on extracellular matrix (ECM accumulation induced by TGF-β1 in mouse glomerular mesangial cells (GMCs remain unknown. Previously, we have identified that TGF-β1 stimulates the expression of FN and Col I in mouse GMCs. Here we asked whether stimulation of EP4 receptors would exacerbate renal fibrosis associated with enhanced glomerular ECM accumulation. We generated EP4(Flox/Flox and EP4(+/- mice, cultured primary WT, EP4(Flox/Flox and EP4(+/- GMCs, AD-EP4 transfected WT GMCs (EP4 overexpression and AD-Cre transfected EP4(Flox/Flox GMCs (EP4 deleted. We found that TGF-β1-induced cAMP and PGE2 synthesis decreased in EP4 deleted GMCs and increased in EP4 overexpressed GMCs. Elevated EP4 expression in GMCs augmented the coupling of TGF-β1 to FN, Col I expression and COX2/PGE2 signaling, while TGF-β1 induced FN, Col I expression and COX2/PGE2 signaling were down-regulated in EP4 deficiency GMCs. 8 weeks after 5/6 nephrectomy (Nx, WT and EP4(+/- mice exhibited markedly increased accumulation of ECM compared with sham-operated controls. Albuminuria, blood urea nitrogen and creatinine (BUN and Cr concentrations were significantly increased in WT mice as compared to those of EP4(+/- mice. Urine osmotic pressure was dramatically decreased after 5/6 Nx surgery in WT mice as compared to EP4(+/- mice. The pathological changes in kidney of EP4(+/- mice was markedly alleviated compared with WT mice. Immunohistochemical analysis showed significant reductions of Col I and FN in the kidney of EP4(+/- mice compared with WT mice. Collectively, this investigation established EP4 as a potent mediator of the pro-TGF-β1 activities elicited by COX2/PGE2 in mice GMCs. Our findings suggested that prostaglandin E2, acting via EP4 receptors contributed to accumulation of ECM in GMCs and promoted renal fibrosis.

Extracellular polymeric substances (EPS) producing bacterial strains of municipal wastewater sludge: isolation, molecular identification, EPS characterization and performance for sludge settling and dewatering.

Science.gov (United States)

Bala Subramanian, S; Yan, S; Tyagi, R D; Surampalli, R Y

2010-04-01

Wastewater treatment plants often face the problems of sludge settling mainly due to sludge bulking. Generally, synthetic organic polymer and/or inorganic coagulants (ferric chloride, alum and quick lime) are used for sludge settling. These chemicals are very expensive and further pollute the environment. Whereas, the bioflocculants are environment friendly and may be used to flocculate the sludge. Extracellular polymeric substances (EPS) produced by sludge microorganisms play a definite role in sludge flocculation. In this study, 25 EPS producing strains were isolated from municipal wastewater treatment plant. Microorganisms were selected based on EPS production properties on solid agar medium. Three types of EPS (slime, capsular and bacterial broth mixture of both slime and capsular) were harvested and their characteristics were studied. EPS concentration (dry weight), viscosity and their charge (using a Zetaphoremeter) were also measured. Bioflocculability of obtained EPS was evaluated by measuring the kaolin clay flocculation activity. Six bacterial strains (BS2, BS8, BS9, BS11, BS15 and BS25) were selected based on the kaolin clay flocculation. The slime EPS was better for bioflocculation than capsular EPS and bacterial broth. Therefore, extracted slime EPS (partially purified) from six bacterial strains was studied in terms of sludge settling [sludge volume index (SVI)] and dewatering [capillary suction time (CST)]. Biopolymers produced by individual strains substantially improved dewaterability. The extracted slime EPS from six different strains were partially characterized. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Family planning providers' role in offering PrEP to women.

Science.gov (United States)

Seidman, Dominika; Weber, Shannon; Carlson, Kimberly; Witt, Jacki

2018-03-09

Pre-exposure prophylaxis (PrEP) provides a radically different HIV prevention option for women. Not only is PrEP the first discrete, woman-controlled method that is taken in advance of exposure, but it is both safe and highly effective, offering over 90% protection if taken daily. While multiple modalities of PrEP are in development ranging from vaginal rings to injectables and implants, only PrEP with oral tenofovir/emtricitabine is currently FDA-approved. Family planning clinics provide key access points for many women to learn about and obtain PrEP. By incorporating PrEP services into family planning care, family planning providers have the opportunity to meet women's expectations, ensure women are aware of and offered comprehensive HIV prevention options, and reverse emerging disparities in PrEP access. Despite real and perceived barriers to integrating PrEP into family planning care, providing PrEP services, ranging from education to onsite provision, is not only possible but an important component of providing high-quality sexual and reproductive healthcare to women. Lessons learned from early adopters will help guide those in family planning settings initiating or enhancing PrEP services. Copyright © 2018. Published by Elsevier Inc.

Highlights from e-EPS: Hetland to receive EPS-PED Award for Secondary School Teaching

CERN Multimedia

Urbaan Titulaer

2013-01-01

e-EPS News is an addition to the CERN Bulletin line-up, showcasing articles from e-EPS – the European Physical Society newsletter – as part of a collaboration between the two publications.   The EPS Physics Education Division selected Karl Thorstein Hetland, West Telemark Secondary School, Norway, as this year’s recipient of its Secondary School Teaching Award. K.T. Hetland developed the Energy Network, which aims to make students energy conscious and focus on renewable energy. The Energy Network, created in 2005, consists of 15 local networks, each involving an upper secondary school and several lower secondary schools, 55 schools in all. Material from the Network is used in physics classes in a large number of schools at national level and plays a major role in recruiting university physics students. K.T. Hetland will receive his award at the International Physics Education Conference, held together with the European Physics Educati...

PGE2 maintains the tone of the guinea pig trachea through a balance between activation of contractile EP1 receptors and relaxant EP2 receptors

Science.gov (United States)

Säfholm, J; Dahlén, S-E; Delin, I; Maxey, K; Stark, K; Cardell, L-O; Adner, M

2013-01-01

Background and Purpose The guinea pig trachea (GPT) is commonly used in airway pharmacology. The aim of this study was to define the expression and function of EP receptors for PGE2 in GPT as there has been ambiguity concerning their role. Experimental Approach Expression of mRNA for EP receptors and key enzymes in the PGE2 pathway were assessed by real-time PCR using species-specific primers. Functional studies of GPT were performed in tissue organ baths. Key Results Expression of mRNA for the four EP receptors was found in airway smooth muscle. PGE2 displayed a bell-shaped concentration–response curve, where the initial contraction was inhibited by the EP1 receptor antagonist ONO-8130 and the subsequent relaxation by the EP2 receptor antagonist PF-04418948. Neither EP3 (ONO-AE5-599) nor EP4 (ONO-AE3-208) selective receptor antagonists affected the response to PGE2. Expression of COX-2 was greater than COX-1 in GPT, and the spontaneous tone was most effectively abolished by selective COX-2 inhibitors. Furthermore, ONO-8130 and a specific PGE2 antibody eliminated the spontaneous tone, whereas the EP2 antagonist PF-04418948 increased it. Antagonists of other prostanoid receptors had no effect on basal tension. The relaxant EP2 response to PGE2 was maintained after long-term culture, whereas the contractile EP1 response showed homologous desensitization to PGE2, which was prevented by COX-inhibitors. Conclusions and Implications Endogenous PGE2, synthesized predominantly by COX-2, maintains the spontaneous tone of GPT by a balance between contractile EP1 receptors and relaxant EP2 receptors. The model may be used to study interactions between EP receptors. PMID:22934927

EpHLA software: a timesaving and accurate tool for improving identification of acceptable mismatches for clinical purposes.

Science.gov (United States)

Filho, Herton Luiz Alves Sales; da Mata Sousa, Luiz Claudio Demes; von Glehn, Cristina de Queiroz Carrascosa; da Silva, Adalberto Socorro; dos Santos Neto, Pedro de Alcântara; do Nascimento, Ferraz; de Castro, Adail Fonseca; do Nascimento, Liliane Machado; Kneib, Carolina; Bianchi Cazarote, Helena; Mayumi Kitamura, Daniele; Torres, Juliane Roberta Dias; da Cruz Lopes, Laiane; Barros, Aryela Loureiro; da Silva Edlin, Evelin Nildiane; de Moura, Fernanda Sá Leal; Watanabe, Janine Midori Figueiredo; do Monte, Semiramis Jamil Hadad

2012-06-01

The HLAMatchmaker algorithm, which allows the identification of “safe” acceptable mismatches (AMMs) for recipients of solid organ and cell allografts, is rarely used in part due to the difficulty in using it in the current Excel format. The automation of this algorithm may universalize its use to benefit the allocation of allografts. Recently, we have developed a new software called EpHLA, which is the first computer program automating the use of the HLAMatchmaker algorithm. Herein, we present the experimental validation of the EpHLA program by showing the time efficiency and the quality of operation. The same results, obtained by a single antigen bead assay with sera from 10 sensitized patients waiting for kidney transplants, were analyzed either by conventional HLAMatchmaker or by automated EpHLA method. Users testing these two methods were asked to record: (i) time required for completion of the analysis (in minutes); (ii) number of eplets obtained for class I and class II HLA molecules; (iii) categorization of eplets as reactive or non-reactive based on the MFI cutoff value; and (iv) determination of AMMs based on eplets' reactivities. We showed that although both methods had similar accuracy, the automated EpHLA method was over 8 times faster in comparison to the conventional HLAMatchmaker method. In particular the EpHLA software was faster and more reliable but equally accurate as the conventional method to define AMMs for allografts. The EpHLA software is an accurate and quick method for the identification of AMMs and thus it may be a very useful tool in the decision-making process of organ allocation for highly sensitized patients as well as in many other applications.

Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4

Science.gov (United States)

Torres-Atencio, Ivonne; Ainsua-Enrich, Erola; de Mora, Fernando; Picado, César; Martín, Margarita

2014-01-01

Background Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle to cause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the refractory period observed in patients with EIB. Objective This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction. Methods We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP) antagonists for EP1–4 were assayed on the activated mast cells. Beta-hexosaminidase release, protein phosphorylation, and calcium mobilization were assessed. Results Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogen-activated protein kinase (MAPK) pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP2 and EP4 receptors, as measured by beta-hexosaminidase release, and consequently calcium influx. Extracellular-signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 phosphorylation were diminished when compared with mannitol activation alone. Conclusions Our data show a protective role for the PGE2 receptors EP2 and EP4 following osmotic changes, through the reduction of human mast cell activity caused by calcium influx impairment and MAP kinase inhibition. PMID:25329458

Prostaglandin E2-Induced COX-2 Expressions via EP2 and EP4 Signaling Pathways in Human LoVo Colon Cancer Cells

Directory of Open Access Journals (Sweden)

Hsi-Hsien Hsu

2017-05-01

Full Text Available Metastasis is the most dangerous risk faced by patients with hereditary non-polyposis colon cancer (HNPCC. The expression of matrix metalloproteinases (MMPs has been observed in several types of human cancers and regulates the efficacy of many therapies. Here, we show that treatment with various concentrations of prostaglandin E2 (PGE2; 0, 1, 5 or 10 μM promotes the migration ability of the human LoVo colon cancer cell line. As demonstrated by mRNA and protein expression analyses, EP2 and EP4 are the major PGE2 receptors expressed on the LoVo cell membrane. The Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K/Akt cell survival pathway was upregulated by EP2 and EP4 activation. Following the activation of the PI3K/Akt pathway, β-catenin translocated into the nucleus and triggered COX2 transcription via LEF-1 and TCF-4 and its subsequent translation. COX2 expression correlated with the elevation in the migration ability of LoVo cells. The experimental evidence shows a possible mechanism by which PGE2 induces cancer cell migration and further suggests PGE2 to be a potential therapeutic target in colon cancer metastasis. On inhibition of PGE2, in order to determine the downstream pathway, the levels of PI3K/Akt pathway were suppressed and the β-catenin expression was also modulated. Inhibition of EP2 and EP4 shows that PGE2 induces protein expression of COX-2 through EP2 and EP4 receptors in LoVo colon cancer cells.

PrEP implementation research in Africa: what is new?

Science.gov (United States)

Cowan, Frances M; Delany-Moretlwe, Sinead; Sanders, Eduard J; Mugo, Nelly R; Guedou, Fernand A; Alary, Michel; Behanzin, Luc; Mugurungi, Owen; Bekker, Linda-Gail

2016-01-01

Of the two million new HIV infections in adults in 2014, 70% occurred in sub-Saharan Africa. Several African countries have already approved guidelines for pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV as part of combination HIV prevention but key questions remain about how to identify and deliver PrEP to those at greatest need. Throughout the continent, individuals in sero-discordant relationships, and members of key populations (sex workers, men who have sex with men (MSM), transgender women and injection drug users) are likely to benefit from the availability of PrEP. In addition, adolescent girls and young women (AGYW) are at substantial risk in some parts of the continent. It has been estimated that at least three million individuals in Africa are likely to be eligible for PrEP according to WHO's criteria. Tens of demonstration projects are planned or underway across the continent among a range of countries, populations and delivery settings. In each of the target populations, there are overarching issues related to (i) creating demand for PrEP, (ii) addressing supply-side issues and (iii) providing appropriate and tailored adherence support. Critical for creating demand for PrEP is the normalization of HIV prevention. Community-level interventions which engage opinion leaders as well as empowerment interventions for those at highest risk will be key. Critical to supply of PrEP is that services are accessible for all, including for stigmatized populations. Establishing accessible integrated services provides the opportunity to address other public health priorities including the unmet need for HIV testing, contraception and sexually transmitted infections treatment. National policies need to include minimum standards for training and quality assurance for PrEP implementation and to address supply chain issues. Adherence support needs to recognize that social and structural factors are likely to have an important influence

Afforest sDSS: a metamodel based spatial decision support system for afforestation of agricultural land

NARCIS (Netherlands)

Gilliams, S.; Orshoven, van J.; Muys, B.; Kros, J.; Heil, G.W.; Deursen, van W.

2005-01-01

The concept and structure of the Spatial Decision Support System AFFOREST sDSS dealing with environmental performance (EP) of afforestation on agricultural land in northwestern Europe, is presented. EP is defined in terms of three environmental impact categories: (1) carbon sequestration (2)

Clinical Applications for EPs in the ICU.

Science.gov (United States)

Koenig, Matthew A; Kaplan, Peter W

2015-12-01

In critically ill patients, evoked potential (EP) testing is an important tool for measuring neurologic function, signal transmission, and secondary processing of sensory information in real time. Evoked potential measures conduction along the peripheral and central sensory pathways with longer-latency potentials representing more complex thalamocortical and intracortical processing. In critically ill patients with limited neurologic exams, EP provides a window into brain function and the potential for recovery of consciousness. The most common EP modalities in clinical use in the intensive care unit include somatosensory evoked potentials, brainstem auditory EPs, and cortical event-related potentials. The primary indications for EP in critically ill patients are prognostication in anoxic-ischemic or traumatic coma, monitoring for neurologic improvement or decline, and confirmation of brain death. Somatosensory evoked potentials had become an important prognostic tool for coma recovery, especially in comatose survivors of cardiac arrest. In this population, the bilateral absence of cortical somatosensory evoked potentials has nearly 100% specificity for death or persistent vegetative state. Historically, EP has been regarded as a negative prognostic test, that is, the absence of cortical potentials is associated with poor outcomes while the presence cortical potentials are prognostically indeterminate. In recent studies, the presence of middle-latency and long-latency potentials as well as the amplitude of cortical potentials is more specific for good outcomes. Event-related potentials, particularly mismatch negativity of complex auditory patterns, is emerging as an important positive prognostic test in patients under comatose. Multimodality predictive algorithms that combine somatosensory evoked potentials, event-related potentials, and clinical and radiographic factors are gaining favor for coma prognostication.

PrEP implementation in the Asia-Pacific region: opportunities, implementation and barriers

Science.gov (United States)

Zablotska, Iryna; Grulich, Andrew E; Phanuphak, Nittaya; Anand, Tarandeep; Janyam, Surang; Poonkasetwattana, Midnight; Baggaley, Rachel; van Griensven, Frits; Lo, Ying-Ru

2016-01-01

Introduction HIV epidemics in the Asia-Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia-Pacific region, including opportunities and barriers. Discussion Awareness about PrEP in the Asia-Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non-existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger-scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher-, facility- and community-led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific. Conclusions Countries of the Asia-Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes. PMID:27760688

What Is the Optimal Threshold at Which to Recommend Breast Biopsy?

OpenAIRE

Burnside, Elizabeth S.; Chhatwal, Jagpreet; Alagoz, Oguzhan

2012-01-01

Background A 2% threshold, traditionally used as a level above which breast biopsy recommended, has been generalized to all patients from several specific situations analyzed in the literature. We use a sequential decision analytic model considering clinical and mammography features to determine the optimal general threshold for image guided breast biopsy and the sensitivity of this threshold to variation of these features. Methodology/Principal Findings We built a decision analytical model c...

Epstein-Barr Virus Nuclear Antigen Leader Protein Coactivates EP300.

Science.gov (United States)

Wang, Chong; Zhou, Hufeng; Xue, Yong; Liang, Jun; Narita, Yohei; Gerdt, Catherine; Zheng, Amy Y; Jiang, Runsheng; Trudeau, Stephen; Peng, Chih-Wen; Gewurz, Benjamin E; Zhao, Bo

2018-05-01

Epstein-Barr virus nuclear antigen (EBNA) leader protein (EBNALP) is one of the first viral genes expressed upon B-cell infection. EBNALP is essential for EBV-mediated B-cell immortalization. EBNALP is thought to function primarily by coactivating EBNA2-mediated transcription. Chromatin immune precipitation followed by deep sequencing (ChIP-seq) studies highlight that EBNALP frequently cooccupies DNA sites with host cell transcription factors (TFs), in particular, EP300, implicating a broader role in transcription regulation. In this study, we investigated the mechanisms of EBNALP transcription coactivation through EP300. EBNALP greatly enhanced EP300 transcription activation when EP300 was tethered to a promoter. EBNALP coimmunoprecipitated endogenous EP300 from lymphoblastoid cell lines (LCLs). EBNALP W repeat serine residues 34, 36, and 63 were required for EP300 association and coactivation. Deletion of the EP300 histone acetyltransferase (HAT) domain greatly reduced EBNALP coactivation and abolished the EBNALP association. An EP300 bromodomain inhibitor also abolished EBNALP coactivation and blocked the EP300 association with EBNALP. EBNALP sites cooccupied by EP300 had significantly higher ChIP-seq signals for sequence-specific TFs, including SPI1, RelA, EBF1, IRF4, BATF, and PAX5. EBNALP- and EP300-cooccurring sites also had much higher H3K4me1 and H3K27ac signals, indicative of activated enhancers. EBNALP-only sites had much higher signals for DNA looping factors, including CTCF and RAD21. EBNALP coactivated reporters under the control of NF-κB or SPI1. EP300 inhibition abolished EBNALP coactivation of these reporters. Clustered regularly interspaced short palindromic repeat interference targeting of EBNALP enhancer sites significantly reduced target gene expression, including that of EP300 itself. These data suggest a previously unrecognized mechanism by which EBNALP coactivates transcription through subverting of EP300 and thus affects the expression of

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

Directory of Open Access Journals (Sweden)

Keisuke Nagao

Full Text Available BACKGROUND: EpCAM (CD326 is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts, eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

Science.gov (United States)

Nagao, Keisuke; Zhu, Jianjian; Heneghan, Mallorie B; Hanson, Jeffrey C; Morasso, Maria I; Tessarollo, Lino; Mackem, Susan; Udey, Mark C

2009-12-31

EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

COX-2 and Prostaglandin EP3/EP4 Signaling Regulate the Tumor Stromal Proangiogenic Microenvironment via CXCL12-CXCR4 Chemokine Systems

Science.gov (United States)

Katoh, Hiroshi; Hosono, Kanako; Ito, Yoshiya; Suzuki, Tatsunori; Ogawa, Yasufumi; Kubo, Hidefumi; Kamata, Hiroki; Mishima, Toshiaki; Tamaki, Hideaki; Sakagami, Hiroyuki; Sugimoto, Yukihiko; Narumiya, Shuh; Watanabe, Masahiko; Majima, Masataka

2010-01-01

Bone marrow (BM)–derived hematopoietic cells, which are major components of tumor stroma, determine the tumor microenvironment and regulate tumor phenotypes. Cyclooxygenase (COX)−2 and endogenous prostaglandins are important determinants for tumor growth and tumor-associated angiogenesis; however, their contributions to stromal formation and angiogenesis remain unclear. In this study, we observed that Lewis lung carcinoma cells implanted in wild-type mice formed a tumor mass with extensive stromal formation that was markedly suppressed by COX-2 inhibition, which reduced the recruitment of BM cells. Notably, COX-2 inhibition attenuated CXCL12/CXCR4 expression as well as expression of several other chemokines. Indeed, in a Matrigel model, prostaglandin (PG) E2 enhanced stromal formation and CXCL12/CXCR4 expression. In addition, a COX-2 inhibitor suppressed stromal formation and reduced expression of CXCL12/CXCR4 and a fibroblast marker (S100A4) in a micropore chamber model. Moreover, stromal formation after tumor implantation was suppressed in EP3−/− mice and EP4−/− mice, in which stromal expression of CXCL12/CXCR4 and S100A4 was reduced. The EP3 or EP4 knockout suppressed S100A4+ fibroblasts, CXCL12+, and/or CXCR4+ stromal cells as well. Immunofluorescent analyses revealed that CXCL12+CXCR4+S100A4+ fibroblasts mainly comprised stromal cells and most of these were recruited from the BM. Additionally, either EP3- or EP4-specific agonists stimulated CXCL12 expression by fibroblasts in vitro. The present results address the novel activities of COX-2/PGE2-EP3/EP4 signaling that modulate tumor biology and show that CXCL12/CXCR4 axis may play a crucial role in tumor stromal formation and angiogenesis under the control of prostaglandins. PMID:20110411

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.

Science.gov (United States)

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.

R&D for the Post-EP Processes of Superconducting RF Cavity

Energy Technology Data Exchange (ETDEWEB)

Saeki, Takayuki [KEK; Funahashi, Y. [KEK; Hayano, H. [KEK; Kato, Seigo [KEK; Nishiwaki, Michiru [KEK; Sawabe, Motoaki [KEK; Ueno, Kenji [KEK; Watanabe, K. [KEK; Antoine, Claire [CEA, Gif-sur-Yvette; Berry, Stefurn [CEA, Gif-sur-Yvette; Eozenou, F. [CEA, Gif-sur-Yvette; Gasser, Y. [CEA, Gif-sur-Yvette; Visentin, B. [CEA, Gif-sur-Yvette; Clemens, William A. [JLAB; Geng, Rongli [JLAB; Manus, Robert [JLAB; Tyagi, Puneet [GUAS/AS, Ibaraki

2009-11-01

The Electro-Polishing (EP) process is the best candidate of final surface treatment for the production of ILC cavities. Nevertheless, the broad distribution of the gradient caused by field emitters in cavities is sitll a serious problem for the EP process. A candidate source of field emitter is the sulfur component which is produced in the EP process and remains the inner-surface of cavities. We studied the effect of Ethanole- and degreaser-rinse processes after the EP process by a unique method. Moreover, we tried to test the sponge cleaning as the post-EP process to remove the field emitter inside the cavcity. This article describe the results of series tests of the post-EP process at KEK.

EpsA is an essential gene in exopolysaccharide production in Lactobacillus johnsonii FI9785.

Science.gov (United States)

Dertli, Enes; Mayer, Melinda J; Colquhoun, Ian J; Narbad, Arjan

2016-07-01

Lactobacillus johnsonii FI9785 has an eps gene cluster which is required for the biosynthesis of homopolymeric exopolysaccharides (EPS)-1 and heteropolymeric EPS-2 as a capsular layer. The first gene of the cluster, epsA, is the putative transcriptional regulator. In this study we showed the crucial role of epsA in EPS biosynthesis by demonstrating that deletion of epsA resulted in complete loss of both EPS-1 and EPS-2 on the cell surface. Plasmid complementation of the epsA gene fully restored EPS production, as confirmed by transmission electron microscopy and nuclear magnetic resonance (NMR) analysis. Furthermore, this complementation resulted in a twofold increase in the expression levels of this gene, which almost doubled amounts of EPS production in comparison with the wild-type strain. Analysis of EPS by NMR showed an increased ratio of the heteropolysaccharide to homopolysaccharide in the complemented strain and allowed identification of the acetylated residue in EPS-2 as the (1,4)-linked βGlcp unit, with the acetyl group located at O-6. These findings indicate that epsA is a positive regulator of EPS production and that EPS production can be manipulated by altering its expression. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

High-Intensity Laser Diagnostics for OMEGA EP

International Nuclear Information System (INIS)

Bromage, J.; Zuegel, J.D.; Bahk, S.-W.; Vickery, D.S.; Waxer, L.J.; Irwin, D.; Bagnoud, V.; Boni, R.; Moore, M.D.; Junquist, R.; Stoeckl, C.

2006-01-01

OMEGA EP is a new high-energy petawatt laser system under construction at the University of Rochester's Laboratory for Laser Energetics. This paper describes our designs for two diagnostics critical to OMEGA EP's mission. The focal-spot diagnostic (FSD) is responsible for characterizing the focal spot of OMEGA EP's off-axis parabolic mirror at full energy. The ultrafast temporal diagnostic (UTD) is responsible for characterizing pulse shapes of full-energy target shots ranging in width from <1 to 100 ps as well as setting the desired pulse width before the shot. These diagnostics will enable, for the first time, complete spatial and temporal characterization of the focus of a high-energy petawatt laser at full energy

Epidermal growth factor pathway substrate 15, Eps15

DEFF Research Database (Denmark)

Salcini, A E; Chen, H; Iannolo, G

1999-01-01

Eps15 was originally identified as a substrate for the kinase activity of the epidermal growth factor receptor (EGFR). Eps15 has a tripartite structure comprising a NH2-terminal portion, which contains three EH domains, a central putative coiled-coil region, and a COOH-terminal domain containing...... multiple copies of the amino acid triplet Aspartate-Proline-Phenylalanine. A pool of Eps15 is localized at clathrin coated pits where it interacts with the clathrin assembly complex AP-2 and a novel AP-2 binding protein, Epsin. Perturbation of Eps15 and Epsin function inhibits receptor-mediated endocytosis...... of EGF and transferrin, demonstrating that both proteins are components of the endocytic machinery. Since the family of EH-containing proteins is implicated in various aspects of intracellular sorting, biomolecular strategies aimed at interfering with these processes can now be envisioned...

Exopolysaccharide (EPS synthesis by Oenococcus oeni: from genes to phenotypes.

Directory of Open Access Journals (Sweden)

Maria Dimopoulou

Full Text Available Oenococcus oeni is the bacterial species which drives malolactic fermentation in wine. The analysis of 50 genomic sequences of O. oeni (14 already available and 36 newly sequenced ones provided an inventory of the genes potentially involved in exopolysaccharide (EPS biosynthesis. The loci identified are: two gene clusters named eps1 and eps2, three isolated glycoside-hydrolase genes named dsrO, dsrV and levO, and three isolated glycosyltransferase genes named gtf, it3, it4. The isolated genes were present or absent depending on the strain and the eps gene clusters composition diverged from one strain to another. The soluble and capsular EPS production capacity of several strains was examined after growth in different culture media and the EPS structure was determined. Genotype to phenotype correlations showed that several EPS biosynthetic pathways were active and complementary in O. oeni. Can be distinguished: (i a Wzy-dependent synthetic pathway, allowing the production of heteropolysaccharides made of glucose, galactose and rhamnose, mainly in a capsular form, (ii a glucan synthase pathway (Gtf, involved in β-glucan synthesis in a free and a cell-associated form, giving a ropy phenotype to growth media and (iii homopolysaccharide synthesis from sucrose (α-glucan or β-fructan by glycoside-hydrolases of the GH70 and GH68 families. The eps gene distribution on the phylogenetic tree was examined. Fifty out of 50 studied genomes possessed several genes dedicated to EPS metabolism. This suggests that these polymers are important for the adaptation of O. oeni to its specific ecological niche, wine and possibly contribute to the technological performance of malolactic starters.

Influence of extracellular polymeric substances (EPS) on Cd adsorption by bacteria

Energy Technology Data Exchange (ETDEWEB)

Wei Xing [State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070 (China); Fang Linchuan [Key Laboratory of Subtropical Agricultural Resources and Environment, Ministry of Agriculture, College of Resources and Environment, Huazhong Agricultural University, Wuhan 430070 (China); Cai Peng, E-mail: cp@mail.hzau.edu.cn [State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Subtropical Agricultural Resources and Environment, Ministry of Agriculture, College of Resources and Environment, Huazhong Agricultural University, Wuhan 430070 (China); Huang Qiaoyun [State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Subtropical Agricultural Resources and Environment, Ministry of Agriculture, College of Resources and Environment, Huazhong Agricultural University, Wuhan 430070 (China); Chen Hao [College of Science, Huazhong Agricultural University, Wuhan 430070 (China); Liang Wei; Rong, Xinming [Key Laboratory of Subtropical Agricultural Resources and Environment, Ministry of Agriculture, College of Resources and Environment, Huazhong Agricultural University, Wuhan 430070 (China)

2011-05-15

The role of extracellular polymeric substances (EPS) in Cd adsorption by Bacillus subtilis and Pseudomonas putida was investigated using a combination of batch adsorption experiments, potentiometric titrations, Fourier transform infrared spectroscopy (FTIR). An increased adsorption capacity of Cd was observed for untreated bacteria relative to that for EPS-free bacteria. Surface complexation modeling of titration data showed the similar pK{sub a} values of functional groups (carboxyl, phosphate and hydroxyl) between untreated and EPS-free bacteria. However, site concentrations on the untreated bacteria were found to be higher than those on the EPS-free bacteria. FTIR spectra also showed that no significant difference in peak positions was observed between untreated and EPS-free bacteria and carboxyl and phosphate groups were responsible for Cd adsorption on bacterial cells. The information obtained in this study is of fundamental significance for understanding the interaction mechanisms between heavy metals and biofilms in natural environments. - Highlights: > The presence of EPS on bacterial surfaces facilitates the adsorption of Cd. > The promoting effects on Cd adsorption are more remarkable on Gram-positive B. subtilis cells than that on Gram-negative P. putida cells. > Carboxyl and phosphate groups are mostly responsible for Cd binding on untreated and EPS-free cells. > Intact bacterial cells and EPS-free cells have similar binding mechanisms for Cd. - Intact bacterial cells and EPS-free cells have similar binding mechanisms for Cd.

Determinants of Change in the Cost-effectiveness Threshold.

Science.gov (United States)

Paulden, Mike; O'Mahony, James; McCabe, Christopher

2017-02-01

The cost-effectiveness threshold in health care systems with a constrained budget should be determined by the cost-effectiveness of displacing health care services to fund new interventions. Using comparative statics, we review some potential determinants of the threshold, including the budget for health care, the demand for existing health care interventions, the technical efficiency of existing interventions, and the development of new health technologies. We consider the anticipated direction of impact that would affect the threshold following a change in each of these determinants. Where the health care system is technically efficient, an increase in the health care budget unambiguously raises the threshold, whereas an increase in the demand for existing, non-marginal health interventions unambiguously lowers the threshold. Improvements in the technical efficiency of existing interventions may raise or lower the threshold, depending on the cause of the improvement in efficiency, whether the intervention is already funded, and, if so, whether it is marginal. New technologies may also raise or lower the threshold, depending on whether the new technology is a substitute for an existing technology and, again, whether the existing technology is marginal. Our analysis permits health economists and decision makers to assess if and in what direction the threshold may change over time. This matters, as threshold changes impact the cost-effectiveness of interventions that require decisions now but have costs and effects that fall in future periods.

Biodistribution studies of epithelial cell adhesion molecule (EpCAM)-directed monoclonal antibodies in the EpCAM-transgenic mouse tumor model

NARCIS (Netherlands)

Kosterink, Jos G. W.; McLaughlin, Pamela M. J.; Lub-de Hooge, Marjolijn N.; Hendrikse, Harry H.; Van Zanten, Jacoba; Van Garderen, Evert; Harmsen, Martin C.; De Leij, Lou F. M. H.

2007-01-01

The human pancarcinoma-associated epithelial cell adhesion molecule (EpCAM) (EGP-2, CO17-1A) is a well-known target for carcinoma-directed immunotherapy. Mouse-derived mAbs directed to EpCAM have been used to treat colon carcinoma patients showing well-tolerable toxic side effects but limited

EpCAM-Independent Enrichment of Circulating Tumor Cells in Metastatic Breast Cancer

Science.gov (United States)

Schneck, Helen; Gierke, Berthold; Uppenkamp, Frauke; Behrens, Bianca; Niederacher, Dieter; Stoecklein, Nikolas H.; Templin, Markus F.; Pawlak, Michael; Fehm, Tanja; Neubauer, Hans

2015-01-01

Circulating tumor cells (CTCs) are the potential precursors of metastatic disease. Most assays established for the enumeration of CTCs so far–including the gold standard CellSearch—rely on the expression of the cell surface marker epithelial cell adhesion molecule (EpCAM). But, these approaches may not detect CTCs that express no/low levels of EpCAM, e.g. by undergoing epithelial-to-mesenchymal transition (EMT). Here we present an enrichment strategy combining different antibodies specific for surface proteins and extracellular matrix (ECM) components to capture an EpCAMlow/neg cell line and EpCAMneg CTCs from blood samples of breast cancer patients depleted for EpCAM-positive cells. The expression of respective proteins (Trop2, CD49f, c-Met, CK8, CD44, ADAM8, CD146, TEM8, CD47) was verified by immunofluorescence on EpCAMpos (e.g. MCF7, SKBR3) and EpCAMlow/neg (MDA-MB-231) breast cancer cell lines. To test antibodies and ECM proteins (e.g. hyaluronic acid (HA), collagen I, laminin) for capturing EpCAMneg cells, the capture molecules were first spotted in a single- and multi-array format onto aldehyde-coated glass slides. Tumor cell adhesion of EpCAMpos/neg cell lines was then determined and visualized by Coomassie/MitoTracker staining. In consequence, marginal binding of EpCAMlow/neg MDA-MB-231 cells to EpCAM-antibodies could be observed. However, efficient adhesion/capturing of EpCAMlow/neg cells could be achieved via HA and immobilized antibodies against CD49f and Trop2. Optimal capture conditions were then applied to immunomagnetic beads to detect EpCAMneg CTCs from clinical samples. Captured CTCs were verified/quantified by immunofluorescence staining for anti-pan-Cytokeratin (CK)-FITC/anti-CD45 AF647/DAPI. In total, in 20 out of 29 EpCAM-depleted fractions (69%) from 25 metastatic breast cancer patients additional EpCAMneg CTCs could be identified [range of 1–24 CTCs per sample] applying Trop2, CD49f, c-Met, CK8 and/or HA magnetic enrichment. Ep

High-intensity laser diagnostics for OMEGA EP

Energy Technology Data Exchange (ETDEWEB)

Bromage, J.; Zuegel, J.D.; Bahk, S.W.; Vickery, D.S.; Waxer, L.J.; Irwin, D.; Bagnoud, V.; Boni, R.; Moore, M.D.; Jungquist, R.; Stoeckl, C. [Rochester Univ., Lab. for Laser Energetics, NY (United States)

2006-06-15

OMEGA EP (Extended Performance) is a new high-energy peta-watt laser system under construction at the University of Rochester's Laboratory for Laser Energetics. This paper describes our designs for two diagnostics critical to OMEGA EP's mission. The focal-spot diagnostic (FSD) is responsible for characterizing the focal spot of OMEGA EP's off-axis parabolic mirror at full energy. The ultrafast temporal diagnostic (UTD) is responsible for characterizing pulse shapes of full-energy target shots ranging in width from < 1 to 100 ps as well as setting the desired pulse width before the shot. These diagnostics will enable, for the first time, complete spatial and temporal characterization of the focus of a high-energy peta-watt laser at full energy. (authors)

High-intensity laser diagnostics for OMEGA EP

International Nuclear Information System (INIS)

Bromage, J.; Zuegel, J.D.; Bahk, S.W.; Vickery, D.S.; Waxer, L.J.; Irwin, D.; Bagnoud, V.; Boni, R.; Moore, M.D.; Jungquist, R.; Stoeckl, C.

2006-01-01

OMEGA EP (Extended Performance) is a new high-energy peta-watt laser system under construction at the University of Rochester's Laboratory for Laser Energetics. This paper describes our designs for two diagnostics critical to OMEGA EP's mission. The focal-spot diagnostic (FSD) is responsible for characterizing the focal spot of OMEGA EP's off-axis parabolic mirror at full energy. The ultrafast temporal diagnostic (UTD) is responsible for characterizing pulse shapes of full-energy target shots ranging in width from < 1 to 100 ps as well as setting the desired pulse width before the shot. These diagnostics will enable, for the first time, complete spatial and temporal characterization of the focus of a high-energy peta-watt laser at full energy. (authors)

e-EPS News: Light for Development

CERN Multimedia

e-EPS

2011-01-01

e-EPS News is a monthly addition to the CERN Bulletin line-up, showcasing articles by the e-EPS – the European Physical Society newsletter – as part of a collaboration between the two publications.   A central goal of the EPS International Year of Light project will be to promote optical technologies and optics education to improve the quality of life in the developing world – under the theme of ‘Light for Development’. Light plays a central role in human activities in science, technology and culture. On a fundamental scientific level, light is necessary for the existence of life itself, whilst on a more technical level, light-based technologies will underpin the future development of human society. The systematic study of the physics of light and electromagnetic waves has been central to the evolution of modern science and – in the 20th century alone – there have been many fundamental ...

Optimal threshold functions for fault detection and isolation

DEFF Research Database (Denmark)

Stoustrup, J.; Niemann, Hans Henrik; Cour-Harbo, A. la

2003-01-01

Fault diagnosis systems usually comprises two parts: a filtering part and a decision part, the latter typically based on threshold functions. In this paper, systematic ways to choose the threshold values are proposed. Two different test functions for the filtered signals are discussed and a method...

Do we need a threshold conception of competence?

Science.gov (United States)

den Hartogh, Govert

2016-03-01

On the standard view we assess a person's competence by considering her relevant abilities without reference to the actual decision she is about to make. If she is deemed to satisfy certain threshold conditions of competence, it is still an open question whether her decision could ever be overruled on account of its harmful consequences for her ('hard paternalism'). In practice, however, one normally uses a variable, risk dependent conception of competence, which really means that in considering whether or not to respect a person's decision-making authority we weigh her decision on several relevant dimensions at the same time: its harmful consequences, its importance in terms of the person's own relevant values, the infringement of her autonomy involved in overruling it, and her decision-making abilities. I argue that we should openly recognize the multi-dimensional nature of this judgment. This implies rejecting both the threshold conception of competence and the categorical distinction between hard and soft paternalism.

Preparing for the Rollout of Pre-Exposure Prophylaxis (PrEP: A Vignette Survey to Identify Intended Sexual Behaviors among Women in Kenya and South Africa if Using PrEP.

Directory of Open Access Journals (Sweden)

Amy Corneli

Full Text Available Several clinical trials have demonstrated the efficacy of pre-exposure prophylaxis (PrEP in reducing HIV risk. One concern with introducing PrEP is whether users will engage in riskier sexual behaviors.We assessed the effect that PrEP may have on sexual risk behaviors by administering a survey to 799 women in Bondo, Kenya, and Pretoria, South Africa. Participants were asked about their sexual behavior intentions twice--once as if they were taking PrEP and once as if they were not taking PrEP--within four risk situations (vignettes. They responded using a 5-point ordinal scale. We used a series of linear mixed effects models with an unstructured residual covariance matrix to estimate the between- and within-subject differences in the mean likelihood of engaging in risky sexual behavior across the PrEP and non-PrEP contexts. We also calculated the total percentage of participants who reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP, by vignette.We found statistically significant differences in the mean likelihood of engaging in risky sexual behavior with the between-subject comparison (-0.17, p < 0.01 and with the within-subject comparison (-0.31, p < 0.001. Depending on the vignette, 27% to 40% of participants reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP.Our findings indicate that modest increases in risky sexual behavior could occur with PrEP. Although responses from the majority of participants suggest they would not be more likely to engage in risky sexual behavior if they took PrEP, a substantial proportion might. Programs rolling out PrEP should be prepared to assist similar women in making informed choices about reducing their risk of HIV and about their sexual health beyond HIV prevention.

EP 1000 -The European Passive Plant

International Nuclear Information System (INIS)

Cummins, Ed; Oyarzabal, Mariano; Saiu, Gianfranco

1998-01-01

A group of European utilities, along with Westinghouse and its industrial partner GENESI (an Italian consortium including ANSALDO and FIAT) initiated a program to evaluate Westinghouse passive nuclear plant technology for application in Europe. The European utility group consisted of: Agrupacion electrica para al Desarrollo Technologico Nuclear (DTN), Spain; Electricite de France; ENEL, SpA., Italy; IVO Power Engineering, Ltd., Finland; Scottish Nuclear Limited (acting for itself on behalf of Nuclear Electric plc, U.K.; Tractebel Energy Engineering, Belgium; UAK (represented by NOK-Beznau), Switzerland; and Vattenfall AB, Ringhals, Sweden. The European Passive Plant (EPP) program, which began in 1994, is an evaluation of the Westinghouse 600 MWe AP 600 and 1000 MWe Simplified Pressurized Water Reactor (SPWR) designs in meeting the European Utility Requirements (EUR), and where necessary, modifying the design to achieve compliance. Phase 1 or the EPP program was completed and included the two major tasks of evaluating the effect of the EUR on the Westinghouse nuclear island and developing the EP 1000, a 1000 MWe passive plant reference design that conforms to the EUR and would be licensable in Europe. The EP 1000 closely follows the Westinghouse SPWR design for safety systems and containment and the AP 600 design for auxiliary systems. It also includes features that where required to meet the EUR and key European licensing requirements. The primary circuit of the EP 1000 retains most of the general features of the current-day designs, but some evolutionary features to enhance reliability, simplicity of operation, ease of maintenance, and plant safety have been incorporated into the design. The core, reactor vessel, and reactor internals of the EP 1000 are similar to those of currently operating Westinghouse PWR plants, but several new features are included to enhance the performance characteristics. The basic EP 1000 safety philosophy is based on use of inherent

A Life Below the Threshold?: Examining Conflict Between Ethical Principles and Parental Values in Neonatal Treatment Decision Making.

Science.gov (United States)

Cunningham, Thomas V

2016-01-01

Three common ethical principles for establishing the limits of parental authority in pediatric treatment decision-making are the harm principle, the principle of best interest, and the threshold view. This paper considers how these principles apply to a case of a premature neonate with multiple significant co-morbidities whose mother wanted all possible treatments, and whose health care providers wondered whether it would be ethically permissible to allow him to die comfortably despite her wishes. Whether and how these principles help in understanding what was morally right for the child is questioned. The paper concludes that the principles were of some value in understanding the moral geography of the case; however, this case reveals that common bioethical principles for medical decision-making are problematically value-laden because they are inconsistent with the widespread moral value of medical vitalism.

EpCAM nuclear localization identifies aggressive Thyroid Cancer and is a marker for poor prognosis

International Nuclear Information System (INIS)

Ralhan, Ranju; Cao, Jun; Lim, Terence; MacMillan, Christina; Freeman, Jeremy L; Walfish, Paul G

2010-01-01

Proteolytic cleavage of the extracellular domain (EpEx) of Epithelial cell adhesion molecule (EpCAM) and nuclear signaling by its intracellular oncogenic domain Ep-ICD has recently been implicated in increased proliferation of cancer cells. The clinical significance of Ep-ICD in human tumors remains an enigma. EpEx, Ep-ICD and β-catenin immunohistochemistry using specific antibodies was conducted on 58 archived thyroid cancer (TC) tissue blocks from 34 patients and correlated with survival analysis of these patients for up to 17 years. The anaplastic (ATC) and aggressive thyroid cancers showed loss of EpEx and increased nuclear and cytoplasmic accumulation of Ep-ICD. In contrast, the low grade papillary thyroid cancers (PTC) showed membranous EpEx and no detectable nuclear Ep-ICD. The ATC also showed concomitant nuclear expression of Ep-ICD and β-catenin. Kaplan-Meier Survival analysis revealed reduced overall survival (OS) for TC patients showing nuclear Ep-ICD expression or loss of membranous EpEx (p < 0.0004), median OS = 5 months as compared to 198 months for patients who did not show nuclear Ep-ICD or demonstrated only membranous EpE. We report reciprocal loss of membrane EpEx but increased nuclear and cytoplasmic accumulation of Ep-ICD in aggressive TC; nuclear Ep-ICD correlated with poor OS of TC patients. Thus nuclear Ep-ICD localization may serve as a useful biomarker for aggressive TC and may represent a novel diagnostic, prognostic and therapeutic target for aggressive TC

Characterisation of the exopolysaccharide (EPS)-producing Lactobacillus paraplantarum BGCG11 and its non-EPS producing derivative strains as potential probiotics.

Science.gov (United States)

Nikolic, Milica; López, Patricia; Strahinic, Ivana; Suárez, Ana; Kojic, Milan; Fernández-García, María; Topisirovic, Ljubisa; Golic, Natasa; Ruas-Madiedo, Patricia

2012-08-17

Traditional fermented foods are the best source for the isolation of strains with specific traits to act as functional starters and to keep the biodiversity of the culture collections. Besides, these strains could be used in the formulation of foods claimed to promote health benefits, i.e. those containing probiotic microorganisms. For the rational selection of strains acting as probiotics, several in vitro tests have been proposed. In the current study, we have characterized the probiotic potential of the strain Lactobacillus paraplantarum BGCG11, isolated from a Serbian soft, white, homemade cheese, which is able to produce a "ropy" exopolysaccharide (EPS). Three novobiocin derivative strains, which have lost the ropy phenotype, were characterized as well in order to determine the putative role of the EPS in the probiotic potential. Under chemically gastrointestinal conditions, all strains were able to survive around 1-2% (10(6)-10(7)cfu/ml cultivable bacteria) only when they were included in a food matrix (1% skimmed milk). The strains were more resistant to acid conditions than to bile salts and gastric or pancreatic enzymes, which could be due to a pre-adaptation of the parental strain to acidic conditions in the cheese habitat. The ropy EPS did not improve the survival of the producing strain. On the contrary, the presence of an EPS layer surrounding the strain BGCG11 hindered its adhesion to the three epithelial intestinal cell lines tested, since the adhesion of the three non-ropy derivatives was higher than the parental one and also than that of the reference strain Lactobacillus rhamnosus GG. Aiming to propose a potential target application of these strains as probiotics, the cytokine production of peripheral blood mononuclear cells (PBMC) was analyzed. The EPS-producing L. paraplantarum BGCG11 strain showed an anti-inflammatory or immunosuppressor profile whereas the non-ropy derivative strains induced higher pro-inflammatory response. In addition, when

Highlights from e-EPS: the 2015 EPS High Energy Physics Prize winners

CERN Multimedia

Thomas Lohse, e-EPS News

2015-01-01

The EPS High Energy Physics Division announces the winners of its 2015 prizes, which will be awarded at the Europhysics Conference on High-Energy Physics (EPS-HEP 2015), Vienna (Austria) 22−29 July. Many people from CERN were among the winners.   The 2015 High Energy and Particle Physics Prize, for an outstanding contribution to High Energy Physics, is awarded to James D. Bjorken “for his prediction of scaling behaviour in the structure of the proton that led to a new understanding of the b interaction”, and to Guido Altarelli, Yuri L. Dokshitzer, Lev Lipatov, and Giorgio Parisi “for developing a probabilistic field theory framework for the dynamics of quarks and gluons, enabling a quantitative understanding of high-energy collisions involving hadrons”. The 2015 Giuseppe and Vanna Cocconi Prize, for an outstanding contribution to Particle Astrophysics and Cosmology in the past 15 years, is awarded to Francis Halzen “for his visiona...

EpCAM nuclear localization identifies aggressive Thyroid Cancer and is a marker for poor prognosis

Directory of Open Access Journals (Sweden)

MacMillan Christina

2010-06-01

Full Text Available Abstract Background Proteolytic cleavage of the extracellular domain (EpEx of Epithelial cell adhesion molecule (EpCAM and nuclear signaling by its intracellular oncogenic domain Ep-ICD has recently been implicated in increased proliferation of cancer cells. The clinical significance of Ep-ICD in human tumors remains an enigma. Methods EpEx, Ep-ICD and β-catenin immunohistochemistry using specific antibodies was conducted on 58 archived thyroid cancer (TC tissue blocks from 34 patients and correlated with survival analysis of these patients for up to 17 years. Results The anaplastic (ATC and aggressive thyroid cancers showed loss of EpEx and increased nuclear and cytoplasmic accumulation of Ep-ICD. In contrast, the low grade papillary thyroid cancers (PTC showed membranous EpEx and no detectable nuclear Ep-ICD. The ATC also showed concomitant nuclear expression of Ep-ICD and β-catenin. Kaplan-Meier Survival analysis revealed reduced overall survival (OS for TC patients showing nuclear Ep-ICD expression or loss of membranous EpEx (p Conclusion We report reciprocal loss of membrane EpEx but increased nuclear and cytoplasmic accumulation of Ep-ICD in aggressive TC; nuclear Ep-ICD correlated with poor OS of TC patients. Thus nuclear Ep-ICD localization may serve as a useful biomarker for aggressive TC and may represent a novel diagnostic, prognostic and therapeutic target for aggressive TC.

Druhý Čep

Czech Academy of Sciences Publication Activity Database

Kubíček, Tomáš

2014-01-01

Roč. 62, č. 1 (2014), s. 35-45 ISSN 0009-0468 R&D Projects: GA ČR GAP406/11/1421 Institutional support: RVO:68378068 Keywords : Czech literature * modern prose * Čep, Jan * narrative analysis Subject RIV: AJ - Letters, Mass-media, Audiovision

Preferences for Long-Acting Pre-exposure Prophylaxis (PrEP), Daily Oral PrEP, or Condoms for HIV Prevention Among U.S. Men Who Have Sex with Men.

Science.gov (United States)

Greene, George J; Swann, Greg; Fought, Angela J; Carballo-Diéguez, Alex; Hope, Thomas J; Kiser, Patrick F; Mustanski, Brian; D'Aquila, Richard T

2017-05-01

HIV prevention method preferences were evaluated among 512 U.S. men who have sex with men (MSM; median age: 22 years). Approximately 90 % consistently preferred one option across pairwise comparisons of condoms, daily oral pre-exposure prophylaxis (PrEP), and long-acting PrEP delivered via either an injectable or one of two types of PrEP implants differing in visibility. Condoms were most frequently preferred (33.8 %), followed by non-visible implants (21.5 %), and oral PrEP (17.0 %); HIV risk was reported by more choosing implants. In a follow-up question comparing the four PrEP options only, daily oral pills and non-visible implants were most frequently preferred (35.5 and 34.3 %, respectively), followed by injections (25.2 %) and visible implants (4.3 %). An inductive, open-coding approach determined that convenience, duration of protection, and privacy were the most commonly cited reasons for a PrEP method choice, and associated with self-report of HIV risk. Tailoring PrEP product development to privacy and other concerns important to those at highest HIV risk may improve HIV prevention.

Purification and properties of extracellular polysaccharide (EPS) antigens produced by different mould species.

Science.gov (United States)

Notermans, S; Wieten, G; Engel, H W; Rombouts, F M; Hoogerhout, P; van Boom, J H

1987-02-01

Extracellular polysaccharide (EPS) antigens produced by different mould species were purified and partially characterized. Purification included (NH4)2SO4 treatment, Sepharose CL-4B column chromatography and Con A-sepharose chromatography. The EPS of Penicillium digitatum, Mucor racemosus and Cladosporium cladosporioides showed high antigenic capacities. Immunologically the EPS were partially genus-specific, but cross-reactivity was observed. The EPS antigens produced by species of Penicillium, Aspergillus repens and Geotrichum candidum lost their immunological activity upon heating (100 degrees C) at pH 1.8, while the EPS antigen of M. racemosus, Rhizopus oligosporus and C. cladosporioides were stable under the same conditions. The dominant monosaccharides present in the EPS antigen were mannose, galactose and glucose. The EPS obtained from cultures of M. racemosus and R. oligosporus also contained rhamnose. In the EPS produced by Penicillium spp. and A. repens the galactose residues were determined to be immunodominant.

Structural features of subtype-selective EP receptor modulators.

Science.gov (United States)

Markovič, Tijana; Jakopin, Žiga; Dolenc, Marija Sollner; Mlinarič-Raščan, Irena

2017-01-01

Prostaglandin E2 is a potent endogenous molecule that binds to four different G-protein-coupled receptors: EP1-4. Each of these receptors is a valuable drug target, with distinct tissue localisation and signalling pathways. We review the structural features of EP modulators required for subtype-selective activity, as well as the structural requirements for improved pharmacokinetic parameters. Novel EP receptor subtype selective agonists and antagonists appear to be valuable drug candidates in the therapy of many pathophysiological states, including ulcerative colitis, glaucoma, bone healing, B cell lymphoma, neurological diseases, among others, which have been studied in vitro, in vivo and in early phase clinical trials. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

Science.gov (United States)

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.

Directory of Open Access Journals (Sweden)

Jamie Frankis

Full Text Available 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.

Living with encapsulating peritoneal sclerosis (EPS): the patient's perspective.

Science.gov (United States)

Hurst, Helen; Summers, Angela; Beaver, Kinta; Caress, Ann-Louise

2014-01-01

Although relatively rare, encapsulating peritoneal sclerosis (EPS) is nonetheless a major concern within the renal community. Risk of developing EPS is associated with long-term peritoneal dialysis (PD). High mortality was previously reported, although surgery has since improved outcomes. Research into EPS focuses on imaging and early detection methods, genetics, biomarkers and preventive strategies. No previous studies have examined patients' experiences of EPS. The aim of the present study was to explore the experience of patients who have undergone surgery for EPS in one center in the North of England. A qualitative phenomenological approach, involving in-depth interviews, was adopted. Nine participants were recruited out of a total of 18 eligible. Most participants were interviewed twice over a 12-month period (October 2009 to October 2010). Interpretive data analysis was conducted, following the philosophical tradition of hermeneutics, to draw out themes from the data. Data collection and analysis took place concurrently and participants were sent a summary of their first interview to allow a period of reflection prior to the subsequent interview. EPS presented the most serious challenge participants had faced since developing chronic kidney disease (CKD). Three major themes were identified, each with subcategories. The key issues for patients were related to identification of early symptoms and lack of understanding. The patients' sense of 'not being heard' by health care professionals led to a loss of trust and enhanced their feelings of uncertainty. The enormity of the surgery, the suffering, and what they had to endure had an enormous impact, but an overriding aspect of this experience was also the loss they felt for their independence and for the PD therapy over which they had control. The findings of this study highlight a number of important issues relevant to clinical practice, including lack of information and understanding of EPS, particularly its

Functional and bioinformatics analysis of an exopolysaccharide-related gene (epsN) from Lactobacillus kefiranofaciens ZW3.

Science.gov (United States)

Wang, Jingrui; Tang, Wei; Zheng, Yongna; Xing, Zhuqing; Wang, Yanping

2016-09-01

A novel lactic acid bacteria strain Lactobacillus kefiranofaciens ZW3 exhibited the characteristics of high production of exopolysaccharide (EPS). The epsN gene, located in the eps gene cluster of this strain, is associated with EPS biosynthesis. Bioinformatics analysis of this gene was performed. The conserved domain analysis showed that the EpsN protein contained MATE-Wzx-like domains. Then the epsN gene was amplified to construct the recombinant expression vector pMG36e-epsN. The results showed that the EPS yields of the recombinants were significantly improved. By determining the yields of EPS and intracellular polysaccharide, it was considered that epsN gene could play its Wzx flippase role in the EPS biosynthesis. This is the first time to prove the effect of EpsN on L. kefiranofaciens EPS biosynthesis and further prove its functional property.

GUIDED TOUR OF A WEB-BASED ENVIRONMENTAL DECISION TOOLKIT

Science.gov (United States)

Decision-making regarding the targeting of vulnerable resources and prioritization of actions requires synthesis of data on condition, vulnerability, and feasibility of risk management alternatives. EP A's Regional Vulnerability Assessment (ReV A) Program has evaluated existing a...

Confronting Decision Cliffs: Diagnostic Assessment of Multi-Objective Evolutionary Algorithms' Performance for Addressing Uncertain Environmental Thresholds

Science.gov (United States)

Ward, V. L.; Singh, R.; Reed, P. M.; Keller, K.

2014-12-01

As water resources problems typically involve several stakeholders with conflicting objectives, multi-objective evolutionary algorithms (MOEAs) are now key tools for understanding management tradeoffs. Given the growing complexity of water planning problems, it is important to establish if an algorithm can consistently perform well on a given class of problems. This knowledge allows the decision analyst to focus on eliciting and evaluating appropriate problem formulations. This study proposes a multi-objective adaptation of the classic environmental economics "Lake Problem" as a computationally simple but mathematically challenging MOEA benchmarking problem. The lake problem abstracts a fictional town on a lake which hopes to maximize its economic benefit without degrading the lake's water quality to a eutrophic (polluted) state through excessive phosphorus loading. The problem poses the challenge of maintaining economic activity while confronting the uncertainty of potentially crossing a nonlinear and potentially irreversible pollution threshold beyond which the lake is eutrophic. Objectives for optimization are maximizing economic benefit from lake pollution, maximizing water quality, maximizing the reliability of remaining below the environmental threshold, and minimizing the probability that the town will have to drastically change pollution policies in any given year. The multi-objective formulation incorporates uncertainty with a stochastic phosphorus inflow abstracting non-point source pollution. We performed comprehensive diagnostics using 6 algorithms: Borg, MOEAD, eMOEA, eNSGAII, GDE3, and NSGAII to ascertain their controllability, reliability, efficiency, and effectiveness. The lake problem abstracts elements of many current water resources and climate related management applications where there is the potential for crossing irreversible, nonlinear thresholds. We show that many modern MOEAs can fail on this test problem, indicating its suitability as a

Identifying thresholds for ecosystem-based management.

Directory of Open Access Journals (Sweden)

Jameal F Samhouri

Full Text Available BACKGROUND: One of the greatest obstacles to moving ecosystem-based management (EBM from concept to practice is the lack of a systematic approach to defining ecosystem-level decision criteria, or reference points that trigger management action. METHODOLOGY/PRINCIPAL FINDINGS: To assist resource managers and policymakers in developing EBM decision criteria, we introduce a quantitative, transferable method for identifying utility thresholds. A utility threshold is the level of human-induced pressure (e.g., pollution at which small changes produce substantial improvements toward the EBM goal of protecting an ecosystem's structural (e.g., diversity and functional (e.g., resilience attributes. The analytical approach is based on the detection of nonlinearities in relationships between ecosystem attributes and pressures. We illustrate the method with a hypothetical case study of (1 fishing and (2 nearshore habitat pressure using an empirically-validated marine ecosystem model for British Columbia, Canada, and derive numerical threshold values in terms of the density of two empirically-tractable indicator groups, sablefish and jellyfish. We also describe how to incorporate uncertainty into the estimation of utility thresholds and highlight their value in the context of understanding EBM trade-offs. CONCLUSIONS/SIGNIFICANCE: For any policy scenario, an understanding of utility thresholds provides insight into the amount and type of management intervention required to make significant progress toward improved ecosystem structure and function. The approach outlined in this paper can be applied in the context of single or multiple human-induced pressures, to any marine, freshwater, or terrestrial ecosystem, and should facilitate more effective management.

Dual processing model of medical decision-making

Science.gov (United States)

2012-01-01

Background Dual processing theory of human cognition postulates that reasoning and decision-making can be described as a function of both an intuitive, experiential, affective system (system I) and/or an analytical, deliberative (system II) processing system. To date no formal descriptive model of medical decision-making based on dual processing theory has been developed. Here we postulate such a model and apply it to a common clinical situation: whether treatment should be administered to the patient who may or may not have a disease. Methods We developed a mathematical model in which we linked a recently proposed descriptive psychological model of cognition with the threshold model of medical decision-making and show how this approach can be used to better understand decision-making at the bedside and explain the widespread variation in treatments observed in clinical practice. Results We show that physician’s beliefs about whether to treat at higher (lower) probability levels compared to the prescriptive therapeutic thresholds obtained via system II processing is moderated by system I and the ratio of benefit and harms as evaluated by both system I and II. Under some conditions, the system I decision maker’s threshold may dramatically drop below the expected utility threshold derived by system II. This can explain the overtreatment often seen in the contemporary practice. The opposite can also occur as in the situations where empirical evidence is considered unreliable, or when cognitive processes of decision-makers are biased through recent experience: the threshold will increase relative to the normative threshold value derived via system II using expected utility threshold. This inclination for the higher diagnostic certainty may, in turn, explain undertreatment that is also documented in the current medical practice. Conclusions We have developed the first dual processing model of medical decision-making that has potential to enrich the current medical

Dual processing model of medical decision-making.

Science.gov (United States)

Djulbegovic, Benjamin; Hozo, Iztok; Beckstead, Jason; Tsalatsanis, Athanasios; Pauker, Stephen G

2012-09-03

Dual processing theory of human cognition postulates that reasoning and decision-making can be described as a function of both an intuitive, experiential, affective system (system I) and/or an analytical, deliberative (system II) processing system. To date no formal descriptive model of medical decision-making based on dual processing theory has been developed. Here we postulate such a model and apply it to a common clinical situation: whether treatment should be administered to the patient who may or may not have a disease. We developed a mathematical model in which we linked a recently proposed descriptive psychological model of cognition with the threshold model of medical decision-making and show how this approach can be used to better understand decision-making at the bedside and explain the widespread variation in treatments observed in clinical practice. We show that physician's beliefs about whether to treat at higher (lower) probability levels compared to the prescriptive therapeutic thresholds obtained via system II processing is moderated by system I and the ratio of benefit and harms as evaluated by both system I and II. Under some conditions, the system I decision maker's threshold may dramatically drop below the expected utility threshold derived by system II. This can explain the overtreatment often seen in the contemporary practice. The opposite can also occur as in the situations where empirical evidence is considered unreliable, or when cognitive processes of decision-makers are biased through recent experience: the threshold will increase relative to the normative threshold value derived via system II using expected utility threshold. This inclination for the higher diagnostic certainty may, in turn, explain undertreatment that is also documented in the current medical practice. We have developed the first dual processing model of medical decision-making that has potential to enrich the current medical decision-making field, which is still to the

NUMERICAL SIMULATION OF FRAME STRUCTURE ON SHALLOW FOUNDATION WITH EXPANDED POLYSTYRENE (EPS

Directory of Open Access Journals (Sweden)

Indra Waluyohadi

2015-08-01

test results. A series of parametric study is conducted including the interface element and the variations of size of EPS. The use of EPS underneath shallow foundation do not show the correlation with the seismic response of structure if there is no interface element constructed. Variation of EPS size used were contributed to the acceleration and displacement of  structure with shallow foundation. As the larger size of EPS applied, the larger reduction of seismic responses will be obtained.

Measurement of beauty photoproduction near threshold using di-electron events with the H1 detector at HERA

Energy Technology Data Exchange (ETDEWEB)

Aaron, F. D.; Alexa, C.; Andreev, V.; Backovic, S.; Baghdasaryan, A.; Baghdasaryan, S.; Barrelet, E.; Bartel, W.; Begzsuren, K.; Belousov, A.; Belov, P.; Bizot, J. C.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Britzger, D.; Bruncko, D.; Bunyatyan, A.; Bylinkin, A.; Bystritskaya, L.; Campbell, A. J.; Cantun Avila, K. B.; Ceccopieri, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Contreras, J. G.; Coughlan, J. A.; Cvach, J.; Dainton, J. B.; Daum, K.; Delcourt, B.; Delvax, J.; De Wolf, E. A.; Diaconu, C.; Dobre, M.; Dodonov, V.; Dossanov, A.; Dubak, A.; Eckerlin, G.; Egli, S.; Eliseev, A.; Elsen, E.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Fischer, D. -J.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, S.; Glazov, A.; Goerlich, L.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Grebenyuk, A.; Greenshaw, T.; Grindhammer, G.; Habib, S.; Haidt, D.; Henderson, R. C. W.; Hennekemper, E.; Henschel, H.; Herbst, M.; Herrera, G.; Hildebrandt, M.; Hiller, K. H.; Hoffmann, D.; Horisberger, R.; Hreus, T.; Huber, F.; Jacquet, M.; Janssen, X.; Jönsson, L.; Jung, A. W.; Jung, H.; Kapichine, M.; Kenyon, I. R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Kogler, R.; Kostka, P.; Krämer, M.; Kretzschmar, J.; Krüger, K.; Landon, M. P. J.; Lange, W.; Laštovička-Medin, G.; Laycock, P.; Lebedev, A.; Lendermann, V.; Levonian, S.; Lipka, K.; List, B.; List, J.; Lobodzinski, B.; Lopez-Fernandez, R.; Lubimov, V.; Malinovski, E.; Martyn, H. -U.; Maxfield, S. J.; Mehta, A.; Meyer, A. B.; Meyer, H.; Meyer, J.; Mikocki, S.; Milcewicz-Mika, I.; Moreau, F.; Morozov, A.; Morris, J. V.; Müller, K.; Naumann, Th.; Newman, P. R.; Niebuhr, C.; Nikitin, D.; Nowak, G.; Nowak, K.; Olivier, B.; Olsson, J. E.; Ozerov, D.; Pahl, P.; Palichik, V.; Pandurovic, M.; Pascaud, C.; Patel, G. D.; Perez, E.; Petrukhin, A.; Picuric, I.; Pirumov, H.; Pitzl, D.; Plačakytė, R.; Pokorny, B.; Polifka, R.; Povh, B.; Radescu, V.; Raicevic, N.; Ravdandorj, T.; Reimer, P.; Rizvi, E.; Robmann, P.; Roosen, R.; Rostovtsev, A.; Rotaru, M.; Ruiz Tabasco, J. E.; Rusakov, S.; Šálek, D.; Sankey, D. P. C.; Sauter, M.; Sauvan, E.; Schmitt, S.; Schoeffel, L.; Schöning, A.; Schultz-Coulon, H. -C.; Sefkow, F.; Shtarkov, L. N.; Shushkevich, S.; Sloan, T.; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, A.; Staykova, Z.; Steder, M.; Stella, B.; Stoicea, G.; Straumann, U.; Sykora, T.; Thompson, P. D.; Tran, T. H.; Traynor, D.; Truöl, P.; Tsakov, I.; Tseepeldorj, B.; Turnau, J.; Valkárová, A.; Vallée, C.; Van Mechelen, P.; Vazdik, Y.; Wegener, D.; Wünsch, E.; Žáček, J.; Zálešák, J.; Zhang, Z.; Zhokin, A.; Žlebčík, R.; Zohrabyan, H.; Zomer, F.

2012-10-01

The cross section for $ep \\to e b\\bar{b} X$ in photoproduction is measured with the H1 detector at the $ep$-collider HERA. The decay channel $b\\bar{b} \\to ee X^\\prime$ is selected by identifying the semi-electronic decays of the b-quarks. The total production cross section is measured in the kinematic range given by the photon virtuality $Q^2 \\le 1 GeV^2$, the inelasticity $0.05 \\le y \\le 0.65$ and the pseudorapidity of the $b$-quarks $|\\eta(b)|$,$|\\eta(\\bar{b})| \\le 2$. The differential production cross section is measured as a function of the average transverse momentum of the beauty quarks <$P_T$(b)> down to the threshold. The results are compared to next-to-leading-order QCD predictions.

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

Science.gov (United States)

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

PrEP implementation: moving from trials to policy and practice.

Science.gov (United States)

Cáceres, Carlos F; O'Reilly, Kevin R; Mayer, Kenneth H; Baggaley, Rachel

2015-01-01

It is increasingly clear that the HIV response will not be sustainable if the number of infections is not significantly reduced. For two decades, research has been ongoing to identify new behavioural and biomedical strategies to prevent HIV infection. In the past few years, the efficacy of several new strategies has been demonstrated, including oral pre-exposure prophylaxis (PrEP; i.e. daily use of tenofovir/emtricitabine). Because several social, political and logistic barriers remain, however, optimal PrEP implementation will require a better dissemination of new evidence in a number of areas and additional implementation research from various disciplinary perspectives (i.e. social science, policy and ethics; health systems; and economics, including cost-effectiveness studies). Discussion of new evidence on those topics, as well as case studies of potential PrEP implementation in diverse environments, can improve the understanding of the role that PrEP may play in addressing the global HIV/AIDS epidemic.In light of these needs, the Network for Multidisciplinary Studies in ARV-based HIV Prevention (NEMUS) and the World Health Organization (WHO) were honoured to co-organize a special issue of JIAS aimed at contributing to a scholarly discussion of current conditions surrounding PrEP implementation, potential impact and efficiency, social science concerns and the study of PrEP implementation in specific country cases. The papers included in this monograph identify and cover many of the main aspects of the complex yet promising discussions around PrEP implementation today. This is a collection of timely contributions from global leaders in HIV research and policy that addresses geographic diversity, uses a trans-disciplinary approach and covers a variety of the complex issues raised by PrEP. As this publication will become accessible to all, we hope that it will remain a valuable resource for policy makers, programme managers, researchers and activists around the

Temporal characteristics of decisions in hospital encounters: a threshold for shared decision making? A qualitative study.

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Ofstad, Eirik H; Frich, Jan C; Schei, Edvin; Frankel, Richard M; Gulbrandsen, Pål

2014-11-01

To identify and characterize physicians' statements that contained evidence of clinically relevant decisions in encounters with patients in different hospital settings. Qualitative analysis of 50 videotaped encounters from wards, the emergency room (ER) and outpatient clinics in a department of internal medicine at a Norwegian university hospital. Clinical decisions could be grouped in a temporal order: decisions which had already been made, and were brought into the encounter by the physician (preformed decisions), decisions made in the present (here-and-now decisions), and decisions prescribing future actions given a certain course of events (conditional decisions). Preformed decisions were a hallmark in the ward and conditional decisions a main feature of ER encounters. Clinical decisions related to a patient-physician encounter spanned a time frame exceeding the duration of the encounter. While a distribution of decisions over time and space fosters sharing and dilution of responsibility between providers, it makes the decision making process hard to access for patients. In order to plan when and how to involve patients in decisions, physicians need increased awareness of when clinical decisions are made, who usually makes them, and who should make them. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

PrEP in Europe - expectations, opportunities and barriers.

Science.gov (United States)

McCormack, Sheena Mary; Noseda, Veronica; Molina, Jean-Michel

2016-01-01

In contrast to the global trend showing a decline in new HIV infections, the number reported in the World Health Organization (WHO) region of Europe is increasing. Health systems are disparate, but even countries with free access to screening and treatment observe continuing high rates of new infections in key populations, notably men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) is only available in France. This commentary describes the European epidemics and healthcare settings where PrEP could be delivered, how need might be estimated for MSM and the residual barriers to access. Health systems and government commitment to HIV prevention and care, both financial and political, differ considerably between the countries that make up Europe. A common feature is that funds for prevention are a small fraction of funds for care. Although care is generally good, access is limited in the middle-income countries of Eastern Europe and central Asia, and only 19% of people living with HIV received antiretroviral therapy in 2014. It is challenging to motivate governments or civil society to implement PrEP in the context of this unmet treatment need, which is driven by limited national health budgets and diminishing assistance from foreign aid. The high-income countries of Western Europe have hesitated to embrace PrEP for different reasons, initially due to key gaps in the evidence. Now that PrEP has been shown to be highly effective in European MSM in two randomized controlled trials, it is clear that the major barrier is the cost of the drug which is still on patent, although inadequate health systems and diminishing investment in civil society are also key challenges to overcome. The momentum to implement PrEP in European countries is increasing and provides a welcome opportunity to expand and improve clinical services and civil society support focused on HIV and related infections including other sexually transmitted and blood-borne infections.

OMEGA EP high-energy petawatt laser: progress and prospects

International Nuclear Information System (INIS)

Maywar, D N; Kelly, J H; Waxer, L J; Morse, S F B; Begishev, I A; Bromage, J; Dorrer, C; Edwards, J L; Folnsbee, L; Guardalben, M J; Jacobs, S D; Jungquist, R; Kessler, T J; Kidder, R W; Kruschwitz, B E; Loucks, S J; Marciante, J R; McCrory, R L; Meyerhofer, D D; Okishev, A V

2008-01-01

OMEGA EP (extended performance) is a petawatt-class addition to the existing 30-kJ, 60-beam OMEGA Laser Facility at the University of Rochester. It will enable high-energy picosecond backlighting of high-energy-density experiments and inertial confinement fusion implosions, the investigation of advanced-ignition experiments such as fast ignition, and the exploration of high-energy-density phenomena. The OMEGA EP short-pulse beams have the flexibility to be directed to either the existing OMEGA target chamber, or the new, auxiliary OMEGA EP target chamber for independent experiments. This paper will detail progress made towards activation, which is on schedule for completion in April 2008

When is rational to order a diagnostic test, or prescribe treatment: the threshold model as an explanation of practice variation.

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Djulbegovic, Benjamin; van den Ende, Jef; Hamm, Robert M; Mayrhofer, Thomas; Hozo, Iztok; Pauker, Stephen G

2015-05-01

The threshold model represents an important advance in the field of medical decision-making. It is a linchpin between evidence (which exists on the continuum of credibility) and decision-making (which is a categorical exercise - we decide to act or not act). The threshold concept is closely related to the question of rational decision-making. When should the physician act, that is order a diagnostic test, or prescribe treatment? The threshold model embodies the decision theoretic rationality that says the most rational decision is to prescribe treatment when the expected treatment benefit outweighs its expected harms. However, the well-documented large variation in the way physicians order diagnostic tests or decide to administer treatments is consistent with a notion that physicians' individual action thresholds vary. We present a narrative review summarizing the existing literature on physicians' use of a threshold strategy for decision-making. We found that the observed variation in decision action thresholds is partially due to the way people integrate benefits and harms. That is, explanation of variation in clinical practice can be reduced to a consideration of thresholds. Limited evidence suggests that non-expected utility threshold (non-EUT) models, such as regret-based and dual-processing models, may explain current medical practice better. However, inclusion of costs and recognition of risk attitudes towards uncertain treatment effects and comorbidities may improve the explanatory and predictive value of the EUT-based threshold models. The decision when to act is closely related to the question of rational choice. We conclude that the medical community has not yet fully defined criteria for rational clinical decision-making. The traditional notion of rationality rooted in EUT may need to be supplemented by reflective rationality, which strives to integrate all aspects of medical practice - medical, humanistic and socio-economic - within a coherent

EPS-LASSO: Test for High-Dimensional Regression Under Extreme Phenotype Sampling of Continuous Traits.

Science.gov (United States)

Xu, Chao; Fang, Jian; Shen, Hui; Wang, Yu-Ping; Deng, Hong-Wen

2018-01-25

Extreme phenotype sampling (EPS) is a broadly-used design to identify candidate genetic factors contributing to the variation of quantitative traits. By enriching the signals in extreme phenotypic samples, EPS can boost the association power compared to random sampling. Most existing statistical methods for EPS examine the genetic factors individually, despite many quantitative traits have multiple genetic factors underlying their variation. It is desirable to model the joint effects of genetic factors, which may increase the power and identify novel quantitative trait loci under EPS. The joint analysis of genetic data in high-dimensional situations requires specialized techniques, e.g., the least absolute shrinkage and selection operator (LASSO). Although there are extensive research and application related to LASSO, the statistical inference and testing for the sparse model under EPS remain unknown. We propose a novel sparse model (EPS-LASSO) with hypothesis test for high-dimensional regression under EPS based on a decorrelated score function. The comprehensive simulation shows EPS-LASSO outperforms existing methods with stable type I error and FDR control. EPS-LASSO can provide a consistent power for both low- and high-dimensional situations compared with the other methods dealing with high-dimensional situations. The power of EPS-LASSO is close to other low-dimensional methods when the causal effect sizes are small and is superior when the effects are large. Applying EPS-LASSO to a transcriptome-wide gene expression study for obesity reveals 10 significant body mass index associated genes. Our results indicate that EPS-LASSO is an effective method for EPS data analysis, which can account for correlated predictors. The source code is available at https://github.com/xu1912/EPSLASSO. hdeng2@tulane.edu. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please

Clinical effectiveness and cost-effectiveness of HIV pre-exposure prophylaxis in men who have sex with men: risk calculators for real-world decision-making.

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Anders Chen

Full Text Available BACKGROUND: Oral pre-exposure prophylaxis (PrEP can be clinically effective and cost-effective for HIV prevention in high-risk men who have sex with men (MSM. However, individual patients have different risk profiles, real-world populations vary, and no practical tools exist to guide clinical decisions or public health strategies. We introduce a practical model of HIV acquisition, including both a personalized risk calculator for clinical management and a cost-effectiveness calculator for population-level decisions. METHODS: We developed a decision-analytic model of PrEP for MSM. The primary clinical effectiveness and cost-effectiveness outcomes were the number needed to treat (NNT to prevent one HIV infection, and the cost per quality-adjusted life-year (QALY gained. We characterized patients according to risk factors including PrEP adherence, condom use, sexual frequency, background HIV prevalence and antiretroviral therapy use. RESULTS: With standard PrEP adherence and national epidemiologic parameters, the estimated NNT was 64 (95% uncertainty range: 26, 176 at a cost of $160,000 (cost saving, $740,000 per QALY--comparable to other published models. With high (35% HIV prevalence, the NNT was 35 (21, 57, and cost per QALY was $27,000 (cost saving, $160,000, and with high PrEP adherence, the NNT was 30 (14, 69, and cost per QALY was $3,000 (cost saving, $200,000. In contrast, for monogamous, serodiscordant relationships with partner antiretroviral therapy use, the NNT was 90 (39, 157 and cost per QALY was $280,000 ($14,000, $670,000. CONCLUSIONS: PrEP results vary widely across individuals and populations. Risk calculators may aid in patient education, clinical decision-making, and cost-effectiveness evaluation.

Existence and control of Go/No-Go decision transition threshold in the striatum.

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Jyotika Bahuguna

2015-04-01

Full Text Available A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

Existence and control of Go/No-Go decision transition threshold in the striatum.

Science.gov (United States)

Bahuguna, Jyotika; Aertsen, Ad; Kumar, Arvind

2015-04-01

A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs) in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

Structures and Logic of EP Implementation and Administration in China

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Dieter Grunow

2011-01-01

Full Text Available This paper describes empirical observations gathered during a research project on the implementation of environmental protection (EP policies in China. The project focused on local EP in both urban and rural areas. Policy field analysis was used as a conceptual framework for structuring the observations. The paper develops in three main steps discussing the following topics: 1 Collective problems within the policy field of EP show that EP issues in general are unlike those of other policy fields. Official EP policies in China today resemble those of other countries – but they are separating issues and responsibilities, making local implementation very demanding. 2 China lags behind in its willingness and ability to implement these policies – leading to implementation gaps. To explore the causes and consequences, specific sites in China are described in an extended look at local implementation structures. It was found that although policies in China are basically the same everywhere, the structures for implementing them and the quality of their implementation vary widely with regard to resources, organization, coordination, staff qualifications, personnel placement, and other aspects. 3 Not all of the challenges hampering local implementation of environmental policies were China-specific; however, some of those which are can be described as the macro-context: an ineffective rule of law, insufficient involvement of civil society, and complicated macro-structures of public administration prevent a generally high level of successful EP implementation in China.

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.

Science.gov (United States)

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.

The problem of the detection threshold in radiation measurement

International Nuclear Information System (INIS)

Rose, E.; Wueneke, C.D.

1983-01-01

In all cases encountered in practical radiation measurement, the basic problem is to differentiate between the lowest measured value and the zero value (background, natural background radiation, etc.). For this purpose, on the mathematical side, tests based on hypotheses are to be applied. These will show the probability of differentiation between two values having the same random spread. By means of these tests and the corresponding error theory, a uniform treatment of the subject, applicable to all problems relating to measuring technique alike, can be found. Two basic concepts are found in this process, which have to be defined in terms of semantics and nomenclature: Decision threshold and detection threshold, or 'minimum detectable mean value'. At the decision threshold, one has to decide (with a given statistical error probability) whether a measured value is to be attributed to the background radiation, accepting the zero hypothesis, or whether this value differs significantly from the background radiation (error of 1rst kind). The minimum detectable mean value is the value which, with a given decision threshold, can be determined with sufficient significance to be a measured value and thus cannot be mistaken as background radiation (alternative hypothesis, error of 2nd kind). Normally, the two error types are of equal importance. It may happen, however, that one type of error gains more importance, depending on the approach. (orig.) [de

Nuclear Ep-ICD expression is a predictor of poor prognosis in "low risk" prostate adenocarcinomas.

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Jasmeet Assi

Full Text Available Molecular markers for predicting prostate cancer (PCa that would have poor prognosis are urgently needed for a more personalized treatment for patients. Regulated intramembrane proteolysis of Epithelial cell adhesion molecule results in shedding of the extracellular domain (EpEx and release of its intracellular domain (Ep-ICD which triggers oncogenic signaling and might correlate to tumor aggressiveness. This study aimed to explore the potential of Ep-ICD and EpEx to identify PCa that have poor prognosis.Immunohistochemical analysis of Ep-ICD and EpEx was carried out in normal prostate tissues (n = 100, benign prostate hyperplasia (BPH, n = 83, and prostate cancer (n = 249 using domain specific antibodies. The expression of Ep-ICD and EpEx was correlated with clinico- pathological parameters and disease free survival (DFS.Reduced expression of nuclear Ep-ICD and membrane EpEx was observed in PCa in comparison with BPH and normal prostate tissues (p = 0.006, p < 0.001 respectively. For patients who had PCa with Gleason Score less than 7, preserved nuclear Ep-ICD emerged as the most significant marker in multivariate analysis for prolonged DFS, where these patients did not have recurrence during follow up of up to 12 years (p = 0.001.Reduced expression of nuclear Ep-ICD was associated with shorter disease free survival in patients with a Gleason Score less than 7 and may be useful in identifying patients likely to have aggressive tumors with poor prognosis. Furthermore, nuclear Ep-ICD can differentiate between normal and prostate cancer tissues for ambiguous cases.

Investigation of Multi-Criteria Decision Consistency: A Triplex Approach to Optimal Oilfield Portfolio Investment Decisions

Science.gov (United States)

Qaradaghi, Mohammed

Complexity of the capital intensive oil and gas portfolio investments is continuously growing. It is manifested in the constant increase in the type, number and degree of risks and uncertainties, which consequently lead to more challenging decision making problems. A typical complex decision making problem in petroleum exploration and production (E&P) is the selection and prioritization of oilfields/projects in a portfolio investment. Prioritizing oilfields maybe required for different purposes, including the achievement of a targeted production and allocation of limited available development resources. These resources cannot be distributed evenly nor can they be allocated based on the oilfield size or production capacity alone since various other factors need to be considered simultaneously. These factors may include subsurface complexity, size of reservoir, plateau production and needed infrastructure in addition to other issues of strategic concern, such as socio-economic, environmental and fiscal policies, particularly when the decision making involves governments or national oil companies. Therefore, it would be imperative to employ decision aiding tools that not only address these factors, but also incorporate the decision makers' preferences clearly and accurately. However, the tools commonly used in project portfolio selection and optimization, including intuitive approaches, vary in their focus and strength in addressing the different criteria involved in such decision problems. They are also disadvantaged by a number of drawbacks, which may include lacking the capacity to address multiple and interrelated criteria, uncertainty and risk, project relationship with regard to value contribution and optimum resource utilization, non-monetary attributes, decision maker's knowledge and expertise, in addition to varying levels of ease of use and other practical and theoretical drawbacks. These drawbacks have motivated researchers to investigate other tools and

Dual processing model of medical decision-making

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Djulbegovic Benjamin

2012-09-01

Full Text Available Abstract Background Dual processing theory of human cognition postulates that reasoning and decision-making can be described as a function of both an intuitive, experiential, affective system (system I and/or an analytical, deliberative (system II processing system. To date no formal descriptive model of medical decision-making based on dual processing theory has been developed. Here we postulate such a model and apply it to a common clinical situation: whether treatment should be administered to the patient who may or may not have a disease. Methods We developed a mathematical model in which we linked a recently proposed descriptive psychological model of cognition with the threshold model of medical decision-making and show how this approach can be used to better understand decision-making at the bedside and explain the widespread variation in treatments observed in clinical practice. Results We show that physician’s beliefs about whether to treat at higher (lower probability levels compared to the prescriptive therapeutic thresholds obtained via system II processing is moderated by system I and the ratio of benefit and harms as evaluated by both system I and II. Under some conditions, the system I decision maker’s threshold may dramatically drop below the expected utility threshold derived by system II. This can explain the overtreatment often seen in the contemporary practice. The opposite can also occur as in the situations where empirical evidence is considered unreliable, or when cognitive processes of decision-makers are biased through recent experience: the threshold will increase relative to the normative threshold value derived via system II using expected utility threshold. This inclination for the higher diagnostic certainty may, in turn, explain undertreatment that is also documented in the current medical practice. Conclusions We have developed the first dual processing model of medical decision-making that has potential to

Measurement of beauty photoproduction near threshold using Di-electron events with the H1 detector at HERA

Energy Technology Data Exchange (ETDEWEB)

Aaron, F.D. [National Institute for Physics and Nuclear Engineering (NIPNE), Bucharest (Romania); Bucharest Univ. (Romania). Faculty of Physics; Alexa, C. [National Institute for Physics and Nuclear Engineering (NIPNE), Bucharest (Romania); Andreev, V. [Lebedev Physical Institute, Moscow (RU)] (and others)

2012-05-15

The cross section for ep {yields} eb anti bX in photoproduction is measured with the H1 detector at the ep-collider HERA. The decay channel b anti b {yields} eeX' is selected by identifying the semi-electronic decays of the b-quarks. The total production cross section is measured in the kinematic range given by the photon virtuality Q{sup 2} {<=}1 GeV{sup 2}, the inelasticity 0.05{<=} y {<=}0.65 and the pseudorapidity of the b-quarks vertical stroke {eta}(b) vertical stroke, vertical stroke {eta}(anti b) vertical stroke {<=}2. The differential production cross section is measured as a function of the average transverse momentum of the beauty quarks left angle P{sub T}(b) right angle down to the threshold. The results are compared to next-to-leading-order QCD predictions.

Measurement of beauty photoproduction near threshold using Di-electron events with the H1 detector at HERA

International Nuclear Information System (INIS)

Aaron, F.D.; Andreev, V.

2012-05-01

The cross section for ep → eb anti bX in photoproduction is measured with the H1 detector at the ep-collider HERA. The decay channel b anti b → eeX' is selected by identifying the semi-electronic decays of the b-quarks. The total production cross section is measured in the kinematic range given by the photon virtuality Q 2 ≤1 GeV 2 , the inelasticity 0.05≤ y ≤0.65 and the pseudorapidity of the b-quarks vertical stroke η(b) vertical stroke, vertical stroke η(anti b) vertical stroke ≤2. The differential production cross section is measured as a function of the average transverse momentum of the beauty quarks left angle P T (b) right angle down to the threshold. The results are compared to next-to-leading-order QCD predictions.

Role of the Prostaglandin E2 EP1 Receptor in Traumatic Brain Injury

Science.gov (United States)

Glushakov, Alexander V.; Fazal, Jawad A.; Narumiya, Shuh; Doré, Sylvain

2014-01-01

Brain injuries promote upregulation of so-called proinflammatory prostaglandins, notably prostaglandin E2 (PGE2), leading to overactivation of a class of its cognate G-protein-coupled receptors, including EP1, which is considered a promising target for treatment of ischemic stroke. However, the role of the EP1 receptor is complex and depends on the type of brain injury. This study is focused on the investigation of the role of the EP1 receptor in a controlled cortical impact (CCI) model, a preclinical model of traumatic brain injury (TBI). The therapeutic effects of post-treatments with a widely studied EP1 receptor antagonist, SC-51089, were examined in wildtype and EP1 receptor knockout C57BL/6 mice. Neurological deficit scores (NDS) were assessed 24 and 48 h following CCI or sham surgery, and brain immunohistochemical pathology was assessed 48 h after surgery. In wildtype mice, CCI resulted in an obvious cortical lesion and localized hippocampal edema with an associated significant increase in NDS compared to sham-operated animals. Post-treatments with the selective EP1 receptor antagonist SC-51089 or genetic knockout of EP1 receptor had no significant effects on cortical lesions and hippocampal swelling or on the NDS 24 and 48 h after CCI. Immunohistochemistry studies revealed CCI-induced gliosis and microglial activation in selected ipsilateral brain regions that were not affected by SC-51089 or in the EP1 receptor-deleted mice. This study provides further clarification on the respective contribution of the EP1 receptor in TBI and suggests that, under this experimental paradigm, the EP1 receptor would have limited effects in modulating acute neurological and anatomical pathologies following contusive brain trauma. Findings from this protocol, in combination with previous studies demonstrating differential roles of EP1 receptor in ischemic, neurotoxic, and hemorrhagic conditions, provide scientific background and further clarification of potential therapeutic

Tyrosine phosphorylation of Eps15 is required for ligand-regulated, but not constitutive, endocytosis

DEFF Research Database (Denmark)

Confalonieri, S; Salcini, A E; Puri, C

2000-01-01

for endocytosis of the epidermal growth factor receptor (EGFR), the prototypical ligand-inducible receptor, but not of the transferrin receptor (TfR), the prototypical constitutively internalized receptor. Eps15, an endocytic protein that is tyrosine phosphorylated by EGFR, is a candidate for such a function....... Here, we show that tyrosine phosphorylation of Eps15 is necessary for internalization of the EGFR, but not of the TfR. We mapped Tyr 850 as the major in vivo tyrosine phosphorylation site of Eps15. A phosphorylation-negative mutant of Eps15 acted as a dominant negative on the internalization...... of the EGFR, but not of the TfR. A phosphopeptide, corresponding to the phosphorylated sequence of Eps15, inhibited EGFR endocytosis, suggesting that phosphotyrosine in Eps15 serves as a docking site for a phosphotyrosine binding protein. Thus, tyrosine phosphorylation of Eps15 represents the first molecular...

Spacecraft Electrical Power System (EPS) generic analysis tools and techniques

Science.gov (United States)

Morris, Gladys M.; Sheppard, Mark A.

1992-01-01

An overview is provided of the analysis tools and techiques used in modeling the Space Station Freedom electrical power system, as well as future space vehicle power systems. The analysis capabilities of the Electrical Power System (EPS) are described and the EPS analysis tools are surveyed.

Ep option at the SSC

International Nuclear Information System (INIS)

Prescott, C.Y.

1984-05-01

The possibilities for colliding electrons with the 20 TeV proton beams of the SSC are considered. Kinematics of ep colliding beams is reviewed. Energies that may be possible and interesting are suggested, and detector problems associated with the highly imbalanced collisions are briefly considered

The future of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection.

Science.gov (United States)

Özdener, Ayşe Elif; Park, Tae Eun; Kalabalik, Julie; Gupta, Rachna

2017-05-01

People at high risk for HIV acquisition should be offered pre-exposure prophylaxis (PrEP). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is currently the only medication recommended for pre-exposure prophylaxis (PrEP) by the Centers for Disease Control and Prevention (CDC) in people at high risk for HIV acquisition. This article will review medications currently under investigation and the future landscape of PrEP therapy. Areas covered: This article will review clinical trials that have investigated nontraditional regimens of TDF/FTC, antiretroviral agents from different drug classes such as integrase strand transfer inhibitors (INSTI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) as potential PrEP therapies. Expert commentary: Currently, there are several investigational drugs in the pipeline for PrEP against HIV infection. Increased utilization of PrEP therapy depends on provider identification of people at high risk for HIV transmission. Advances in PrEP development will expand options and access for people and reduce the risk of HIV acquisition.

Application of threshold concepts to ecological management problems: occupancy of Golden Eagles in Denali National Park, Alaska: Chapter 5

Science.gov (United States)

Eaton, Mitchell J.; Martin, Julien; Nichols, James D.; McIntyre, Carol; McCluskie, Maggie C.; Schmutz, Joel A.; Lubow, Bruce L.; Runge, Michael C.; Edited by Guntenspergen, Glenn R.

2014-01-01

In this chapter, we demonstrate the application of the various classes of thresholds, detailed in earlier chapters and elsewhere, via an actual but simplified natural resource management case study. We intend our example to provide the reader with the ability to recognize and apply the theoretical concepts of utility, ecological and decision thresholds to management problems through a formalized decision-analytic process. Our case study concerns the management of human recreational activities in Alaska’s Denali National Park, USA, and the possible impacts of such activities on nesting Golden Eagles, Aquila chrysaetos. Managers desire to allow visitors the greatest amount of access to park lands, provided that eagle nesting-site occupancy is maintained at a level determined to be acceptable by the managers themselves. As these two management objectives are potentially at odds, we treat minimum desired occupancy level as a utility threshold which, then, serves to guide the selection of annual management alternatives in the decision process. As human disturbance is not the only factor influencing eagle occupancy, we model nesting-site dynamics as a function of both disturbance and prey availability. We incorporate uncertainty in these dynamics by considering several hypotheses, including a hypothesis that site occupancy is affected only at a threshold level of prey abundance (i.e., an ecological threshold effect). By considering competing management objectives and accounting for two forms of thresholds in the decision process, we are able to determine the optimal number of annual nesting-site restrictions that will produce the greatest long-term benefits for both eagles and humans. Setting a utility threshold of 75 occupied sites, out of a total of 90 potential nesting sites, the optimization specified a decision threshold at approximately 80 occupied sites. At the point that current occupancy falls below 80 sites, the recommended decision is to begin restricting

Hombro doloroso en trabajadores afiliados a eps-privada

OpenAIRE

Blandón Rodríguez, Jairo Alcibíades

2014-01-01

Objetivo: Describir los elementos diagnósticos de la patología de hombro doloroso, en trabajadores calificados en medicina laboral EPS-privada, Bogotá (Colombia), año 2012. Método: Estudio descriptivo de corte transversal sobre una muestra de trabajadores afiliados a EPS-privada año 2012 calificados por patología de hombro doloroso de origen profesional. La muestra estudiada fue de 343 registros de trabajadores, que representa el 2.3% del total de la enfermedades profesionales y acci...

Deposition kinetics of extracellular polymeric substances (EPS) on silica in monovalent and divalent salts.

Science.gov (United States)

Zhu, Pingting; Long, Guoyu; Ni, Jinren; Tong, Meiping

2009-08-01

The deposition kinetics of extracellular polymeric substances (EPS) on silica surfaces were examined in both monovalent and divalent solutions under a variety of environmentally relevant ionic strength and pH conditions by employing a quartz crystal microbalance with dissipation (DCM-D). Soluble EPS (SEPS) and bound EPS (BEPS) were extracted from four bacterial strains with different characteristics. Maximum favorable deposition rates (k(fa)) were observed for all EPS at low ionic strengths in both NaCl and CaCl2 solutions. With the increase of ionic strength, k(fa) decreased due to the simultaneous occurrence of EPS aggregation in solutions. Deposition efficiency (alpha; the ratio of deposition rates obtained under unfavorable versus corresponding favorable conditions) for all EPS increased with increasing ionic strength in both NaCl and CaCl2 solutions, which agreed with the trends of zeta potentials and was consistent with the classic Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Comparison of alpha for SEPS and BEPS extracted from the same strain showed that the trends of alpha did not totally agree with trends of zeta potentials, indicating the deposition kinetics of EPS on silica surfaces were not only controlled by DLVO interactions, but also non-DLVO forces. Close comparison of alpha for EPS extracted from different sources showed alpha increased with increasing proteins to polysaccharides ratio. Subsequent experiments for EPS extracted from the same strain but with different proteins to polysaccharides ratios and from activated sludge also showed that alpha were largest for EPS with greatest proteins to polysaccharides ratio. Additional experiments for pure protein and solutions with different pure proteins to pure saccharides ratios further corroborated that larger proteins to polysaccharides ratio resulted in greater EPS deposition.

Relation between EPS adherence, viscoelastic properties, and MBR operation: Biofouling study with QCM-D.

Science.gov (United States)

Sweity, Amer; Ying, Wang; Ali-Shtayeh, Mohammed S; Yang, Fei; Bick, Amos; Oron, Gideon; Herzberg, Moshe

2011-12-01

Membrane fouling is one of the main constraints of the wide use of membrane bioreactor (MBR) technology. The biomass in MBR systems includes extracellular polymeric substances (EPS), metabolic products of active microbial secretion that adversely affect the membrane performance. Solids retention time (SRT) in the MBR is one of the most important parameters affecting membrane fouling in MBR systems, where fouling is minimized at optimal SRT. Among the operating parameters in MBR systems, SRT is known to strongly influence the ratio of proteins to polysaccharides in the EPS matrix. In this study, we have direct evidence for changes in EPS adherence and viscoelastic properties due to changes in the sludge removal rate that strongly correlate with the membrane fouling rate and EPS composition. EPS were extracted from a UF membrane in a hybrid growth MBR operated at sludge removal rates of 59, 35.4, 17.7, and 5.9 L day(-1) (corresponding SRT of 3, 5, 10, and 30 days, respectively). The EPS adherence and adsorption kinetics were carried out in a quartz crystal microbalance with dissipation monitoring (QCM-D) technology in several adsorption measurements to a gold sensor coated with Polyvinylidene Fluoride (PVDF). EPS adsorption to the sensor surface is characterized by a decrease of the oscillation frequency and an increase in the dissipation energy of the sensor during parallel flow of aqueous media, supplemented with EPS, above the sensor surface. The results from these experiments were further modeled using the Voigt based model, in which the thickness, shear modulus, and shear viscosity values of the adsorbed EPS layers on the PVDF crystal were calculated. The observations in the QCM-D suggested that the elevated fouling of the UF membrane is due to higher adherence of the EPS as well as reduction in viscosity and elasticity of the EPS adsorbed layer and elevation of the EPS fluidity. These results corroborate with confocal laser scanning microscopy (CLSM) image

Review of HIV Pre exposure prophylaxis (PrEP) and example of HIV PrEP Toolkit

Science.gov (United States)

2017-08-28

at Initiation of Sexual Activity Correct & Consistent Condom Use Prevention of mother-to- child transmission July 16, 2012: FDA approves...Okulicz JF, Medicine 2016 PrEP Utilization in a Managed Care System (Kaiser Permanente) 1200 ~ 1045 1000 . 800 600 . 400 200 0 835 657 0

Environmental protection in actual circumstances of EPS recovery

International Nuclear Information System (INIS)

Gavrilovic, M.

2002-01-01

The paper presents a brief summary of the state of environmental protection in the vicinity of Electric Power Industry of Serbia (EPS) power facilities, both when economy of FR Yugoslavia (FRY) was at an acceptable level and the current situation resulting from a drastic decline of economic power of country and EPS itself, from unfavourable political development from the past period, from the sanctions imposed by UN Security Council, from a prolonged isolation from modern courses worldwide as well as from bombing of facilities during NATO aggression against Yugoslavia. The paper is focused on the analysis of the possibilities of taking certain activities aimed at environmental protection under expected realistic circumstances of EPS recovery and its further development, in accordance with the overall economic recovery and development of the country, and to estimate the price of all environmental protection measures which, would otherwise have been realised in the course of the past period if sanctions of UN Security Council have not been imposed on FR Yugoslavia. (author)

ep possibility for ISABELLE

International Nuclear Information System (INIS)

Wilson, R.

1977-01-01

The feasibility of adding an electron ring to ISABELLE is discussed in terms of cost, physics goals, count rate estimates, the detector requirements, and the possibility of producing intermediate bosons. The purpose of adding an electron ring to ISABELLE must be considered to be the study of e + p → e + x, e - p → νx, and e + p → anti νx. Other processes, such as W production, are less interesting for an ep ring than for a pp ring. However, there may be other new particles--such as leptonic quarks--that only turn up here. These processes are, however, exciting. In a 30 day run at L = 10 32 cm -2 sec -1 300 neutrino events are expected at q 2 > 5000 GeV 2 where the propagator is expected to be less than 1 / 4 . Thus the value of the mass in the propagator can be measured to 5%. The ep cross section would be measured over the momentum transfer range 1 2 2 ). This range is large enough that a logarithmic deviation from scaling can be distinguished easily from a power law approach to scaling

Key developments of the EP1000 design

International Nuclear Information System (INIS)

Noviello, L.

1999-01-01

In 1994, a group of European utilities initiated, together with Westinghouse and its industrial partner GENESI (an Italian consortium including ANSALDO and FIAT), a program designated EPP (European Passive Plant) to evaluate Westinghouse passive nuclear plant technology for application in Europe. The Phase I of the European Passive Plant program involved the evaluation of the Westinghouse 600 MWe AP600 and 1000 MWe Simplified Pressurized Water Reactor (SPWR) designs against the European Utility Requirements (EUR), and when necessary, the investigation of possible modifications to achieve compliance with the EUR. In Phase 1 of the program, which has been completed in 1996, the following major tasks were accomplished: The impacts of the European Utility Requirements (EUR) on the Westinghouse nuclear island design were evaluated. A 1000 MWe passive plant reference design (EP1000) was developed which conforms to the EUR and is expected to be licensable in Europe. With respect to the NSSS and containment, the EP1000 reference design closely follows those of the Westinghouse SPWR design, while the AP600 design has been taken as the basis for the design of the auxiliary systems. Extensive design and testing efforts have been made for the AP600 and SPWR during the respective multi-year programs. While the results of these programs have been and will continue to be utilised, at the maximum extent, to minimise the work to be performed on the EP1000 design, the compliance with EUR is a key design requirement for the EP1000 The ultimate objective of Phase 2 of the program is to develop design details and perform supporting analyses to produce a Safety Case Report (SCR) for submittal to European Safety Authorities. The first part of Phase 2, hereafter referred as Phase 2A, started at the beginning of 1997 and will be completed at the end of 1998. Scope of this phase of the program is to develop the design modifications of important systems and structures so to comply with the

INVESTIGATING THE Ep, i –Eiso CORRELATION

Directory of Open Access Journals (Sweden)

Lorenzo Amati

2013-12-01

Full Text Available The correlation between the spectral peak photon energy, Ep, and the radiated energy or luminosity (i.e., the “Amati relation” and other correlations derived from it is one of the central and most debated topics in GRB astrophysics, with implications for physics and the geometry of prompt emission, the identification and understanding of various classes of GRBs (short/long, XRFs,sub-energetic, and GRB cosmology. Fermi is exceptionally suited to provide, also in conjunction with Swift observations, a significant step forward in this field of research. Indeed, one of the main goals of Fermi/GBM is to make accurate measurements of Ep, by exploiting its unprecedented broad energy band from ~8 keV to ~30MeV; in addition, for a small fraction of GRBs, the LAT can extend the spectral measurements up to the GeV energy range, thus allowing a reliable estimate of the bolometric radiated energy/luminosity. We provide a review, an update and a discussion of the impact of Fermi observations in the investigation, understanding and testing of the Ep,i –Eiso (“Amati” relation.

Rainfall threshold definition using an entropy decision approach and radar data

Directory of Open Access Journals (Sweden)

V. Montesarchio

2011-07-01

Full Text Available Flash flood events are floods characterised by a very rapid response of basins to storms, often resulting in loss of life and property damage. Due to the specific space-time scale of this type of flood, the lead time available for triggering civil protection measures is typically short. Rainfall threshold values specify the amount of precipitation for a given duration that generates a critical discharge in a given river cross section. If the threshold values are exceeded, it can produce a critical situation in river sites exposed to alluvial risk. It is therefore possible to directly compare the observed or forecasted precipitation with critical reference values, without running online real-time forecasting systems. The focus of this study is the Mignone River basin, located in Central Italy. The critical rainfall threshold values are evaluated by minimising a utility function based on the informative entropy concept and by using a simulation approach based on radar data. The study concludes with a system performance analysis, in terms of correctly issued warnings, false alarms and missed alarms.

EP4 as a Therapeutic Target for Aggressive Human Breast Cancer

Directory of Open Access Journals (Sweden)

Mousumi Majumder

2018-03-01

Full Text Available G-protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G-protein. When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5′-triphosphate (GTP for guanosine diphosphate (GDP. They play a major role in many physiological functions, as well as in the pathology of many diseases, including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review briefly summarizes the signaling pathways utilized by the EP (prostaglandin E receptor family of GPCR, their physiological and pathological roles in carcinogenesis, with special emphasis on the roles of EP4 in breast cancer progression. We make a case for EP4 as a promising newer therapeutic target for treating breast cancer. We show that an aberrant over-expression of cyclooxygenase (COX-2, which is an inflammation-associated enzyme, occurring in 40–50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG E2 production in the tumor milieu. They include inactivation of host anti-tumor immune cells, such as Natural Killer (NK and T cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis, due to upregulation of multiple angiogenic factors including Vascular Endothelial Growth Factor (VEGF-A, increased lymphangiogenesis (due to upregulation of VEGF-C/D, and a stimulation of stem-like cell (SLC phenotype in cancer cells. All of these events were primarily mediated by activation of the Prostaglandin (PG E receptor EP4 on tumor or host cells. We show that

Rationality, practice variation and person-centred health policy: a threshold hypothesis.

Science.gov (United States)

Djulbegovic, Benjamin; Hamm, Robert M; Mayrhofer, Thomas; Hozo, Iztok; Van den Ende, Jef

2015-12-01

Variation in practice of medicine is one of the major health policy issues of today. Ultimately, it is related to physicians' decision making. Similar patients with similar likelihood of having disease are often managed by different doctors differently: some doctors may elect to observe the patient, others decide to act based on diagnostic testing and yet others may elect to treat without testing. We explain these differences in practice by differences in disease probability thresholds at which physicians decide to act: contextual social and clinical factors and emotions such as regret affect the threshold by influencing the way doctors integrate objective data related to treatment and testing. However, depending on a theoretical construct each of the physician's behaviour can be considered rational. In fact, we showed that the current regulatory policies lead to predictably low thresholds for most decisions in contemporary practice. As a result, we may expect continuing motivation for overuse of treatment and diagnostic tests. We argue that rationality should take into account both formal principles of rationality and human intuitions about good decisions along the lines of Rawls' 'reflective equilibrium/considered judgment'. In turn, this can help define a threshold model that is empirically testable. © 2015 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

Added economic value of limited area multi-EPS weather forecasting applications

Directory of Open Access Journals (Sweden)

Alex Deckmyn

2012-07-01

Full Text Available We compare the GLAMEPS system, a pan-European limited area ensemble prediction system, with ECMWF's EPS over Belgium for an extended period from March 2010 until the end of December 2010. In agreement with a previous study, we find GLAMEPS scores considerably better than ECMWF's EPS. To compute the economic value, we introduce a new relative economic value score for continuous forecasts. The added value of combining the GLAMEPS system with the LAEF system over Belgium is studied. We conclude that adding LAEF to GLAMEPS increases the value, although the increase is small compared to the improvement of GLAMEPS to ECMWF's EPS. As an added benefit we find that the combined GLAMEPS-LAEF multi-EPS system is more robust, that is, it is less vulnerable to the (accidental removal of one of its components.

Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines

International Nuclear Information System (INIS)

Martowicz, Agnieszka; Spizzo, Gilbert; Gastl, Guenther; Untergasser, Gerold

2012-01-01

The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAM high breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAM low breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAM high cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAM low cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer

Dual Criteria Decisions

DEFF Research Database (Denmark)

Andersen, Steffen; Harrison, Glenn W.; Lau, Morten Igel

2014-01-01

The most popular models of decision making use a single criterion to evaluate projects or lotteries. However, decision makers may actually consider multiple criteria when evaluating projects. We consider a dual criteria model from psychology. This model integrates the familiar tradeoffs between...... to the clear role that income thresholds play in such decision making, but does not rule out a role for tradeoffs between risk and utility or probability weighting....

Learning to maximize reward rate: a model based on semi-Markov decision processes.

Science.gov (United States)

Khodadadi, Arash; Fakhari, Pegah; Busemeyer, Jerome R

2014-01-01

WHEN ANIMALS HAVE TO MAKE A NUMBER OF DECISIONS DURING A LIMITED TIME INTERVAL, THEY FACE A FUNDAMENTAL PROBLEM: how much time they should spend on each decision in order to achieve the maximum possible total outcome. Deliberating more on one decision usually leads to more outcome but less time will remain for other decisions. In the framework of sequential sampling models, the question is how animals learn to set their decision threshold such that the total expected outcome achieved during a limited time is maximized. The aim of this paper is to provide a theoretical framework for answering this question. To this end, we consider an experimental design in which each trial can come from one of the several possible "conditions." A condition specifies the difficulty of the trial, the reward, the penalty and so on. We show that to maximize the expected reward during a limited time, the subject should set a separate value of decision threshold for each condition. We propose a model of learning the optimal value of decision thresholds based on the theory of semi-Markov decision processes (SMDP). In our model, the experimental environment is modeled as an SMDP with each "condition" being a "state" and the value of decision thresholds being the "actions" taken in those states. The problem of finding the optimal decision thresholds then is cast as the stochastic optimal control problem of taking actions in each state in the corresponding SMDP such that the average reward rate is maximized. Our model utilizes a biologically plausible learning algorithm to solve this problem. The simulation results show that at the beginning of learning the model choses high values of decision threshold which lead to sub-optimal performance. With experience, however, the model learns to lower the value of decision thresholds till finally it finds the optimal values.

Deuteron breakup in the 2H(e,e'p) reaction at low momentum transfer and close to threshold

International Nuclear Information System (INIS)

Neumann-Cosel, P. von; Richter, A.; Schrieder, G.; Shevchenko, A.; Stiller, A.; Arenhoevel, H.

2002-04-01

Deuteron breakup has been studied in a 2 H(e, e'p) coincidence experiment at low momentum transfer and for energies close to threshold. The longitudinal-plus-transverse (L + T) and longitudinal-transverse interference (LT) cross sections are deduced. Nonrelativistic calculations based on the Bonn potential and including leading order relativistic contributions, meson exchange currents and isobar configurations describe the (L + T) data well. Surprisingly large deviations of 30 to 45% are observed for the LT contribution. (orig.)

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

Science.gov (United States)

Roth, Caleb C.; Barnes Jr., Ronald A.; Ibey, Bennett L.; Beier, Hope T.; Christopher Mimun, L.; Maswadi, Saher M.; Shadaram, Mehdi; Glickman, Randolph D.

2015-01-01

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane. PMID:26450165

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure.

Science.gov (United States)

Roth, Caleb C; Barnes, Ronald A; Ibey, Bennett L; Beier, Hope T; Christopher Mimun, L; Maswadi, Saher M; Shadaram, Mehdi; Glickman, Randolph D

2015-10-09

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane.

Implications of HIV PrEP Trials Results

Science.gov (United States)

Anton, Peter; Fletcher, Courtney V.; DeGruttola, Victor; McGowan, Ian; Becker, Stephen; Zwerski, Sheryl; Burns, David

2011-01-01

Abstract Six randomized clinical trials have been implemented to examine the efficacy of tenofovir disoproxil fumarate (TDF) and/or TDF/emtricitabine (TDF/FTC) as preexposure prophylaxis for HIV-1 infection (PrEP). Although largely complementary, the six trials have many similar features. As the earliest results become available, an urgent question may arise regarding whether changes should be made in the conduct of the other trials. To consider this in advance, a Consultation on the Implications of HIV Pre-Exposure Prophylaxis (PrEP) Trials Results sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Bill and Melinda Gates Foundation (BMGF) was held on January 29, 2010, at the Natcher Conference Center, NIH, Bethesda, MD. Participants included basic scientists, clinical researchers (including investigators performing the current PrEP trials), and representatives from the U.S. Food and Drug Administration (FDA) and the agencies sponsoring the trials: the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Agency for International Development (USAID), the BMGF, and the U.S. NIH. We report here a summary of the presentations and highlights of salient discussion topics from this workshop. PMID:20969483

Heavy quark physics in ep collisions at LEP+LHC

International Nuclear Information System (INIS)

Ali, A.; Barreiro, F.; Troconiz, J.F. de; Schuler, G.A.; Bij, J.J. van der

1990-12-01

We study electroweak production of heavy quarks - charm, beauty, and top - in deep inelastic electron-proton collisions at the proposed LEP+LHC collider at CERN. The assumed energy for the collisions is E e =50 GeV, E p =8000 GeV, providing an ep center of mass energy, √s≅1.26 TeV. We invoke the boson-gluon fusion model to estimate theoretical cross sections and distributions for the heavy quarks. Higher order QCD corrections are only approximately taken into account, by assuming a (normalization) K-factor of 2 for the charm and beauty quark production rates and incorporating the parton shower cascades. With these assumptions and the parameterization of Eichten et al. for the structure functions (EHLQ, set 1), we find the following cross sections: σ(ep→c+X)≅O(3 μb), σ(ep→b+X)≅O(40 nb), and σ(ep→t+X)≅4 pb for m t =120 GeV, decreasing to 0.5 pb for m t =250 GeV. These cross sections would provide O(6x10 9 ) charmed hadrons, O(8x10 7 ) beauty hadrons, and O(10 3 ) top hadrons, for an integrated ep luminosity of 1000 pb -1 . The heavy quark rates in ep collisions are considerably smaller than the corresponding rates in pp collisions at LHC, with √s=16 TeV. This gives a clear advantage to pp collisions for top searches. However, for the charmed and beauty quarks only a tiny fraction of the cross sections in p+p→Q+X can be triggered in comparison to the corresponding cross sections in e+p→Q+X, resulting in comparable number of measured heavy quark events in the ep and pp mode. We sketch the energy-momentum profile of heavy quark events in ep collisions and illustrate the kind of analyses that experiments at the LEP+LHC collider would undertake to quantitatively study heavy quark physics. In particular, prospects of measuring the particle-antiparticle mixing parameter x s =ΔM/Γ for the B s 0 -anti B s 0 meson system are evaluated, and search strategies for the top quark in ep collisions are presented. (orig.)

EpCAM as multi-tumour target for near-infrared fluorescence guided surgery

International Nuclear Information System (INIS)

Driel, P. B. A. A. van; Boonstra, M. C.; Prevoo, H. A. J. M.; Giessen, M. van de; Snoeks, T. J. A.; Tummers, Q. R. J. G.; Keereweer, S.; Cordfunke, R. A.; Fish, A.; Eendenburg, J. D. H. van; Lelieveldt, B. P. F.; Dijkstra, J.; Velde, C. J. H. van de; Kuppen, P. J. K.; Vahrmeijer, A. L.; Löwik, C. W. G. M.; Sier, C. F. M.

2016-01-01

Evaluation of resection margins during cancer surgery can be challenging, often resulting in incomplete tumour removal. Fluorescence-guided surgery (FGS) aims to aid the surgeon to visualize tumours and resection margins during surgery. FGS relies on a clinically applicable imaging system in combination with a specific tumour-targeting contrast agent. In this study EpCAM (epithelial cell adhesion molecule) is evaluated as target for FGS in combination with the novel Artemis imaging system. The NIR fluorophore IRDye800CW was conjugated to the well-established EpCAM specific monoclonal antibody 323/A3 and an isotype IgG1 as control. The anti-EpCAM/800CW conjugate was stable in serum and showed preserved binding capacity as evaluated on EpCAM positive and negative cell lines, using flow cytometry and cell-based plate assays. Four clinically relevant orthotopic tumour models, i.e. colorectal cancer, breast cancer, head and neck cancer, and peritonitis carcinomatosa, were used to evaluate the performance of the anti-EpCAM agent with the clinically validated Artemis imaging system. The Pearl Impulse small animal imaging system was used as reference. The specificity of the NIRF signal was confirmed using bioluminescence imaging and green-fluorescent protein. All tumour types could clearly be delineated and resected 72 h after injection of the imaging agent. Using NIRF imaging millimetre sized tumour nodules were detected that were invisible for the naked eye. Fluorescence microscopy demonstrated the distribution and tumour specificity of the anti-EpCAM agent. This study shows the potential of an EpCAM specific NIR-fluorescent agent in combination with a clinically validated intraoperative imaging system to visualize various tumours during surgery

CERN's LHC is awarded the 2012 EPS Edison Volta Prize

CERN Multimedia

CERN Bulletin

2012-01-01

The European Physical Society (EPS), the Centro di Cultura Scientifica “Alessandro Volta” and Edison S.p.A. have awarded the 2012 EPS Edison Volta Prize for outstanding contributions to physics to three CERN physicists.   The award was given to: • Rolf-Dieter Heuer, CERN Director-General, • Sergio Bertolucci, CERN Director for Research and Computing, • Stephen Myers, CERN Director for Accelerators and Technology, for having led - building on decades of dedicated work by their predecessors - the culminating efforts in the direction, research and operation of the CERN Large Hadron Collider (LHC), which resulted in many significant advances in high energy particle physics, in particular, the first evidence of a Higgs-like boson in July 2012. To learn more, check out e-EPS News.

A Precision Measurement of the Inclusive ep Scattering Cross Section at HERA

CERN Document Server

Aaron, F.D.; Alimujiang, K.; Andreev, V.; Antunovic, B.; Asmone, A.; Backovic, S.; Baghdasaryan, A.; Barrelet, E.; Bartel, W.; Begzsuren, K.; Belousov, A.; Bizot, J.C.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Bruncko, D.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A.J.; Cantun Avila, K.B.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Cholewa, A.; Contreras, J.G.; Coughlan, J.A.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Daum, K.; Deak, M.; de Boer, Y.; Delcourt, B.; Del Degan, M.; Delvax, J.; De Roeck, A.; De Wolf, E.A.; Diaconu, C.; Dodonov, V.; Dossanov, A.; Dubak, A.; Eckerlin, G.; Efremenko, V.; Egli, S.; Eliseev, A.; Elsen, E.; Falkiewicz, A.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Fischer, D.-J.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, Samvel; Glazov, A.; Glushkov, I.; Goerlich, L.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Greenshaw, T.; Grell, B.R.; Grindhammer, G.; Habib, S.; Haidt, D.; Helebrant, C.; Henderson, R.C.W.; Hennekemper, E.; Henschel, H.; Herbst, M.; Herrera, G.; Hildebrandt, M.; Hiller, K.H.; Hoffmann, D.; Horisberger, R.; Hreus, T.; Jacquet, M.; Janssen, M.E.; Janssen, X.; Jemanov, V.; Jonsson, L.; Jung, Andreas Werner; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I.R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Kluge, T.; Knutsson, A.; Kogler, R.; Korbel, V.; Kostka, P.; Kraemer, M.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Kruger, K.; Kutak, K.; Landon, M.P.J.; Lange, W.; Lastovicka-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Lendermann, V.; Levonian, S.; Li, G.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lytkin, L.; Makankine, A.; Malinovski, E.; Marage, P.; Marti, Ll.; Martyn, H.-U.; Maxfield, S.J.; Mehta, A.; Meyer, A.B.; Meyer, H.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Moreau, F.; Morozov, A.; Morris, J.V.; Mozer, Matthias Ulrich; Mudrinic, M.; Muller, K.; Murin, P.; Naroska, B.; Naumann, Th.; Newman, P.R.; Niebuhr, C.; Nikiforov, A.; Nowak, G.; Nowak, K.; Nozicka, M.; Olivier, B.; Olsson, J.E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Pandurovic, M.; Papadopoulou, Th.; Pascaud, C.; Patel, G.D.; Pejchal, O.; Perez, E.; Petrukhin, A.; Picuric, I.; Piec, S.; Pitzl, D.; Placakyte, R.; Pokorny, B.; Polifka, R.; Povh, B.; Preda, T.; Radescu, V.; Rahmat, A.J.; Raicevic, N.; Raspiareza, A.; Ravdandorj, T.; Reimer, P.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rotaru, M.; Ruiz Tabasco, J.E.; Rurikova, Z.; Rusakov, S.; Salek, D.; Sankey, D.P.C.; Sauter, M.; Sauvan, E.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schoning, A.; Schultz-Coulon, H.-C.; Sefkow, F.; Shaw-West, R.N.; Sheviakov, I.; Shtarkov, L.N.; Shushkevich, S.; Sloan, T.; Smiljanic, Ivan; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, Arnd E.; Staykova, Z.; Steder, M.; Stella, B.; Stoicea, G.; Straumann, U.; Sunar, D.; Sykora, T.; Tchoulakov, V.; Thompson, G.; Thompson, P.D.; Toll, T.; Tomasz, F.; Tran, T.H.; Traynor, D.; Trinh, T.N.; Truol, P.; Tsakov, I.; Tseepeldorj, B.; Turnau, J.; Urban, K.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Vargas Trevino, A.; Vazdik, Y.; Vinokurova, S.; Volchinski, V.; von den Driesch, M.; Wegener, D.; Wallny, R.; Wissing, Ch.; Wunsch, E.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhokin, A.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.; Zus, R.

2009-01-01

A measurement of the inclusive deep-inelastic neutral current e+p scattering cross section is reported in the region of four-momentum transfer squared, 12<=Q^2<=150 GeV^2, and Bjorken x, 2x10^-4<=x<=0.1. The results are based on data collected by the H1 Collaboration at the ep collider HERA at positron and proton beam energies of E_e=27.6 GeV and E_p=920 GeV, respectively. The data are combined with previously published data, taken at E_p=820 GeV. The accuracy of the combined measurement is typically in the range of 1.3-2%. A QCD analysis at next-to-leading order is performed to determine the parton distributions in the proton based on H1 data.

Bayesian-statistical decision threshold, detection limit, and confidence interval in nuclear radiation measurement

International Nuclear Information System (INIS)

Weise, K.

1998-01-01

When a contribution of a particular nuclear radiation is to be detected, for instance, a spectral line of interest for some purpose of radiation protection, and quantities and their uncertainties must be taken into account which, such as influence quantities, cannot be determined by repeated measurements or by counting nuclear radiation events, then conventional statistics of event frequencies is not sufficient for defining the decision threshold, the detection limit, and the limits of a confidence interval. These characteristic limits are therefore redefined on the basis of Bayesian statistics for a wider applicability and in such a way that the usual practice remains as far as possible unaffected. The principle of maximum entropy is applied to establish probability distributions from available information. Quantiles of these distributions are used for defining the characteristic limits. But such a distribution must not be interpreted as a distribution of event frequencies such as the Poisson distribution. It rather expresses the actual state of incomplete knowledge of a physical quantity. The different definitions and interpretations and their quantitative consequences are presented and discussed with two examples. The new approach provides a theoretical basis for the DIN 25482-10 standard presently in preparation for general applications of the characteristic limits. (orig.) [de

The USC-OSA-EPS section activities in optics

Science.gov (United States)

Aymerich, María.; Cambronero-López, Ferran; Aragón, Ángel L.; Delgado, Tamara; Blanco, Manuel; Gómez Varela, Ana I.; Gargallo, Ana; Williamson, Sandra; Amorín, Adán.; Sánchez-García, Ángel; Bao-Varela, Carmen; Flores-Arias, M. Teresa

2017-08-01

The USC-OSA Student Chapter and USC-EPS Young Minds Section is a group financed by The Optical Society (OSA) and the European Physical Society (EPS). It is formed by PhD and degree students from the Universidade de Santiago de Compostela (USC) and one supervisor of the Faculty of Physics. Its main goal is to promote and diffuse Optics in the society. For this purpose, the group carries out several activities in the academic and non-academic community. The group is also committed to the professional development of our members and motivates the exposition of our work into the scientific community.

Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis.

Directory of Open Access Journals (Sweden)

Jingwei Cheng

2017-10-01

Full Text Available Merkel cell carcinoma (MCC frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen (LT and an intact Small T antigen (ST. While LT binds RB and inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. We performed a large-scale immunoprecipitation for ST and identified co-precipitating proteins by mass spectrometry. In addition to protein phosphatase 2A (PP2A subunits, we identified MYCL and its heterodimeric partner MAX plus the EP400 complex. Immunoprecipitation for MAX and EP400 complex components confirmed their association with ST. We determined that the ST-MYCL-EP400 complex binds together to specific gene promoters and activates their expression by integrating chromatin immunoprecipitation with sequencing (ChIP-seq and RNA-seq. MYCL and EP400 were required for maintenance of cell viability and cooperated with ST to promote gene expression in MCC cell lines. A genome-wide CRISPR-Cas9 screen confirmed the requirement for MYCL and EP400 in MCPyV-positive MCC cell lines. We demonstrate that ST can activate gene expression in a EP400 and MYCL dependent manner and this activity contributes to cellular transformation and generation of induced pluripotent stem cells.

Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis.

Science.gov (United States)

Cheng, Jingwei; Park, Donglim Esther; Berrios, Christian; White, Elizabeth A; Arora, Reety; Yoon, Rosa; Branigan, Timothy; Xiao, Tengfei; Westerling, Thomas; Federation, Alexander; Zeid, Rhamy; Strober, Benjamin; Swanson, Selene K; Florens, Laurence; Bradner, James E; Brown, Myles; Howley, Peter M; Padi, Megha; Washburn, Michael P; DeCaprio, James A

2017-10-01

Merkel cell carcinoma (MCC) frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen (LT) and an intact Small T antigen (ST). While LT binds RB and inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC) and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. We performed a large-scale immunoprecipitation for ST and identified co-precipitating proteins by mass spectrometry. In addition to protein phosphatase 2A (PP2A) subunits, we identified MYCL and its heterodimeric partner MAX plus the EP400 complex. Immunoprecipitation for MAX and EP400 complex components confirmed their association with ST. We determined that the ST-MYCL-EP400 complex binds together to specific gene promoters and activates their expression by integrating chromatin immunoprecipitation with sequencing (ChIP-seq) and RNA-seq. MYCL and EP400 were required for maintenance of cell viability and cooperated with ST to promote gene expression in MCC cell lines. A genome-wide CRISPR-Cas9 screen confirmed the requirement for MYCL and EP400 in MCPyV-positive MCC cell lines. We demonstrate that ST can activate gene expression in a EP400 and MYCL dependent manner and this activity contributes to cellular transformation and generation of induced pluripotent stem cells.

Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

Science.gov (United States)

Arosh, Joe A.; Lee, JeHoon; Balasubbramanian, Dakshnapriya; Stanley, Jone A.; Long, Charles R.; Meagher, Mary W.; Osteen, Kevin G.; Bruner-Tran, Kaylon L.; Burghardt, Robert C.; Starzinski-Powitz, Anna; Banu, Sakhila K.

2015-01-01

Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis, and this increased PGE2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis. PMID:26199416

Modeling Bacteria-Water Interactions in Soil: EPS Dynamics Under Evaporative Conditions

Science.gov (United States)

Furrer, J.; Hinestroza, H. F.; Guo, Y. S.; Gage, D. J.; Cho, Y. K.; Shor, L. M.

2017-12-01

The soil habitat represents a major linkage between the water and carbon cycles: the ability of soils to sequester or release carbon is determined primarily by soil moisture. Water retention and distribution in soils controls the abundance and activity of soil microbes. Microbes in turn impact water retention by creating biofilms, composed of extracellular polymeric substances (EPS). We model the effects of bacterial EPS on water retention at the pore scale. We use the lattice Boltzmann method (LBM), a well-established fluid dynamics modeling platform, and modify it to include the effects of water uptake and release by the swelling/shrinking EPS phase. The LB model is implemented in 2-D, with a non-ideal gas equation of state that allows condensation and evaporation of fluid in pore spaces. Soil particles are modeled according to experimentally determined particle size distributions and include realistic pore geometries, in contrast to many soil models which use spherical soil particles for simplicity. Model results are compared with evaporation experiments in soil micromodels and other simpler experimental systems, and model parameters are tuned to match experimental results. Drying behavior and solid-gel contact angle of EPS produced by the soil bacteria Sinorhizobium meliloti has been characterized and compared to the behavior of deionized water under the same conditions. The difference in behavior between the fluids is used to parameterize the model. The model shows excellent qualitative agreement for soil micromodels with both aggregated and non-aggregated particle arrangements under no-EPS conditions, and reproduces realistic drying behavior for EPS. This work represents a multi-disciplinary approach to understanding microbe-soil interactions at the pore scale.

The Pre-Exposure Prophylaxis-Stigma Paradox: Learning from Canada's First Wave of PrEP Users.

Science.gov (United States)

Grace, Daniel; Jollimore, Jody; MacPherson, Paul; Strang, Matthew J P; Tan, Darrell H S

2018-01-01

With the emergence of daily oral tenofovir disoproxil fumarate and emtricitabine-based pre-exposure prophylaxis (PrEP) use in Canada, questions have emerged concerning the impacts of this HIV prevention tool on gay men's social and sexual lives. We conducted small focus groups and individual qualitative interviews with 16 gay men in Toronto who were part of the 'first wave' of Canadian PrEP users. Participants were on PrEP for at least one year as part of a demonstration project (November 2014-June 2016). These participants accessed PrEP before regulatory approval by Health Canada in February 2016. The mean age of participants was 37.6 years (SD 11.02); 94% completed secondary education, and 69% were white. Sex-stigma emerged as a complex theme in men's accounts of PrEP use across three overlapping domains: (1) PrEP-related stigma, including discussions of concealment and stigma from friends, family, and sexual partners, (2) PrEP as a perceived tool for combating HIV-related stigma, where some men said that they no longer discussed HIV status with sexual partners, and (3) PrEP as illuminating structural stigma, where it was attributed to unmasking stigma related to sex and sexuality. For some participants, PrEP has allowed for liberating sex and a self-described return to normalcy-normal, exciting, pleasurable sex that was no longer reliant on condom use. Paradoxically, some men said that PrEP use both led them to experience stigmatizing reactions within their social and sexual networks, while also helping to remove stigma, shame, and fear related to HIV, sexuality, and sex with gay men living with HIV.

The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway

DEFF Research Database (Denmark)

Olesen, Emma Tina Bisgaard; Moeller, Hanne Bjerregaard; Assentoft, Mette

2016-01-01

Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be c...

The EUMETSAT Polar System - Second Generation (EPS-SG) micro-wave imaging (MWI) mission

Science.gov (United States)

Bojkov, B. R.; Accadia, C.; Klaes, D.; Canestri, A.; Cohen, M.

2017-12-01

The EUMETSAT Polar System (EPS) will be followed by a second generation system called EPS-SG. This new family of missions will contribute to the Joint Polar System being jointly set up with NOAA in the timeframe 2020-2040. These satellites will fly, like Metop (EPS), in a sun synchronous, low earth orbit at 830 km altitude and 09:30 local time descending node, providing observations over the full globe with revisit times of 12 hours. EPS-SG consists of two different satellites configurations, the EPS-SGa series dedicated to IR and MW sounding, and the EPS-SGb series dedicated to microwave imaging and scatterometry. The EPS-SG family will consist of three successive launches of each satellite-type. The Microwave Imager (MWI) will be hosted on Metop-SGb series of satellites, with the primary objective of supporting Numerical Weather Prediction (NWP) at regional and global scales. Other applications will be observation of surface parameters such as sea ice concentration and hydrology applications. The 18 MWI instrument frequencies range from 18.7 GHz to 183 GHz. All MWI channels up to 89 GHz will measure V- and H polarizations. The MWI was also designed to provide continuity of measurements for select heritage microwave imager channels (e.g. SSM/I, AMSR-E). The additional sounding channels such as the 50-55 and 118 GHz bands will provide additional cloud and precipitation information over sea and land. This combination of channels was successfully tested on the NPOESS Aircraft Sounder Testbed - Microwave Sounder (NAST-M) airborne radiometer, and it is the first time that will be implemented in a conical scanning configuration in a single instrument. An overview of the EPS-SG programme and the MWI instrument will be presented.

The utiquity and many roles of exopolymers (EPS in aquatic systems

Directory of Open Access Journals (Sweden)

Roger S. Wotton

2004-04-01

Full Text Available Exopolymers (EPS are produced by unicellular and multicellular organisms. They consist largely of polysaccharides that hydrate rapidly on contact with water and link to form gels. EPS have many uses: in attachment; in locomotion on substrata; as a protection against predators, pathogens and changes in physico-chemical conditions; as a means of overcoming the threat of desiccation; in preventing abrasion; and in feeding. When free of organisms, some EPS form loosely associated polymer gels that are important in the development of organic matter aggregates. These aggregates, together with mucus-bound faecal pellets, play an essential role in nutrient cycling, and in the metabolism of ecosystems.;

Multi-thresholds for fault isolation in the presence of uncertainties.

Science.gov (United States)

Touati, Youcef; Mellal, Mohamed Arezki; Benazzouz, Djamel

2016-05-01

Monitoring of the faults is an important task in mechatronics. It involves the detection and isolation of faults which are performed by using the residuals. These residuals represent numerical values that define certain intervals called thresholds. In fact, the fault is detected if the residuals exceed the thresholds. In addition, each considered fault must activate a unique set of residuals to be isolated. However, in the presence of uncertainties, false decisions can occur due to the low sensitivity of certain residuals towards faults. In this paper, an efficient approach to make decision on fault isolation in the presence of uncertainties is proposed. Based on the bond graph tool, the approach is developed in order to generate systematically the relations between residuals and faults. The generated relations allow the estimation of the minimum detectable and isolable fault values. The latter is used to calculate the thresholds of isolation for each residual. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients.

Science.gov (United States)

Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

2018-01-02

Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy.

Distinct roles of Eps8 in the maturation of cochlear and vestibular hair cells.

Science.gov (United States)

Tavazzani, Elisa; Spaiardi, Paolo; Zampini, Valeria; Contini, Donatella; Manca, Marco; Russo, Giancarlo; Prigioni, Ivo; Marcotti, Walter; Masetto, Sergio

2016-07-22

Several genetic mutations affecting the development and function of mammalian hair cells have been shown to cause deafness but not vestibular defects, most likely because vestibular deficits are sometimes centrally compensated. The study of hair cell physiology is thus a powerful direct approach to ascertain the functional status of the vestibular end organs. Deletion of Epidermal growth factor receptor pathway substrate 8 (Eps8), a gene involved in actin remodeling, has been shown to cause deafness in mice. While both inner and outer hair cells from Eps8 knockout (KO) mice showed abnormally short stereocilia, inner hair cells (IHCs) also failed to acquire mature-type ion channels. Despite the fact that Eps8 is also expressed in vestibular hair cells, Eps8 KO mice show no vestibular deficits. In the present study we have investigated the properties of vestibular Type I and Type II hair cells in Eps8-KO mice and compared them to those of cochlear IHCs. In the absence of Eps8, vestibular hair cells show normally long kinocilia, significantly shorter stereocilia and a normal pattern of basolateral voltage-dependent ion channels. We have also found that while vestibular hair cells from Eps8 KO mice show normal voltage responses to injected sinusoidal currents, which were used to mimic the mechanoelectrical transducer current, IHCs lose their ability to synchronize their responses to the stimulus. We conclude that the absence of Eps8 produces a weaker phenotype in vestibular hair cells compared to cochlear IHCs, since it affects the hair bundle morphology but not the basolateral membrane currents. This difference is likely to explain the absence of obvious vestibular dysfunction in Eps8 KO mice. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Should Earnings per Share (EPS) Be Taught as a Means of Comparing Intercompany Performance?

Science.gov (United States)

Jordan, Charles E.; Clark, Stanley J.; Smith, W. Robert

2007-01-01

Accounting standards state that the purpose of presenting earnings per share (EPS) is to provide financial statement users with information on the performance of a single entity. Yet, several textbook authors go further to state that EPS can be used to make comparisons among firms. In this article, the authors show that although EPS comparisons…

e-EPS News: Consultation on European Research, Innovation & Gender

CERN Document Server

e-EPS

2011-01-01

e-EPS News is a monthly addition to the CERN Bulletin line-up, showcasing an article by the e-EPS – the European Physical Society newsletter – as part of a new collaboration between the two publications.   EPS members have been invited to take part in a Public Consultation on the Future of Gender and Innovation in Europe. The consultation, which is intended to complement the EC Green Paper ‘From Challenges to Opportunities: Towards a Common Strategic Framework for EU Research and Innovation Funding’, will be published and discussed during the first European Gender Summit in Brussels on 8-9 November this year. It is hoped that the consultation – which is being coordinated by genSET and the organisers of the European Gender Summit – will create a better understanding of how Europe might benefit from a more effective mainstreaming of the gender dimension in research, innovation and scientific systems. Responses from the co...

Immunohistochemical analysis based Ep-ICD subcellular localization index (ESLI) is a novel marker for metastatic papillary thyroid microcarcinoma

International Nuclear Information System (INIS)

Kunavisarut, Tada; Kak, Ipshita; MacMillan, Christina; Ralhan, Ranju; Walfish, Paul G

2012-01-01

Thyroid cancer is among the fastest growing malignancies; almost fifty-percent of these rapidly increasing incidence tumors are less than or equal to 1cm in size, termed papillary thyroid microcarcinoma (PTMC). The management of PTMC remains a controversy due to differing natural history of these patients. Epithelial cell adhesion molecule (EpCAM) is comprised of an extracellular domain (EpEx), a single transmembrane domain and an intracellular domain (Ep-ICD). Our group reported nuclear Ep-ICD correlated with poor prognosis in thyroid cancer (Ralhan et al., BMC Cancer 2010,10:331). Here in, we hypothesized nuclear and cytoplasmic accumulation of Ep-ICD and loss of membranous EpEx may aid in distinguishing metastatic from non-metastatic PTMC, which is an important current clinical challenge. To test our hypothesis, Ep-ICD and EpEx expression levels were analyzed in PTMC and the staining was correlated with metastatic potential of these carcinomas. Thirty-six PTMC patients (tumor size 0.5 - 1cm; metastatic 8 cases and non-metastatic 28 cases) who underwent total thyroidectomy were selected. The metastatic group consisted of patients who developed lymph node or distant metastasis at diagnosis or during follow up. The patients’ tissues were stained for Ep-ICD and EpEx using domain specific antibodies by immunohistochemistry and evaluated. PTMC patients with metastasis had higher scores for nuclear and cytoplasmic Ep-ICD immunostaining than the patients without metastasis (1.96 ± 0.86 vs. 1.22 ± 0.45; p = 0.007 and 5.37 ± 0.33 vs. 4.72 ± 1.07; p = 0.016, respectively). Concomitantly, the former had lower scores for membrane EpEx than the non-metastatic group (4.64 ± 1.08 vs. 5.64 ± 1.51; p = 0.026). An index of aggressiveness, Ep-ICD subcellular localization index (ESLI), was defined as sum of the IHC scores for accumulation of nuclear and cytoplasmic Ep-ICD and loss of membranous EpEx; ESLI = [Ep − ICD nuc + Ep − ICD cyt + loss of membranous EpEx]. Notably

Beef Quality Identification Using Thresholding Method and Decision Tree Classification Based on Android Smartphone

Directory of Open Access Journals (Sweden)

Kusworo Adi

2017-01-01

Full Text Available Beef is one of the animal food products that have high nutrition because it contains carbohydrates, proteins, fats, vitamins, and minerals. Therefore, the quality of beef should be maintained so that consumers get good beef quality. Determination of beef quality is commonly conducted visually by comparing the actual beef and reference pictures of each beef class. This process presents weaknesses, as it is subjective in nature and takes a considerable amount of time. Therefore, an automated system based on image processing that is capable of determining beef quality is required. This research aims to develop an image segmentation method by processing digital images. The system designed consists of image acquisition processes with varied distance, resolution, and angle. Image segmentation is done to separate the images of fat and meat using the Otsu thresholding method. Classification was carried out using the decision tree algorithm and the best accuracies were obtained at 90% for training and 84% for testing. Once developed, this system is then embedded into the android programming. Results show that the image processing technique is capable of proper marbling score identification.

Soil thresholds and a decision tool to manage food safety of crops grown in chlordecone polluted soil in the French West Indies.

Science.gov (United States)

Clostre, Florence; Letourmy, Philippe; Lesueur-Jannoyer, Magalie

2017-04-01

Due to the persistent pollution of soils by an organochlorine, chlordecone (CLD also known as Kepone © ) in the French West Indies, some crops may be contaminated beyond the European regulatory threshold, the maximum residue limit (MRL). Farmers need to be able to foresee the risk of not complying with the regulatory threshold in each field and for each crop, if not, farmers whose fields are contaminated would have to stop cultivating certain crops in the fields concerned. To help farmers make the right choices, we studied the relationship between contamination of the soil and contamination of crops. We showed that contamination of a crop by CLD depended on the crop concerned, the soil CLD content and the type of soil. We grouped crop products in three categories: (i) non-uptakers and low-uptakers, (ii) medium-uptakers, and (iii) high-uptakers, according to their level of contamination and the resulting risk of exceeding MRL. Using a simulation model, we computed the soil threshold required to ensure the risk of not complying with MRL was sufficiently low for each crop product and soil type. Threshold values ranged from 0.02 μgkg -1 for dasheen grown in nitisol to 1.7 μgkg -1 for yam grown in andosol in the high-uptake category, and from 1 μgkg -1 for lettuce grown in nitisol to 45 μgkg -1 for the leaves of spring onions grown in andosol in the medium-uptake category. Contamination of non-uptakers and low-uptakers did not depend on soil contamination. With these results, we built an easy-to-use decision support tool based on two soil thresholds (0.1 and 1 μgkg -1 ) to enable growers to adapt their cropping system and hence to be able to continue farming. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluating the impact of prioritization of antiretroviral pre-exposure prophylaxis (PrEP) in New York City

Science.gov (United States)

Kessler, Jason; Myers, Julie E.; Nucifora, Kimberly A.; Mensah, Nana; Toohey, Christopher; Khademi, Amin; Cutler, Blayne; Braithwaite, R. Scott

2015-01-01

Objective To compare the value and effectiveness of different prioritization strategies of pre-exposure prophylaxis (PrEP) in New York City (NYC). Design Mathematical modeling utilized as clinical trial is not feasible. Methods Using a model accounting for both sexual and parenteral transmission of HIV we compare different prioritization strategies (PPS) for PrEP to two scenarios—no PrEP and PrEP for all susceptible at-risk individuals. The PPS included PrEP for all MSM, only high-risk MSM, high-risk heterosexuals, and injection drug users, and all combinations of these four strategies. Outcomes included HIV infections averted, and incremental cost effectiveness (per-infection averted) ratios. Initial assumptions regarding PrEP included a 44% reduction in HIV transmission, 50% uptake in the prioritized population and an annual cost per person of $9,762. Sensitivity analyses on key parameters were conducted. Results Prioritization to all MSM results in a 19% reduction in new HIV infections. Compared to PrEP for all persons at-risk this PPS retains 79% of the preventative effect at 15% of the total cost. PrEP prioritized to only high-risk MSM results in a reduction in new HIV infections of 15%. This PPS retains 60% of the preventative effect at 6% of the total cost. There are diminishing returns when PrEP utilization is expanded beyond this group. Conclusions PrEP implementation is relatively cost-inefficient under our initial assumptions. Our results suggest that PrEP should first be promoted among MSM who are at particularly high-risk of HIV acquisition. Further expansion beyond this group may be cost-effective, but is unlikely to be cost-saving. PMID:25493594

A novel biosorbent for dye removal: Extracellular polymeric substance (EPS) of Proteus mirabilis TJ-1

Energy Technology Data Exchange (ETDEWEB)

Zhang Zhiqiang [State Key Laboratory of Pollution Control and Resource Reuse, Key Laboratory of Yangtze River Water Environment of Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China); Laboratoire de Sciences Analytiques (UMR CNRS 5180), Universite Claude Bernard Lyon 1, Universite de Lyon, 69622 Villeurbanne Cedex (France); Xia Siqing [State Key Laboratory of Pollution Control and Resource Reuse, Key Laboratory of Yangtze River Water Environment of Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China)], E-mail: siqingxia@mail.tongji.edu.cn; Wang Xuejiang; Yang Aming; Xu Bin; Chen Ling; Zhu Zhiliang; Zhao Jianfu [State Key Laboratory of Pollution Control and Resource Reuse, Key Laboratory of Yangtze River Water Environment of Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092 (China); Jaffrezic-Renault, Nicole; Leonard, Didier [Laboratoire de Sciences Analytiques (UMR CNRS 5180), Universite Claude Bernard Lyon 1, Universite de Lyon, 69622 Villeurbanne Cedex (France)

2009-04-15

This paper deals with the extracellular polymeric substance (EPS) of Proteus mirabilis TJ-1 used as a novel biosorbent to remove dye from aqueous solution in batch systems. As a widely used and hazardous dye, basic blue 54 (BB54) was chosen as the model dye to examine the adsorption performance of the EPS. The effects of pH, initial dye concentration, contact time and temperature on the sorption of BB54 to the EPS were examined. At various initial dye concentrations (50-400 mg/L), the batch sorption equilibrium can be obtained in only 5 min. Kinetic studies suggested that the sorption followed the internal transport mechanism. According to the Langmuir model, the maximum BB54 uptake of 2.005 g/g was obtained. Chemical analysis of the EPS indicated the presence of protein (30.9%, w/w) and acid polysaccharide (63.1%, w/w). Scanning electron microscopy (SEM) images showed that the EPS with a crystal-linear structure was whole enwrapped by adsorbed dye molecules. FTIR spectrum result revealed the presence of adsorbing groups such as carboxyl, hydroxyl and amino groups in the EPS. High-molecular weight of the EPS with more binding-sites and stronger van der Waals forces together with its specific construct leads to the excellent performance of dye adsorption. The EPS shows potential board application as a biosorbent for both environmental protection and dye recovery.

A novel biosorbent for dye removal: Extracellular polymeric substance (EPS) of Proteus mirabilis TJ-1

International Nuclear Information System (INIS)

Zhang Zhiqiang; Xia Siqing; Wang Xuejiang; Yang Aming; Xu Bin; Chen Ling; Zhu Zhiliang; Zhao Jianfu; Jaffrezic-Renault, Nicole; Leonard, Didier

2009-01-01

This paper deals with the extracellular polymeric substance (EPS) of Proteus mirabilis TJ-1 used as a novel biosorbent to remove dye from aqueous solution in batch systems. As a widely used and hazardous dye, basic blue 54 (BB54) was chosen as the model dye to examine the adsorption performance of the EPS. The effects of pH, initial dye concentration, contact time and temperature on the sorption of BB54 to the EPS were examined. At various initial dye concentrations (50-400 mg/L), the batch sorption equilibrium can be obtained in only 5 min. Kinetic studies suggested that the sorption followed the internal transport mechanism. According to the Langmuir model, the maximum BB54 uptake of 2.005 g/g was obtained. Chemical analysis of the EPS indicated the presence of protein (30.9%, w/w) and acid polysaccharide (63.1%, w/w). Scanning electron microscopy (SEM) images showed that the EPS with a crystal-linear structure was whole enwrapped by adsorbed dye molecules. FTIR spectrum result revealed the presence of adsorbing groups such as carboxyl, hydroxyl and amino groups in the EPS. High-molecular weight of the EPS with more binding-sites and stronger van der Waals forces together with its specific construct leads to the excellent performance of dye adsorption. The EPS shows potential board application as a biosorbent for both environmental protection and dye recovery

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

OpenAIRE

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

2016-01-01

Background:\\ud 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.\\ud Methods:\\ud Quantitative surveys of n = 690 MSM recruited online via social a...

Data of evolutionary structure change: 1EP7B-1FAAA [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1EP7B-1FAAA 1EP7 1FAA B A -------------GGSVIVIDSKAAWDAQLAKGKEEHKP...IVVDFTATWCGPCKMIAPLFETLSNDYAGKVIFLKVD-VDAVAAVAEAAGITAMPTFHVYKDGVKADDLVGASQDKLKALVAKHAAA LELALGT...AA A 1FAAA FLKLDCNQENK A 1FAAA VTEVN-KDTFW

Tufting enteropathy with EpCAM mutation: case report

Directory of Open Access Journals (Sweden)

Karla Lais Pêgas

2014-06-01

Full Text Available Tufting enteropathy (TE, also known as intestinal epithelial dysplasia (IED, is a rare congenital enteropathy related to an earlyonset of severe intractable diarrhea due to specific abnormalities of the intestinal epithelium and mutations of the EpCAM gene. TE is characterized by clinical and histological heterogeneity, such as with low or without mononuclear cell infiltration of the lamina propria, and abnormalities of basement membrane. TE can be associated with malformations, other epithelial diseases, or to abnormal enterocytes development and/or differentiation. The authors report a case of a Brazilian child with TE associated with c.556-14A>G mutation in the EpCAM gene (NM_002354.2.

Proneoplastic effects of PGE2 mediated by EP4 receptor in colorectal cancer.

LENUS (Irish Health Repository)

Doherty, Glen A

2009-01-01

BACKGROUND: Prostaglandin E2 (PGE2) is the major product of Cyclooxygenase-2 (COX-2) in colorectal cancer (CRC). We aimed to assess PGE2 cell surface receptors (EP 1-4) to examine the mechanisms by which PGE2 regulates tumour progression. METHODS: Gene expression studies were performed by quantitative RT-PCR. Cell cycle was analysed by flow cytometry with cell proliferation quantified by BrdU incorporation measured by enzyme immunoassay. Immunohistochemistry was employed for expression studies on formalin fixed paraffin embedded tumour tissue. RESULTS: EP4 was the most abundant subtype of PGE2 receptor in HT-29 and HCA7 cells (which show COX-2 dependent PGE2 generation) and was consistently the most abundant transcript in human colorectal tumours (n = 8) by qRT-PCR (ANOVA, p = 0.01). G0\\/G1 cell cycle arrest was observed in HT-29 cells treated with SC-236 5 microM (selective COX-2 inhibitor) for 24 hours (p = 0.02), an effect abrogated by co-incubation with PGE2 (1 microM). G0\\/G1 arrest was also seen with a specific EP4 receptor antagonist (EP4A, L-161982) (p = 0.01). Treatment of HT-29 cells with either SC-236 or EP4A caused reduction in intracellular cAMP (ANOVA, p = 0.01). Early induction in p21WAF1\\/CIP1 expression (by qRT-PCR) was seen with EP4A treatment (mean fold increase 4.4, p = 0.04) while other genes remained unchanged. Similar induction in p21WAF1\\/CIP1 was also seen with PD153025 (1 microM), an EGFR tyrosine kinase inhibitor, suggesting EGFR transactivation by EP4 as a potential mechanism. Additive inhibition of HCA7 proliferation was observed with the combination of SC-236 and neutralising antibody to amphiregulin (AR), a soluble EGFR ligand. Concordance in COX-2 and AR localisation in human colorectal tumours was noted. CONCLUSION: COX-2 regulates cell cycle transition via EP4 receptor and altered p21WAF1\\/CIP1 expression. EGFR pathways appear important. Specific targeting of the EP4 receptor or downstream targets may offer a safer alternative

Barriers and Facilitators to Oral PrEP Use Among Transgender Women in New York City.

Science.gov (United States)

Rael, Christine Tagliaferri; Martinez, Michelle; Giguere, Rebecca; Bockting, Walter; MacCrate, Caitlin; Mellman, Will; Valente, Pablo; Greene, George J; Sherman, Susan; Footer, Katherine H A; D'Aquila, Richard T; Carballo-Diéguez, Alex

2018-03-27

Transgender women may face a disparate risk for HIV/AIDS compared to other groups. In 2012, Truvada was approved for daily use as HIV pre-exposure prophylaxis (PrEP). However, there is a dearth of research about barriers and facilitators to PrEP in transgender women. This paper will shed light on transgender women living in New York City's perceived and actual challenges to using PrEP and potential strategies to overcome them. After completing an initial screening process, four 90-min focus groups were completed with n = 18 transgender women. Participants were asked what they like and dislike about PrEP. Participants identified the following barriers: uncomfortable side effects, difficulty taking pills, stigma, exclusion of transgender women in advertising, and lack of research on transgender women and PrEP. Facilitators included: reducing pill size, increasing the types of available HIV prevention products, and conducting scientific studies to evaluate PrEP in transgender women.

Polyadenylation site prediction using PolyA-iEP method.

Science.gov (United States)

Kavakiotis, Ioannis; Tzanis, George; Vlahavas, Ioannis

2014-01-01

This chapter presents a method called PolyA-iEP that has been developed for the prediction of polyadenylation sites. More precisely, PolyA-iEP is a method that recognizes mRNA 3'ends which contain polyadenylation sites. It is a modular system which consists of two main components. The first exploits the advantages of emerging patterns and the second is a distance-based scoring method. The outputs of the two components are finally combined by a classifier. The final results reach very high scores of sensitivity and specificity.

30 CFR 250.214 - What geological and geophysical (G&G) information must accompany the EP?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What geological and geophysical (G&G... and Information Contents of Exploration Plans (ep) § 250.214 What geological and geophysical (G&G) information must accompany the EP? The following G&G information must accompany your EP: (a) Geological...

Environmental Performance and Financing Decisions Impact on Sustainable Financial Development of Chinese Environmental Protection Enterprises

Directory of Open Access Journals (Sweden)

Kai Quan Zhang

2017-12-01

Full Text Available Environmental protection firms need to improve their ability to access financing while maintaining good economic performance under mounting environmental pressures. After the integration of trade-off and stakeholder theories, we have constructed a number of mathematical models to investigate the relationship among financing decisions, environmental performance (EP, and economic performance. Unbalanced panel data from environmental protection companies listed on Chinese stock exchanges from 2007 to 2016 were collected and analyzed. Our results have confirmed that debt financing has a significant impact on short- and long-term economic performance. Firms prefer long-term debt over short-term debt to improve their financial sustainability. Internal financing is positively related to performance because the cost of financing is lower. Environmental performance can cause extra financial burden in the short run, but will improve stakeholder relations and profitability in the long run. Our study suggests that environmental performance affects the relationship between financing decisions and economic performance. When EP initiatives are high, debt financing has a greater negative influence on short-term performance, and the effect on long-term performance is mitigated. High EP also reduces the impact of internal financing on performance.

The issue of threshold states

International Nuclear Information System (INIS)

Luck, L.

1994-01-01

The states which have not joined the Non-proliferation Treaty nor have undertaken any other internationally binding commitment not to develop or otherwise acquire nuclear weapons are considered a threshold states. Their nuclear status is rendered opaque as a conscious policy. Nuclear threshold status remains a key disarmament issue. For those few states, as India, Pakistan, Israel, who have put themselves in this position, the security returns have been transitory and largely illusory. The cost to them, and to the international community committed to the norm of non-proliferation, has been huge. The decisions which could lead to recovery from the situation in which they find themselves are essentially at their own hands. Whatever assistance the rest of international community is able to extend, it will need to be accompanied by a vital political signal

Methane oxidation and formation of EPS in compost: effect of oxygen concentration

International Nuclear Information System (INIS)

Wilshusen, J.H.; Hettiaratchi, J.P.A.; Visscher, A. de; Saint-Fort, R.

2004-01-01

Oxygen concentration plays an important role in the regulation of methane oxidation and the microbial ecology of methanotrophs. However, this effect is still poorly quantified in soil and compost ecosystems. The effect of oxygen on the formation of exopolymeric substances (EPS) is as yet unknown. We studied the effect of oxygen on the evolution of methanotrophic activity. At both high and low oxygen concentrations, peak activity was observed twice within a period of 6 months. Phospholipid fatty acid analysis showed that there was a shift from type I to type II methanotrophs during this period. At high oxygen concentration, EPS production was about 250% of the amount at low oxygen concentration. It is hypothesized that EPS serves as a carbon cycling mechanism for type I methanotrophs when inorganic nitrogen is limiting. Simultaneously, EPS stimulates nitrogenase activity in type II methanotrophs by creating oxygen-depleted zones. The kinetic results were incorporated in a simulation model for gas transport and methane oxidation in a passively aerated biofilter. Comparison between the model and experimental data showed that, besides acting as a micro-scale diffusion barrier, EPS can act as a barrier to macro-scale diffusion, reducing the performance of such biofilters. - 1.5% oxygen resulted in a slightly higher and more stable methane oxidation activity

Data of evolutionary structure change: 1EP8B-1FAAA [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1EP8B-1FAAA 1EP8 1FAA B A -------------GGSVIVIDSKAAWDAQLAKGKEEHKP...IVVAFTATWCGPCKMIAPLFETLSNDYAGKVIFLKVDVD-AVAAVAEAAGITAMPTFHVYKDGVKADDLVGASQDKLKALVAKHAAA LELALGT.../pdbChain> 1FAAA KLDCNQENKTL EEE HHH 1 1FAA A 1FAAA

76 FR 52952 - Student Services Contract EP-11-D-000403 Yin Gu; Transfer of Data

Science.gov (United States)

2011-08-24

... will enable Student Services Contract EP-11-D-000403 Yin Gu to fulfill the obligations of the contract... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2011-0038; FRL-8884-1] Student Services Contract EP-11... Business Information (CBI) by the submitter, will be transferred to Student Services Contract EP- 11-D...

EPS Young Physicist Prize - CORRECTION

CERN Multimedia

2009-01-01

The original text for the article 'Prizes aplenty in Krakow' in Bulletin 30-31 assigned the award of the EPS HEPP Young Physicist Prize to Maurizio Pierini. In fact he shared the prize with Niki Saoulidou of Fermilab, who was rewarded for her contribution to neutrino physics, as the article now correctly indicates. We apologise for not having named Niki Saoulidou in the original article.

Overexpression, purification, crystallization and preliminary X-ray studies of Vibrio cholerae EpsG

International Nuclear Information System (INIS)

Jens, Jason; Raghunathan, Kannan; Vago, Frank; Arvidson, Dennis

2009-01-01

Recombinant V. cholerae EpsG has been expressed, purified and crystallized. The crystals diffracted to 2.26 Å resolution. EpsG is the major pseudopilin protein of the Vibrio cholerae type II secretion system. An expression plasmid that encodes an N-terminally truncated form of EpsG with a C-terminal noncleavable His tag was constructed. Recombinant EpsG was expressed in Escherichia coli; the truncated protein was purified and crystallized by hanging-drop vapor diffusion against a reservoir containing 6 mM zinc sulfate, 60 mM MES pH 6.5, 15% PEG MME 550. The crystals diffracted X-rays to a resolution of 2.26 Å and belonged to space group P2 1 , with unit-cell parameters a = 88.61, b = 70.02, c = 131.54 Å

Kliininen päättely epäspesifin alaselkäkivun fysioterapeuttisessa arvioinnissa : narratiivinen kirjallisuuskatsaus

OpenAIRE

Penttilä, Maria

2014-01-01

Tämä opinnäytetyö tarkastelee, mitä on kliininen päättely ja miten fysioterapeutin tulisi arvioida epäspesifiä alaselkäkipua kliinisen päättelyn näkökulmasta. Toteutusmuotona on narratiivinen eli kuvaileva kirjallisuuskatsaus, joka ei tutkimusmetodina tarjoa analyyttistä tulosta vaan pyrkii kuvailemaan ilmiöitä sekä ajantasaistamaan tietoa. Epäspesifi alaselkäkipu on aiheena ajankohtainen, sillä noin 90 % alaselkäkivuista on epäspesifiä alaselkäkipua. Kuitenkin epäspesifin alaselkäkivun l...

EP1000 passive plant description

International Nuclear Information System (INIS)

Saiu, G.

1999-01-01

In 1994, a group of European Utilities, together with Westinghouse and its Industrial Partner GENESI (an Italian consortium including ANSALDO and FIAT), initiated a program designated EPP (European Passive Plant) to evaluate Westinghouse Passive Nuclear Plant Technology for application in Europe. In Phase I of the European Passive Plant Program which was completed in 1996, a 1000 MWe passive plant reference design (EP1000) was established which conforms to the European Utility Requirements (EUR) and is expected to meet the European Safety Authorities requirements. Phase 2 of the program was initiated in 1997 with the objective of developing the Nuclear Island design details and performing supporting analyses to start development of Safety Case Report (SCR) for submittal to European Licensing Authorities. The first part of Phase 2, 'Design Definition' phase (Phase 2A) will be completed at the end of 1998, the main efforts being design definition of key systems and structures, development of the Nuclear Island layout, and performing preliminary safety analyses to support design efforts. The second part, 'Phase 2B', includes both the analyses and evaluations required to demonstrate the adequacy of the design, and to support the preparation of Safety Case Report. The second part of Phase 2 of the program will start at the beginning of 1999 and will be completed in the 2001. Incorporation of the EUR has been a key design requirement for the EP1000 from the beginning of the program. Detailed design solutions to meet the EUR have been defined and the safety approach has also been developed based on the EUR guidelines. This paper integrates and updates the plant description reported in the IAEA TECDOC-968. The most significant developments of the EP1000 plant design during Phase 2A of the EPP program are described and reference is made to the key design requirements set by the EUR Rev. B document. (author)

EPS insulated façade fires from a fire and rescue perspective

Directory of Open Access Journals (Sweden)

Kumm M.

2013-11-01

Full Text Available This paper highlights the challenges the fire and rescue services can meet at façade fires involving EPS insulation during construction and use of a building. The EPS characteristics are discussed in respect to the fire and rescue operation and results from orientating fire tests performed at a fire and rescue services training and test field are presented. Types of evacuation solutions, involving the fire and rescue services, where façade fires can delay or completely rule out the possibilities for safe evacuation, are presented. The restrictions in the Swedish building codes regarding use of combustible insulation are analysed and reflections over the practical problems with following the instructions to keep an EPS insulated façade safe through the building's whole lifespan are made. A number of occurred fires involving EPS are discussed and analysed from a fire and rescue perspective. Finally, recommendations are given for the fire and rescue services and future research fields are proposed.

Pre-Exposure Prophylaxis: A Narrative Review of Provider Behavior and Interventions to Increase PrEP Implementation in Primary Care.

Science.gov (United States)

Silapaswan, Andrew; Krakower, Douglas; Mayer, Kenneth H

2017-02-01

Since FDA approval of HIV pre-exposure prophylaxis (PrEP) for HIV prevention, attention has been focused on PrEP implementation. The CDC estimates that 1.2 million U.S. adults might benefit from PrEP, but only a minority are using PrEP, so there is a significant unmet need to increase access for those at risk for HIV. Given the large numbers of individuals who have indications for PrEP, there are not enough practicing specialists to meet the growing need for providers trained in providing PrEP. Moreover, since PrEP is a preventive intervention for otherwise healthy individuals, primary care providers (PCPs) should be primary prescribers of PrEP. There are important clinical considerations that providers should take into account when planning to prescribe PrEP, which are highlighted in the clinical case discussed. A growing body of research also suggests that some providers may be cautious about prescribing PrEP because of concerns regarding its "real-world" effectiveness, anticipated unintended consequences associated with its use, and ambiguity as to who should prescribe it. This review summarizes findings from studies that have assessed prescriber behavior regarding provision of PrEP, and offers recommendations on how to optimize PrEP implementation in primary care settings. Development and dissemination of educational interventions for PCPs and potential PrEP users are needed, including improved methods to assist clinicians in identifying appropriate PrEP candidates, and programs to promote medication adherence and access to social and behavioral health services. PCPs are well-positioned to prescribe PrEP and coordinate health-related services to improve the sexual health of their patients, but tailored educational programs are needed.

Systemic EP4 Inhibition Increases Adhesion Formation in a Murine Model of Flexor Tendon Repair.

Directory of Open Access Journals (Sweden)

Michael B Geary

Full Text Available Flexor tendon injuries are a common clinical problem, and repairs are frequently complicated by post-operative adhesions forming between the tendon and surrounding soft tissue. Prostaglandin E2 and the EP4 receptor have been implicated in this process following tendon injury; thus, we hypothesized that inhibiting EP4 after tendon injury would attenuate adhesion formation. A model of flexor tendon laceration and repair was utilized in C57BL/6J female mice to evaluate the effects of EP4 inhibition on adhesion formation and matrix deposition during flexor tendon repair. Systemic EP4 antagonist or vehicle control was given by intraperitoneal injection during the late proliferative phase of healing, and outcomes were analyzed for range of motion, biomechanics, histology, and genetic changes. Repairs treated with an EP4 antagonist demonstrated significant decreases in range of motion with increased resistance to gliding within the first three weeks after injury, suggesting greater adhesion formation. Histologic analysis of the repair site revealed a more robust granulation zone in the EP4 antagonist treated repairs, with early polarization for type III collagen by picrosirius red staining, findings consistent with functional outcomes. RT-PCR analysis demonstrated accelerated peaks in F4/80 and type III collagen (Col3a1 expression in the antagonist group, along with decreases in type I collagen (Col1a1. Mmp9 expression was significantly increased after discontinuing the antagonist, consistent with its role in mediating adhesion formation. Mmp2, which contributes to repair site remodeling, increases steadily between 10 and 28 days post-repair in the EP4 antagonist group, consistent with the increased matrix and granulation zones requiring remodeling in these repairs. These findings suggest that systemic EP4 antagonism leads to increased adhesion formation and matrix deposition during flexor tendon healing. Counter to our hypothesis that EP4 antagonism

Expression of EpCam and Villin in Barrett’s Esophagus and in Gastric Cardia

Directory of Open Access Journals (Sweden)

Mario Anders

2008-01-01

Full Text Available In the current study we aimed to clarify the potential of EpCAM and villin as in vivo biomarkers for both Barrett esophagus (BE-associated neoplasia and BE versus cardiac mucosa. Immunohistochemical staining in BE with various degrees of intraepithelial neoplasia (IN, Barrett carcinoma (BC and in normal cardiac mucosa (CM revealed a lack of EpCam and villin in squamous esophageal epithelium. All specimens of IN and BC showed EpCam with varying staining intensities. In 57% of CM samples a weak signal was detected; the remainder displayed strong EpCam expression. Villin was found in 97% of BE specimens and in all those with IN; 37% of BC and 75% of CM specimens were also positive. We conclude that expression of EpCam and villin differs only between squamous epithelium and BE. Determination of these proteins does not allow discrimination between different degrees of neoplasia or between esophageal intestinal metaplasia and cardiac mucosa.

Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis

International Nuclear Information System (INIS)

Somasundaram, Raj Thani; Kaur, Jatinder; Leong, Iona; MacMillan, Christina; Witterick, Ian J.; Walfish, Paul G.; Ralhan, Ranju

2016-01-01

Identification of patients with oral dysplasia at high risk of cancer development and oral squamous cell carcinoma (OSCC) at increased risk of disease recurrence will enable rigorous personalized treatment. Regulated intramembranous proteolysis of Epithelial cell adhesion molecule (EpCAM) resulting in release of its intracellular domain Ep-ICD into cytoplasm and nucleus triggers oncogenic signaling. We analyzed the expression of Ep-ICD in oral dysplasia and cancer and determined its clinical significance in disease progression and prognosis. In a retrospective study, immunohistochemical analysis of nuclear and cytoplasmic Ep-ICD and EpEx (extracellular domain of EpCAM), was carried out in 115 OSCC, 97 oral dysplasia and 105 normal oral tissues, correlated with clinicopathological parameters and disease outcome over 60 months for oral dysplasia and OSCC patients. Disease-free survival (DFS) was determined by Kaplan-Meier method and multivariate Cox regression analysis. In comparison with normal oral tissues, significant increase in nuclear Ep-ICD and membrane EpEx was observed in dysplasia, and OSCC (p = 0.013 and < 0.001 respectively). Oral dysplasia patients with increased overall Ep-ICD developed cancer in short time period (mean = 47 months; p = 0.044). OSCC patients with increased nuclear Ep-ICD and membrane EpEx had significantly reduced mean DFS of 33.7 months (p = 0.018). Our study provided clinical evidence for Ep-ICD as a predictor of cancer development in patients with oral dysplasia and recurrence in OSCC patients, suggesting its potential utility in enhanced management of those patients detected to have increased risk of progression to cancer and recurrence in OSCC patients

Response threshold variance as a basis of collective rationality.

Science.gov (United States)

Yamamoto, Tatsuhiro; Hasegawa, Eisuke

2017-04-01

Determining the optimal choice among multiple options is necessary in various situations, and the collective rationality of groups has recently become a major topic of interest. Social insects are thought to make such optimal choices by collecting individuals' responses relating to an option's value (=a quality-graded response). However, this behaviour cannot explain the collective rationality of brains because neurons can make only 'yes/no' responses on the basis of the response threshold. Here, we elucidate the basic mechanism underlying the collective rationality of such simple units and show that an ant species uses this mechanism. A larger number of units respond 'yes' to the best option available to a collective decision-maker using only the yes/no mechanism; thus, the best option is always selected by majority decision. Colonies of the ant Myrmica kotokui preferred the better option in a binary choice experiment. The preference of a colony was demonstrated by the workers, which exhibited variable thresholds between two options' qualities. Our results demonstrate how a collective decision-maker comprising simple yes/no judgement units achieves collective rationality without using quality-graded responses. This mechanism has broad applicability to collective decision-making in brain neurons, swarm robotics and human societies.

Setting conservation management thresholds using a novel participatory modeling approach.

Science.gov (United States)

Addison, P F E; de Bie, K; Rumpff, L

2015-10-01

We devised a participatory modeling approach for setting management thresholds that show when management intervention is required to address undesirable ecosystem changes. This approach was designed to be used when management thresholds: must be set for environmental indicators in the face of multiple competing objectives; need to incorporate scientific understanding and value judgments; and will be set by participants with limited modeling experience. We applied our approach to a case study where management thresholds were set for a mat-forming brown alga, Hormosira banksii, in a protected area management context. Participants, including management staff and scientists, were involved in a workshop to test the approach, and set management thresholds to address the threat of trampling by visitors to an intertidal rocky reef. The approach involved trading off the environmental objective, to maintain the condition of intertidal reef communities, with social and economic objectives to ensure management intervention was cost-effective. Ecological scenarios, developed using scenario planning, were a key feature that provided the foundation for where to set management thresholds. The scenarios developed represented declines in percent cover of H. banksii that may occur under increased threatening processes. Participants defined 4 discrete management alternatives to address the threat of trampling and estimated the effect of these alternatives on the objectives under each ecological scenario. A weighted additive model was used to aggregate participants' consequence estimates. Model outputs (decision scores) clearly expressed uncertainty, which can be considered by decision makers and used to inform where to set management thresholds. This approach encourages a proactive form of conservation, where management thresholds and associated actions are defined a priori for ecological indicators, rather than reacting to unexpected ecosystem changes in the future. © 2015 The

When the science fails and the ethics works: 'Fail-safe' ethics in the FEM-PrEP study.

Science.gov (United States)

Kingori, Patricia

2015-12-01

This paper will explore the concept of 'fail safe' ethics in the FEM PrEP trial, and the practice of research and ethics on the ground. FEM-PrEP examined the efficacy of PrEP in African women after promising outcomes in research conducted with MSM. This was a hugely optimistic time and FEM-PrEP was mobilised using rights-based ethical arguments that women should have access to PrEP. This paper will present data collected during an ethnographic study of frontline research workers involved in FEM-PrEP. During our discussions, 'fail-safe' ethics emerged as concept that encapsulated their confidence that their ethics could not fail. However, in 2011, FEM-PrEP was halted and deemed a failure. The women involved in the study were held responsible because contrary to researcher's expectations they were not taking the oral PrEP being researched. This examination of FEM-PrEP will show that ethical arguments are increasingly deployed to mobilise, maintain and in some cases stop trials in ways which, at times, are superseded or co-opted by other interests. While promoting the interests of women, rights-based approaches are argued to indirectly justify the continuation of individualised, biomedical interventions which have been problematic in other women-centred trials. In this examination of FEM-PrEP, the rights-based approach obscured: ethical concerns beyond access to PrEP; the complexities of power relationships between donor and host countries; the operations of the HIV industry in research-saturated areas and the cumulative effect of unfilled expectations in HIV research and how this has shaped ideas of research and ethics.

PrEP adopted by the brazilian national health system: What is the size of the demand?

Science.gov (United States)

Luz, Paula M; Benzaken, Adele; Alencar, Tatianna M de; Pimenta, Cristina; Veloso, Valdilea G; Grinsztejn, Beatriz

2018-05-01

Brazil's response to the HIV epidemic now includes free access to preexposure prophylaxis (PrEP) to populations at substantial risk for HIV infection including men who have sex with men (MSM). We used nationally representative demographic, epidemiologic, and surveillance data to offer estimates for the number of MSM at substantial risk for HIV infection who might be eligible and willing to use PrEP in Brazil. Starting from the age/sex-stratified population, we calculated the number of men aged 15 to 64 years, in 5-year age groups, and the proportion of those who report sex with other men during their lifetime. We focused on 11 cities (representing all regions) that are responsible for a significant fraction of the HIV burden of the country and used city-specific HIV prevalence estimates to infer the fraction of MSM who are HIV-negative. We then derived the proportion of HIV-negative MSM under substantial risk for HIV infection defined as having unprotected receptive anal intercourse in the 6 months before study participation. Finally, PrEP uptake among the eligible was inferred from the PrEP Brazil study. Our results show that PrEP demand in these 11 cities is of 66,120 men aged 15 to 64 years. When we consider the lower and upper bounds for the available parameters, we find that PrEP demand in these 11 cities might vary from 33,378 to 97,962 men. If PrEP is restricted to those aged 15 to 49 years, demand drops by 20%. PrEP demand varies considerably by city, mostly because of the differences in population size and city-specific HIV prevalence. We have shed light on the probable size of PrEP demand in Brazil certain that the incorporation of PrEP as part of Brazil's combination prevention for populations at substantial risk for HIV infection is a necessary challenge. PrEP will not only prevent HIV infections, it will also expand testing among the most vulnerable with the added benefit of offering combination prevention for the uninfected and immediate treatment for

Towards a fair consideration of PrEP as part of combination HIV prevention in Latin America.

Science.gov (United States)

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

Decrease in zinc adsorption onto soil in the presence of EPS-rich and EPS-poor Pseudomonas aureofaciens.

Science.gov (United States)

Drozdova, O Yu; Pokrovsky, O S; Lapitskiy, S A; Shirokova, L S; González, A G; Demin, V V

2014-12-01

The adsorption of Zn onto the humic and illuvial horizons of the podzol soil in the presence of soil bacteria was studied using a batch-reactor technique as a function of the pH (from 2 to 9) and the Zn concentration in solution (from 0.076mM to 0.760mM). Exopolysaccharides-forming aerobic heterotrophs Pseudomonas aureofaciens were added at 0.1 and 1.0gwetL(-1) concentrations to two different soil horizons, and Zn adsorption was monitored as a function of the pH and the dissolved-Zn concentration. The pH-dependent adsorption edge demonstrated more efficient Zn adsorption by the humic horizon than the mineral horizon at otherwise similar soil concentrations. The Zn adsorption onto the EPS-poor strain was on slightly lower than that onto EPS-rich bacteria. Similar differences in the adsorption capacities between the soil and bacteria were also detected by "langmuirian" constant-pH experiments conducted in soil-Zn and bacteria-Zn binary systems. The addition of 0.1gwetL(-1)P. aureofaciens to a soil-bacteria system (4gdryL(-1)soil) resulted in statistically significant decrease in the adsorption yield, which was detectable from both the pH-dependent adsorption edge and the constant-pH isotherm experiments. Increasing the amount of added bacteria to 1gwetL(-1) further decreased the overall adsorption in the full range of the pH. This decrease was maximal for the EPS-rich bacteria and minimal for the EPS-poor bacteria (a factor of 2.8 and 2.2 at pH=6.9, respectively). These observations in binary and ternary systems were further rationalized by linear-programming modeling of surface equilibria that revealed the systematic differences in the number of binding sites and the surface-adsorption constant of zinc onto the two soil horizons with and without bacteria. The main finding of this work is that the adsorption of Zn onto the humic soil-bacteria system is lower than that in pure, bacteria-free soil systems. This difference is statistically significant (psoil particles

Perceptual learning effect on decision and confidence thresholds.

Science.gov (United States)

Solovey, Guillermo; Shalom, Diego; Pérez-Schuster, Verónica; Sigman, Mariano

2016-10-01

Practice can enhance of perceptual sensitivity, a well-known phenomenon called perceptual learning. However, the effect of practice on subjective perception has received little attention. We approach this problem from a visual psychophysics and computational modeling perspective. In a sequence of visual search experiments, subjects significantly increased the ability to detect a "trained target". Before and after training, subjects performed two psychophysical protocols that parametrically vary the visibility of the "trained target": an attentional blink and a visual masking task. We found that confidence increased after learning only in the attentional blink task. Despite large differences in some observables and task settings, we identify common mechanisms for decision-making and confidence. Specifically, our behavioral results and computational model suggest that perceptual ability is independent of processing time, indicating that changes in early cortical representations are effective, and learning changes decision criteria to convey choice and confidence. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk perception and sex behaviour in pregnancy and breastfeeding in high HIV prevalence settings: Programmatic implications for PrEP delivery

Science.gov (United States)

Farley, Elise; Towriss, Catriona; Gomba, Yolanda; Bekker, Linda-Gail; Gorbach, Pamina; Shoptaw, Steven; Coates, Thomas; Myer, Landon

2018-01-01

HIV acquisition during pregnancy and breastfeeding significantly contributes toward paediatric HIV infection; however, little is known about risk behaviours in HIV-uninfected pregnant and postpartum women. We conducted twenty-six in-depth-interviews between July and December 2016 using a semi-structured interview guide among HIV-uninfected pregnant and recently postpartum women at-risk of HIV acquisition (defined as reporting ≥1 of the following: partner’s serostatus unknown or HIV-infected, recent condomless sex in pregnancy, and/or alcohol use during pregnancy) who attended primary healthcare services. Our study contextualizes factors related to risky sexual behaviours during pregnancy and postpartum periods and assesses knowledge and hypothetical acceptability of pre-exposure prophylaxis (PrEP) in pregnancy. Translated and transcribed data were coded and analysed by three researchers using a thematic analysis approach. In interviews with HIV-uninfected pregnant/postpartum women at-risk of HIV acquisition, we identified common themes associated with sexual risk behaviours during pregnancy, including: lack of control over decisions in sex and condom use in pregnancy, low perceived risk (e.g. beliefs that their partner has the same HIV-negative serostatus), and socio-cultural beliefs around condom use during pregnancy (e.g. contact with sperm is essential for baby’s development). PrEP knowledge was low among HIV-uninfected pregnant and breastfeeding women, and potential acceptability was good, though primary concerns were around the potential impact on the infant. While mothers presented a clear desire to protect themselves from HIV acquisition once pregnant, they also reported lack of control, and socio-cultural beliefs, like sex is good for the baby, that increased their risk of seroconversion. Mothers had limited PrEP awareness but reported hypothetical willingness to use PrEP because of concerns over HIV acquisition and onward mother to child transmission

Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker

Directory of Open Access Journals (Sweden)

Peiper Matthias

2006-06-01

Full Text Available Abstract Background To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM in esophageal squamous cell carcinoma (SCC to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies. Methods The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up. Results Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%, 2+ (11% and 3+ (41%. Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001 and median overall survival (log rank, p = 0.0003. Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor. Conclusion Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention.

Microcalorimetric and potentiometric titration studies on the adsorption of copper by extracellular polymeric substances (EPS), minerals and their composites.

Science.gov (United States)

Fang, Linchuan; Huang, Qiaoyun; Wei, Xing; Liang, Wei; Rong, Xinming; Chen, Wenli; Cai, Peng

2010-08-01

Equilibrium adsorption experiments, isothermal titration calorimetry and potentiometric titration techniques were employed to investigate the adsorption of Cu(II) by extracellular polymeric substances (EPS) extracted from Pseudomonas putida X4, minerals (montmorillonite and goethite) and their composites. Compared with predicted values of Cu(II) adsorption on composites, the measured values of Cu(II) on EPS-montmorillonite composite increased, however, those on EPS-goethite composite decreased. Potentiometric titration results also showed that more surface sites were observed on EPS-montmorillonite composite and less reactive sites were found on EPS-goethite composite. The adsorption of Cu(II) on EPS molecules and their composites with minerals was an endothermic reaction, while that on minerals was exothermic. The positive values of enthalpy change (Delta H) and entropy change (DeltaS) for Cu(II) adsorption on EPS and mineral-EPS composites indicated that Cu(II) mainly interacts with carboxyl and phosphoryl groups as inner-sphere complexes on EPS molecules and their composites with minerals. (c) 2010 Elsevier Ltd. All rights reserved.

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.

Science.gov (United States)

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

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

Science.gov (United States)

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.

Transcription factors and molecular epigenetic marks underlying EpCAM overexpression in ovarian cancer

NARCIS (Netherlands)

van der Gun, B. T. F.; de Groote, M. L.; Kazemier, H. G.; Arendzen, A. J.; Terpstra, P.; Ruiters, M. H. J.; McLaughlin, P. M. J.; Rots, M. G.

2011-01-01

BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is overexpressed on carcinomas, and its downregulation inhibits the oncogenic potential of multiple tumour types. Here, we investigated underlying mechanisms of epcam overexpression in ovarian carcinoma. METHODS: Expression of EpCAM and DNA

Nature of the endogenous pyrogen (EP) induced by influenza viruses: lack of correlation between EP levels and content of the known pyrogenic cytokines, interleukin 1, interleukin 6 and tumour necrosis factor.

Science.gov (United States)

Jakeman, K J; Bird, C R; Thorpe, R; Smith, H; Sweet, C

1991-03-01

Fever in influenza results from the release of endogenous pyrogen (EP) following virus-phagocyte interaction and its level correlates with the differing virulence of virus strains. However, the different levels of fever produced in ferrets by intracardial inoculation of EP obtained from the interaction of different virus strains with ferret of human phagocytes did not correlate with the levels of interleukin 1 (IL-1), IL-6 or tumour necrosis factor in the same samples as assayed by conventional in vitro methods. Hence, the EP produced by influenza virus appears to be different to these cytokines.

Is Ep-CAM Expression a Diagnostic and Prognostic Biomarker for Colorectal Cancer? A Systematic Meta-Analysis

Directory of Open Access Journals (Sweden)

Susu Han

2017-06-01

Conclusions: The present findings suggest that Ep-CAM expression may be associated with CRC carcinogenesis, while the loss of Ep-CAM expression is correlated with the progression, metastasis, and poor prognosis of CRC. Ep-CAM expression may be a useful biomarker for the clinical diagnosis of CRC.

Search for Lepton Flavour Violation in ep Collisions at HERA

CERN Document Server

Aktas, A.; Andreev, V.; Anthonis, T.; Antunovic, B.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Backovic, S.; Baghdasaryan, A.; Baranov, P.; Barrelet, E.; Bartel, W.; Baudrand, S.; Beckingham, M.; Begzsuren, K.; Behnke, O.; Behrendt, O.; Belousov, A.; Berger, N.; Bizot, J.C.; Boenig, M.-O.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Bruncko, D.; Busser, F.W.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A.J.; Cantun Avila, K.B.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Cholewa, A.; Contreras, J.G.; Coughlan, J.A.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Daum, K.; de Boer, Y.; Delcourt, B.; Del Degan, M.; De Roeck, A.; De Wolf, E.A.; Diaconu, C.; Dodonov, V.; Dubak, A.; Eckerlin, Guenter; Efremenko, V.; Egli, S.; Eichler, R.; Eisele, F.; Eliseev, A.; Elsen, E.; Essenov, S.; Falkewicz, A.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Finke, L.; Fleischer, M.; Fomenko, A.; Franke, G.; Frisson, T.; Gabathuler, E.; Garutti, E.; Gayler, J.; Ghazaryan, Samvel; Ginzburgskaya, S.; Glazov, A.; Glushkov, I.; Goerlich, L.; Goettlich, M.; Gogitidze, N.; Gorbounov, S.; Gouzevitch, M.; Grab, C.; Greenshaw, T.; Gregori, M.; Grell, B.R.; Grindhammer, G.; Habib, S.; Haidt, D.; Hansson, M.; Heinzelmann, G.; Helebrant, C.; Henderson, R.C.W.; Henschel, H.; Herrera, G.; Hildebrandt, M.; Hiller, K.H.; Hoffmann, D.; Horisberger, R.; Hovhannisyan, A.; Hreus, T.; Hussain, S.; Jacquet, M.; Janssen, M.E.; Janssen, X.; Jemanov, V.; Jonsson, L.; Johnson, D.P.; Jung, Andreas Werner; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I.R.; Kiesling, Christian M.; Klein, M.; Kleinwort, C.; Klimkovich, T.; Kluge, T.; Knies, G.; Knutsson, A.; Korbel, V.; Kostka, P.; Kraemer, M.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Kruger, K.; Landon, M.P.J.; Lange, W.; Lastovicka-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Lendermann, V.; Levonian, S.; Lindfeld, L.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lucaci-Timoce, A.-I.; Lueders, H.; Lytkin, L.; Makankine, A.; Malinovski, E.; Marage, P.; Marti, Ll.; Martisikova, M.; Martyn, H.-U.; Maxfield, S.J.; Mehta, A.; Meier, K.; Meyer, A.B.; Meyer, H.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Mladenov, D.; Mohamed, A.; Moreau, F.; Morozov, A.; Morris, J.V.; Mozer, Matthias Ulrich; Muller, K.; Murin, P.; Nankov, K.; Naroska, B.; Naumann, Th.; Newman, Paul R.; Niebuhr, C.; Nikiforov, A.; Nowak, G.; Nowak, K.; Nozicka, M.; Oganezov, R.; Olivier, B.; Olsson, J.E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Pandurovic, M.; Papadopoulou, Th.; Pascaud, C.; Patel, G.D.; Peng, H.; Perez, E.; Perez-Astudillo, D.; Perieanu, A.; Petrukhin, A.; Picuric, I.; Piec, S.; Pitzl, D.; Placakyte, R.; Povh, B.; Preda, T.; Prideaux, P.; Rahmat, A.J.; Raicevic, N.; Ravdandorj, T.; Reimer, P.; Rimmer, A.; Risler, C.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rurikova, Z.; Rusakov, S.; Salvaire, F.; Sankey, D.P.C.; Sauter, M.; Sauvan, E.; Schmidt, S.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schoning, A.; Schultz-Coulon, H.-C.; Sefkow, F.; Shaw-West, R.N.; Sheviakov, I.; Shtarkov, L.N.; Sloan, T.; Smiljanic, Ivan; Smirnov, P.; Soloviev, Y.; South, D.; Spaskov, V.; Specka, Arnd E.; Steder, M.; Stella, B.; Stiewe, J.; Straumann, U.; Sunar, D.; Sykora, T.; Tchoulakov, V.; Thompson, G.; Thompson, P.D.; Toll, T.; Tomasz, F.; Traynor, D.; Trinh, T.N.; Truol, P.; Tsakov, I.; Tseepeldorj, B.; Tsipolitis, G.; Tsurin, I.; Turnau, J.; Tzamariudaki, E.; Urban, K.; Usik, A.; Utkin, D.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Trevino, A.Vargas; Vazdik, Y.; Vinokurova, S.; Volchinski, V.; Wacker, K.; Weber, G.; Weber, R.; Wegener, D.; Werner, C.; Wessels, M.; Wissing, Ch.; Wolf, R.; Wunsch, E.; Xella, S.; Yan, W.; Yeganov, V.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhelezov, A.; Zhokin, A.; Zhu, Y.C.; Zimmermann, J.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.

2007-01-01

A search for the lepton flavour violating processes ep->mu X and ep -> tau X is performed with the H1 experiment at HERA. Final states with a muon or tau and a hadronic jet are searched for in a data sample corresponding to an integrated luminosity of 66.5 pb-1 for e^+ p collisions and 13.7 pb^-1 for e^- p collisions at a centre-of-mass energy of 319 GeV. No evidence for lepton flavour violation is found. Limits are derived on the mass and the couplings of leptoquarks inducing lepton flavour violation in an extension of the Buchm"uller-R"uckl-Wyler effective model. Leptoquarks produced in ep collisions with a coupling strength of lambda=0.3 and decaying with the same coupling strength to a muon-quark pair or a tau-quark pair are excluded at 95% confidence level up to masses of 459 GeV and 379 GeV, respectively.

Search for lepton flavour violation in ep collisions at HERA

Energy Technology Data Exchange (ETDEWEB)

Aktas, A. [DESY, Hamburg (Germany); Alexa, C. [DESY, Hamburg (Germany)]|[National Institute for Physics and Nuclear Engineering, Magurele, Bucharest (Romania); Andreev, V. [Lebedev Physical Institute, Moscow (RU)] (and others)

2007-02-15

A search for the lepton flavour violating processes ep{yields}{mu}X and ep{yields}{tau}X is performed with the H1 experiment at HERA. Final states with a muon or tau and a hadronic jet are searched for in a data sample corresponding to an integrated luminosity of 66.5 pb{sup -1} for e{sup +}p collisions and 13.7 pb{sup -1} for e{sup -}p collisions at a centre-of-mass energy of 319 GeV. No evidence for lepton flavour violation is found. Limits are derived on the mass and the couplings of leptoquarks inducing lepton flavour violation in an extension of the Buchmueller-Rueckl-Wyler effective model. Leptoquarks produced in ep collisions with a coupling strength of {lambda}=0.3 and decaying with the same coupling strength to a muon-quark pair or a tau-quark pair are excluded at 95% confidence level up to masses of 459 GeV and 379 GeV, respectively. (orig.)

Search for lepton flavour violation in ep collisions at HERA

Science.gov (United States)

Aktas, A.; Alexa, C.; Andreev, V.; Anthonis, T.; Antunovic, B.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Babaev, A.; Backovic, S.; Baghdasaryan, A.; Baranov, P.; Barrelet, E.; Bartel, W.; Baudrand, S.; Beckingham, M.; Begzsuren, K.; Behnke, O.; Behrendt, O.; Belousov, A.; Berger, N.; Bizot, J. C.; Boenig, M.-O.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Bruncko, D.; Büsser, F. W.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A. J.; Cantun Avila, K. B.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Cholewa, A.; Contreras, J. G.; Coughlan, J. A.; Cozzika, G.; Cvach, J.; Dainton, J. B.; Daum, K.; de Boer, Y.; Delcourt, B.; Del Degan, M.; de Roeck, A.; de Wolf, E. A.; Diaconu, C.; Dodonov, V.; Dubak, A.; Eckerlin, G.; Efremenko, V.; Egli, S.; Eichler, R.; Eisele, F.; Eliseev, A.; Elsen, E.; Essenov, S.; Falkewicz, A.; Faulkner, P. J. W.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Finke, L.; Fleischer, M.; Fomenko, A.; Franke, G.; Frisson, T.; Gabathuler, E.; Garutti, E.; Gayler, J.; Ghazaryan, S.; Ginzburgskaya, S.; Glazov, A.; Glushkov, I.; Goerlich, L.; Goettlich, M.; Gogitidze, N.; Gorbounov, S.; Gouzevitch, M.; Grab, C.; Greenshaw, T.; Gregori, M.; Grell, B. R.; Grindhammer, G.; Habib, S.; Haidt, D.; Hansson, M.; Heinzelmann, G.; Helebrant, C.; Henderson, R. C. W.; Henschel, H.; Herrera, G.; Hildebrandt, M.; Hiller, K. H.; Hoffmann, D.; Horisberger, R.; Hovhannisyan, A.; Hreus, T.; Hussain, S.; Jacquet, M.; Janssen, M. E.; Janssen, X.; Jemanov, V.; Jönsson, L.; Johnson, D. P.; Jung, A. W.; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I. R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Klimkovich, T.; Kluge, T.; Knies, G.; Knutsson, A.; Korbel, V.; Kostka, P.; Kraemer, M.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Krüger, K.; Landon, M. P. J.; Lange, W.; Laštovička-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Lendermann, V.; Levonian, S.; Lindfeld, L.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lucaci-Timoce, A.-I.; Lueders, H.; Lytkin, L.; Makankine, A.; Malinovski, E.; Marage, P.; Marti, L.; Martisikova, M.; Martyn, H.-U.; Maxfield, S. J.; Mehta, A.; Meier, K.; Meyer, A. B.; Meyer, H.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Mladenov, D.; Mohamed, A.; Moreau, F.; Morozov, A.; Morris, J. V.; Mozer, M. U.; Müller, K.; Murín, P.; Nankov, K.; Naroska, B.; Naumann, T.; Newman, P. R.; Niebuhr, C.; Nikiforov, A.; Nowak, G.; Nowak, K.; Nozicka, M.; Oganezov, R.; Olivier, B.; Olsson, J. E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Pandurovic, M.; Papadopoulou, T.; Pascaud, C.; Patel, G. D.; Peng, H.; Perez, E.; Perez-Astudillo, D.; Perieanu, A.; Petrukhin, A.; Picuric, I.; Piec, S.; Pitzl, D.; Plačakytė, R.; Povh, B.; Preda, T.; Prideaux, P.; Rahmat, A. J.; Raicevic, N.; Ravdandorj, T.; Reimer, P.; Rimmer, A.; Risler, C.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rurikova, Z.; Rusakov, S.; Salvaire, F.; Sankey, D. P. C.; Sauter, M.; Sauvan, E.; Schmidt, S.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schöning, A.; Schultz-Coulon, H.-C.; Sefkow, F.; Shaw-West, R. N.; Sheviakov, I.; Shtarkov, L. N.; Sloan, T.; Smiljanic, I.; Smirnov, P.; Soloviev, Y.; South, D.; Spaskov, V.; Specka, A.; Steder, M.; Stella, B.; Stiewe, J.; Straumann, U.; Sunar, D.; Sykora, T.; Tchoulakov, V.; Thompson, G.; Thompson, P. D.; Toll, T.; Tomasz, F.; Traynor, D.; Trinh, T. N.; Truöl, P.; Tsakov, I.; Tseepeldorj, B.; Tsipolitis, G.; Tsurin, I.; Turnau, J.; Tzamariudaki, E.; Urban, K.; Usik, A.; Utkin, D.; Valkárová, A.; Vallée, C.; van Mechelen, P.; Vargas Trevino, A.; Vazdik, Y.; Vinokurova, S.; Volchinski, V.; Wacker, K.; Weber, G.; Weber, R.; Wegener, D.; Werner, C.; Wessels, M.; Wissing, C.; Wolf, R.; Wünsch, E.; Xella, S.; Yan, W.; Yeganov, V.; Žáček, J.; Zálešák, J.; Zhang, Z.; Zhelezov, A.; Zhokin, A.; Zhu, Y. C.; Zimmermann, J.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.

2007-12-01

A search for the lepton flavour violating processes ep→μX and ep→τX is performed with the H1 experiment at HERA. Final states with a muon or tau and a hadronic jet are searched for in a data sample corresponding to an integrated luminosity of 66.5 pb-1 for e+p collisions and 13.7 pb-1 for e-p collisions at a centre-of-mass energy of 319 GeV. No evidence for lepton flavour violation is found. Limits are derived on the mass and the couplings of leptoquarks inducing lepton flavour violation in an extension of the Buchmüller Rückl Wyler effective model. Leptoquarks produced in ep collisions with a coupling strength of λ=0.3 and decaying with the same coupling strength to a muon quark pair or a tau quark pair are excluded at 95% confidence level up to masses of 459 GeV and 379 GeV, respectively.

Summary report of a workshop on establishing cumulative effects thresholds : a suggested approach for establishing cumulative effects thresholds in a Yukon context

International Nuclear Information System (INIS)

2003-01-01

Increasingly, thresholds are being used as a land and cumulative effects assessment and management tool. To assist in the management of wildlife species such as woodland caribou, the Department of Indian and Northern Affairs (DIAND) Environment Directorate, Yukon sponsored a workshop to develop and use cumulative thresholds in the Yukon. The approximately 30 participants reviewed recent initiatives in the Yukon and other jurisdictions. The workshop is expected to help formulate a strategic vision for implementing cumulative effects thresholds in the Yukon. The key to success resides in building relationships with Umbrella Final Agreement (UFA) Boards, the Development Assessment Process (DAP), and the Yukon Environmental and Socio-Economic Assessment Act (YESAA). Broad support is required within an integrated resource management framework. The workshop featured discussions on current science and theory of cumulative effects thresholds. Potential data and implementation issues were also discussed. It was concluded that thresholds are useful and scientifically defensible. The threshold research results obtained in Alberta, British Columbia and the Northwest Territories are applicable to the Yukon. One of the best tools for establishing and tracking thresholds is habitat effectiveness. Effects must be monitored and tracked. Biologists must share their information with decision makers. Interagency coordination and assistance should be facilitated through the establishment of working groups. Regional land use plans should include thresholds. 7 refs.

QCD studies in ep collisions

International Nuclear Information System (INIS)

Smith, W.H.

1997-01-01

These lectures describe QCD physics studies over the period 1992--1996 from data taken with collisions of 27 GeV electrons and positrons with 820 GeV protons at the HERA collider at DESY by the two general-purpose detectors H1 and ZEUS. The focus of these lectures is on structure functions and jet production in deep inelastic scattering, photoproduction, and diffraction. The topics covered start with a general introduction to HERA and ep scattering. Structure functions are discussed. This includes the parton model, scaling violation, and the extraction of F 2 , which is used to determine the gluon momentum distribution. Both low and high Q 2 regimes are discussed. The low Q 2 transition from perturbative QCD to soft hadronic physics is examined. Jet production in deep inelastic scattering to measure α s , and in photoproduction to study resolved and direct photoproduction, is also presented. This is followed by a discussion of diffraction that begins with a general introduction to diffraction in hadronic collisions and its relation to ep collisions, and moves on to deep inelastic scattering, where the structure of diffractive exchange is studied, and in photoproduction, where dijet production provides insights into the structure of the Pomeron. 95 refs., 39 figs

QCD studies in ep collisions

Energy Technology Data Exchange (ETDEWEB)

Smith, W.H. [Univ. of Wisconsin, Madison, WI (United States). Physics Dept.

1997-06-01

These lectures describe QCD physics studies over the period 1992--1996 from data taken with collisions of 27 GeV electrons and positrons with 820 GeV protons at the HERA collider at DESY by the two general-purpose detectors H1 and ZEUS. The focus of these lectures is on structure functions and jet production in deep inelastic scattering, photoproduction, and diffraction. The topics covered start with a general introduction to HERA and ep scattering. Structure functions are discussed. This includes the parton model, scaling violation, and the extraction of F{sub 2}, which is used to determine the gluon momentum distribution. Both low and high Q{sup 2} regimes are discussed. The low Q{sup 2} transition from perturbative QCD to soft hadronic physics is examined. Jet production in deep inelastic scattering to measure {alpha}{sub s}, and in photoproduction to study resolved and direct photoproduction, is also presented. This is followed by a discussion of diffraction that begins with a general introduction to diffraction in hadronic collisions and its relation to ep collisions, and moves on to deep inelastic scattering, where the structure of diffractive exchange is studied, and in photoproduction, where dijet production provides insights into the structure of the Pomeron. 95 refs., 39 figs.

Quorum decision-making in foraging fish shoals.

Directory of Open Access Journals (Sweden)

Ashley J W Ward

Full Text Available Quorum responses provide a means for group-living animals to integrate and filter disparate social information to produce accurate and coherent group decisions. A quorum response may be defined as a steep increase in the probability of group members performing a given behaviour once a threshold minimum number of their group mates already performing that behaviour is exceeded. In a previous study we reported the use of a quorum response in group decision-making of threespine sticklebacks (Gasterosteus aculeatus under a simulated predation threat. Here we examine the use of quorum responses by shoals of sticklebacks in first locating and then leaving a foraging patch. We show that a quorum rule explains movement decisions by threespine sticklebacks toward and then away from a food patch. Following both to and from a food patch occurred when a threshold number of initiators was exceeded, with the threshold being determined by the group size.

Heavy Quark Production in ep Collisions at HERA

International Nuclear Information System (INIS)

Bloch, I.

2006-01-01

Collisions of electrons with protons at a centre-of-mass energy of 318 GeV are being recorded by the two experiments H1 and ZEUS at the ep accelerator HERA at DESY, Hamburg (Germany). Measurements involving beauty and charm quarks, performed by these experiments, provide a good environment to test perturbative QCD predictions as the large quark mass supplies a hard scale. Recent measurements of beauty and charm production in ep collisions are presented here. QCD predictions at next-to-leading order are found to generally agree with the measurements. Beauty measurements however are sometimes slightly higher than the predicted cross sections. Beauty and charm contributions to the proton structure were also measured and are well described by QCD predictions

Production of Z0 bosons in elastic and quasi-elastic ep collisions at HERA

International Nuclear Information System (INIS)

Abramowicz, H.; Abt, I.; Adamczyk, L.

2012-10-01

The production of Z 0 bosons in the reaction ep → eZ 0 p (*) , where p (*) stands for a proton or a low-mass nucleon resonance, has been studied in ep collisions at HERA using the ZEUS detector. The analysis is based on a data sample collected between 1996 and 2007, amounting to 496 pb -1 of integrated luminosity. The Z 0 was measured in the hadronic decay mode. The elasticity of the events was ensured by a cut on η max max is the maximum pseudorapidity of energy deposits in the calorimeter defined with respect to the proton beam direction. A signal was observed at the Z 0 mass. The cross section of the reaction ep → eZ 0 p (*) was measured to be σ (ep → eZ 0 p (*) ) = 0.13 ± 0.06 (stat.) ± 0.01 (syst.) pb, in agreement with the Standard Model prediction of 0.16 pb. This is the first measurement of Z 0 production in ep collisions.

Humans Optimize Decision-Making by Delaying Decision Onset

Science.gov (United States)

Teichert, Tobias; Ferrera, Vincent P.; Grinband, Jack

2014-01-01

Why do humans make errors on seemingly trivial perceptual decisions? It has been shown that such errors occur in part because the decision process (evidence accumulation) is initiated before selective attention has isolated the relevant sensory information from salient distractors. Nevertheless, it is typically assumed that subjects increase accuracy by prolonging the decision process rather than delaying decision onset. To date it has not been tested whether humans can strategically delay decision onset to increase response accuracy. To address this question we measured the time course of selective attention in a motion interference task using a novel variant of the response signal paradigm. Based on these measurements we estimated time-dependent drift rate and showed that subjects should in principle be able trade speed for accuracy very effectively by delaying decision onset. Using the time-dependent estimate of drift rate we show that subjects indeed delay decision onset in addition to raising response threshold when asked to stress accuracy over speed in a free reaction version of the same motion-interference task. These findings show that decision onset is a critical aspect of the decision process that can be adjusted to effectively improve decision accuracy. PMID:24599295

Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors.

Science.gov (United States)

Tunaru, Sorin; Althoff, Till F; Nüsing, Rolf M; Diener, Martin; Offermanns, Stefan

2012-06-05

Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP(3) prostanoid receptor is specifically activated by ricinoleic acid and that it mediates the pharmacological effects of castor oil. In mice lacking EP(3) receptors, the laxative effect and the uterus contraction induced via ricinoleic acid are absent. Although a conditional deletion of the EP(3) receptor gene in intestinal epithelial cells did not affect castor oil-induced diarrhea, mice lacking EP(3) receptors only in smooth-muscle cells were unresponsive to this drug. Thus, the castor oil metabolite ricinoleic acid activates intestinal and uterine smooth-muscle cells via EP(3) prostanoid receptors. These findings identify the cellular and molecular mechanism underlying the pharmacological effects of castor oil and indicate a role of the EP(3) receptor as a target to induce laxative effects.

Social accountability and the finance sector: the case of Equator Principles (EP) institutionalisation

NARCIS (Netherlands)

O'Sullivan, N.A.

2010-01-01

In June 2003, the Equator Principles (EP) were launched by ten international commercial banks. The EP were designed as a set of voluntary environmental and social risk management guidelines for project finance. Whilst lauded as a revolutionary initiative by the financial sector, the Principles were

Further case of Rubinstein-Taybi syndrome due to a deletion in EP300.

LENUS (Irish Health Repository)

Foley, Patricia

2012-02-01

Rubinstein-Taybi syndrome (RSTS) is a heterogeneous disorder with approximately 45-55% of patients showing mutations in the CREB binding protein and a further 3% of patients having mutations in EP300. We report a male child with a deletion of exons 3-8 of the EP300 gene who has RSTS. He has a milder skeletal phenotype, a finding that has been described in other cases with EP300 mutations. The mother suffered from pre-eclampsia and HELLP syndrome in the pregnancy. She subsequently developed a mullerian tumor of her cervix 6 years after the birth of her son.

Positron annihilation analysis of epoxy/hydroxyl terminated butyl nitrile rubber (EP/HTBN) system

International Nuclear Information System (INIS)

Zeng Minfeng; Chen Ning; Ji Genzhong; Sun Xudong; Zhao Rener; Xiao Huiquan; Qi Chenze; Wang Baoyi

2007-01-01

The free volume properties of epoxy/hydroxyl terminated butyl nitrile rubber (EP/HTBN) have been studied by means of positron annihilation technique. The toughness effect is found to be correlated with the content of HTBN and the free volume properties of the EP/HTBN interfaces. When the content of HTBN component is 5%, the free volume size in the interface is close to that of EP, and the toughness effect is strong. But with further addition of HTBN, holes with big size free volume are formed in the interface, and the toughness effect is limited. (authors)

Cost-effectiveness thresholds in health care: a bookshelf guide to their meaning and use.

Science.gov (United States)

Culyer, Anthony J

2016-10-01

There is misunderstanding about both the meaning and the role of cost-effectiveness thresholds in policy decision making. This article dissects the main issues by use of a bookshelf metaphor. Its main conclusions are as follows: it must be possible to compare interventions in terms of their impact on a common measure of health; mere effectiveness is not a persuasive case for inclusion in public insurance plans; public health advocates need to address issues of relative effectiveness; a 'first best' benchmark or threshold ratio of health gain to expenditure identifies the least effective intervention that should be included in a public insurance plan; the reciprocal of this ratio - the 'first best' cost-effectiveness threshold - will rise or fall as the health budget rises or falls (ceteris paribus); setting thresholds too high or too low costs lives; failure to set any cost-effectiveness threshold at all also involves avertable deaths and morbidity; the threshold cannot be set independently of the health budget; the threshold can be approached from either the demand side or the supply side - the two are equivalent only in a health-maximising equilibrium; the supply-side approach generates an estimate of a 'second best' cost-effectiveness threshold that is higher than the 'first best'; the second best threshold is the one generally to be preferred in decisions about adding or subtracting interventions in an established public insurance package; multiple thresholds are implied by systems having distinct and separable health budgets; disinvestment involves eliminating effective technologies from the insured bundle; differential weighting of beneficiaries' health gains may affect the threshold; anonymity and identity are factors that may affect the interpretation of the threshold; the true opportunity cost of health care in a community, where the effectiveness of interventions is determined by their impact on health, is not to be measured in money - but in health

Are current cost-effectiveness thresholds for low- and middle-income countries useful? Examples from the world of vaccines.

Science.gov (United States)

Newall, A T; Jit, M; Hutubessy, R

2014-06-01

The World Health Organization's CHOosing Interventions that are Cost Effective (WHO-CHOICE) thresholds for averting a disability-adjusted life-year of one to three times per capita income have been widely cited and used as a measure of cost effectiveness in evaluations of vaccination for low- and middle-income countries (LMICs). These thresholds were based upon criteria set out by the WHO Commission on Macroeconomics and Health, which reflected the potential economic returns of interventions. The CHOICE project sought to evaluate a variety of health interventions at a subregional level and classify them into broad categories to help assist decision makers, but the utility of the thresholds for within-country decision making for individual interventions (given budgetary constraints) has not been adequately explored. To examine whether the 'WHO-CHOICE thresholds' reflect funding decisions, we examined the results of two recent reviews of cost-effectiveness analyses of human papillomavirus and rotavirus vaccination in LMICs, and we assessed whether the results of these studies were reflected in funding decisions for these vaccination programmes. We found that in many cases, programmes that were deemed cost effective were not subsequently implemented in the country. We consider the implications of this finding, the advantages and disadvantages of alternative methods to estimate thresholds, and how cost perspectives and the funders of healthcare may impact on these choices.

Overview of the 2014 Edition of the International Handbook of Evaluated Reactor Physics Benchmark Experiments (IRPhEP Handbook)

Energy Technology Data Exchange (ETDEWEB)

John D. Bess; J. Blair Briggs; Jim Gulliford; Ian Hill

2014-10-01

The International Reactor Physics Experiment Evaluation Project (IRPhEP) is a widely recognized world class program. The work of the IRPhEP is documented in the International Handbook of Evaluated Reactor Physics Benchmark Experiments (IRPhEP Handbook). Integral data from the IRPhEP Handbook is used by reactor safety and design, nuclear data, criticality safety, and analytical methods development specialists, worldwide, to perform necessary validations of their calculational techniques. The IRPhEP Handbook is among the most frequently quoted reference in the nuclear industry and is expected to be a valuable resource for future decades.

'PrEP is not ready for our community, and our community is not ready for PrEP': pre-exposure prophylaxis for HIV for people who inject drugs and limits to the HIV prevention response.

Science.gov (United States)

Guise, Andy; Albers, Eliot Ross; Strathdee, Steffanie A

2017-04-01

Pre-exposure prophylaxis for HIV, or 'PrEP', is the use of antiretroviral medicines by people who are HIV-negative to protect themselves against acquiring HIV. PrEP has shown efficacy for preventing HIV acquisition. Despite the potential, many concerns have been voiced by people who inject drugs (PWID) and their organizations. There is a need to engage with these views and ensure their integration in to policy and strategy. This paper presents PWID views on PrEP to foster the uptake of these opinions into scientific and policy debate around PrEP METHODS: Critical analysis of a report of a community consultation led by the International Network of People who Use Drugs (INPUD). The INPUD report highlights enthusiasm from PWID for PrEP, but also three main concerns: the feasibility and ethics of PrEP, its potential use as a substitute for other harm reduction strategies and how a focus on PrEP heralds a re-medicalization of HIV. Each concern relates to evidenced gaps in essential services or opposition to harm reduction and PWID human rights. People who use drugs have fundamental concerns about the potential impacts of pre-exposure prophylaxis for HIV which reflect a 'fault line' in HIV prevention: a predominance of biomedical approaches over community perspectives. Greater community engagement in HIV prevention strategy is needed, or we risk continuing to ignore the need for action on the underlying structural drivers and social context of the HIV epidemic. © 2016 Society for the Study of Addiction.

Component analysis and heavy metal adsorption ability of extracellular polymeric substances (EPS) from sulfate reducing bacteria.

Science.gov (United States)

Yue, Zheng-Bo; Li, Qing; Li, Chuan-chuan; Chen, Tian-hu; Wang, Jin

2015-10-01

Extracellular polymeric substances (EPS) play an important role in the treatment of acid mine drainage (AMD) by sulfate-reducing bacteria (SRB). In this paper, Desulfovibrio desulfuricans was used as the test strain to explore the effect of heavy metals on the components and adsorption ability of EPS. Fourier-transform infrared (FTIR) spectroscopy analysis results showed that heavy metals did not influence the type of functional groups of EPS. Potentiometric titration results indicated that the acidic constants (pKa) of the EPS fell into three ranges of 3.5-4.0, 5.9-6.7, and 8.9-9.8. The adsorption site concentrations of the surface functional groups also increased. Adsorption results suggested that EPS had a specific binding affinity for the dosed heavy metal, and that EPS extracted from the Zn(2+)-dosed system had a higher binding affinity for all heavy metals. Additionally, Zn(2+) decreased the inhibitory effects of Cd(2+) and Cu(2+) on the SRB. Copyright © 2015 Elsevier Ltd. All rights reserved.

Threshold values in acquisitions in the power market

International Nuclear Information System (INIS)

2002-01-01

This report discusses weather the authorities should define threshold values for the market concentration in the power market for reasons of future competition. It is shown that special circumstances in the power market dictate that the competition authorities may have good reasons to adopt a precautionary attitude to acquisitions in that market. The assessment must consider the fact that it is the competition in individual hours that is relevant for the market. Thus the competition authorities should use threshold values based on the producers' share of the power capacity in all relevant market areas that are affected by the acquisition. The threshold values may still be used only as a first filtering out procedure. A final decision about intervention must be founded on a closer assessment of all the socioeconomic consequences of the acquisition in each case

Thresholds of Extinction: Simulation Strategies in Environmental Values Education.

Science.gov (United States)

Glew, Frank

1990-01-01

Describes a simulation exercise for campers and an accompanying curriculum unit--"Thresholds of Extinction"--that addresses the issues of endangered species. Uses this context to illustrate steps in the process of values development: awareness, gathering data, resolution (decision making), responsibility (acting on values), and…

Discriminating the precipitation phase based on different temperature thresholds in the Songhua River Basin, China

Science.gov (United States)

Zhong, Keyuan; Zheng, Fenli; Xu, Ximeng; Qin, Chao

2018-06-01

Different precipitation phases (rain, snow or sleet) differ greatly in their hydrological and erosional processes. Therefore, accurate discrimination of the precipitation phase is highly important when researching hydrologic processes and climate change at high latitudes and mountainous regions. The objective of this study was to identify suitable temperature thresholds for discriminating the precipitation phase in the Songhua River Basin (SRB) based on 20-year daily precipitation collected from 60 meteorological stations located in and around the basin. Two methods, the air temperature method (AT method) and the wet bulb temperature method (WBT method), were used to discriminate the precipitation phase. Thirteen temperature thresholds were used to discriminate snowfall in the SRB. These thresholds included air temperatures from 0 to 5.5 °C at intervals of 0.5 °C and the wet bulb temperature (WBT). Three evaluation indices, the error percentage of discriminated snowfall days (Ep), the relative error of discriminated snowfall (Re) and the determination coefficient (R2), were applied to assess the discrimination accuracy. The results showed that 2.5 °C was the optimum threshold temperature for discriminating snowfall at the scale of the entire basin. Due to differences in the landscape conditions at the different stations, the optimum threshold varied by station. The optimal threshold ranged 1.5-4.0 °C, and 19 stations, 17 stations and 18 stations had optimal thresholds of 2.5 °C, 3.0 °C, and 3.5 °C respectively, occupying 90% of all stations. Compared with using a single suitable temperature threshold to discriminate snowfall throughout the basin, it was more accurate to use the optimum threshold at each station to estimate snowfall in the basin. In addition, snowfall was underestimated when the temperature threshold was the WBT and when the temperature threshold was below 2.5 °C, whereas snowfall was overestimated when the temperature threshold exceeded 4

Prostaglandin E2 EP2 Receptor Deletion Attenuates Intracerebral Hemorrhage-Induced Brain Injury and Improves Functional Recovery

Directory of Open Access Journals (Sweden)

Jenna L. Leclerc

2015-04-01

Full Text Available Intracerebral hemorrhage (ICH is a devastating type of stroke characterized by bleeding into the brain parenchyma and secondary brain injury resulting from strong neuroinflammatory responses to blood components. Production of prostaglandin E2 (PGE2 is significantly upregulated following ICH and contributes to this inflammatory response in part through its E prostanoid receptor subtype 2 (EP2. Signaling through the EP2 receptor has been shown to affect outcomes of many acute and chronic neurological disorders; although, not yet explored in the context of ICH. Wildtype (WT and EP2 receptor knockout (EP2−/− mice were subjected to ICH, and various anatomical and functional outcomes were assessed by histology and neurobehavioral testing, respectively. When compared with age-matched WT controls, EP2−/− mice had 41.9 ± 4.7% smaller ICH-induced brain lesions and displayed significantly less ipsilateral hemispheric enlargement and incidence of intraventricular hemorrhage. Anatomical outcomes correlated with improved functional recovery as identified by neurological deficit scoring. Histological staining was performed to begin investigating the mechanisms involved in EP2-mediated neurotoxicity after ICH. EP2−/− mice exhibited 45.5 ± 5.8% and 41.4 ± 8.1% less blood and ferric iron accumulation, respectively. Furthermore, significantly less striatal and cortical microgliosis, striatal and cortical astrogliosis, blood–brain barrier breakdown, and peripheral neutrophil infiltration were seen in EP2−/− mice. This study is the first to suggest a deleterious role for the PGE2-EP2 signaling axis in modulating brain injury, inflammation, and functional recovery following ICH. Targeting the EP2 G protein-coupled receptor may represent a new therapeutic avenue for the treatment of hemorrhagic stroke.

Commentary: the value of PrEP for people who inject drugs

OpenAIRE

Rosalind L Coleman; Susie McLean

2016-01-01

Introduction: 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 ...

Corporate actions for the climate - Greenhouse gas reduction practices at EpE member companies

International Nuclear Information System (INIS)

Chalendar, Pierre-Andre de

2012-11-01

Corporate awareness of the reality of climate change and the impact of human activity on global warming goes back some twenty years. It was at this time that EpE members decided to take voluntary action towards lowering greenhouse gas emissions. EpE member companies started out by measuring their emissions (see EpE publication entitled 'Measuring and Controlling Greenhouse Gas Emissions'), then worked to identify initiatives easiest to implement and those that would have the best reduction potential. This booklet is prepared to contribute to other businesses improving their knowledge and understanding of the best practices identified and implemented by EpE members, in order to speed up the reduction of global emissions, without hampering their competitiveness. The practices showcased here have intentionally been detailed so that they can be easier to adopt. (authors)

E&P data lifecycle: a case study in Petrobras Company

Science.gov (United States)

Mastella, Laura; Campinho, Vania; Alonso, João

2013-04-01

Petrobras, the biggest Brazilian Petroleum Company, has been studying and working on Brazilian sedimentary basins for nearly 60 years. The corporate database currently registers over 25000 wells and all their associated products (geophysical logs, cores, sidewall samples) and analyses. There are thousands of samples, descriptions, pictures, measures, and other scientific data resulted from petroleum exploration and production. This data constitutes a huge scientific database which is applied to support Petrobras economic strategy. Geological models built during the exploration phase continue to be refined during both the development and production phases: data should be continually manipulated, correlated and integrated. As E&P assets reach maturity, a new cycle starts: data is re-analyzed and new hypotheses are made in order to increase hydrocarbon productivity. Initial geological models then evolve from accumulated knowledge throughout all the E&P phases. Therefore the quality control must be performed in the first phases of data acquisition, i.e., during the exploration phase, to avoid reworking and loss of information. The last decade witnessed a great evolution in petroleum industry technology. As a consequence, the complexity and particulars of the information generated have increased accordingly. Current technology has also facilitated access to networks and databases, making it possible to store large amounts of information. This scenario makes available a large mass of information from difference sources, which uses heterogeneous vocabulary as well as different scales and measurement units. In this context, knowledge might be diluted and the total amount of information cannot be applied in E&P process. In order to provide adequate data governance, data input is controlled by rules, standards and policies, implemented by corporate software systems. Petrobras' integrated E&P database is a centralized repository to which all E&P systems can have access. The

Effects of lead(II) on the extracellular polysaccharide (EPS) production and colony formation of cultured Microcystis aeruginosa.

Science.gov (United States)

Bi, Xiang-dong; Zhang, Shu-lin; Dai, Wei; Xing, Ke-zhing; Yang, Fan

2013-01-01

To investigate the effects of lead(II) on the production of extracellular polysaccharides (EPS), including bound extracellular polysaccharides (bEPS) and soluble extracellular polysaccharides (sEPS), and the colony formation of Microcystis aeruginosa, cultures of M. aeruginosa were exposed to four concentrations (5.0, 10.0, 20.0 and 40.0 mg/L) of lead(II) for 10 d under controlled laboratory conditions. The results showed that 5.0 and 10.0 mg/L lead(II) stimulated M. aeruginosa growth throughout the experiment while 20.0 and 40.0 mg/L lead(II) inhibited M. aeruginosa growth in the first 2 d exposure and then stimulated it. As compared to the control group, significant increases in the bEPS and sEPS production were observed in 20.0 and 40.0 mg/L lead(II) treatments (P bEPS production, which conversely promoted colony formation, suggesting that heavy metals might be contributing to the bloom-forming of M. aeruginosa in natural conditions.

A model for emergency department end-of-life communications after acute devastating events--part I: decision-making capacity, surrogates, and advance directives.

Science.gov (United States)

Limehouse, Walter E; Feeser, V Ramana; Bookman, Kelly J; Derse, Arthur

2012-09-01

Making decisions for a patient affected by sudden devastating illness or injury traumatizes a patient's family and loved ones. Even in the absence of an emergency, surrogates making end-of-life treatment decisions may experience negative emotional effects. Helping surrogates with these end-of-life decisions under emergent conditions requires the emergency physician (EP) to be clear, making medical recommendations with sensitivity. This model for emergency department (ED) end-of-life communications after acute devastating events comprises the following steps: 1) determine the patient's decision-making capacity; 2) identify the legal surrogate; 3) elicit patient values as expressed in completed advance directives; 4) determine patient/surrogate understanding of the life-limiting event and expectant treatment goals; 5) convey physician understanding of the event, including prognosis, treatment options, and recommendation; 6) share decisions regarding withdrawing or withholding of resuscitative efforts, using available resources and considering options for organ donation; and 7) revise treatment goals as needed. Emergency physicians should break bad news compassionately, yet sufficiently, so that surrogate and family understand both the gravity of the situation and the lack of long-term benefit of continued life-sustaining interventions. EPs should also help the surrogate and family understand that palliative care addresses comfort needs of the patient including adequate treatment for pain, dyspnea, or anxiety. Part I of this communications model reviews determination of decision-making capacity, surrogacy laws, and advance directives, including legal definitions and application of these steps; Part II (which will appear in a future issue of AEM) covers communication moving from resuscitative to end-of-life and palliative treatment. EPs should recognize acute devastating illness or injuries, when appropriate, as opportunities to initiate end-of-life discussions and to

Rooting gene trees without outgroups: EP rooting.

Science.gov (United States)

Sinsheimer, Janet S; Little, Roderick J A; Lake, James A

2012-01-01

Gene sequences are routinely used to determine the topologies of unrooted phylogenetic trees, but many of the most important questions in evolution require knowing both the topologies and the roots of trees. However, general algorithms for calculating rooted trees from gene and genomic sequences in the absence of gene paralogs are few. Using the principles of evolutionary parsimony (EP) (Lake JA. 1987a. A rate-independent technique for analysis of nucleic acid sequences: evolutionary parsimony. Mol Biol Evol. 4:167-181) and its extensions (Cavender, J. 1989. Mechanized derivation of linear invariants. Mol Biol Evol. 6:301-316; Nguyen T, Speed TP. 1992. A derivation of all linear invariants for a nonbalanced transversion model. J Mol Evol. 35:60-76), we explicitly enumerate all linear invariants that solely contain rooting information and derive algorithms for rooting gene trees directly from gene and genomic sequences. These new EP linear rooting invariants allow one to determine rooted trees, even in the complete absence of outgroups and gene paralogs. EP rooting invariants are explicitly derived for three taxon trees, and rules for their extension to four or more taxa are provided. The method is demonstrated using 18S ribosomal DNA to illustrate how the new animal phylogeny (Aguinaldo AMA et al. 1997. Evidence for a clade of nematodes, arthropods, and other moulting animals. Nature 387:489-493; Lake JA. 1990. Origin of the metazoa. Proc Natl Acad Sci USA 87:763-766) may be rooted directly from sequences, even when they are short and paralogs are unavailable. These results are consistent with the current root (Philippe H et al. 2011. Acoelomorph flatworms are deuterostomes related to Xenoturbella. Nature 470:255-260).

Search for Leptoquark Bosons in ep Collisions at HERA

CERN Document Server

Aktas, A.; Anthonis, T.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Babaev, A.; Backovic, S.; Bahr, J.; Baghdasaryan, A.; Baranov, P.; Barrelet, E.; Bartel, W.; Baudrand, S.; Baumgartner, S.; Becker, J.; Beckingham, M.; Behnke, O.; Behrendt, O.; Belousov, A.; Berger, Ch.; Berger, N.; Bizot, J.C.; Boenig, M.-O.; Boudry, V.; Bracinik, J.; Brandt, G.; Brisson, V.; Brown, D.P.; Bruncko, D.; Busser, F.W.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A.J.; Caron, S.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Contreras, J.G.; Coughlan, J.A.; Cox, B.E.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Dau, W.D.; Daum, K.; de Boer, Y.; Delcourt, B.; De Roeck, A.; Desch, K.; De Wolf, E.A.; Diaconu, C.; Dodonov, V.; Dubak, A.; Eckerlin, Guenter; Efremenko, V.; Egli, S.; Eichler, R.; Eisele, F.; Ellerbrock, M.; Elsen, E.; Erdmann, W.; Essenov, S.; Falkewicz, A.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Ferencei, J.; Finke, L.; Fleischer, M.; Fleischmann, P.; Fleming, Y.H.; Flucke, G.; Fomenko, A.; Foresti, I.; Franke, G.; Frisson, T.; Gabathuler, E.; Garutti, E.; Gayler, J.; Gerlich, C.; Ghazaryan, Samvel; Ginzburgskaya, S.; Glazov, A.; Glushkov, I.; Goerlich, L.; Goettlich, M.; Gogitidze, N.; Gorbounov, S.; Goyon, C.; Grab, C.; Greenshaw, T.; Gregori, M.; Grell, B.R.; Grindhammer, Guenter; Gwilliam, C.; Haidt, D.; Hajduk, L.; Hansson, M.; Heinzelmann, G.; Henderson, R.C.W.; Henschel, H.; Henshaw, O.; Herrera, G.; Hildebrandt, M.; Hiller, K.H.; Hoffmann, D.; Horisberger, R.; Hovhannisyan, A.; Hreus, T.; Ibbotson, M.; Ismail, M.; Jacquet, M.; Janauschek, L.; Janssen, X.; Jemanov, V.; Jonsson, L.; Johnson, D.P.; Jung, Andreas Werner; Jung, H.; Kapichine, M.; Katzy, J.; Keller, N.; Kenyon, I.R.; Kiesling, Christian M.; Klein, M.; Kleinwort, C.; Klimkovich, T.; Kluge, T.; Knies, G.; Knutsson, A.; Korbel, V.; Kostka, P.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Kruger, K.; Kuckens, J.; Landon, M.P.J.; Lange, W.; Lastovicka, T.; Lastovicka-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Leiner, B.; Lendermann, V.; Levonian, S.; Lindfeld, L.; Lipka, K.; Liptaj, A.; List, B.; Lobodzinska, E.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lucaci-Timoce, A.-I.; Lueders, H.; Luke, D.; Lux, T.; Lytkin, L.; Makankine, A.; Malden, N.; Malinovski, E.; Mangano, S.; Marage, P.; Marshall, R.; Martisikova, M.; Martyn, H.-U.; Maxeld, S.J.; Meer, D.; Mehta, A.; Meier, K.; Meyer, A.B.; Meyer, H.; Meyer, J.; Mikocki, S.; Milcewicz-Mika, I.; Milstead, D.; Mladenov, D.; Mohamed, A.; Moreau, F.; Morozov, A.; Morris, J.V.; Mozer, Matthias Ulrich; Muller, K.; Murin, P.; Nankov, K.; Naroska, B.; Naumann, Th.; Newman, Paul R.; Niebuhr, C.; Nikiforov, A.; Nikitin, D.; Nowak, G.; Nozicka, M.; Oganezov, R.; Olivier, B.; Olsson, J.E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Papadopoulou, T.; Pascaud, C.; Patel, G.D.; Peez, M.; Perez, E.; Perez-Astudillo, D.; Perieanu, A.; Petrukhin, A.; Pitzl, D.; Placakyte, R.; Portheault, B.; Povh, B.; Prideaux, P.; Raicevic, N.; Reimer, P.; Rimmer, A.; Risler, C.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rurikova, Z.; Rusakov, S.; Salvaire, F.; Sankey, D.P.C.; Sauvan, E.; Schatzel, S.; Schilling, F.-P.; Schmidt, S.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schoning, A.; Schroder, V.; Schultz-Coulon, H.-C.; Sedlak, K.; Sefkow, F.; Shaw-West, R.N.; Sheviakov, I.; Shtarkov, L.N.; Sloan, T.; Smirnov, P.; Soloviev, Y.; South, D.; Spaskov, V.; Specka, Arnd E.; Stella, B.; Stiewe, J.; Strauch, I.; Straumann, U.; Tchoulakov, V.; Thompson, Graham; Thompson, P.D.; Tomasz, F.; Traynor, D.; Truoel, Peter; Tsakov, I.; Tsipolitis, G.; Tsurin, I.; Turnau, J.; Tzamariudaki, E.; Urban, Marcel; Usik, A.; Utkin, D.; Valkar, S.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Van Remortel, N.; Vargas Trevino, A.; Vazdik, Y.; Veelken, C.; Vest, A.; Vinokurova, S.; Volchinski, V.; Vujicic, B.; Wacker, K.; Wagner, J.; Weber, G.; Weber, R.; Wegener, D.; Werner, C.; Werner, N.; Wessels, M.; Wessling, B.; Wigmore, C.; Wissing, Ch.; Wolf, R.; Wunsch, E.; Xella, S.; Yan, W.; Yeganov, V.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhelezov, A.; Zhokin, A.; Zhu, Y.C.; Zimmermann, J.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.

2005-01-01

A search for scalar and vector leptoquarks coupling to first generation fermions is performed using the e^+p and e^-p scattering data collected by the H1 experiment between 1994 and 2000. The data correspond to a total integrated luminosity of 117 pb^{-1}. No evidence for the direct or indirect production of such particles is found in data samples with a large transverse momentum final state electron or with large missing transverse momentum. Constraints on leptoquark models are established. For leptoquark couplings of electromagnetic strength, leptoquarks with masses up to 275-325 GeV are ruled out. These limits improve and supercede earlier H1 limits based on subsamples of the data used here.

Search for leptoquark bosons in ep collisions at HERA

Science.gov (United States)

H1 Collaboration; Aktas, A.; Andreev, V.; Anthonis, T.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Babaev, A.; Backovic, S.; Bähr, J.; Baghdasaryan, A.; Baranov, P.; Barrelet, E.; Bartel, W.; Baudrand, S.; Baumgartner, S.; Becker, J.; Beckingham, M.; Behnke, O.; Behrendt, O.; Belousov, A.; Berger, Ch.; Berger, N.; Bizot, J. C.; Boenig, M.-O.; Boudry, V.; Bracinik, J.; Brandt, G.; Brisson, V.; Brown, D. P.; Bruncko, D.; Büsser, F. W.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A. J.; Caron, S.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Contreras, J. G.; Coughlan, J. A.; Cox, B. E.; Cozzika, G.; Cvach, J.; Dainton, J. B.; Dau, W. D.; Daum, K.; de Boer, Y.; Delcourt, B.; de Roeck, A.; Desch, K.; de Wolf, E. A.; Diaconu, C.; Dodonov, V.; Dubak, A.; Eckerlin, G.; Efremenko, V.; Egli, S.; Eichler, R.; Eisele, F.; Ellerbrock, M.; Elsen, E.; Erdmann, W.; Essenov, S.; Falkewicz, A.; Faulkner, P. J. W.; Favart, L.; Fedotov, A.; Felst, R.; Ferencei, J.; Finke, L.; Fleischer, M.; Fleischmann, P.; Fleming, Y. H.; Flucke, G.; Fomenko, A.; Foresti, I.; Franke, G.; Frisson, T.; Gabathuler, E.; Garutti, E.; Gayler, J.; Gerlich, C.; Ghazaryan, S.; Ginzburgskaya, S.; Glazov, A.; Glushkov, I.; Goerlich, L.; Goettlich, M.; Gogitidze, N.; Gorbounov, S.; Goyon, C.; Grab, C.; Greenshaw, T.; Gregori, M.; Grell, B. R.; Grindhammer, G.; Gwilliam, C.; Haidt, D.; Hajduk, L.; Hansson, M.; Heinzelmann, G.; Henderson, R. C. W.; Henschel, H.; Henshaw, O.; Herrera, G.; Hildebrandt, M.; Hiller, K. H.; Hoffmann, D.; Horisberger, R.; Hovhannisyan, A.; Hreus, T.; Ibbotson, M.; Ismail, M.; Jacquet, M.; Janauschek, L.; Janssen, X.; Jemanov, V.; Jönsson, L.; Johnson, D. P.; Jung, A. W.; Jung, H.; Kapichine, M.; Katzy, J.; Keller, N.; Kenyon, I. R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Klimkovich, T.; Kluge, T.; Knies, G.; Knutsson, A.; Korbel, V.; Kostka, P.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Krüger, K.; Kückens, J.; Landon, M. P. J.; Lange, W.; Laštovička, T.; Laštovička-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Leißner, B.; Lendermann, V.; Levonian, S.; Lindfeld, L.; Lipka, K.; Liptaj, A.; List, B.; Lobodzinska, E.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lucaci-Timoce, A.-I.; Lueders, H.; Lüke, D.; Lux, T.; Lytkin, L.; Makankine, A.; Malden, N.; Malinovski, E.; Mangano, S.; Marage, P.; Marshall, R.; Martisikova, M.; Martyn, H.-U.; Maxfield, S. J.; Meer, D.; Mehta, A.; Meier, K.; Meyer, A. B.; Meyer, H.; Meyer, J.; Mikocki, S.; Milcewicz-Mika, I.; Milstead, D.; Mladenov, D.; Mohamed, A.; Moreau, F.; Morozov, A.; Morris, J. V.; Mozer, M. U.; Müller, K.; Murín, P.; Nankov, K.; Naroska, B.; Naumann, Th.; Newman, P. R.; Niebuhr, C.; Nikiforov, A.; Nikitin, D.; Nowak, G.; Nozicka, M.; Oganezov, R.; Olivier, B.; Olsson, J. E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Papadopoulou, T.; Pascaud, C.; Patel, G. D.; Peez, M.; Perez, E.; Perez-Astudillo, D.; Perieanu, A.; Petrukhin, A.; Pitzl, D.; Plačakytė, R.; Portheault, B.; Povh, B.; Prideaux, P.; Raicevic, N.; Reimer, P.; Rimmer, A.; Risler, C.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rurikova, Z.; Rusakov, S.; Salvaire, F.; Sankey, D. P. C.; Sauvan, E.; Schätzel, S.; Schilling, F.-P.; Schmidt, S.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schöning, A.; Schröder, V.; Schultz-Coulon, H.-C.; Sedlák, K.; Sefkow, F.; Shaw-West, R. N.; Sheviakov, I.; Shtarkov, L. N.; Sirois, Y.; Sloan, T.; Smirnov, P.; Soloviev, Y.; South, D.; Spaskov, V.; Specka, A.; Stella, B.; Stiewe, J.; Strauch, I.; Straumann, U.; Tchoulakov, V.; Thompson, G.; Thompson, P. D.; Tomasz, F.; Traynor, D.; Truöl, P.; Tsakov, I.; Tsipolitis, G.; Tsurin, I.; Turnau, J.; Tzamariudaki, E.; Urban, M.; Usik, A.; Utkin, D.; Valkár, S.; Valkárová, A.; Vallée, C.; van Mechelen, P.; van Remortel, N.; Vargas Trevino, A.; Vazdik, Y.; Veelken, C.; Vest, A.; Vinokurova, S.; Volchinski, V.; Vujicic, B.; Wacker, K.; Wagner, J.; Weber, G.; Weber, R.; Wegener, D.; Werner, C.; Werner, N.; Wessels, M.; Wessling, B.; Wigmore, C.; Wissing, Ch.; Wolf, R.; Wünsch, E.; Xella, S.; Yan, W.; Yeganov, V.; Žáček, J.; Zálešák, J.; Zhang, Z.; Zhelezov, A.; Zhokin, A.; Zhu, Y. C.; Zimmermann, J.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.

2005-11-01

A search for scalar and vector leptoquarks coupling to first generation fermions is performed using the ep and ep scattering data collected by the H1 experiment between 1994 and 2000. The data correspond to a total integrated luminosity of 117 pb. No evidence for the direct or indirect production of such particles is found in data samples with a large transverse momentum final state electron or with large missing transverse momentum. Constraints on leptoquark models are established. For leptoquark couplings of electromagnetic strength, leptoquarks with masses up to 275 325 GeV are ruled out at 95% confidence level. These limits improve and supercede earlier H1 limits based on subsamples of the data used here.

EP-DNN: A Deep Neural Network-Based Global Enhancer Prediction Algorithm.

Science.gov (United States)

Kim, Seong Gon; Harwani, Mrudul; Grama, Ananth; Chaterji, Somali

2016-12-08

We present EP-DNN, a protocol for predicting enhancers based on chromatin features, in different cell types. Specifically, we use a deep neural network (DNN)-based architecture to extract enhancer signatures in a representative human embryonic stem cell type (H1) and a differentiated lung cell type (IMR90). We train EP-DNN using p300 binding sites, as enhancers, and TSS and random non-DHS sites, as non-enhancers. We perform same-cell and cross-cell predictions to quantify the validation rate and compare against two state-of-the-art methods, DEEP-ENCODE and RFECS. We find that EP-DNN has superior accuracy with a validation rate of 91.6%, relative to 85.3% for DEEP-ENCODE and 85.5% for RFECS, for a given number of enhancer predictions and also scales better for a larger number of enhancer predictions. Moreover, our H1 → IMR90 predictions turn out to be more accurate than IMR90 → IMR90, potentially because H1 exhibits a richer signature set and our EP-DNN model is expressive enough to extract these subtleties. Our work shows how to leverage the full expressivity of deep learning models, using multiple hidden layers, while avoiding overfitting on the training data. We also lay the foundation for exploration of cross-cell enhancer predictions, potentially reducing the need for expensive experimentation.

EP-DNN: A Deep Neural Network-Based Global Enhancer Prediction Algorithm

Science.gov (United States)

Kim, Seong Gon; Harwani, Mrudul; Grama, Ananth; Chaterji, Somali

2016-12-01

We present EP-DNN, a protocol for predicting enhancers based on chromatin features, in different cell types. Specifically, we use a deep neural network (DNN)-based architecture to extract enhancer signatures in a representative human embryonic stem cell type (H1) and a differentiated lung cell type (IMR90). We train EP-DNN using p300 binding sites, as enhancers, and TSS and random non-DHS sites, as non-enhancers. We perform same-cell and cross-cell predictions to quantify the validation rate and compare against two state-of-the-art methods, DEEP-ENCODE and RFECS. We find that EP-DNN has superior accuracy with a validation rate of 91.6%, relative to 85.3% for DEEP-ENCODE and 85.5% for RFECS, for a given number of enhancer predictions and also scales better for a larger number of enhancer predictions. Moreover, our H1 → IMR90 predictions turn out to be more accurate than IMR90 → IMR90, potentially because H1 exhibits a richer signature set and our EP-DNN model is expressive enough to extract these subtleties. Our work shows how to leverage the full expressivity of deep learning models, using multiple hidden layers, while avoiding overfitting on the training data. We also lay the foundation for exploration of cross-cell enhancer predictions, potentially reducing the need for expensive experimentation.

Acceptability of Daily Use of Free Oral Pre-exposure Prophylaxis (PrEP) Among Transgender Women Sex Workers in Shenyang, China.

Science.gov (United States)

Wang, Zixin; Lau, Joseph T F; Yang, Xueying; Cai, Yong; Gross, Danielle L; Ma, Tiecheng; Liu, Yan

2017-12-01

This study investigated the acceptability of daily use of free oral pre-exposure prophylaxis (PrEP) and associated factors among transgender women sex workers in Shenyang, China, following a briefing on PrEP. A total of 183 HIV negative or sero-status unknown participants completed the cross-sectional survey. The prevalence of acceptability of daily use of free oral PrEP was 61.2%. Adjusting for education level and monthly income, variables on negative attitudes toward PrEP (i.e., having concerns about the side-effects of PrEP) [Adjusted odds ratios (AOR): 0.26], perceived subjective norms (i.e., perceiving support from male partners to take PrEP) (AOR: 2.08), and perceived behavioral control (e.g., perceiving complete control over using PrEP) (AOR: 2.10-16.72) were significantly associated with acceptability of daily use of free oral PrEP. In addition, experiencing violence during sex work, perceived risk of contracting HIV from clients and probable anxiety were also significant. Future PrEP promotion campaigns should consider these factors.

Preparation and microwave-absorbing property of EP/BaFe{sub 12}O{sub 19}/PANI composites

Energy Technology Data Exchange (ETDEWEB)

Feng, Huixia, E-mail: fenghx@lut.cn [State Key Laboratory of Advanced Processing and Recycling of Nonferrous Metals, Lanzhou University of Technology, Lanzhou 730050 (China); College of Petrochemical Technology, Lanzhou University of Technology, Lanzhou 730050 (China); Bai, Dezhong [College of Petrochemical Technology, Lanzhou University of Technology, Lanzhou 730050 (China); Tan, Lin; Chen, Nali [State Key Laboratory of Advanced Processing and Recycling of Nonferrous Metals, Lanzhou University of Technology, Lanzhou 730050 (China); College of Petrochemical Technology, Lanzhou University of Technology, Lanzhou 730050 (China); Wang, Yueyi [College of Petrochemical Technology, Lanzhou University of Technology, Lanzhou 730050 (China)

2017-07-01

In this paper, we introduced expanded perlite (EP) into the system of ferrite composites for the first time. By sol-gel self-propagating combustion method, expanded perlite/barium ferrite (EP/BaFe{sub 12}O{sub 19}) was prepared, and then ternary composites of expanded perlite/barium ferrite/polyaniline (EP/BaFe{sub 12}O{sub 19}/PANI) were obtained by in-situ oxidative polymerization of aniline on EP/BaFe{sub 12}O{sub 19} mixture. Although, as is well known, the values of saturation magnetization (Ms), remnant magnetization (Mr) and coercivity (Hc) of composites are all lower than the pure BaFe{sub 12}O{sub 19} particles owing to the existence of the nonmagnetic EP and PANI, the EP/BaFe{sub 12}O{sub 19}/PANI composites exhibit absorption characteristics at the range of 2–18 GHz, the effective absorption bandwidth (less than −4 dB) reached 12.12 GHz and the minimum reflection loss of −5.66 dB at 8.48 GHz with only 2 mm thickness of absorbing layer. So the composites could resist urban electromagnetic pollution, such as wireless network, communication and so on, effectively. - Highlights: • The expanded perlite (EP) was introduced into the system of ferrite composites at the first time. • Novel ternary nanocomposite of EP/BaFe{sub 12}O{sub 19}/PANI is prepared by in-situ oxidative polymerization. • Composite absorber exhibit a minimum reflection loss of -5.66 dB at 8.48 GHz with a matching thickness of 2 mm. • Composite absorber possess the features like low-cost, lightweight and wide bandwidth absorption of civil EM radiation.

Stabilizing Effects of Bacterial Biofilms: EPS Penetration and Redistribution of Bed Stability Down the Sediment Profile

Science.gov (United States)

Chen, X. D.; Zhang, C. K.; Zhou, Z.; Gong, Z.; Zhou, J. J.; Tao, J. F.; Paterson, D. M.; Feng, Q.

2017-12-01

Biofilms, consisting of microorganisms and their secreted extracellular polymeric substances (EPSs), serve as "ecosystem engineers" stabilizing sedimentary environments. Natural sediment bed provides an excellent substratum for biofilm growth. The porous structure and rich nutrients allow the EPS matrix to spread deeper into the bed. A series of laboratory-controlled experiments were conducted to investigate sediment colonization of Bacillus subtilis and the penetration of EPS into the sediment bed with incubation time. In addition to EPS accumulation on the bed surface, EPS also penetrated downward. However, EPS distribution developed strong vertical heterogeneity with a much higher content in the surface layer than in the bottom layer. Scanning electron microscope images of vertical layers also displayed different micromorphological properties of sediment-EPS matrix. In addition, colloidal and bound EPSs exhibited distinctive distribution patterns. After the full incubation, the biosedimentary beds were eroded to test the variation of bed stability induced by biological effects. This research provides an important reference for the prediction of sediment transport and hence deepens the understanding of the biologically mediated sediment system and broadens the scope of the burgeoning research field of "biomorphodynamics."

A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution

DEFF Research Database (Denmark)

Wong, W T; Schumacher, C; Salcini, A E

1995-01-01

In this report we structurally and functionally define a binding domain that is involved in protein association and that we have designated EH (for Eps15 homology domain). This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several heteroge......In this report we structurally and functionally define a binding domain that is involved in protein association and that we have designated EH (for Eps15 homology domain). This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several...... heterogeneous proteins of yeast and nematode. The EH domain spans about 70 amino acids and shows approximately 60% overall amino acid conservation. We demonstrated the ability of the EH domain to specifically bind cytosolic proteins in normal and malignant cells of mesenchymal, epithelial, and hematopoietic...... (for Eps15-related). Structural comparison of Eps15 and Eps15r defines a family of signal transducers possessing extensive networking abilities including EH-mediated binding and association with Src homology 3-containing proteins....

Sorption of ferrous iron by EPS from the acidophilic bacterium Acidiphilium Sp.: A mechanism proposal

Energy Technology Data Exchange (ETDEWEB)

Tapia, J.M.; MuNoz, J.; Gonzlez, F.; Blazquez, M.L.; Ballester, A.

2016-07-01

The aim of this work was to assess the uptake of Fe(II) by extracellular polymeric substances (EPS) from the acidophilic bacterium Acidiphillium 3.2Sup(5). These EPS were extracted using EDTA. EPS of A. 3.2Sup(5) loaded in sorption tests with Fe(II), were characterized using the following experimental techniques: scanning electron microscopy (SEM) with energy dispersive X-ray microanalysis (EDX), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The experimental results indicate that EPS adsorb ferrous iron according to Freundlich model with a metal sorption uptake of K = 1.14 mg1−1/n L1/n g−1 and a sorption intensity of 1/n = 1.26. In addition, ferrous iron sorption by EPS took place by preferential interaction with the carboxyl group which promotes the formation of ferrous iron oxalates (FeC2O4). Since the interaction reaction was reversible (Log K = 0.77 ± 0.33), that means that the cation sorption can be reversed at convenience. (Author)

BEHAVIOUR OF UNREINFORCED EXPANDED POLYSTYRENE LIGHTWEIGHT CONCRETE (EPS-LWC WALL PANEL ENHANCED WITH STEEL FIBRE

Directory of Open Access Journals (Sweden)

ROHANA MAMAT

2015-12-01

Full Text Available This study used steel fibre as reinforcement while enhancing the EPS-LWC strength. In line with architectural demand and ventilation requirement, opening within wall panel was also taken into account. Experimental tests were conducted for reinforced and unreinforced EPS-LWC wall panel. Two samples with size of 1500 mm (height x 1000 mm (length x 75 mm (thickness for each group of wall panel were prepared. Samples in each group had opening size of 600 mm (height x 400 mm (length located at 350 mm and 550 mm from upper end respectively. EPS-LWC wall panel had fcu of 20.87 N/mm2 and a density of 1900 kg/m3. The loading capacity, displacement profiles and crack pattern of each sample was analyzed and discussed. Unreinforced EPS-LWC enhanced with steel fibre resist almost similar loading as reinforced EPS-LWC wall panel. The presence of steel fibre as the only reinforcement creates higher lateral displacement. Wall panel experience shear failure at the side of opening. The number of micro cracks reduces significantly due to presence of steel fibre.

Prostaglandin E2 activates the mTORC1 pathway through an EP4/cAMP/PKA- and EP1/Ca2+-mediated mechanism in the human pancreatic carcinoma cell line PANC-1.

Science.gov (United States)

Chang, Hui-Hua; Young, Steven H; Sinnett-Smith, James; Chou, Caroline Ei Ne; Moro, Aune; Hertzer, Kathleen M; Hines, Oscar Joe; Rozengurt, Enrique; Eibl, Guido

2015-11-15

Obesity, a known risk factor for pancreatic cancer, is associated with inflammation and insulin resistance. Proinflammatory prostaglandin E2 (PGE2) and elevated insulin-like growth factor type 1 (IGF-1), related to insulin resistance, are shown to play critical roles in pancreatic cancer progression. We aimed to explore a potential cross talk between PGE2 signaling and the IGF-1/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway in pancreatic cancer, which may be a key to unraveling the obesity-cancer link. In PANC-1 human pancreatic cancer cells, we showed that PGE2 stimulated mTORC1 activity independently of Akt, as evaluated by downstream signaling events. Subsequently, using pharmacological and genetic approaches, we demonstrated that PGE2-induced mTORC1 activation is mediated by the EP4/cAMP/PKA pathway, as well as an EP1/Ca(2+)-dependent pathway. The cooperative roles of the two pathways were supported by the maximal inhibition achieved with the combined pharmacological blockade, and the coexistence of highly expressed EP1 (mediating the Ca(2+) response) and EP2 or EP4 (mediating the cAMP/PKA pathway) in PANC-1 cells and in the prostate cancer line PC-3, which also robustly exhibited PGE2-induced mTORC1 activation, as identified from a screen in various cancer cell lines. Importantly, we showed a reinforcing interaction between PGE2 and IGF-1 on mTORC1 signaling, with an increase in IL-23 production as a cellular outcome. Our data reveal a previously unrecognized mechanism of PGE2-stimulated mTORC1 activation mediated by EP4/cAMP/PKA and EP1/Ca(2+) signaling, which may be of great importance in elucidating the promoting effects of obesity in pancreatic cancer. Ultimately, a precise understanding of these molecular links may provide novel targets for efficacious interventions devoid of adverse effects. Copyright © 2015 the American Physiological Society.

Adhesion strength and spreading characteristics of EPS on membrane surfaces during lateral and central growth.

Science.gov (United States)

Tansel, Berrin; Tansel, Derya Z

2013-11-01

Deposition of extracellular polymeric substances (EPS) on membrane surfaces is a precursor step for bacterial attachment. The purpose of this study was to analyze the morphological changes on a clean polysulfone ultrafilration membrane after exposure to effluent from a membrane bioreactor. The effluent was filtered to remove bacteria before exposing the membrane. The morphological characterization was performed by atomic force microscopy (AFM). The lateral (2D) and central growth characteristics (3D) of the EPS deposits were evaluated by section and topographical analyses of the height images. The contact angle of single EPS units was 9.07 ± 0.50° which increased to 24.41 ± 1.00° for large clusters (over 10 units) and decreased to 18.68 ± 1.00° for the multilayered clusters. The surface tension of the single EPS units was 49.34 ± 1.70 mNm(-1). The surface tension of single layered small and large EPS clusters were 51.26 ± 2.05 and 53.48 ± 2.01 mNm(-1), respectively. For the multilayered clusters, the surface tension was 51.43 ± 2.05 mNm(-1). The spreading values were negative for all deposits on the polysulfone membrane indicating that the EPS clusters did not have tendency to spread but preferred to retain their shapes. Copyright © 2013 Elsevier B.V. All rights reserved.

A strange nucleon probe: the parity violation in ep{yields}ep; Une etrange sonde du nucleon: la violation de parite en diffusion ep{yields}ep

Energy Technology Data Exchange (ETDEWEB)

Cavata, Ch

1998-10-01

Recent experiments have confirmed the importance of strange quarks in the description of the spin structure of the proton. This unexpected fact has spurred an intense experimental activity to study the contribution of strange quarks to other aspects of the nucleon. In this framework experiments have been designed to weigh up this contribution to the charge distribution and the magnetization of the nucleon. The experimental way that leads to the measuring of the s-quark contribution is presented. The strange form factor can be deduced from the weak form factor of the proton combined with its electromagnetic form factors. The weak form factor can be measured by studying parity violation in ep elastic scattering. One of the chapters reviews the experimental equipment required to perform parity breaking measurements.The preliminary results of 2 experiments: SAMPLE and HAPPEX are given. (A.C.)

Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations.

Science.gov (United States)

Fergelot, Patricia; Van Belzen, Martine; Van Gils, Julien; Afenjar, Alexandra; Armour, Christine M; Arveiler, Benoit; Beets, Lex; Burglen, Lydie; Busa, Tiffany; Collet, Marie; Deforges, Julie; de Vries, Bert B A; Dominguez Garrido, Elena; Dorison, Nathalie; Dupont, Juliette; Francannet, Christine; Garciá-Minaúr, Sixto; Gabau Vila, Elisabeth; Gebre-Medhin, Samuel; Gener Querol, Blanca; Geneviève, David; Gérard, Marion; Gervasini, Cristina Giovanna; Goldenberg, Alice; Josifova, Dragana; Lachlan, Katherine; Maas, Saskia; Maranda, Bruno; Moilanen, Jukka S; Nordgren, Ann; Parent, Philippe; Rankin, Julia; Reardon, Willie; Rio, Marlène; Roume, Joëlle; Shaw, Adam; Smigiel, Robert; Sojo, Amaia; Solomon, Benjamin; Stembalska, Agnieszka; Stumpel, Constance; Suarez, Francisco; Terhal, Paulien; Thomas, Simon; Touraine, Renaud; Verloes, Alain; Vincent-Delorme, Catherine; Wincent, Josephine; Peters, Dorien J M; Bartsch, Oliver; Larizza, Lidia; Lacombe, Didier; Hennekam, Raoul C

2016-12-01

Rubinstein-Taybi syndrome (RSTS) is a developmental disorder characterized by a typical face and distal limbs abnormalities, intellectual disability, and a vast number of other features. Two genes are known to cause RSTS, CREBBP in 60% and EP300 in 8-10% of clinically diagnosed cases. Both paralogs act in chromatin remodeling and encode for transcriptional co-activators interacting with >400 proteins. Up to now 26 individuals with an EP300 mutation have been published. Here, we describe the phenotype and genotype of 42 unpublished RSTS patients carrying EP300 mutations and intragenic deletions and offer an update on another 10 patients. We compare the data to 308 individuals with CREBBP mutations. We demonstrate that EP300 mutations cause a phenotype that typically resembles the classical RSTS phenotype due to CREBBP mutations to a great extent, although most facial signs are less marked with the exception of a low-hanging columella. The limb anomalies are more similar to those in CREBBP mutated individuals except for angulation of thumbs and halluces which is very uncommon in EP300 mutated individuals. The intellectual disability is variable but typically less marked whereas the microcephaly is more common. All types of mutations occur but truncating mutations and small rearrangements are most common (86%). Missense mutations in the HAT domain are associated with a classical RSTS phenotype but otherwise no genotype-phenotype correlation is detected. Pre-eclampsia occurs in 12/52 mothers of EP300 mutated individuals versus in 2/59 mothers of CREBBP mutated individuals, making pregnancy with an EP300 mutated fetus the strongest known predictor for pre-eclampsia. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

OpenAIRE

Caleb C. Roth; Ronald A. Barnes Jr.; Bennett L. Ibey; Hope T. Beier; L. Christopher Mimun; Saher M. Maswadi; Mehdi Shadaram; Randolph D. Glickman

2015-01-01

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, el...

Slepton and squark production and decay in ep collision at the LHC

International Nuclear Information System (INIS)

Bartl, A.; Majerotto, W.; Oshimo, N.; Moesslacher, B.

1991-06-01

We present a detailed study of e+p → e+q+X and e+p → v+q+X and the subsequent decays of e,v, and q at the LHC (√s = 1.4 TeV). We explore the relevant supersymmetry parameter range. We calculate the cross section as well as the rates for interesting signatures such as the production of one or two leptons on the lepton side. (authors)

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

Science.gov (United States)

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.

Neuronal thresholds and choice-related activity of otolith afferent fibers during heading perception.

Science.gov (United States)

Yu, Xiong-jie; Dickman, J David; DeAngelis, Gregory C; Angelaki, Dora E

2015-05-19

How activity of sensory neurons leads to perceptual decisions remains a challenge to understand. Correlations between choices and single neuron firing rates have been found early in vestibular processing, in the brainstem and cerebellum. To investigate the origins of choice-related activity, we have recorded from otolith afferent fibers while animals performed a fine heading discrimination task. We find that afferent fibers have similar discrimination thresholds as central cells, and the most sensitive fibers have thresholds that are only twofold or threefold greater than perceptual thresholds. Unlike brainstem and cerebellar nuclei neurons, spike counts from afferent fibers do not exhibit trial-by-trial correlations with perceptual decisions. This finding may reflect the fact that otolith afferent responses are poorly suited for driving heading perception because they fail to discriminate self-motion from changes in orientation relative to gravity. Alternatively, if choice probabilities reflect top-down inference signals, they are not relayed to the vestibular periphery.

Threefold Increase in PrEP Uptake Over Time with High Adherence Among Young Men Who Have Sex With Men in Chicago.

Science.gov (United States)

Morgan, Ethan; Moran, Kevin; Ryan, Daniel T; Mustanski, Brian; Newcomb, Michael E

2018-05-04

The goal of this work is to better understand utilization and uptake of pre-exposure prophylaxis (PrEP) among young men who have sex with men (YMSM) and transgender women (TGW). We assessed trends and correlates of PrEP use and adherence across three time points of longitudinal data collection among 885 YMSM and TGW (aged 16-29) from the RADAR cohort in Chicago, 2015-2017. Past 6-month PrEP use increased across three visits: from 6.6 to 17.5%. In multivariable models, past 6-month PrEP use was significantly associated with participation in condomless sex, having more sexual partners, and older age. At least three-quarters of current PrEP users reported being ≥ 90% adherent to PrEP medication across all visits. Past 6-month PrEP use increased over time with those who participated in high-risk HIV behaviors also those most likely to have taken PrEP. As PrEP uptake continues to rise, more research will be needed to understand predictors of PrEP usage, as well as patterns of sexual behavior change following uptake.

Search for excited electrons in ep collisions at HERA

Science.gov (United States)

H1 Collaboration; Aaron, F. D.; Alexa, C.; Andreev, V.; Antunovic, B.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Bacchetta, A.; Backovic, S.; Baghdasaryan, A.; Baranov, P.; Barrelet, E.; Bartel, W.; Beckingham, M.; Begzsuren, K.; Behnke, O.; Belousov, A.; Berger, N.; Bizot, J. C.; Boenig, M.-O.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Bruncko, D.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A. J.; Cantun Avila, K. B.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Cholewa, A.; Contreras, J. G.; Coughlan, J. A.; Cozzika, G.; Cvach, J.; Dainton, J. B.; Daum, K.; Deák, M.; de Boer, Y.; Delcourt, B.; Del Degan, M.; Delvax, J.; de Roeck, A.; de Wolf, E. A.; Diaconu, C.; Dodonov, V.; Dossanov, A.; Dubak, A.; Eckerlin, G.; Efremenko, V.; Egli, S.; Eliseev, A.; Elsen, E.; Essenov, S.; Falkiewicz, A.; Faulkner, P. J. W.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Finke, L.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, S.; Glazov, A.; Glushkov, I.; Goerlich, L.; Goettlich, M.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Greenshaw, T.; Grell, B. R.; Grindhammer, G.; Habib, S.; Haidt, D.; Hansson, M.; Helebrant, C.; Henderson, R. C. W.; Henschel, H.; Herrera, G.; Hildebrandt, M.; Hiller, K. H.; Hoffmann, D.; Horisberger, R.; Hovhannisyan, A.; Hreus, T.; Jacquet, M.; Janssen, M. E.; Janssen, X.; Jemanov, V.; Jönsson, L.; Johnson, D. P.; Jung, A. W.; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I. R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Klimkovich, T.; Kluge, T.; Knutsson, A.; Kogler, R.; Korbel, V.; Kostka, P.; Kraemer, M.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Krüger, K.; Kutak, K.; Landon, M. P. J.; Lange, W.; Laštovička-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Lendermann, V.; Levonian, S.; Li, G.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lucaci-Timoce, A.-I.; Lytkin, L.; Makankine, A.; Malinovski, E.; Marage, P.; Marti, Ll.; Martyn, H.-U.; Maxfield, S. J.; Mehta, A.; Meier, K.; Meyer, A. B.; Meyer, H.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Moreau, F.; Morozov, A.; Morris, J. V.; Mozer, M. U.; Mudrinic, M.; Müller, K.; Murín, P.; Nankov, K.; Naroska, B.; Naumann, Th.; Newman, P. R.; Niebuhr, C.; Nikiforov, A.; Nowak, G.; Nowak, K.; Nozicka, M.; Olivier, B.; Olsson, J. E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Pandurovic, M.; Papadopoulou, Th.; Pascaud, C.; Patel, G. D.; Pejchal, O.; Peng, H.; Perez, E.; Petrukhin, A.; Picuric, I.; Piec, S.; Pitzl, D.; Plačakytė, R.; Polifka, R.; Povh, B.; Preda, T.; Radescu, V.; Rahmat, A. J.; Raicevic, N.; Raspiareza, A.; Ravdandorj, T.; Reimer, P.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rotaru, M.; Ruiz Tabasco, J. E.; Rurikova, Z.; Rusakov, S.; Salek, D.; Salvaire, F.; Sankey, D. P. C.; Sauter, M.; Sauvan, E.; Schmidt, S.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schöning, A.; Schultz-Coulon, H.-C.; Sefkow, F.; Shaw-West, R. N.; Sheviakov, I.; Shtarkov, L. N.; Shushkevich, S.; Sloan, T.; Smiljanic, I.; Smirnov, P.; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, A.; Staykova, Z.; Steder, M.; Stella, B.; Straumann, U.; Sunar, D.; Sykora, T.; Tchoulakov, V.; Thompson, G.; Thompson, P. D.; Toll, T.; Tomasz, F.; Tran, T. H.; Traynor, D.; Trinh, T. N.; Truöl, P.; Tsakov, I.; Tseepeldorj, B.; Tsurin, I.; Turnau, J.; Tzamariudaki, E.; Urban, K.; Valkárová, A.; Vallée, C.; van Mechelen, P.; Vargas Trevino, A.; Vazdik, Y.; Vinokurova, S.; Volchinski, V.; Wegener, D.; Wessels, M.; Wissing, Ch.; Wünsch, E.; Yeganov, V.; Žáček, J.; Zálešák, J.; Zhang, Z.; Zhelezov, A.; Zhokin, A.; Zhu, Y. C.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.

2008-08-01

A search for excited electrons is performed using the full ep data sample collected by the H1 experiment at HERA, corresponding to a total luminosity of 475 pb-1. The electroweak decays of excited electrons e→eγ, e→eZ and e→νW with subsequent hadronic or leptonic decays of the W and Z bosons are considered. No evidence for excited electron production is found. Mass dependent exclusion limits on e production cross sections and on the ratio f/Λ of the coupling to the compositeness scale are derived within gauge mediated models. These limits extend the excluded region compared to previous excited electron searches. The e production via contact interactions is also addressed for the first time in ep collisions.

Special 2005 EPS HEPP prize colloquium

CERN Multimedia

CERN. Geneva; Wahl, Heinrich; Alvarez-Gaumé, Luís

2005-01-01

First evidence and measurement of direct CP violation by the NA31 experiment This is a colloquium celebrating the awarding of the 2005 EPS High Energy Particle Physics prize to Heinrich Wahl and the NA31 collaboration which showed for the first time Direct CP Violation in the decay of neutral K mesons. There will be an introduction to direct CP violation, followed by a review of experimental results.

Social Thresholds and their Translation into Social-ecological Management Practices

Directory of Open Access Journals (Sweden)

Lisa Christensen

2012-03-01

Full Text Available The objective of this paper is to provide a preliminary discussion of how to improve our conceptualization of social thresholds using (1 a more sociological analysis of social resilience, and (2 results from research carried out in collaboration with the Champagne and Aishihik First Nations of the Yukon Territory, Canada. Our sociological analysis of the concept of resilience begins with a review of the literature followed by placement of the concept in the domain of sociological theory to gain insight into its strengths and limitations. A new notion of social thresholds is proposed and case study research discussed to support the proposition. Our findings suggest that rather than view social thresholds as breakpoints between two regimes, as thresholds are typically conceived in the resilience literature, that they be viewed in terms of collectively recognized points that signify new experiences. Some examples of thresholds identified in our case study include power in decision making, level of healing from historical events, and a preference for small-scale development over large capital intensive projects.

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

Science.gov (United States)

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

Role of the pharmacist in pre-exposure chemoprophylaxis (PrEP therapy for HIV prevention

Directory of Open Access Journals (Sweden)

Clauson KA

2009-03-01

Full Text Available With a global estimate of 2.5 million new infections of HIV occurring yearly, discovering novel methods to help stem the spread of the virus is critical. The use of antiretroviral chemoprophylaxis for preventing HIV after accidental or occupational exposure and in maternal to fetal transmission has become a widely accepted method to combat HIV. Based on this success, pre-exposure chemoprophylaxis (PrEP is being explored in at-risk patient populations such as injecting drug users, female sex workers and men who have sex with men. This off-label and unmonitored use has created a need for education and intervention by pharmacists and other healthcare professionals. Pharmacists should educate themselves on PrEP and be prepared to counsel patients about their means of obtaining it (e.g. borrowing or sharing medications and ordering from disreputable Internet pharmacies. They should also be proactive about medication therapy management in these patients due to clinically important drug interactions with PrEP medications. Only one trial exploring the safety and efficacy of tenofovir as PrEP has been completed thus far. However, five ongoing trials are in various stages and two additional studies are scheduled for the near future. Unfortunately, studies in this arena have met with many challenges that have threatened to derail progress. Ethical controversy surrounding post-trial care of participants who seroconvert during studies, as well as concerns over emerging viral resistance and logistical site problems, have already halted several PrEP trials. Information about these early trials has already filtered down to affected individuals who are experimenting with this unproven therapy as an “evening before pill”. The potential for PrEP is promising; however, more extensive trials are necessary to establish its safety and efficacy. Pharmacists are well-positioned to play a key role in helping patients make choices about PrEP, managing their therapy

Subthalamic nucleus stimulation reverses mediofrontal influence over decision threshold

NARCIS (Netherlands)

Cavanagh, J.F.; Wiecki, T.V.; Cohen, M.X.; Figueroa, C.M.; Samanta, J.; Sherman, S.J.; Frank, M.J.

2011-01-01

It takes effort and time to tame one's impulses. Although medial prefrontal cortex (mPFC) is broadly implicated in effortful control over behavior, the subthalamic nucleus (STN) is specifically thought to contribute by acting as a brake on cortico-striatal function during decision conflict, buying

Optimization of Cultural Conditions for Production of Extracellular Polymeric Substances (EPS) by Serpentine Rhizobacterium Cupriavidus pauculus KPS 201

OpenAIRE

Arundhati Pal; A. K. Paul

2013-01-01

Extracellular polymeric substances (EPS) are complex biopolymers produced by a wide array of microorganisms for protection against dessication, aggregation, adhesion, and expression of virulence. Growth associated production of EPS by Ni-resistant Cupriavidus pauculus KPS 201 was determined in batch culture using sodium gluconate as the sole carbon source. The optimum pH and temperature for EPS production were 6.5 and 25°C, respectively. Optimal EPS yield (118 μg/mL) was attained at 0.35% Na-...

Exopolysaccharides (EPS) as anti-corrosive additives for coatings

NARCIS (Netherlands)

Scheerder, J.; Breur, R.; Slaghek, T.; Holtman, W.; Vennik, M.; Ferrari, G.

2012-01-01

Exopolysaccharides (EPS) are a class of renewable polymers that show interesting anti-corrosive properties and could potentially be used as an alternative for zinc phosphates. When combined with a waterborne styrene-acrylic polymer dispersion (SA-1), exopolysaccharides were shown to give an

Beam-strahlung effects in e-p collider

International Nuclear Information System (INIS)

Cho, Y.

1982-09-01

The electromagnetic fields produced by one beam in an interaction point of a colliding-beam facility cause to the emission of synchrotron radiation by the other beam. This effect, the beam strahlung, for the e+e - colliders has been considered by several authors, and they have pointed out that the effect is very important consideration at very-high-energy e+e - colliders. At the first glance, the beam-strahlung effect can play an important role in the e-p collision due to the fact that the circulating currents in the collider are much higher than those of the e+e - machine. However the detailed study shows that is not the case because of the collision geometry involved. What follows in this note is the beam-strahlung derivations using the method previously used by Hofmann and Keil. The difference between this note and that of Hofman and Keil is that in the case of e+e - collider, equal mass particles are involved in the consideration and, in the e-p case, the electrons radiate and the protons provide the electromagnetic fields

Highlights from e-EPS: Physics for fun

CERN Multimedia

e-EPS

2013-01-01

e-EPS News is a monthly addition to the CERN Bulletin line-up, showcasing articles from e-EPS – the European Physical Society newsletter – as part of a collaboration between the two publications.   For many who measure time according to a university calendar, summer is a time to unwind. My experience, however, is that it is rare to find physics departments empty over the summer break. Many of us use the vacation period without classes to catch up with research, and I imagine that a colleague of mine speaks for many when he says that summer provides him with the freedom to do the physics he wants to do, and this is all the break needed to prepare for the next academic year! This reminds me a little of the Wobbling Plate story in “Surely You’re Joking Mr Feynman”? When Richard Feynman had just started at Cornell following his time at Los Alamos, he felt burned out, and was wondering why he did not feel the same enthusiasm for physics t...

NREL- and Sandia-Developed HyStEP Device Receives Far West FLC Award | News

Science.gov (United States)

| NREL NREL- and Sandia-Developed HyStEP Device Receives Far West FLC Award NREL- and Sandia -Developed HyStEP Device Receives Far West FLC Award September 1, 2016 The National Renewable Energy technologies and boost the regional economy. As FLC awards are granted for outstanding achievements in

Damping the e-p instability in the SNS accumulator ring

Science.gov (United States)

Evans, N. J.; Deibele, C.; Aleksandrov, A.; Xie, Z.

2018-03-01

A broadband, digital damper system for both transverse planes developed for the SNS accumulator ring has recently damped the first indications of the broadband 50-150 MHz e-p instability in a 1.2 MW neutron production beam. This paper presents details of the design and operation of the SNS damper system as well as results of active damping of the e-p instability in the SNS ring showing a reduction in power of betatron oscillation over the 10-300 MHz band of up to 70%. The spectral content of the beam during operation, with and without the damper system is presented and performance of the damper system is evaluated.

Biosorption of Cadmium by Non-Toxic Extracellular Polymeric Substances (EPS Synthesized by Bacteria from Marine Intertidal Biofilms

Directory of Open Access Journals (Sweden)

Juan Carlos Camacho-Chab

2018-02-01

Full Text Available Cadmium is a major heavy metal found in polluted aquatic environments, mainly derived from industrial production processes. We evaluated the biosorption of solubilized Cd2+ using the extracellular polymeric substances (EPS produced by Bacillus sp. MC3B-22 and Microbacterium sp. MC3B-10 (Microbactan; these bacteria were originally isolated from intertidal biofilms off the coast of Campeche, Mexico. EPS were incubated with different concentrations of cadmium in ultrapure water. Residual Cd2+ concentrations were determined by Inductive Coupled Plasma-Optic Emission Spectrometry and the maximum sorption capacity (Qmax was calculated according to the Langmuir model. EPS were characterized by X-ray photoelectron spectroscopy (XPS before and after sorption. The Qmax of Cd2+ was 97 mg g−1 for Microbactan and 141 mg g−1 for MC3B-22 EPS, these adsorption levels being significantly higher than previously reported for other microbial EPS. In addition, XPS analysis revealed changes in structure of EPS after biosorption and showed that amino functional groups contributed to the binding of Cd2+, unlike other studies that show the carbohydrate fraction is responsible for this activity. This work expands the current view of bacterial species capable of synthesizing EPS with biosorbent potential for cadmium and provides evidence that different chemical moieties, other than carbohydrates, participate in this process.

Nuclear regulatory policy concept on safety, security, safeguards and emergency preparedness (3S+EP)

International Nuclear Information System (INIS)

Ilyas, Zurias

2009-01-01

Regulatory Policy is formulated in regulations that stipulate the assurance of workers and public safety and environmental protection. Legislation and regulations on nuclear energy should consider nuclear safety, security and safeguards, as well as nuclear emergency preparedness (3S+EP) and liability for nuclear damage. Specific requirements stipulated in international conventions and agreements should also be taken into account. Regulatory Policy is formulated in regulations that stipulate the assurance of workers and public safety and environmental protection. Legislation and regulations on nuclear energy should consider nuclear safety, security and safeguards, as well as nuclear emergency preparedness (3S+EP) and liability for nuclear damage. Specific requirements stipulated in international conventions and agreements should also be taken into account. By undertaking proper regulatory oversight on Safety, Security and Emergency Preparedness (3S+EP) as an integrated and comprehensive system, safe and secure use of nuclear energy can be assured. Licence requirements and conditions should fulfil regulatory requirements pertaining to 3S+EP for nuclear installation as an integrated system. An effective emergency capacity that can be immediately mobilized is important. The capacity in protecting the personnel before, during and after the disaster should also be planned. Thus, proper emergency preparedness should be supported by adequate resources. The interface between safety, security, safeguards and emergency preparedness has to be set forth in nuclear regulations, such as regulatory requirements; 3S+EP; components, systems and structures of nuclear installations and human resources. Licensing regulations should stipulate, among others, DIQ, installations security system, safety analysis report, emergency preparedness requirements and necessary human resources that meet the 3S+EP requirements.

Optimal threshold of error decision related to non-uniform phase distribution QAM signals generated from MZM based on OCS

Science.gov (United States)

Han, Xifeng; Zhou, Wen

2018-03-01

Optical vector radio-frequency (RF) signal generation based on optical carrier suppression (OCS) in one Mach-Zehnder modulator (MZM) can realize frequency-doubling. In order to match the phase or amplitude of the recovered quadrature amplitude modulation (QAM) signal, phase or amplitude pre-coding is necessary in the transmitter side. The detected QAM signals usually have one non-uniform phase distribution after square-law detection at the photodiode because of the imperfect characteristics of the optical and electrical devices. We propose to use optimal threshold of error decision for non-uniform phase contribution to reduce the bit error rate (BER). By employing this scheme, the BER of 16 Gbaud (32 Gbit/s) quadrature-phase-shift-keying (QPSK) millimeter wave signal at 36 GHz is improved from 1 × 10-3 to 1 × 10-4 at - 4 . 6 dBm input power into the photodiode.

Production of Z{sup 0} bosons in elastic and quasi-elastic ep collisions at HERA

Energy Technology Data Exchange (ETDEWEB)

Abramowicz, H. [Tel Aviv Univ. (Israel). School of Physics; Max Planck Institute for Physics, Munich (Germany); Abt, I. [Max Planck Institute for Physics, Munich (Germany); Adamczyk, L. [AGH-Univ. of Science and Technology, Krakow (Poland). Faculty of Physics and Applied Computer Science] [and others; Collaboration: ZEUS Collaboration

2012-10-15

The production of Z{sup 0} bosons in the reaction ep {yields} eZ{sup 0}p{sup (*)}, where p{sup (*)} stands for a proton or a low-mass nucleon resonance, has been studied in ep collisions at HERA using the ZEUS detector. The analysis is based on a data sample collected between 1996 and 2007, amounting to 496 pb{sup -1} of integrated luminosity. The Z{sup 0} was measured in the hadronic decay mode. The elasticity of the events was ensured by a cut on {eta}{sub max} < 3.0, where {eta}{sub max} is the maximum pseudorapidity of energy deposits in the calorimeter defined with respect to the proton beam direction. A signal was observed at the Z{sup 0} mass. The cross section of the reaction ep {yields} eZ{sup 0}p{sup (*)} was measured to be {sigma} (ep {yields} eZ{sup 0}p{sup (*)}) = 0.13 {+-} 0.06 (stat.) {+-} 0.01 (syst.) pb, in agreement with the Standard Model prediction of 0.16 pb. This is the first measurement of Z{sup 0} production in ep collisions.

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

Science.gov (United States)

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.

The impact of pre-exposure prophylaxis (PrEP) on HIV epidemics in Africa and India: A simulation study

NARCIS (Netherlands)

D.C.J. Vissers (Debby); H.A.C.M. Voeten (Hélène); N.J.D. Nagelkerke (Nico); J.D.F. Habbema (Dik); S.J. de Vlas (Sake)

2008-01-01

textabstractBackground: Pre-exposure prophylaxis (PrEP) is a promising new HIV prevention method, especially for women. An urgent demand for implementation of PrEP is expected at the moment efficacy has been demonstrated in clinical trials. We explored the long-term impact of PrEP on HIV

[Detection and clinical value of epithelial cellular adhesion molecule (EpCAM) mRNA positive circulating tumor cells in metastatic breast cancer].

Science.gov (United States)

Yan, Ying; Cheng, Jian-ping; Di, Li-jun; Song, Guo-hong; Ren, Jun

2012-04-18

To test for circulating tumor cells (CTCs) relying on epithelial cellular adhesion molecule (EpCAM) expression in metastatic breast cancer by quantitative real-time reverse transcription-PCR. In the study,47 metastatic breast cancer patients were evaluated by quantitative real-time PCR for detecting EpCAM mRNA. In addition, analyses were carried out for their correlation with patients' clinicopathologic features, response, and the time to progression (TTP). The sensitivity of EpCAM mRNA in the metastatic breast cancer patients was about 40%. However, the specificity of EpCAM mRNA for 20 healthy controls was 100%. TTP was calculated, and compared with that between EpCAM mRNA-positive and EpCAM mRNA-negative groups. For the retrospective study, the median TTP was 7.1 months and 11.1 months (P=0.013) for patients with EpCAM mRNA-positive and EpCAM mRNA-negative, respectively, after the first cycle chemotherapy. Moreover, a statistically significant correlation was demonstrated between EpCAM mRNA and TTP in patients who underwent the first or the second-line chemotherapy (P=0.018), but there was no significance in the patients pretreated with two or more previous chemotherapy lines (P=0.471). This study provides evidence of the presence of EpCAM mRNA in approximately 40% of patients with metastatic breast cancer. There is a strong correlation between EpCAM mRNA results after the first cycle therapy and TTP in metastatic breast cancer patients, and EpCAM mRNA positive after chemotherapy may predict shorter TTP.

E.P.S. HUAYCO: DECLARACIONES

OpenAIRE

Falla, Ricardo

2015-01-01

EL ARTISTA Y LA ÉPOCA: UN «HUAYCO» DE CREACIÓN COLECTIVA» RICARDO FALLA Hace aproximadamente 3 años [sic], apareció en Barranco el Taller de Arte «Huayco» EPS con el deliberado propósito de mostrar las esencias de nuestro ser nacional. Francisco Mariotti (36), María Luy (30), Charo Noriega (23), Mariela Zevallos (21), Herbert Rodríguez (21), Armando Williams (24) y juan Javier Salazar (25), integrantes de esta singular experiencia, decidieron apoyarse mutuamente para «crear una alternativa o ...

What Primary Care Providers Need to Know about Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: Narrative Review

Science.gov (United States)

Krakower, Douglas; Mayer, Kenneth H.

2013-01-01

As HIV prevalence climbs globally, including more than 50,000 new infections per year in the United States, we need effective HIV prevention strategies. The use of antiretrovirals for pre-exposure prophylaxis (known as “PrEP”) among high-risk HIV-uninfected persons is emerging as one such strategy. Randomized controlled trials have demonstrated that once daily oral PrEP decreased HIV incidence among at-risk MSM and African heterosexuals, including HIV serodiscordant couples. An additional randomized control trial of a pericoital topical application of antiretroviral microbicide gel reduced HIV incidence among at-risk heterosexual South African women. Two other studies in African women did not demonstrate the efficacy of oral or topical PrEP, raising concerns about adherence patterns and efficacy in this population. The FDA Antiretroviral Advisory Panel reviewed these studies and additional data in May 2012 and recommended the approval of oral tenofovir-emtricitabine for PrEP in high-risk populations. Patients may seek PrEP from their primary care providers and those on PrEP require monitoring. Thus, primary care providers should become familiar with PrEP. This review outlines the current state of knowledge about PrEP as it pertains to primary care including identification of individuals likely to benefit from PrEP, counseling to maximize adherence and minimize potential increases in risky behavior, and monitoring for potential drug toxicities, HIV acquisition, and antiretroviral drug resistance. Issues related to cost and insurance coverage are also discussed. Recent data suggest that PrEP, in conjunction with other prevention strategies, holds promise in helping to curtail the HIV epidemic. PMID:22821365

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

Science.gov (United States)

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.

The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling

DEFF Research Database (Denmark)

Salcini, A E; Hilliard, M A; Croce, A

2001-01-01

implicated Eps15 in endocytosis, its function in the endocytic machinery remains unclear. Here we show that the Caenorhabditis elegans gene, zk1248.3 (ehs-1), is the orthologue of Eps15 in nematodes, and that its product, EHS-1, localizes to synaptic-rich regions. ehs-1-impaired worms showed temperature...

Dual Processing Model for Medical Decision-Making: An Extension to Diagnostic Testing.

Science.gov (United States)

Tsalatsanis, Athanasios; Hozo, Iztok; Kumar, Ambuj; Djulbegovic, Benjamin

2015-01-01

Dual Processing Theories (DPT) assume that human cognition is governed by two distinct types of processes typically referred to as type 1 (intuitive) and type 2 (deliberative). Based on DPT we have derived a Dual Processing Model (DPM) to describe and explain therapeutic medical decision-making. The DPM model indicates that doctors decide to treat when treatment benefits outweigh its harms, which occurs when the probability of the disease is greater than the so called "threshold probability" at which treatment benefits are equal to treatment harms. Here we extend our work to include a wider class of decision problems that involve diagnostic testing. We illustrate applicability of the proposed model in a typical clinical scenario considering the management of a patient with prostate cancer. To that end, we calculate and compare two types of decision-thresholds: one that adheres to expected utility theory (EUT) and the second according to DPM. Our results showed that the decisions to administer a diagnostic test could be better explained using the DPM threshold. This is because such decisions depend on objective evidence of test/treatment benefits and harms as well as type 1 cognition of benefits and harms, which are not considered under EUT. Given that type 1 processes are unique to each decision-maker, this means that the DPM threshold will vary among different individuals. We also showed that when type 1 processes exclusively dominate decisions, ordering a diagnostic test does not affect a decision; the decision is based on the assessment of benefits and harms of treatment. These findings could explain variations in the treatment and diagnostic patterns documented in today's clinical practice.

Dual Processing Model for Medical Decision-Making: An Extension to Diagnostic Testing.

Directory of Open Access Journals (Sweden)

Athanasios Tsalatsanis

Full Text Available Dual Processing Theories (DPT assume that human cognition is governed by two distinct types of processes typically referred to as type 1 (intuitive and type 2 (deliberative. Based on DPT we have derived a Dual Processing Model (DPM to describe and explain therapeutic medical decision-making. The DPM model indicates that doctors decide to treat when treatment benefits outweigh its harms, which occurs when the probability of the disease is greater than the so called "threshold probability" at which treatment benefits are equal to treatment harms. Here we extend our work to include a wider class of decision problems that involve diagnostic testing. We illustrate applicability of the proposed model in a typical clinical scenario considering the management of a patient with prostate cancer. To that end, we calculate and compare two types of decision-thresholds: one that adheres to expected utility theory (EUT and the second according to DPM. Our results showed that the decisions to administer a diagnostic test could be better explained using the DPM threshold. This is because such decisions depend on objective evidence of test/treatment benefits and harms as well as type 1 cognition of benefits and harms, which are not considered under EUT. Given that type 1 processes are unique to each decision-maker, this means that the DPM threshold will vary among different individuals. We also showed that when type 1 processes exclusively dominate decisions, ordering a diagnostic test does not affect a decision; the decision is based on the assessment of benefits and harms of treatment. These findings could explain variations in the treatment and diagnostic patterns documented in today's clinical practice.

Poppers and PrEP: Use of Pre-exposure Prophylaxis Among Men Who Have Sex with Men Who Use Inhaled Nitrites.

Science.gov (United States)

Hambrick, H Rhodes; Park, Su Hyun; Schneider, John A; Mayer, Kenneth H; Carrico, Adam W; Sherman, Scott E; Duncan, Dustin T

2018-05-09

Men who have sex with men (MSM) commonly use inhaled nitrites, or poppers, though their use is a risk factor HIV seroconversion. Pre-exposure prophylaxis, or PrEP, is effective for HIV prevention, but is not widely used, and little is known regarding PrEP use and acceptability among MSM who use inhaled nitrites. We surveyed 580 MSM in Paris, France in 2016 about popper use, sexual behaviors including condomless anal intercourse (CAI), serosorting, and sexual positioning, PrEP use, PrEP candidacy, and interest in alternate PrEP delivery modalities. We included 444 HIV negative participants for the current study. 46.2% reported popper use in the prior 3 months. Using multivariate adjusted logistic regression, we found that popper users were more likely than non-users to consider themselves candidates for PrEP [adjusted relative risk ratio (aRRR) = 2.73; 95% CI 1.54-4.83], but they were not more likely to be current (aRRR = 1.54; 95% CI 0.71-3.33) or past (aRRR = 1.37; 95% CI 0.44-4.28) PrEP users. Mediation analyses indicated that increased CAI and serosorting partly explained the relationship between popper use and PrEP candidacy. There was considerable interest in alternate proposed PrEP delivery modalities, particularly long-acting injectable PrEP [adjusted risk ratio (aRR) = 1.43; 95% CI 1.15-1.79].

Hybrid modeling of microbial exopolysaccharide (EPS) production: The case of Enterobacter A47.

Science.gov (United States)

Marques, Rodolfo; von Stosch, Moritz; Portela, Rui M C; Torres, Cristiana A V; Antunes, Sílvia; Freitas, Filomena; Reis, Maria A M; Oliveira, Rui

2017-03-20

Enterobacter A47 is a bacterium that produces high amounts of a fucose-rich exopolysaccharide (EPS) from glycerol residue of the biodiesel industry. The fed-batch process is characterized by complex non-linear dynamics with highly viscous pseudo-plastic rheology due to the accumulation of EPS in the culture medium. In this paper, we study hybrid modeling as a methodology to increase the predictive power of models for EPS production optimization. We compare six hybrid structures that explore different levels of knowledge-based and machine-learning model components. Knowledge-based components consist of macroscopic material balances, Monod type kinetics, cardinal temperature and pH (CTP) dependency and power-law viscosity models. Unknown dependencies are set to be identified by a feedforward artificial neural network (ANN). A semiparametric identification schema is applied resorting to a data set of 13 independent fed-batch experiments. A parsimonious hybrid model was identified that describes the dynamics of the 13 experiments with the same parameterization. The final model is specific to Enterobacter A47 but can be easily extended to other microbial EPS processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Provider perspectives on PrEP for adolescent girls and young women in Tanzania: The role of provider biases and quality of care.

Directory of Open Access Journals (Sweden)

Nanlesta Pilgrim

Full Text Available Oral pre-exposure prophylaxis (PrEP has the potential to reduce HIV acquisition among adolescent girls and young women (AGYW in sub-Saharan Africa. However, health care providers' (HCPs perspectives and interactions with potential clients can substantially influence effective provision of quality health services. We examine if HCPs' knowledge, attitude, and skills, as well as their perceptions of facility readiness to provide PrEP are associated with their willingness to provide PrEP to AGYW at high risk of HIV in Tanzania.A self-administered questionnaire was given to 316 HCPs from 74 clinics in two districts and 24 HCPs participated in follow-up in-depth interviews (IDIs. We conducted bivariate and multivariable Poisson regression to assess factors associated with willingness to provide PrEP to AGYW. Thematic content analysis was used to analyze the IDIs, which expanded upon the quantitative results.Few HCPs (3.5% had prior PrEP knowledge, but once informed, 61.1% were willing to prescribe PrEP to AGYW. Higher negative attitudes toward adolescent sexuality and greater concerns about behavioral disinhibition due to PrEP use were associated with lower willingness to prescribe PrEP. Qualitatively, HCPs acknowledged that biases, rooted in cultural norms, often result in stigmatizing and discriminatory care toward AGYW, a potential barrier for PrEP provision. However, better training to provide HIV services was associated with greater willingness to prescribe PrEP. Conversely, HCPs feared the potential negative impact of PrEP on the provision of existing HIV services (e.g., overburdened staff, and suggested the integration of PrEP into non-HIV services and the use of paramedical professionals to facilitate PrEP provision.Preparing for PrEP introduction requires more than solely training HCPs on the clinical aspects of providing PrEP. It requires a two-pronged strategy: addressing HCPs' biases regarding sexual health services to AGYW; and preparing

Eps8 regulates hair bundle length and functional maturation of mammalian auditory hair cells.

Directory of Open Access Journals (Sweden)

Valeria Zampini

2011-04-01

Full Text Available Hair cells of the mammalian cochlea are specialized for the dynamic coding of sound stimuli. The transduction of sound waves into electrical signals depends upon mechanosensitive hair bundles that project from the cell's apical surface. Each stereocilium within a hair bundle is composed of uniformly polarized and tightly packed actin filaments. Several stereociliary proteins have been shown to be associated with hair bundle development and function and are known to cause deafness in mice and humans when mutated. The growth of the stereociliar actin core is dynamically regulated at the actin filament barbed ends in the stereociliary tip. We show that Eps8, a protein with actin binding, bundling, and barbed-end capping activities in other systems, is a novel component of the hair bundle. Eps8 is localized predominantly at the tip of the stereocilia and is essential for their normal elongation and function. Moreover, we have found that Eps8 knockout mice are profoundly deaf and that IHCs, but not OHCs, fail to mature into fully functional sensory receptors. We propose that Eps8 directly regulates stereocilia growth in hair cells and also plays a crucial role in the physiological maturation of mammalian cochlear IHCs. Together, our results indicate that Eps8 is critical in coordinating the development and functionality of mammalian auditory hair cells.

Eps8 regulates hair bundle length and functional maturation of mammalian auditory hair cells.

Science.gov (United States)

Zampini, Valeria; Rüttiger, Lukas; Johnson, Stuart L; Franz, Christoph; Furness, David N; Waldhaus, Jörg; Xiong, Hao; Hackney, Carole M; Holley, Matthew C; Offenhauser, Nina; Di Fiore, Pier Paolo; Knipper, Marlies; Masetto, Sergio; Marcotti, Walter

2011-04-01

Hair cells of the mammalian cochlea are specialized for the dynamic coding of sound stimuli. The transduction of sound waves into electrical signals depends upon mechanosensitive hair bundles that project from the cell's apical surface. Each stereocilium within a hair bundle is composed of uniformly polarized and tightly packed actin filaments. Several stereociliary proteins have been shown to be associated with hair bundle development and function and are known to cause deafness in mice and humans when mutated. The growth of the stereociliar actin core is dynamically regulated at the actin filament barbed ends in the stereociliary tip. We show that Eps8, a protein with actin binding, bundling, and barbed-end capping activities in other systems, is a novel component of the hair bundle. Eps8 is localized predominantly at the tip of the stereocilia and is essential for their normal elongation and function. Moreover, we have found that Eps8 knockout mice are profoundly deaf and that IHCs, but not OHCs, fail to mature into fully functional sensory receptors. We propose that Eps8 directly regulates stereocilia growth in hair cells and also plays a crucial role in the physiological maturation of mammalian cochlear IHCs. Together, our results indicate that Eps8 is critical in coordinating the development and functionality of mammalian auditory hair cells.

Establishment of an isolation method of Nostoc commune cells free from extracellular polysaccharides (EPS using Percoll centrifugation

Directory of Open Access Journals (Sweden)

Makiko Kosugi

2012-11-01

Full Text Available The terrestrial cyanobacterium Nostoc commune Vaucher ex Bornet et Flahault occurs worldwide, including in Japan and Antarctica. N. commune has a large amount of extracellular polysaccharides (EPS that hold moisture and protect the cells and at the same time accumulate light-blocking substances which is believed to play an important part in adaptation to a severe environment. To evaluate the photoadaptation processes in N. commune and clarify the role(s of EPS under ambient environmental condition at Antarctica, separation of cells from EPS is necessary. High yield is a prerequisite for the use of only small amount of natural N. commune from Antarctica. For this purpose, we developed a separation method by improving the Percoll density gradient centrifugation method using an EPS-coated field-grown Nostoc population. We established the most suitable condition to separate naked cells from EPS at high yield retaining high photosynthetic activity. The method is composed of centrifugation of cell homogenated N. commune in 10% (v/v Percoll to separate cells efficiently from EPS followed by fractionating centrifugation to remove impurities using the gradient of Percoll (80% and 50%, v/v.

Complex and Conflicting Social Norms: Implications for Implementation of Future HIV Pre-Exposure Prophylaxis (PrEP Interventions in Vancouver, Canada.

Directory of Open Access Journals (Sweden)

Rod Knight

Full Text Available HIV Pre-Exposure Prophylaxis (PrEP has been found to be efficacious in preventing HIV acquisition among seronegative individuals in a variety of risk groups, including men who have sex with men and people who inject drugs. To date, however, it remains unclear how socio-cultural norms (e.g., attitudes towards HIV; social understandings regarding HIV risk practices may influence the scalability of future PrEP interventions. The objective of this study is to assess how socio-cultural norms may influence the implementation and scalability of future HIV PrEP interventions in Vancouver, Canada.We conducted 50 interviews with young men (ages 18-24 with a variety of HIV risk behavioural profiles (e.g., young men who inject drugs; MSM. Interviews focused on participants' experiences and perceptions with various HIV interventions and policies, including PrEP.While awareness of PrEP was generally low, perceptions about the potential personal and public health gains associated with PrEP were interconnected with expressions of complex and sometimes conflicting social norms. Some accounts characterized PrEP as a convenient form of reliable protection against HIV, likening it to the female birth control pill. Other accounts cast PrEP as a means to facilitate 'socially unacceptable' behaviour (e.g., promiscuity. Stigmatizing rhetoric was used to position PrEP as a tool that could promote some groups' proclivities to take 'risks'.Stigma regarding 'risky' behaviour and PrEP should not be underestimated as a serious implementation challenge. Pre-implementation strategies that concomitantly aim to improve knowledge about PrEP, while addressing associated social prejudices, may be key to effective implementation and scale-up.

VCS-SSA Mainz Experiment. Measurement of the beam spin asymmetry in (e polarized p {yields} ep{gamma}) and (e polarized p {yields} ep{pi}{sup 0}). Final analysis - MEMO I

Energy Technology Data Exchange (ETDEWEB)

Fonvieille, H.; Bensafa, I. [LPC-Clermont-Fd, Universite Blaise Pascal, F-63170 Aubiere Cedex (France)

2006-02-15

This note gives details on the final analysis of the VCS-SSA experiment in terms of Beam Spin Asymmetry. It summarizes the changes between the first and second pass analysis. Then the measured asymmetry is presented for both channels e polarized p {yields} ep{gamma} and e polarized p {yields} ep{pi}{sup 0} including systematic studies. The final experimental result is briefly compared to some model predictions. (authors)

Strong relationship between oral dose and tenofovir hair levels in a randomized trial: hair as a potential adherence measure for pre-exposure prophylaxis (PrEP.

Directory of Open Access Journals (Sweden)

Albert Y Liu

Full Text Available Pre-exposure prophylaxis (PrEP trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults.A phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs.Over 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60-93% increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair.This study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for adherence monitoring may also

[Randomized clinical trial of IEP and EP regimens in the treatment of patients with small cell lung cancer].

Science.gov (United States)

Zhou, Hui; Wang, Anlan; Huang, Zhihua; Zhou, Wenwei

2004-06-20

To observe and compare the efficacy and safety of IEP and EP regimens for small cell lung cancer (SCLC). Sixty-four patients with SCLC pathologically proved were randomly divided into IEP group ( n =32) and EP group ( n =32). All the 64 patients were evaluable for response and toxicity. In IEP group, the total responsive rate, responsive rates of limited-stage patients and extensive-stage patients were 84.4%(27/32), 100.0%(15/15) and 70.6%(12/17) respectively; while in EP group, those were 75.0%(24/32), 85.7%(12/14) and 66.7% (12/18) respectively. The median duration of remission was 6 months and 1-year survival rate was 62.5% in IEP group, and 5 months and 56.2% in EP group. There was no significant difference in response rate, median duration of remission and 1-year survival between the two groups ( P > 0.05). The main toxicity was myelosuppression. Incidences of leukopenia at grade III-IV, nausea, vomiting and alopecia were significantly higher in the IEP arm than those in the EP arm ( P IEP and EP. IEP regimen shows a similar response rate compared with EP regimen. They might be considered as relevant regimens in initial patients with small cell lung cancer.

Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions.

Science.gov (United States)

Nakamura, Y; Nakamura, K; Morrison, S F

2009-06-30

The central mechanism of fever induction is triggered by an action of prostaglandin E(2) (PGE(2)) on neurons in the preoptic area (POA) through the EP3 subtype of prostaglandin E receptor. EP3 receptor (EP3R)-expressing POA neurons project directly to the dorsomedial hypothalamus (DMH) and to the rostral raphe pallidus nucleus (rRPa), key sites for the control of thermoregulatory effectors. Based on physiological findings, we hypothesize that the febrile responses in brown adipose tissue (BAT) and those in cutaneous vasoconstrictors are controlled independently by separate neuronal pathways: PGE(2) pyrogenic signaling is transmitted from EP3R-expressing POA neurons via a projection to the DMH to activate BAT thermogenesis and via another projection to the rRPa to increase cutaneous vasoconstriction. In this case, DMH-projecting and rRPa-projecting neurons would constitute segregated populations within the EP3R-expressing neuronal group in the POA. Here, we sought direct anatomical evidence to test this hypothesis with a double-tracing experiment in which two types of the retrograde tracer, cholera toxin b-subunit (CTb), conjugated with different fluorophores were injected into the DMH and the rRPa of rats and the resulting retrogradely labeled populations of EP3R-immunoreactive neurons in the POA were identified with confocal microscopy. We found substantial numbers of EP3R-immunoreactive neurons in both the DMH-projecting and the rRPa-projecting populations. However, very few EP3R-immunoreactive POA neurons were labeled with both the CTb from the DMH and that from the rRPa, although a substantial number of neurons that were not immunoreactive for EP3R were double-labeled with both CTbs. The paucity of the EP3R-expressing neurons that send collaterals to both the DMH and the rRPa suggests that pyrogenic signals are sent independently to these caudal brain regions from the POA and that such pyrogenic outputs from the POA reflect different control mechanisms for BAT

Rainfall intensity-duration thresholds for postfire debris-flow emergency-response planning

Science.gov (United States)

Cannon, S.H.; Boldt, E.M.; Laber, J.L.; Kean, J.W.; Staley, D.M.

2011-01-01

Following wildfires, emergency-response and public-safety agencies can be faced with evacuation and resource-deployment decisions well in advance of coming winter storms and during storms themselves. Information critical to these decisions is provided for recently burned areas in the San Gabriel Mountains of southern California. A compilation of information on the hydrologic response to winter storms from recently burned areas in southern California steeplands is used to develop a system for classifying magnitudes of hydrologic response. The four-class system describes combinations of reported volumes of individual debris flows, consequences of debris flows and floods in an urban setting, and spatial extents of the hydrologic response. The range of rainfall conditions associated with different magnitude classes is defined by integrating local rainfall data with the response magnitude information. Magnitude I events can be expected when within-storm rainfall accumulations (A) of given durations (D) fall above the threshold A = 0.4D0.5 and below A = 0.5D0.6 for durations greater than 1 h. Magnitude II events will be generated in response to rainfall accumulations and durations between A = 0.4D0.5 and A = 0.9D0.5 for durations less than 1 h, and between A = 0.5D0.6 and A = 0.9D0.5 or durations greater than 1 h. Magnitude III events can be expected in response to rainfall conditions above the threshold A = 0.9D0.5. Rainfall threshold-magnitude relations are linked with potential emergency-response actions as an emergency-response decision chart, which leads a user through steps to determine potential event magnitudes and identify possible evacuation and resource-deployment levels. Use of this information in planning and response decision-making process could result in increased safety for both the public and emergency responders. ?? 2011 US Government.

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

Science.gov (United States)

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

Evolving the JET virtual reality system for delivering the JET EP2 shutdown remote handling tasks

Energy Technology Data Exchange (ETDEWEB)

Williams, Adrian, E-mail: adrian.williams@oxfordtechnologies.co.uk [Oxford Technologies Ltd., 7 Nuffield Way, Abingdon, Oxon, OX14 1RJ (United Kingdom); JET-EFDA, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); Sanders, Stephen [Oxford Technologies Ltd., 7 Nuffield Way, Abingdon, Oxon, OX14 1RJ (United Kingdom); JET-EFDA, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); Weder, Gerard [Tree-C Technology BV, Buys Ballotstraat 8, 6716 BL Ede (Netherlands); JET-EFDA, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); Bastow, Roger; Allan, Peter; Hazel, Stuart [CCFE, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); JET-EFDA, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom)

2011-10-15

The quality, functionality and performance of the virtual reality (VR) system used at JET for preparation and implementation of remote handling (RH) operations has been progressively enhanced since its first use in the original JET remote handling shutdown in 1998. As preparation began for the JET EP2 (Enhanced Performance 2) shutdown it was recognised that the VR system being used was unable to cope with the increased functionality and the large number of 3D models needed to fully represent the JET in-vessel components and tooling planned for EP2. A bespoke VR software application was developed in collaboration with the OEM, which allowed enhancements to be made to the VR system to meet the requirements of JET remote handling in preparation for EP2. Performance improvements required to meet the challenges of EP2 could not be obtained from the development of the new VR software alone. New methodologies were also required to prepare source, CATIA models for use in the VR using a collection of 3D software packages. In collaboration with the JET drawing office, techniques were developed within CATIA using polygon reduction tools to reduce model size, while retaining surface detail at required user limits. This paper will discuss how these developments have played an essential part in facilitating EP2 remote handling task development and examine their impact during the EP2 shutdown.

Evolving the JET virtual reality system for delivering the JET EP2 shutdown remote handling tasks

International Nuclear Information System (INIS)

Williams, Adrian; Sanders, Stephen; Weder, Gerard; Bastow, Roger; Allan, Peter; Hazel, Stuart

2011-01-01

The quality, functionality and performance of the virtual reality (VR) system used at JET for preparation and implementation of remote handling (RH) operations has been progressively enhanced since its first use in the original JET remote handling shutdown in 1998. As preparation began for the JET EP2 (Enhanced Performance 2) shutdown it was recognised that the VR system being used was unable to cope with the increased functionality and the large number of 3D models needed to fully represent the JET in-vessel components and tooling planned for EP2. A bespoke VR software application was developed in collaboration with the OEM, which allowed enhancements to be made to the VR system to meet the requirements of JET remote handling in preparation for EP2. Performance improvements required to meet the challenges of EP2 could not be obtained from the development of the new VR software alone. New methodologies were also required to prepare source, CATIA models for use in the VR using a collection of 3D software packages. In collaboration with the JET drawing office, techniques were developed within CATIA using polygon reduction tools to reduce model size, while retaining surface detail at required user limits. This paper will discuss how these developments have played an essential part in facilitating EP2 remote handling task development and examine their impact during the EP2 shutdown.

Mechanisms Underlying Decision-Making as Revealed by Deep-Brain Stimulation in Patients with Parkinson's Disease.

Science.gov (United States)

Herz, Damian M; Little, Simon; Pedrosa, David J; Tinkhauser, Gerd; Cheeran, Binith; Foltynie, Tom; Bogacz, Rafal; Brown, Peter

2018-04-23

To optimally balance opposing demands of speed and accuracy during decision-making, we must flexibly adapt how much evidence we require before making a choice. Such adjustments in decision thresholds have been linked to the subthalamic nucleus (STN), and therapeutic STN deep-brain stimulation (DBS) has been shown to interfere with this function. Here, we performed continuous as well as closed-loop DBS of the STN while Parkinson's disease patients performed a perceptual decision-making task. Closed-loop STN DBS allowed temporally patterned STN stimulation and simultaneous recordings of STN activity. This revealed that DBS only affected patients' ability to adjust decision thresholds if applied in a specific temporally confined time window during deliberation. Only stimulation in that window diminished the normal slowing of response times that occurred on difficult trials when DBS was turned off. Furthermore, DBS eliminated a relative, time-specific increase in STN beta oscillations and compromised its functional relationship with trial-by-trial adjustments in decision thresholds. Together, these results provide causal evidence that the STN is involved in adjusting decision thresholds in distinct, time-limited processing windows during deliberation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Handwriting Movement Kinematics for Quantifying EPS in Patients Treated with Atypical Antipsychotics

Science.gov (United States)

Caligiuri, Michael P.; Teulings, Hans-Leo; Dean, Charles E.; Niculescu, Alexander B.; Lohr, James B.

2009-01-01

Ongoing monitoring of neuroleptic-induced extrapyramidal side effects (EPS) is important to maximize treatment outcome, improve medication adherence and reduce re-hospitalization. Traditional approaches for assessing EPS such as parkinsonism, tardive akathisia, or dyskinesia rely upon clinical ratings. However, these observer-based EPS severity ratings can be unreliable and are subject to examiner bias. In contrast, quantitative instrumental methods are less subject to bias. Most instrumental methods have only limited clinical utility because of their complexity and costs. This paper describes an easy-to-use instrumental approach based on handwriting movements for quantifying EPS. Here, we present findings from psychiatric patients treated with atypical (second generation) antipsychotics. The handwriting task consisted of a sentence written several times within a 2 cm vertical boundary at a comfortable speed using an inkless pen and digitizing tablet. Kinematic variables including movement duration, peak vertical velocity and the number of acceleration peaks, and average normalized jerk (a measure of smoothness) for each up or down stroke and their submovements were analyzed. Results from 59 psychosis patients and 46 healthy comparison subjects revealed significant slowing and dysfluency in patients compared to controls. We observed differences across medications and daily dose. These findings support the ecological validity of handwriting movement analysis as an objective behavioral biomarker for quantifying the effects of antipsychotic medication and dose on the motor system. PMID:20381875

Eps15R is a tyrosine kinase substrate with characteristics of a docking protein possibly involved in coated pits-mediated internalization

DEFF Research Database (Denmark)

Coda, L; Salcini, A E; Confalonieri, S

1998-01-01

in NIH-3T3 cells overexpressing the receptor, even at low levels of receptor occupancy, thus behaving as physiological substrates. A role for eps15R in clathrin-mediated endocytosis is suggested by its localization in plasma membrane-coated pits and in vivo association to the coated pits' adapter protein...... AP-2. Finally, we demonstrate that a sizable fraction of eps15R exists in the cell as a complex with eps15 and that its EH domains exhibit binding specificities that are partially distinct from those of eps15. We propose that eps15 and eps15R are multifunctional binding proteins that serve...

Prostanoid receptor EP2 as a therapeutic target.

Science.gov (United States)

Ganesh, Thota

2014-06-12

Cycoloxygenase-2 (COX-2) induction is prevalent in a variety of (brain and peripheral) injury models where COX-2 levels correlate with disease progression. Thus, COX-2 has been widely explored for anti-inflammatory therapy with COX-2 inhibitors, which proved to be effective in reducing the pain and inflammation in patients with arthritis and menstrual cramps, but they have not provided any benefit to patients with chronic inflammatory neurodegenerative disease. Recently, two COX-2 drugs, rofecoxib and valdecoxib, were withdrawn from the United States market due to cardiovascular side effects. Thus, future anti-inflammatory therapy could be targeted through a specific prostanoid receptor downstream of COX-2. The PGE2 receptor EP2 is emerging as a pro-inflammatory target in a variety of CNS and peripheral diseases. Here we highlight the latest developments on the role of EP2 in diseases, mechanism of activation, and small molecule discovery targeted either to enhance or to block the function of this receptor.

Inhibition of Nitzschia ovalis biofilm settlement by a bacterial bioactive compound through alteration of EPS and epiphytic bacteria

Directory of Open Access Journals (Sweden)

Claudia D. Infante

2018-05-01

Full Text Available Background: Marine ecosystems contain benthic microalgae and bacterial species that are capable of secreting extracellular polymeric substances (EPS, suggesting that settlement of these microorganisms can occur on submerged surfaces, a key part of the first stage of biofouling. Currently, anti-fouling treatments that help control this phenomenon involve the use of biocides or antifouling paints that contain heavy metals, which over a long period of exposure can spread to the environment. The bacterium Alteromonas sp. Ni1-LEM has an inhibitory effect on the adhesion of Nitzschia ovalis, an abundant diatom found on submerged surfaces. Results: We evaluated the effect of the bioactive compound secreted by this bacterium on the EPS of biofilms and associated epiphytic bacteria. Three methods of EPS extraction were evaluated to determine the most appropriate and efficient methodology based on the presence of soluble EPS and the total protein and carbohydrate concentrations. Microalgae were cultured with the bacterial compound to evaluate its effect on EPS secretion and variations in its protein and carbohydrate concentrations. An effect of the bacterial supernatant on EPS was observed by assessing biofilm formation and changes in the concentration of proteins and carbohydrates present in the biofilm. Conclusions: These results indicate that a possible mechanism for regulating biofouling could be through alteration of biofilm EPS and alteration of the epiphytic bacterial community associated with the microalga.How to cite: Infante, C.D., Castillo, F., Pérez, V., et al. Inhibition of Nitzschia ovalis biofilm settlement by a bacterial bioactive compound through alteration of EPS and epiphytic bacteria. Electron J Biotechnol 2018;33 https://doi.org/10.1016/j.ejbt.2018.03.002. Keywords: Anti-fouling, Benthic microalgae, Biofilm, Biofouling, Epiphytic bacterial community, EPS, Marine ecosystems, Metagenomic, Nitzschia ovalis, Settlement inhibition

Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP.

Directory of Open Access Journals (Sweden)

Caleb C Roth

Full Text Available Nanosecond electrical pulse (nsEP exposure activates signaling pathways, produces oxidative stress, stimulates hormone secretion, causes cell swelling and induces apoptotic and necrotic death. The underlying biophysical connection(s between these diverse cellular reactions and nsEP has yet to be elucidated. Using global genetic analysis, we evaluated how two commonly studied cell types, U937 and Jurkat, respond to nsEP exposure. We hypothesized that by studying the genetic response of the cells following exposure, we would gain direct insight into the stresses experienced by the cell and in turn better understand the biophysical interaction taking place during the exposure. Using Ingenuity Systems software, we found genes associated with cell growth, movement and development to be significantly up-regulated in both cell types 4 h post exposure to nsEP. In agreement with our hypothesis, we also found that both cell lines exhibit significant biological changes consistent with mechanical stress induction. These results advance nsEP research by providing strong evidence that the interaction of nsEPs with cells involves mechanical stress.

Cost-effectiveness of Pre-Exposure Prophylaxis (PrEP) in preventing HIV-1 infections in rural Zambia: a modeling study

NARCIS (Netherlands)

Nichols, B.E.; Boucher, C.A.B.; van Dijk, J.H.; Thuma, P.E.; Nouwen, J.L.; Baltussen, R.; van de Wijgert, J.; Sloot, P.M.A.; van de Vijver, D.A.M.C.

2013-01-01

Background: Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine effectively prevents new HIV infections. The optimal scenario for implementing PrEP where most infections are averted at the lowest cost is unknown. We determined the impact of different PrEP strategies on averting new

Categorization = Decision Making + Generalization

Science.gov (United States)

Seger, Carol A; Peterson, Erik J.

2013-01-01

We rarely, if ever, repeatedly encounter exactly the same situation. This makes generalization crucial for real world decision making. We argue that categorization, the study of generalizable representations, is a type of decision making, and that categorization learning research would benefit from approaches developed to study the neuroscience of decision making. Similarly, methods developed to examine generalization and learning within the field of categorization may enhance decision making research. We first discuss perceptual information processing and integration, with an emphasis on accumulator models. We then examine learning the value of different decision making choices via experience, emphasizing reinforcement learning modeling approaches. Next we discuss how value is combined with other factors in decision making, emphasizing the effects of uncertainty. Finally, we describe how a final decision is selected via thresholding processes implemented by the basal ganglia and related regions. We also consider how memory related functions in the hippocampus may be integrated with decision making mechanisms and contribute to categorization. PMID:23548891

Toxicological effects, mechanisms, and implied toxicity thresholds in the roots of Vicia faba L. seedlings grown in copper-contaminated soil.

Science.gov (United States)

Xu, Xianghua; Huang, Zhicheng; Wang, Chengrun; Zhong, Li; Tian, Yuan; Li, Dongdong; Zhang, Gaojian; Shi, Jian

2015-09-01

Copper (Cu) contamination has become a global concern because of industrial, agricultural, and other anthropogenic activities. In the present experiments, the toxicological effects, mechanisms, and potential toxicity thresholds were investigated in the roots of Vicia faba L. seedlings that were cultivated in Cu-amended soils (0, 6.25, 12.5, 25, 50, 100, 200, 400, and 600 mg kg(-1)) for 20 days, based on an analysis of the soil physicochemical properties, native Cu, available Cu, and root-enriched Cu contents. The superoxide dismutase (SOD), ascorbate peroxidase (APX), and guaiacol peroxidase (POD) isozymes and activities, as well as glutathione (GSH) and heat shock protein 70 (HSP70), changed like biphasic dose-response curves, cooperating to control the redox homeostasis. The APX and POD enzymes exhibited enhanced activities and became H2O2 scavengers primarily when the catalase (CAT) activities tended to decrease. Endoprotease (EP) isozymes and activities might be enhanced to degrade carbonylated proteins and alleviate metabolic disturbance in the roots. Additionally, HSP70 may not be suitable as a biomarker for relatively higher soil Cu concentrations and relatively longer exposure times for the roots. As a result, the isozymes and activities of SOD, CAT, and EP, as well as GSH, can be adopted as the most sensitive biomarkers. The toxicity threshold is estimated as 0.76-1.21 mg kg(-1) of available Cu in the soils or 25.04-36.65 μg Cu g(-1) dry weights (DW) in the roots.

Immunohistochemical expression of epithelial cell adhesion molecule (EpCAM) in mucoepidermoid carcinoma compared to normal salivary gland tissues.

Science.gov (United States)

Kamal, Noura M; Salem, Hend M; Dahmoush, Heba M

2017-07-01

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which displays biological, histological and clinical diversity thus representing a challenge for its diagnosis and management. Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein identified as a tumor specific antigen due to its frequent overexpression in the majority of epithelial carcinomas and its correlation with prognosis. It is considered to be a promising biomarker used as a therapeutic target already in ongoing clinical trials. The purpose of this study was to investigate the pattern, cellular characterization and level of EpCAM expression in MEC and demonstrate its correlation with histologic grading which may benefit future clinical trials using EpCAM targeted therapy. 48 specimens (12 normal salivary gland tissue and 36 MEC) were collected and EpCAM membranous expression was evaluated by immunohistochemistry. Total immunoscore (TIS) was evaluated, the term 'EpCAM overexpression' was given for tissues showing a total immunoscore >4. A highly significant difference was observed between TIS percent values in control and different grades of MEC (p<0.001). High grade MEC (HG-MEC) was the highest EpCAM expressor. In addition, EpCAM expression pattern differed among the different grades. EpCAM expression was detected in MEC, and its overexpression correlated with increasing the histological grade. The diffuse membranous expression in HG-MEC could be of diagnostic value in relation to the patchy expression observed in both low grade and intermediate grade MEC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Are Thai MSM willing to take PrEP for HIV prevention? An analysis of attitudes, preferences and acceptance.

Directory of Open Access Journals (Sweden)

Ana Wheelock

Full Text Available We aimed to understand the attitudes, preferences and acceptance of oral and parenteral PrEP among men who have sex with men (MSM in Thailand.Pre-exposure prophylaxis (PrEP, the use of antiretrovirals to prevent HIV acquisition, has shown promising results in recent trials. To assess the potential impact of this new HIV prevention method, in addition to efficacy data, we need to understand which psychosocial factors are likely to determine its uptake among members of potential user groups.Surveys of willingness to use PrEP products were administered to MSM. Spearman's rank tests were used to uncover associations between questionnaire items. Mann-Whitney tests were performed to ascertain differences between groups. Conjoint analysis was used to examine the attitudes and preferences of MSM towards PrEP attributes. Most participants were willing to consider taking PrEP (39.2% "yes, definitely" and 49.2% "yes, probably" and perceived PrEP as giving them new possibilities in their lives (38.5% "a lot of hope" and 55.8% "some hope", even after being instructed of potential side effects and costs. HIV testing was considered the most important attribute and a daily pill and longer lasting injection in the arm were the preferred routes of administration.Despite its multiple challenges, MSM in Thailand would be willing to take PrEP, even if they had to experience inconvenience and expense. If PrEP were to be implemented in Thailand, our findings show that its uptake could be considerable.

Designing strip footing foundations using expanded polystyrene (EPS) as fill material

DEFF Research Database (Denmark)

Psarropoulos, Prodromos; Zania, Varvara; Spyrakos, Konstantinos

2010-01-01

One of the modern uses of expanded polystyrene (EPS) is in strip footings as fill material. The current study investigates the effect of the geofoam filling in the static and seismic design of the base slab founded on strip footings. For this purpose the finite element method is employed, and three......-dimensional as well as two-dimensional parametric analyses are conducted taking into account static and seismic loading conditions. The interaction of the soil–geofoam–foundation system is taken into consideration. The use of EPS as fill material in foundation systems is proven to be not only technically but also...

OMEGA EP: High-Energy Petawatt Capability for the OMEGA Laser Facility

International Nuclear Information System (INIS)

Kelly, J.H.; Waxer, L.J.; Bagnoud, V.; Begishev, I.A.; Bromage, J.; Kruschwitz, B.E.; Kessler, T.J.; Loucks, S.J.; Maywar, D.N.; McCrory, R.L.; Meyerhofer, D.D.; Morse, S.F.B.; Oliver, J.B.; Rigatti, A.L.; Schmid, A.W.; Stoeckl, C.; Dalton, S.; Folnsbee, L.; Guardalben, M.J.; Jungquist, R.; Puth, J.; Shoup III, M.J.; Weiner, D.; Zuegel, J.D.

2006-01-01

OMEGA EP (Extended Performance) is a petawatt-class addition to the existing 30-kJ, 60-beam OMEGA Laser Facility at the University of Rochester. When completed, it will consist of four beamlines, each capable of producing up to 6.5 kJ at 351 nm in a 1 to 10 ns pulse. Two of the beamlines will produce up to 2.6 kJ in a pulse-width range of 1 to 100 ps at 1053 nm using chirped-pulse amplification (CPA). This paper reviews both the OMEGA EP performance objectives and the enabling technologies required to meet these goals

Solving the E-waste problem (StEP) green paper. E-waste country study Ethiopia

Energy Technology Data Exchange (ETDEWEB)

Manhart, Andreas [Oeko-Institut, Inst. fuer Angewandte Oekologie e.V., Freiburg im Breisgau (Germany); Amera, Tadesse; Belay, Mehari [PAN (Ethiopia)

2013-04-10

The generation and management of waste electrical and electronic equipment (e-waste) is an increasing concern in many African countries. Attempts to bridge the digital divide as well as rapid economic development continue to boost the market penetration of many types of electricity powered devices. This also leads to rapidly increasing e-waste volumes, which are mostly not yet managed in an environmentally sound manner. In order to build a strong foundation for the development of Ethiopia's e-waste management strategy, it was deemed necessary to generate reliable data on e-waste volumes and current management practices and options, as well as to investigate possibilities for improved e-waste management and other relevant aspects. This study, financed by the Solving the E-waste Problem (StEP) Initiative under a grant of the United States Environmental Protection Agency (US-EPA), was jointly carried out by the Oeko-Institut e.V. and PAN-Ethiopia. It aims to fill key knowledge gaps and provide a more solid base for further decision making for both, national decision-makers and co-operation projects in this field. The information contained in this report is derived from existing literature sources and statistics, interviews conducted in Ethiopia, and field assessments in Addis Ababa in August 2012.

Multi-Lepton Production at High Transverse Momenta in ep Collisions at HERA

CERN Document Server

Aaron, F.D.; Andreev, V.; Antunovic, B.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Bacchetta, A.; Backovic, S.; Baghdasaryan, A.; Baranov, P.; Barrelet, E.; Bartel, W.; Beckingham, M.; Begzsuren, K.; Behnke, O.; Belousov, A.; Berger, N.; Bizot, J.C.; Boenig, M.-O.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Bruncko, D.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A.J.; Cantun Avila, K.B.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Cholewa, A.; Contreras, J.G.; Coughlan, J.A.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Daum, K.; Deak, M.; de Boer, Y.; Delcourt, B.; Del Degan, M.; Delvax, J.; De Roeck, A.; De Wolf, E.A.; Diaconu, C.; Dodonov, V.; Dossanov, A.; Dubak, A.; Eckerlin, G.; Efremenko, V.; Egli, S.; Eliseev, A.; Elsen, E.; Essenov, S.; Falkiewicz, A.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, Samvel; Glazov, A.; Glushkov, I.; Goerlich, L.; Goettlich, M.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Greenshaw, T.; Grell, B.R.; Grindhammer, G.; Habib, S.; Haidt, D.; Hansson, M.; Helebrant, C.; Henderson, R.C.W.; Hennekemper, E.; Henschel, H.; Herrera, G.; Hildebrandt, M.; Hiller, K.H.; Hoffmann, D.; Horisberger, R.; Hovhannisyan, A.; Hreus, T.; Jacquet, M.; Janssen, M.E.; Janssen, X.; Jemanov, V.; Jonsson, L.; Johnson, D.P.; Jung, Andreas Werner; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I.R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Klimkovich, T.; Kluge, T.; Knutsson, A.; Kogler, R.; Korbel, V.; Kostka, P.; Kraemer, M.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Kruger, K.; Kutak, K.; Landon, M.P.J.; Lange, W.; Lastovicka-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Lendermann, V.; Levonian, S.; Li, G.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lucaci-Timoce, A.-I.; Lytkin, L.; Makankine, A.; Malinovski, E.; Marage, P.; Marti, Ll.; Martyn, H.-U.; Maxfield, S.J.; Mehta, A.; Meier, K.; Meyer, A.B.; Meyer, H.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Moreau, F.; Morozov, A.; Morris, J.V.; Mozer, Matthias Ulrich; Mudrinic, M.; Muller, K.; Murin, P.; Nankov, K.; Naroska, B.; Naumann, Th.; Newman, Paul R.; Niebuhr, C.; Nikiforov, A.; Nowak, G.; Nowak, K.; Nozicka, M.; Olivier, B.; Olsson, J.E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Pandurovic, M.; Papadopoulou, Th.; Pascaud, C.; Patel, G.D.; Pejchal, O.; Peng, H.; Perez, E.; Petrukhin, A.; Picuric, I.; Piec, S.; Pitzl, D.; Placakyte, R.; Polifka, R.; Povh, B.; Preda, T.; Radescu, V.; Rahmat, A.J.; Raicevic, N.; Raspiareza, A.; Ravdandorj, T.; Reimer, P.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rotaru, M.; Ruiz Tabasco, J.E.; Rurikova, Z.; Rusakov, S.; Salek, D.; Salvaire, F.; Sankey, D.P.C.; Sauter, M.; Sauvan, E.; Schmidt, S.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schoning, A.; Schultz-Coulon, H.-C.; Sefkow, F.; Shaw-West, R.N.; Sheviakov, I.; Shtarkov, L.N.; Shushkevich, S.; Sloan, T.; Smiljanic, Ivan; Smirnov, P.; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, Arnd E.; Staykova, Z.; Steder, M.; Stella, B.; Straumann, U.; Sunar, D.; Sykora, T.; Tchoulakov, V.; Thompson, G.; Thompson, P.D.; Toll, T.; Tomasz, F.; Tran, T.H.; Traynor, D.; Trinh, T.N.; Truol, P.; Tsakov, I.; Tseepeldorj, B.; Tsurin, I.; Turnau, J.; Tzamariudaki, E.; Urban, K.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Vargas Trevino, A.; Vazdik, Y.; Vinokurova, S.; Volchinski, V.; Wegener, D.; Wessels, M.; Wissing, Ch.; Wunsch, E.; Yeganov, V.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhelezov, A.; Zhokin, A.; Zhu, Y.C.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.

2008-01-01

Processes leading to a final state with at least two high transverse momentum leptons (electrons or muons) are studied using the full ep data sample collected by the H1 experiment at HERA. The data correspond to an integrated luminosity of 463 pb-1. Di-lepton and tri-lepton event classes are investigated. Cross sections of the production of e+e- and mu+mu- pairs are derived in a restricted phase space dominated by photon-photon collisions. In general, good agreement is found with Standard Model predictions. Events are observed with a total scalar sum of lepton transverse momenta above 100 GeV where the Standard Model expectation is low. In this region, combining di-lepton and tri-lepton classes, five events are observed in e+p collisions, compared to a Standard Model expectation of 0.96+-0.12, while no such event is observed in e-p data for 0.64+-0.09 expected.

Multi-lepton production at high transverse momenta in ep collisions at HERA

Science.gov (United States)

H1 Collaboration; Aaron, F. D.; Alexa, C.; Andreev, V.; Antunovic, B.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Bacchetta, A.; Backovic, S.; Baghdasaryan, A.; Baranov, P.; Barrelet, E.; Bartel, W.; Beckingham, M.; Begzsuren, K.; Behnke, O.; Belousov, A.; Berger, N.; Bizot, J. C.; Boenig, M.-O.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Bruncko, D.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A. J.; Cantun Avila, K. B.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Cholewa, A.; Contreras, J. G.; Coughlan, J. A.; Cozzika, G.; Cvach, J.; Dainton, J. B.; Daum, K.; Deák, M.; de Boer, Y.; Delcourt, B.; Del Degan, M.; Delvax, J.; de Roeck, A.; de Wolf, E. A.; Diaconu, C.; Dodonov, V.; Dossanov, A.; Dubak, A.; Eckerlin, G.; Efremenko, V.; Egli, S.; Eliseev, A.; Elsen, E.; Essenov, S.; Falkiewicz, A.; Faulkner, P. J. W.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, S.; Glazov, A.; Glushkov, I.; Goerlich, L.; Goettlich, M.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Greenshaw, T.; Grell, B. R.; Grindhammer, G.; Habib, S.; Haidt, D.; Hansson, M.; Helebrant, C.; Henderson, R. C. W.; Hennekemper, E.; Henschel, H.; Herrera, G.; Hildebrandt, M.; Hiller, K. H.; Hoffmann, D.; Horisberger, R.; Hovhannisyan, A.; Hreus, T.; Jacquet, M.; Janssen, M. E.; Janssen, X.; Jemanov, V.; Jönsson, L.; Johnson, D. P.; Jung, A. W.; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I. R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Klimkovich, T.; Kluge, T.; Knutsson, A.; Kogler, R.; Korbel, V.; Kostka, P.; Kraemer, M.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Krüger, K.; Kutak, K.; Landon, M. P. J.; Lange, W.; Laštovička-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Lendermann, V.; Levonian, S.; Li, G.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lucaci-Timoce, A.-I.; Lytkin, L.; Makankine, A.; Malinovski, E.; Marage, P.; Marti, Ll.; Martyn, H.-U.; Maxfield, S. J.; Mehta, A.; Meier, K.; Meyer, A. B.; Meyer, H.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Moreau, F.; Morozov, A.; Morris, J. V.; Mozer, M. U.; Mudrinic, M.; Müller, K.; Murín, P.; Nankov, K.; Naroska, B.; Naumann, Th.; Newman, P. R.; Niebuhr, C.; Nikiforov, A.; Nowak, G.; Nowak, K.; Nozicka, M.; Olivier, B.; Olsson, J. E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Pandurovic, M.; Papadopoulou, Th.; Pascaud, C.; Patel, G. D.; Pejchal, O.; Peng, H.; Perez, E.; Petrukhin, A.; Picuric, I.; Piec, S.; Pitzl, D.; Plačakytė, R.; Polifka, R.; Povh, B.; Preda, T.; Radescu, V.; Rahmat, A. J.; Raicevic, N.; Raspiareza, A.; Ravdandorj, T.; Reimer, P.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rotaru, M.; Ruiz Tabasco, J. E.; Rurikova, Z.; Rusakov, S.; Salek, D.; Salvaire, F.; Sankey, D. P. C.; Sauter, M.; Sauvan, E.; Schmidt, S.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schöning, A.; Schultz-Coulon, H.-C.; Sefkow, F.; Shaw-West, R. N.; Sheviakov, I.; Shtarkov, L. N.; Shushkevich, S.; Sloan, T.; Smiljanic, I.; Smirnov, P.; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, A.; Staykova, Z.; Steder, M.; Stella, B.; Straumann, U.; Sunar, D.; Sykora, T.; Tchoulakov, V.; Thompson, G.; Thompson, P. D.; Toll, T.; Tomasz, F.; Tran, T. H.; Traynor, D.; Trinh, T. N.; Truöl, P.; Tsakov, I.; Tseepeldorj, B.; Tsurin, I.; Turnau, J.; Tzamariudaki, E.; Urban, K.; Valkárová, A.; Vallée, C.; van Mechelen, P.; Vargas Trevino, A.; Vazdik, Y.; Vinokurova, S.; Volchinski, V.; Wegener, D.; Wessels, M.; Wissing, Ch.; Wünsch, E.; Yeganov, V.; Žáček, J.; Zálešák, J.; Zhang, Z.; Zhelezov, A.; Zhokin, A.; Zhu, Y. C.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.

2008-10-01

Processes leading to a final state with at least two high transverse momentum leptons (electrons or muons) are studied using the full ep data sample collected by the H1 experiment at HERA. The data correspond to an integrated luminosity of 463 pb-1. Di-lepton and tri-lepton event classes are investigated. Cross sections of the production of ee and μμ pairs are derived in a restricted phase space dominated by photon photon collisions. In general, good agreement is found with Standard Model predictions. Events are observed with a total scalar sum of lepton transverse momenta above 100 GeV where the Standard Model expectation is low. In this region, combining di-lepton and tri-lepton classes, five events are observed in ep collisions, compared to a Standard Model expectation of 0.96±0.12, while no such event is observed in ep data for 0.64±0.09 expected.

Disrupted latent decision processes in medication-free pediatric OCD patients.

Science.gov (United States)

Erhan, Ceyla; Bulut, Gresa Çarkaxhiu; Gökçe, Sebla; Ozbas, Duru; Turkakin, Esin; Dursun, Onur Burak; Yazgan, Yanki; Balcı, Fuat

2017-01-01

Decision-making in Obsessive Compulsive Disorder has typically been investigated in the adult population. Computational approaches have recently started to get integrated into these studies. However, decision-making research in pediatric OCD populations is scarce. We investigated latent decision processes in 21 medication-free pediatric OCD patients and 23 healthy control participants. We hypothesized that OCD patients would be more cautious and less efficient in evidence accumulation than controls in a two alternative forced choice (2AFC) task. Pediatric OCD patients were less efficient than controls in accumulating perceptual evidence and showed a tendency to be more cautious. In comparison to post-correct decisions, OCD patients increased decision thresholds after erroneous decisions, whereas healthy controls decreased decision thresholds. These changes were coupled with weaker evidence accumulation after errors in both groups. The small sample size limited the power of the study. Our results demonstrate poorer decision-making performance in pediatric OCD patients at the level of latent processes, specifically in terms of evidence accumulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Decision models for use with criterion-referenced tests

NARCIS (Netherlands)

van der Linden, Willem J.

1980-01-01

The problem of mastery decisions and optimizing cutoff scores on criterion-referenced tests is considered. This problem can be formalized as an (empirical) Bayes problem with decisions rules of a monotone shape. Next, the derivation of optimal cutoff scores for threshold, linear, and normal ogive

The Role of Social Relationships in PrEP Uptake and Use Among Transgender Women and Men Who Have Sex with Men.

Science.gov (United States)

Mehrotra, Megha L; Rivet Amico, K; McMahan, Vanessa; Glidden, David V; Defechereux, Patricia; Guanira, Juan V; Grant, Robert M

2018-05-12

Qualitative studies suggest that social relationships play an important role in HIV pre-exposure prophylaxis (PrEP) use, but there have been few quantitative assessments of the role of social relationships in PrEP uptake or adherence. We examined the association between disclosure of study participation or LGBT identity and PrEP use in the 1603 HIV-negative participants enrolled in the iPrEx OLE study. We also evaluated the association between LGBT social group involvement and PrEP use. Study participation disclosure to parents and LGBT identity disclosure to anyone in a participant's social network were associated with greater PrEP uptake. Study participation disclosure to partners was associated with higher probability of having protective PrEP drug concentrations compared [risk difference 0.15 95% CI (0.01, 0.30)]. For each additional type of LGBT organization a participant was involved in, the probability of PrEP uptake and having protective drug concentrations increased by 0.04 [95% CI (0.03, 0.06)] and 0.04 (95% CI (0.02, 0.07)] respectively. Overall, social context was associated with PrEP use in iPrEx OLE, and should be taken into consideration when designing future PrEP implementation programs.

30 CFR 250.235 - If a State objects to the EP's coastal zone consistency certification, what can I do?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false If a State objects to the EP's coastal zone... EP's coastal zone consistency certification, what can I do? If an affected State objects to the coastal zone consistency certification accompanying your proposed EP within the timeframe prescribed in...

Multi-robot Cooperation Behavior Decision Based on Psychological Values

Directory of Open Access Journals (Sweden)

Jian JIANG

2014-01-01

Full Text Available The method based on psychology concept has been proved to be a successful tool used for human-robot interaction. But its related research in multi-robot cooperation has remained scarce until recent studies. To solve the problem, a decision-making mechanism based on psychological values is presented to be regarded as the basis of the multi-robot cooperation. Robots give birth to psychological values based on the estimations of environment, teammates and themselves. The mapping relationship between psychological values and cooperation tendency threshold values is set up with artificial neural network. Robots can make decision on the bases of these threshold values in cooperation scenes. Experiments show that the multi-robot cooperation method presented in the paper not only can ensure the rationality of robots’ decision-making, but also can ensure the speediness of robots’ decision-making.

Objectives, Budgets, Thresholds, and Opportunity Costs-A Health Economics Approach: An ISPOR Special Task Force Report [4].

Science.gov (United States)

Danzon, Patricia M; Drummond, Michael F; Towse, Adrian; Pauly, Mark V

2018-02-01

The fourth section of our Special Task Force report focuses on a health plan or payer's technology adoption or reimbursement decision, given the array of technologies, on the basis of their different values and costs. We discuss the role of budgets, thresholds, opportunity costs, and affordability in making decisions. First, we discuss the use of budgets and thresholds in private and public health plans, their interdependence, and connection to opportunity cost. Essentially, each payer should adopt a decision rule about what is good value for money given their budget; consistent use of a cost-per-quality-adjusted life-year threshold will ensure the maximum health gain for the budget. In the United States, different public and private insurance programs could use different thresholds, reflecting the differing generosity of their budgets and implying different levels of access to technologies. In addition, different insurance plans could consider different additional elements to the quality-adjusted life-year metric discussed elsewhere in our Special Task Force report. We then define affordability and discuss approaches to deal with it, including consideration of disinvestment and related adjustment costs, the impact of delaying new technologies, and comparative cost effectiveness of technologies. Over time, the availability of new technologies may increase the amount that populations want to spend on health care. We then discuss potential modifiers to thresholds, including uncertainty about the evidence used in the decision-making process. This article concludes by discussing the application of these concepts in the context of the pluralistic US health care system, as well as the "excess burden" of tax-financed public programs versus private programs. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

EpSoc: Social-Based Epidemic-Based Routing Protocol in Opportunistic Mobile Social Network

Directory of Open Access Journals (Sweden)

Halikul Lenando

2018-01-01

Full Text Available In opportunistic networks, the nature of intermittent and disruptive connections degrades the efficiency of routing. Epidemic routing protocol is used as a benchmark for most of routing protocols in opportunistic mobile social networks (OMSNs due to its high message delivery and latency. However, Epidemic incurs high cost in terms of overhead and hop count. In this paper, we propose a hybrid routing protocol called EpSoc which utilizes the Epidemic routing forwarding strategy and exploits an important social feature, that is, degree centrality. Two techniques are used in EpSoc. Messages’ TTL is adjusted based on the degree centrality of nodes, and the message blocking mechanism is used to control replication. Simulation results show that EpSoc increases the delivery ratio and decreases the overhead ratio, the average latency, and the hop counts as compared to Epidemic and Bubble Rap.

30 CFR 250.226 - What Coastal Zone Management Act (CZMA) information must accompany the EP?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What Coastal Zone Management Act (CZMA) information must accompany the EP? 250.226 Section 250.226 Mineral Resources MINERALS MANAGEMENT SERVICE... and Information Contents of Exploration Plans (ep) § 250.226 What Coastal Zone Management Act (CZMA...

Production of Z0 bosons in elastic and quasi-elastic ep collisions at HERA

NARCIS (Netherlands)

Abramowicz, H.; Kooijman, P.; Zotkin, D.S.

2013-01-01

The production of Z0 bosons in the reaction ep →eZ0 p(∗), where p(∗) stands for a proton or a lowmass nucleon resonance, has been studied in ep collisions at HERA using the ZEUS detector. The analysis is based on a data sample collected between 1996 and 2007, amounting to 496 pb−1 of integrated

Prospects of the future ep colliders

International Nuclear Information System (INIS)

Alekhin, S.I.; Boos, Eh.Eh.; Borodulin, V.I.; Dzhikiya, G.V.; Slabospitskij, S.R.; Smirnov, A.Yu.; Sultanov, S.F.

1987-01-01

The possibilities of ep colliders with √=1.1 and 2.4 TeV to investigate new physics at the l∼10 -17 cm have been considered. UNK with linear electron accelerator enables to investigate the mechanism of spontaneous symmetry breaking in the standard model, interactions conditioned by new gauge bosons, the properties if excited leptons and quarks of the first family, the structure of contact interactions, predicted by preon models, the properties of SUSY-partners of electrons and light quarks

Uptake of PrEP and condom and sexual risk behavior among MSM during the ANRS IPERGAY trial.

Science.gov (United States)

Sagaon-Teyssier, Luis; Suzan-Monti, Marie; Demoulin, Baptiste; Capitant, Catherine; Lorente, Nicolas; Préau, Marie; Mora, Marion; Rojas Castro, Daniela; Chidiac, Christian; Chas, Julie; Meyer, Laurence; Molina, Jean-Michel; Spire, Bruno

2016-01-01

The double-blind phase of the randomized ANRS IPERGAY trial, evaluating sexual activity-based oral HIV pre-exposure prophylaxis (PrEP), was conducted among high-risk men who have sex with men (MSM). Results showed an 86% (95% CI: 40-98) relative reduction in HIV incidence among participants with tenofovir disoproxil fumarate-emtricitabine vs. placebo. The present pooled analysis aimed to analyze (i) participants' adherence to the prescribed treatment and/or condom use during sexual intercourse and (ii) sexual behavior during the double-blind phase of the study. Four hundred MSM were enrolled in the trial. Every 2 months they completed online questionnaires collecting sexual behavior and PrEP adherence data regarding their most recent sexual intercourse. A total of 2232 questionnaires (M0-M24) were analyzed. Changes over time were evaluated using a mixed model accounting for multiple measures. Irrespective of sexual partner and practice type, on average, 42.6% (min: 32.1-max: 45.8%) reported PrEP use only during their most recent episode of sexual intercourse; 29% (22.9-35.6%) reported both PrEP and condom use; 11.7% (7.2-18.9%) reported condom-use only, and 16.7% (10.8-29.6%) reported no PrEP or condom use with no significant change during the study. Scheduled (i.e., correct) PrEP use was reported on average by 59.0% (47.2-68.5%) of those reporting PrEP use during their most recent sexual intercourse. Overall, 70.3% (65.3-79.4%) and 69.3% (58.3-75.4%) of participants reported, respectively, condomless anal and condomless receptive anal intercourse during their most recent sexual encounter without significant change during follow-up. Overall, on average 83.3% (min: 70.4-max: 89.2%) of participants protected themselves by PrEP intake or condom use or both during the trial, and no increase in at-risk sexual practices was observed. None of these indicators showed significant trend during the follow-up, although we found a tendency toward decrease (p = .19) of the

Cognitive Abilities, Monitoring Confidence, and Control Thresholds Explain Individual Differences in Heuristics and Biases.

Science.gov (United States)

Jackson, Simon A; Kleitman, Sabina; Howie, Pauline; Stankov, Lazar

2016-01-01

In this paper, we investigate whether individual differences in performance on heuristic and biases tasks can be explained by cognitive abilities, monitoring confidence, and control thresholds. Current theories explain individual differences in these tasks by the ability to detect errors and override automatic but biased judgments, and deliberative cognitive abilities that help to construct the correct response. Here we retain cognitive abilities but disentangle error detection, proposing that lower monitoring confidence and higher control thresholds promote error checking. Participants ( N = 250) completed tasks assessing their fluid reasoning abilities, stable monitoring confidence levels, and the control threshold they impose on their decisions. They also completed seven typical heuristic and biases tasks such as the cognitive reflection test and Resistance to Framing. Using structural equation modeling, we found that individuals with higher reasoning abilities, lower monitoring confidence, and higher control threshold performed significantly and, at times, substantially better on the heuristic and biases tasks. Individuals with higher control thresholds also showed lower preferences for risky alternatives in a gambling task. Furthermore, residual correlations among the heuristic and biases tasks were reduced to null, indicating that cognitive abilities, monitoring confidence, and control thresholds accounted for their shared variance. Implications include the proposal that the capacity to detect errors does not differ between individuals. Rather, individuals might adopt varied strategies that promote error checking to different degrees, regardless of whether they have made a mistake or not. The results support growing evidence that decision-making involves cognitive abilities that construct actions and monitoring and control processes that manage their initiation.

Striatal activation reflects urgency in perceptual decision making.

Science.gov (United States)

van Maanen, Leendert; Fontanesi, Laura; Hawkins, Guy E; Forstmann, Birte U

2016-10-01

Deciding between multiple courses of action often entails an increasing need to do something as time passes - a sense of urgency. This notion of urgency is not incorporated in standard theories of speeded decision making that assume information is accumulated until a critical fixed threshold is reached. Yet, it is hypothesized in novel theoretical models of decision making. In two experiments, we investigated the behavioral and neural evidence for an "urgency signal" in human perceptual decision making. Experiment 1 found that as the duration of the decision making process increased, participants made a choice based on less evidence for the selected option. Experiment 2 replicated this finding, and additionally found that variability in this effect across participants covaried with activation in the striatum. We conclude that individual differences in susceptibility to urgency are reflected by striatal activation. By dynamically updating a response threshold, the striatum is involved in signaling urgency in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

An $ep$ collider based on proton-driven plasma wakefield acceleration

CERN Document Server

Wing, M.; Mete, O.; Aimidula, A.; Welsch, C.; Chattopadhyay, S.; Mandry, S.

2014-01-01

Recent simulations have shown that a high-energy proton bunch can excite strong plasma wakefields and accelerate a bunch of electrons to the energy frontier in a single stage of acceleration. This scheme could lead to a future $ep$ collider using the LHC for the proton beam and a compact electron accelerator of length 170 m, producing electrons of energy up to 100 GeV. The parameters of such a collider are discussed as well as conceptual layouts within the CERN accelerator complex. The physics of plasma wakefield acceleration will also be introduced, with the AWAKE experiment, a proof of principle demonstration of proton-driven plasma wakefield acceleration, briefly reviewed, as well as the physics possibilities of such an $ep$ collider.

EP-based wavelet coefficient quantization for linear distortion ECG data compression.

Science.gov (United States)

Hung, King-Chu; Wu, Tsung-Ching; Lee, Hsieh-Wei; Liu, Tung-Kuan

2014-07-01

Reconstruction quality maintenance is of the essence for ECG data compression due to the desire for diagnosis use. Quantization schemes with non-linear distortion characteristics usually result in time-consuming quality control that blocks real-time application. In this paper, a new wavelet coefficient quantization scheme based on an evolution program (EP) is proposed for wavelet-based ECG data compression. The EP search can create a stationary relationship among the quantization scales of multi-resolution levels. The stationary property implies that multi-level quantization scales can be controlled with a single variable. This hypothesis can lead to a simple design of linear distortion control with 3-D curve fitting technology. In addition, a competitive strategy is applied for alleviating data dependency effect. By using the ECG signals saved in MIT and PTB databases, many experiments were undertaken for the evaluation of compression performance, quality control efficiency, data dependency influence. The experimental results show that the new EP-based quantization scheme can obtain high compression performance and keep linear distortion behavior efficiency. This characteristic guarantees fast quality control even for the prediction model mismatching practical distortion curve. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Integration Of Externalized Decision Models In The Definition Of Workflows For Digital Pathology

Directory of Open Access Journals (Sweden)

J. van Leeuwen

2016-06-01

We proposed a workflow solution enabling the representation of decision models as externalized executable tasks in the process definition. Our approach separates the task implementations from the workflow model, ensuring scalability and allowing for the inclusion of complex decision logic in the workflow execution. In we depict a simplified model of a pathology diagnosis workflow (starting with the digitization of the slides, represented according to the BPMN modeling conventions. The example shows a workflow sequence that automatically orders a HER2 FISH when IHC is borderline according to defined customizable thresholds. The process model integrates an image analysis algorithm that scores images. Based on the score and the thresholds the decision model evaluates the condition and recommends the pre-ordering of an additional test when the score falls between the two thresholds. This leads to faster diagnosis and allows balancing the costs of an additional test versus the overhead of the pathologist by choosing the values of the thresholds.  

Preventing regime shifts on the Colorado Plateau: Application of ecological threshold concepts to land management decision making

Science.gov (United States)

Investigating the mechanisms responsible for ecological thresholds is essential to understanding processes leading to ecosystem regime shifts. Dryland ecosystems are especially prone to threshold behavior wherein stressor-mediated alteration of patterns and processes can shift systems to alternative...

Bio-reduction of Cr(VI) by exopolysaccharides (EPS) from indigenous bacterial species of Sukinda chromite mine, India.

Science.gov (United States)

Harish, R; Samuel, Jastin; Mishra, R; Chandrasekaran, N; Mukherjee, A

2012-07-01

Chrome mining activity has contributed intensively towards pollution of hexavalent chromium around Sukinda Valley, Orissa, India. In an attempt to study the specific contribution of exopolysaccharides (EPS) extracted from indigenous isolates towards Cr(VI) reduction, three chromium (VI) tolerant strains were isolated from the effluent mining sludge. Based on the tolerance towards Cr(VI) and EPS production capacity, one of them was selected for further work. The taxonomic identity of the selected strain was confirmed to be Enterobacter cloacae (showing 98% similarity in BLAST search to E. cloacae) through 16S rRNA analysis. The EPS production was observed to increase with increasing Cr(VI) concentration in the growth medium, highest being 0.078 at 100 mg/l Cr(VI). The extracted EPS from Enterobacter cloacae SUKCr1D was able to reduce 31.7% of Cr(VI) at 10 mg/l concentration, which was relevant to the prevailing natural concentrations at Sukinda mine effluent sludge. The FT-IR spectral studies confirmed the surface chemical interactions of hexavalent chromium with EPS.

Plant growth promotion and root colonization by EPS producing Enterobacter sp. RZS5 under heavy metal contaminated soil.

Science.gov (United States)

Sayyed, R Z; Patel, P R; Shaikh, S S

2015-02-01

The heavy metal resistant bacterium isolated from field soil and identified as Enterobacter sp. RZS5 tolerates a high concentration (100-2000 μM) of various heavy metal ions such as Mn2+, Ni2+, Zn2+, Cu2+, CO2+ and Fe2+ when grown in such environment and produces exopolysaccharides (EPS). Here, we have demonstrated EPS production by Enterobacter sp. RZS5 during 60 h of growth in yeast extract mannitol broth (YEMB). The yield increased by two fold after the addition of 60 μM of Ca2+; 50 μM of Fe2+ and 60 μM of Mg2+ ions in YEMB, and the optimization of physico-chemical parameters. EPS was extracted with 30% (v/v) of isopropanol as against the commonly used 50% (v/v) isopropanol method. EPS-rich broth promoted seed germination, shoot height, root length, number of leaves and chlorophyll content of wheat (Triticum aestivum) seed and peanut (Arachis hypogaea) seed. The higher colony-forming unit of Enterobacter sp. in soil inoculated with EPS rich broth of Enterobacter sp. indicated the root colonizing potential and rhizosphere competence of the isolate. The FTIR spectra of the EPS extract confirmed the presence of the functional group characteristics of EPS known to exhibit a high binding affinity towards certain metal ions. This overall growth and vigour in plants along with the effective root colonization, reflected the potential of the isolate as an efficient bio-inoculant in bioremediation.

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

Science.gov (United States)

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.

PREFACE: The EPS High Energy Particle Physics Conference

Science.gov (United States)

Barlow, Roger

2008-03-01

HEPP2007, the EPS High Energy Particle Physics Conference, was held in Manchester from July 19-26 2007. It brought together 580 delegates across the whole subject: from string theorists to detector technologists, from young postgraduate students to senior professors. Geographically they came from the UK, from the rest of Europe, from North America, and from the rest of the world. It covered the whole spectrum of the subject, not only accelerator-based experiments but also its astrophysical and cosmological aspects. The parallel and plenary talks can be found in these proceedings. A key feature of the conference, as always, was the award of the prizes: this year the EPS prize was awarded to Makoto Kobayashi and Toshihide Maskawa for their explanation of CP violation with a 6 quark model—Kobayashi came to accept it in person. The Gribov medal went to Niklas Beisert, the outreach prize to Richard Jacobsson and Charles Timmermans and the Young Physicist prizer to I Furic, G Gomez-Ceballos and S Menzemer. Parallel sessions were held in Manchester University, and plenary talks were held in the Bridgewater Hall in Manchester Town centre, a magnificent modern venue whose positive and co-operative staff enabled the conference to make the most of the impressive surroundings. We were able to put the hall to its proper purpose one evening with a concert by the Fairey Band—one of the distinctive brass bands who form part of the rich musical tradition of the North of England, and came as something new and different to many of the delegates. The conference ran smoothly and successfully, thanks largely to hard work by the local organising committee who devoted a lot of time to planning, producing ideas, and anticipating potential problems. Many of them were not from Manchester itself but from other universities and laboratories in the North of England, so their dedication was especially appreciated. The EPS committee also played a major part, by the selection of plenary

48 CFR 504.570 - Procedures for using the EPS.

Science.gov (United States)

2010-10-01

... GENERAL ADMINISTRATIVE MATTERS Electronic Commerce in Contracting 504.570 Procedures for using the EPS. (a... [Identify address block in the solicitation]. (e) The Electronic Posting System Manual provides detailed... that electronic access to a solicitation will result in adequate competition, distribute the...

A thermo-electro-mechanical simulation model for hot wire cutting of EPS foam

DEFF Research Database (Denmark)

Petkov, Kiril; Hattel, Jesper Henri

2016-01-01

A one-dimensional thermo-electro-mechanical mathematical model describing the effects taking place within a Ni-Cr20% wire used in a hot-wire cutting process for free forming and rapid prototyping of expanded polystyrene (EPS) is investigated and simulated. The model implements and solves three semi...... cutting of EPS in contact with a cutting tool made of an electrically heated metal wire attached to a robot device. The finite difference method is used to solve the coupled equations in the two environments (domains) in which the hot-wire operates, namely air and EPS. The model is calibrated against...... experimentally obtained data. Novel findings are a transient temperature-dependent kerfwidth prediction and a relation between kerfwidth and the cutting angle as measured from the horizontal direction. These are important relations in the aim for higher geometrical accuracy of the hot-wire cutting process. (C...

The Early Psychosis Screener (EPS): Quantitative validation against the SIPS using machine learning.

Science.gov (United States)

Brodey, B B; Girgis, R R; Favorov, O V; Addington, J; Perkins, D O; Bearden, C E; Woods, S W; Walker, E F; Cornblatt, B A; Brucato, G; Walsh, B; Elkin, K A; Brodey, I S

2018-01-18

Machine learning techniques were used to identify highly informative early psychosis self-report items and to validate an early psychosis screener (EPS) against the Structured Interview for Psychosis-risk Syndromes (SIPS). The Prodromal Questionnaire-Brief Version (PQ-B) and 148 additional items were administered to 229 individuals being screened with the SIPS at 7 North American Prodrome Longitudinal Study sites and at Columbia University. Fifty individuals were found to have SIPS scores of 0, 1, or 2, making them clinically low risk (CLR) controls; 144 were classified as clinically high risk (CHR) (SIPS 3-5) and 35 were found to have first episode psychosis (FEP) (SIPS 6). Spectral clustering analysis, performed on 124 of the items, yielded two cohesive item groups, the first mostly related to psychosis and mania, the second mostly related to depression, anxiety, and social and general work/school functioning. Items within each group were sorted according to their usefulness in distinguishing between CLR and CHR individuals using the Minimum Redundancy Maximum Relevance procedure. A receiver operating characteristic area under the curve (AUC) analysis indicated that maximal differentiation of CLR and CHR participants was achieved with a 26-item solution (AUC=0.899±0.001). The EPS-26 outperformed the PQ-B (AUC=0.834±0.001). For screening purposes, the self-report EPS-26 appeared to differentiate individuals who are either CLR or CHR approximately as well as the clinician-administered SIPS. The EPS-26 may prove useful as a self-report screener and may lead to a decrease in the duration of untreated psychosis. A validation of the EPS-26 against actual conversion is underway. Copyright © 2017 Elsevier B.V. All rights reserved.

e-EPS News: Highlights from the European Physical Society

CERN Multimedia

2011-01-01

e-EPS News is a monthly addition to the CERN Bulletin line-up, showcasing articles from e-EPS – the European Physical Society newsletter – as part of a collaboration between the two publications.   European Physical Society Physics Education Division Since 2000, the European Physical Society’s Physics Education Division has been contributing to awareness of the relevance of physics in everyday culture, to interaction amongst schools and universities and to a better quality of physics teaching at all levels. The Physics Education Division achieves this by addressing and promoting physics, the continued education of teachers, large scale educational changes – such as the Bologna process – and successful new teaching methods, taking into account differences and similarities in the European education systems. Since 2008, their More Understanding with Simple Experiments (MUSE) project has offered teachers and researchers a set of nine research-bas...

Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E₂ receptor EP4

Directory of Open Access Journals (Sweden)

Yu Ah Hong

2017-06-01

Full Text Available Background: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS-induced renal proximal tubular cell injury through the prostaglandin E₂ (PGE₂ receptor EP4. Methods: Human renal tubular epithelial (HK-2 cells were pretreated with paricalcitol (2 ng/mL for 1 hour and exposed to LPS (1 μg/mL. The effects of paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA were investigated. Results: The expression of cyclooxygenase-2, PGE₂, and EP4 were significantly increased in LPS-exposed HK-2 cells treated with paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB (NF-κB were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of paricalcitol on p65 NF-κB nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. Conclusion: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and NF-κB signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury.

Cost-Effective Reciprocating Engine Emissions Control and Monitoring for E&P Field and Gathering Engines

Energy Technology Data Exchange (ETDEWEB)

Kirby S. Chapman; Sarah R. Nuss-Warren

2007-02-01

The objective of this project is to identify, develop, test, and commercialize emissions control and monitoring technologies that can be implemented by exploration and production (E&P) operators to significantly lower the cost of environmental compliance and expedite project permitting. The project team takes considerable advantage of the emissions control research and development efforts and practices that have been underway in the gas pipeline industry for the last 12 years. These efforts and practices are expected to closely interface with the E&P industry to develop cost-effective options that apply to widely-used field and gathering engines, and which can be readily commercialized. The project is separated into two phases. Phase 1 work establishes an E&P industry liaison group, develops a frequency distribution of installed E&P field engines, and identifies and assesses commercially available and emerging engine emissions control and monitoring technologies. Current and expected E&P engine emissions and monitoring requirements are reviewed, and priority technologies are identified for further development. The identified promising technologies are tested on a laboratory engine to confirm their generic viability. In addition, a full-scale field test of prototype emissions controls will be conducted on at least ten representative field engine models with challenging emissions profiles. Emissions monitoring systems that are integrated with existing controls packages will be developed. Technology transfer/commercialization is expected to be implemented through compressor fleet leasing operators, engine component suppliers, the industry liaison group, and the Petroleum Technology Transfer Council. This topical report discusses work completed during Phase 1 of the project Cost Effective Reciprocating Engine Emissions Control and Monitoring for E&P Field and Gathering Engines. In this report information, data, and results are compiled and summarized from quarterly

30 CFR 250.220 - If I propose activities in the Alaska OCS Region, what planning information must accompany the EP?

Science.gov (United States)

2010-07-01

... Region, what planning information must accompany the EP? 250.220 Section 250.220 Mineral Resources... activities in the Alaska OCS Region, what planning information must accompany the EP? If you propose exploration activities in the Alaska OCS Region, the following planning information must accompany your EP: (a...

Expression, purification, crystallization and preliminary X-ray studies of Vibrio cholerae pseudopilin EpsH

International Nuclear Information System (INIS)

Raghunathan, Kannan; Vago, Frank S.; Ball, Terry; Yakubova, Nafissa; Grindem, David; Wedemeyer, William J.; Arvidson, Dennis N.

2009-01-01

Recombinant V. cholerae EpsH has been expressed, purified and crystallized. The crystals diffracted to 1.71 Å resolution. EpsH is a minor pseudopilin protein of the Vibrio cholerae type II secretion system. A truncated form of EpsH with a C-terminal noncleavable His tag was constructed and expressed in Escherichia coli, purified and crystallized by sitting-drop vapor diffusion. A complete data set was collected to 1.71 Å resolution. The crystals belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 53.39, b = 71.11, c = 84.64 Å. There were two protein molecules in the asymmetric unit, which gave a Matthews coefficient V M of 2.1 Å 3 Da −1 , corresponding to 41.5% solvent content

Threshold analysis in the presence of both the diagnostic and the therapeutic risk.

Science.gov (United States)

Felder, Stefan; Mayrhofer, Thomas

2017-12-26

The well-established a priori probability of illness threshold in medical decision making, introduced by Pauker and Kassirer (N Engl J Med 293:229-234, 1975; N Engl J Med 302:1109-1117, 1980), involves the diagnostic risk only. We generalize the threshold analysis by adding the therapeutic risk, i.e., in accounting for the risk that a treatment might sometimes fail. We derive a priori probability of illness threshold as a function of the probability of successful treatment, as well as the inverted function, where the successful treatment probability threshold is a function of the a priori probability of illness. The thresholds in the general model are higher than those in the special cases where one of the two risks is absent. Applications show that the changes in the thresholds can be substantial. Our general model might explain empirical findings of much higher thresholds than the Pauker-Kassirer model suggests.

Collaborative Learning with Sustainability-driven Projects: A Summary of the EPS@ISEP Programme

Directory of Open Access Journals (Sweden)

Manuel Fernando Silva

2018-06-01

Full Text Available This paper describes the collaborative learning environment, aligned with the United Nations Millennium Development Goals, provided by the European Project Semester (EPS. EPS is a one semester capstone project programme offered by eighteen European engineering schools as part of their student ex-change programme portfolio. In this international programme, students are organized in teams, grouping individuals from diverse academic backgrounds and nationalities. The teams, after choosing a project proposal, become fully responsible for the conduction of their projects. By default, project proposals refer to open multidisciplinary real problems. The purpose of the project is to expose students to problems of a greater dimension and complexity than those faced throughout the degree programme as well as to put them in con-tact with the so-called real world, in opposition to the academic world. EPS provides an integrated framework for undertaking capstone projects, which is focused on multicultural and multidisciplinary teamwork, communication, problem-solving, creativity, leadership, entrepreneurship, ethical reasoning and global contextual analysis. Specifically, the design and development of sustainable systems for growing food allow students not only to reach the described objectives, but to foster sustainable development practices. As a re-sult, we recommend the adoption of this category of projects within EPS for the benefit of engineering students and of the society as a whole.

The design of an ECRH system for JET-EP

DEFF Research Database (Denmark)

Verhoeven, A.G.A.; Bongers, W.A.; Elzendoorn, B.S.Q.

2003-01-01

An electron cyclotron resonance heating (ECRH) system has been designed for JET in the framework of the JET enhanced performance project (JET-EP) under the European fusion development agreement. Due to financial constraints it has been decided not to implement this project. Nevertheless, the design...

The design of an ECRH system for JET-EP

NARCIS (Netherlands)

Verhoeven, A. G. A.; Bongers, W. A.; Elzendoorn, B. S. Q.; Graswinckel, M.; Hellingman, P.; Kooijman, W.; Kruijt, O. G.; Maagdenberg, J.; Ronden, D.; Stakenborg, J.; Sterk, A. B.; Tichler, J.; Alberti, S.; Goodman, T.; Henderson, M.; Hoekzema, J. A.; Oosterbeek, J. W.; Fernandez, A.; Likin, K.; Bruschi, A.; Cirant, S.; Novaks, S.; Piosczyk, B.; Thumm, M.; Bindslev, H.; Kaye, A.; Fleming, C.; Zohm, H.

2003-01-01

An electron cyclotron resonance heating (ECRH) system has been designed for JET in the framework of the JET enhanced performance project (JET-EP) under the European fusion development agreement. Due to financial constraints it has been decided not to implement this project. Nevertheless, the design

Implementation and Operational Research: A Cost-Effective, Clinically Actionable Strategy for Targeting HIV Preexposure Prophylaxis to High-Risk Men Who Have Sex With Men.

Science.gov (United States)

Ross, Eric L; Cinti, Sandro K; Hutton, David W

2016-07-01

Preexposure prophylaxis (PrEP) is effective at preventing HIV infection among men who have sex with men (MSM), but there is uncertainty about how to identify high-risk MSM who should receive PrEP. We used a mathematical model to assess the cost-effectiveness of using the HIV Incidence Risk Index for MSM (HIRI-MSM) questionnaire to target PrEP to high-risk MSM. We simulated strategies of no PrEP, PrEP available to all MSM, and eligibility thresholds set to HIRI-MSM scores between 5 and 45, in increments of 5 (where a higher score predicts greater HIV risk). Based on the iPrEx, IPERGAY, and PROUD trials, we evaluated PrEP efficacies from 44% to 86% and annual costs from $5900 to 8700. We designate strategies with incremental cost-effectiveness ratio (ICER) ≤$100,000/quality-adjusted life-year (QALY) as "cost-effective." Over 20 years, making PrEP available to all MSM is projected to prevent 33.5% of new HIV infections, with an ICER of $1,474,000/QALY. Increasing the HIRI-MSM score threshold reduces the prevented infections, but improves cost-effectiveness. A threshold score of 25 is projected to be optimal (most QALYs gained while still being cost-effective) over a wide range of realistic PrEP efficacies and costs. At low cost and high efficacy (IPERGAY), thresholds of 15 or 20 are optimal across a range of other input assumptions; at high cost and low efficacy (iPrEx), 25 or 30 are generally optimal. The HIRI-MSM provides a clinically actionable means of guiding PrEP use. Using a score of 25 to determine PrEP eligibility could facilitate cost-effective use of PrEP among high-risk MSM who will benefit from it most.

Pre-Exposure Prophylaxis (PrEP) Use and Condomless Anal Sex: Evidence of Risk Compensation in a Cohort of Young Men Who Have Sex with Men.

Science.gov (United States)

Newcomb, Michael E; Moran, Kevin; Feinstein, Brian A; Forscher, Emily; Mustanski, Brian

2018-04-01

Young men who have sex with men (YMSM) are disproportionately impacted by HIV. Pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV acquisition. It remains unclear if PrEP use increases rates of condomless sex (ie, risk compensation), which may increase risk of infection if PrEP adherence is not optimal. This study aimed to examine whether PrEP use and PrEP adherence were associated with change in sexual risk behaviors in a large longitudinal cohort of YMSM reporting on multiple sexual partnerships over time. Data were obtained from the first 3 visits of an ongoing cohort study of YMSM in Chicago (analytic N = 953; 14.1% HIV-positive at baseline). Participants reported up to 4 sexual partnerships at each visit, including sexual behavior, PrEP use, and PrEP adherence within partnerships. YMSM reported higher rates of receptive condomless anal sex (CAS) in partnerships during which they were on PrEP compared with those when they were not on PrEP. This association was consistent across both HIV-negative and HIV-positive participants reporting on partnerships with both perceived HIV-negative/unknown and HIV-positive partners. The rate of receptive CAS was higher in PrEP nonadherent partnerships compared with non-PrEP partnerships. The rate of receptive CAS was also higher in PrEP nonadherent than adherent partnerships, but this was not statistically significant. These analyses provide compelling data suggesting that YMSM are engaging in risk compensation when on PrEP. If rates of receptive CAS are highest among YMSM who are PrEP nonadherent, PrEP as a prevention strategy could fail to curb HIV incidence among YMSM.

Identification of Optimal Preventive Maintenance Decisions for Composite Components

NARCIS (Netherlands)

Laks, P.; Verhagen, W.J.C.; Gherman, B.; Porumbel, I.

2018-01-01

This research proposes a decision support tool which identifies cost-optimal maintenance decisions for a given planning period. Simultaneously, the reliability state of the component is kept at or below a given reliability threshold: a failure limit policy applies. The tool is developed to support

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.

Science.gov (United States)

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

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

Science.gov (United States)

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

IL-6 Overexpression in ERG-Positive Prostate Cancer Is Mediated by Prostaglandin Receptor EP2.

Science.gov (United States)

Merz, Constanze; von Mässenhausen, Anne; Queisser, Angela; Vogel, Wenzel; Andrén, Ove; Kirfel, Jutta; Duensing, Stefan; Perner, Sven; Nowak, Michael

2016-04-01

Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outcome is still controversial. Prostate tumors produce various soluble factors, including the pleiotropic cytokine IL-6, regulating cellular processes such as proliferation and metastatic segregation. Here, we used prostatectomy samples in a tissue microarray format and analyzed the co-expression and the clinicopathologic data of ERG and IL-6 using immunohistochemical double staining and correlated the read-out with clinicopathologic data. Expression of ERG and IL-6 correlated strongly in prostate tissue samples. Forced expression of ERG in prostate tumor cell lines resulted in significantly increased secretion of IL-6, whereas the down-regulation of ERG decreased IL-6 secretion. By dissecting the underlying mechanism in prostate tumor cell lines we show the ERG-mediated up-regulation of the prostanoid receptors EP2 and EP3. The prostanoid receptor EP2 was overexpressed in human prostate cancer tissue. Furthermore, the proliferation rate and IL-6 secretion in DU145 cells was reduced after treatment with EP2-receptor antagonist. Collectively, our study shows that the expression of ERG in prostate cancer is linked to the expression of IL-6 mediated by the prostanoid receptor EP2. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

[PrEP Forum: an on-line debate on pre-exposure prophylaxis in Brazil].

Science.gov (United States)

Queiroz, Artur Acelino Francisco Luz Nunes; Sousa, Alvaro Francisco Lopes de

2017-11-21

This study aimed to identify health-promoting contents focused on HIV/Aids prevention in messages posted in a Facebook group for debates on the use of pre-exposure prophylaxis (PrEP). This was a prospective observational study using systematic non-participant observation. From July 2015 to June 2016, all the posts in the group were catalogued and formed a corpus. Everything was processed in IRaMuTeQ and analyzed by descending hierarchical classification. The collected data were grouped in three classes: (1) HIV/Aids prevention: discussing prophylaxis, treatment, target public, and side effects; (2) universal access to PrEP in Brazil: discussing government responsibilities; (3) on-line purchase of truvada: exposing a situation of vulnerability. The findings call attention to a potential public health problem and provide backing for understanding facilitators and barriers to the use of PrEP in Brazil through the identification of health-promoting content linked to individual, social, and institutional markers.

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

Science.gov (United States)

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.

OMEGA EP: High-energy peta-watt capability for the OMEGA laser facility

Energy Technology Data Exchange (ETDEWEB)

Kelly, J.H.; Waxer, L.J.; Bagnoud, V.; Begishev, I.A.; Bromage, J.; Kruschwitz, B.E.; Kessler, T.J.; Loucks, S.J.; Maywar, D.N.; McCrory, R.L.; Meyerhofer, D.D.; Morse, S.F.B.; Oliver, J.B.; Rigatti, A.L.; Schmid, A.W.; Stoeckl, C.; Dalton, S.; Folnsbee, L.; Guardalben, M.J.; Jungquist, R.; Puth, J.; Shoup III, M.J.; Weiner, D.; Zuegel, J.D. [Rochester Univ., Lab. for Laser Energetics, NY (United States)

2006-06-15

OMEGA EP (Extended Performance) is a peta-watt-class addition to the existing 30-kJ, 60-beam OMEGA Laser Facility at the University of Rochester. When completed, it will consist of four beamlines, each capable of producing up to 6.5 kJ at 351 nm in a 1 to 10 ns pulse. Two of the beamlines will produce up to 2.6 kJ in a pulse-width range of 1 to 100 ps at 1053 nm using chirped-pulse amplification (CPA). This paper reviews both the OMEGA EP performance objectives and the enabling technologies required to meet these goals. (authors)

OMEGA EP: High-energy peta-watt capability for the OMEGA laser facility

International Nuclear Information System (INIS)

Kelly, J.H.; Waxer, L.J.; Bagnoud, V.; Begishev, I.A.; Bromage, J.; Kruschwitz, B.E.; Kessler, T.J.; Loucks, S.J.; Maywar, D.N.; McCrory, R.L.; Meyerhofer, D.D.; Morse, S.F.B.; Oliver, J.B.; Rigatti, A.L.; Schmid, A.W.; Stoeckl, C.; Dalton, S.; Folnsbee, L.; Guardalben, M.J.; Jungquist, R.; Puth, J.; Shoup III, M.J.; Weiner, D.; Zuegel, J.D.

2006-01-01

OMEGA EP (Extended Performance) is a peta-watt-class addition to the existing 30-kJ, 60-beam OMEGA Laser Facility at the University of Rochester. When completed, it will consist of four beamlines, each capable of producing up to 6.5 kJ at 351 nm in a 1 to 10 ns pulse. Two of the beamlines will produce up to 2.6 kJ in a pulse-width range of 1 to 100 ps at 1053 nm using chirped-pulse amplification (CPA). This paper reviews both the OMEGA EP performance objectives and the enabling technologies required to meet these goals. (authors)

Preventive and corrective maintenance for MINT EPS 3000 electron beam machine

International Nuclear Information System (INIS)

Siti Aiasah Hashim; Shaari Jahar

2005-01-01

Preventive and corrective maintenance of a high energy electron is to ensure that the machine would not fail during operation. MINT's EPS 3000 electron beam machine has been in operation for almost 12 years. Throughout those years, events relating to scheduled overhauls and unscheduled corrective maintenance had provided invaluable experience in the form of informal maintenance training to the operators. With the implementation of ISO 9001:2000 Quality Management System at the facility, the preventive and corrective maintenance program is becoming more structured and orderly. Collected maintenance data shall be used to initiate continual improvement activities in the facility.This paper describes MINT-ALURTRON's 12 years experience in providing maintenance work for the EPS 3000. (Author)

Obligatory Role of EP1 Receptors in the Increase in Cerebral Blood Flow Produced by Hypercapnia in the Mice.

Directory of Open Access Journals (Sweden)

Ken Uekawa

Full Text Available Hypercapnia induces potent vasodilation in the cerebral circulation. Although it has long been known that prostanoids participate in the cerebrovascular effects of hypercapnia, the role of prostaglandin E2 (PGE2 and PGE2 receptors have not been fully investigated. In this study, we sought to determine whether cyclooxygenase-1 (COX-1-derived PGE2 and EP1 receptors are involved in the cerebrovascular response induced by hypercapnia. Cerebral blood flow (CBF was recorded by laser-Doppler flowmetry in the somatosenasory cortex of anesthetized male EP1-/- mice and wild type (WT littermates. In WT mice, neocortical application of the EP1 receptor antagonist SC-51089 attenuated the increase in CBF elicited by systemic hypercapnia (pCO2 = 50-60 mmHg. SC-51089 also attenuated the increase in CBF produced by neocortical treatment of arachidonic acid or PGE2. These CBF responses were also attenuated in EP1-/- mice. In WT mice, the COX-1 inhibitor SC-560, but not the COX-2 inhibitor NS-398, attenuated the hypercapnic CBF increase. Neocortical application of exogenous PGE2 restored the attenuation in resting CBF and the hypercapnic response induced by SC-560. In contrast, exogenous PGE2 failed to rescue the attenuation both in WT mice induced by SC-51089 and EP1-/- mice, attesting to the obligatory role of EP1 receptors in the response. These findings indicate that the hypercapnic vasodilatation depends on COX-1-derived PGE2 acting on EP1 receptors and highlight the critical role that COX-1-derived PGE2 and EP1 receptors play in the hypercapnic regulation of the cerebral circulation.

"Getting Stuck" in Analogue Electronics: Threshold Concepts as an Explanatory Model

Science.gov (United States)

Harlow, A.; Scott, J.; Peter, M.; Cowie, B.

2011-01-01

Could the challenge of mastering threshold concepts be a potential factor that influences a student's decision to continue in electronics engineering? This was the question that led to a collaborative research project between educational researchers and the Faculty of Engineering in a New Zealand university. This paper deals exclusively with the…

e-EPS News: Highlights from the European Physical Society

CERN Multimedia

e-EPS

2011-01-01

e-EPS News is a monthly addition to the CERN Bulletin line-up, showcasing articles from e-EPS – the European Physical Society newsletter – as part of a collaboration between the two publications.   Conseil de Physique Solvay centenary One hundred years ago the celebrated first Conseil de Physique Solvay took place in Brussels, with the participation of the leading physicists of the time. It marked a profound rupture between the old classical physics and the new quantum physics that described the strange behaviour of Nature at the microscopic level. The conference was one of the most important events in the advent of the quantum revolution; no such physics conference since has acquired the same legendary status. To celebrate the centenary of this unique conference, the International Solvay Institutes are organizing a series of exceptional events that will make Brussels the world capital of physics for ten days in October. For more information, please visit the S...

e-EPS News: Highlights from the European Physical Society

CERN Multimedia

e-EPS News

2011-01-01

e-EPS News is a monthly addition to the CERN Bulletin line-up, showcasing articles from e-EPS – the European Physical Society newsletter – as part of a collaboration between the two publications.   DESY and INFN physicists win 2011 Enrico Fermi prize The 2011 Enrico Fermi prize of the Italian Physical Society (Società Italiana di Fisica, SIF) has been awarded, for work in the field of experimental particle physics, to Dieter Haidt of the DESY Laboratory at Hamburg and to Antonino Pullia of the University of Milano Bicocca and Istituto Nazionale di Fisica Nucleare, “for their fundamental contribution to the discovery of weak neutral currents with the Gargamelle bubble chamber at CERN”. The Enrico Fermi Prize is awarded yearly to members of the society who especially honour physics by their discoveries. For more information on the prize, please visit the Italian Physical Society website.   Consultation on the future of European Uni...

Exploring strategies for PrEP adherence and dosing preferences in the context of sexualized recreational drug use among MSM: a qualitative study.

Science.gov (United States)

Closson, Elizabeth F; Mitty, Jennifer A; Malone, Jowanna; Mayer, Kenneth H; Mimiaga, Matthew J

2018-02-01

The use of recreational drugs while having sex is associated with increased HIV incidence among men who have sex with men (MSM). Taking a daily antiretroviral pill, or pre-exposure prophylaxis (PrEP) is a biomedical intervention to prevent HIV. However, the efficacy of PrEP is closely tied with high levels of adherence. While PrEP has the potential to reduce HIV acquisition, the use of recreational drugs may impede adherence. We explored perceptions of PrEP utilization and regimen preferences among 40 HIV-negative, MSM who reported concurrent recreational drug use and condomless anal sex with a man. Semi-structured qualitative interviews were conducted and the data were analyzed using a qualitative descriptive approach. Participants perceived that it would be challenging to take PrEP while high on crystal meth, crack, powder cocaine, ecstasy and/or GHB. However, men identified strategies for using PrEP when they were not high on these drugs, including taking the pill when they started their day and integrating PrEP into an established routine, such as when taking other medications or preparing for sex. PrEP regimen preferences seemed to be shaped by the frequency in which participants used drugs and their ability to plan for sex. Taking PrEP everyday was appealing for those who regularly engaged in sexualized recreational drug use. Accounts depict these sexual interactions as frequent but unpredictable. A daily regimen would allow them to be prepared for sex without having to plan. An event-driven regimen was acceptable to men who occasionally used recreational drugs in the context of sex. For this group, sex usually occurred was generally prearranged. Patterns of sex and recreational drug use figured largely into participants' framings of how they would use PrEP. These behaviors will likely play a role in the uptake of and adherence to PrEP among this population.

Perceived Advantages and Disadvantages of Using Pre-Exposure Prophylaxis (PrEP) among Sexually Active Black Women

Science.gov (United States)

Bond, Keosha T.; Gunn, Alana J.

2017-01-01

Knowledge of pre-exposure prophylaxis (PrEP) continues to remain scarce among Black women who are disproportionally affected by HIV in the United States. A thematic analysis of open-ended questions from a sample of Black women (n=119) who completed a mix-methods, online, e-health study was conducted to examine the perceived advantages and disadvantages of using PrEP. Being a female controlled method, empowerment, option for women with risky sex partners, and serodiscordant couples were advantages described. Disadvantages of PrEP were identified as the complexity of the choice, encouragement of sex with risky partners, increased burden, promotion of unprotected sex, and newness of the drug. PMID:28725660

A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP in clinical settings to prevent HIV infection.

Directory of Open Access Journals (Sweden)

Emily A Arnold

Full Text Available A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC can reduce HIV acquisition among men who have sex with men (MSM and transgender (TG women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States.Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time.Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations.While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP

A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection.

Science.gov (United States)

Arnold, Emily A; Hazelton, Patrick; Lane, Tim; Christopoulos, Katerina A; Galindo, Gabriel R; Steward, Wayne T; Morin, Stephen F

2012-01-01

A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States. Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time. Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations. While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP in their

RESEARCH ARTICLE Co-overexpression of EpCAM and c-myc ...

Indian Academy of Sciences (India)

Purpose:The overexpression of epithelial cell adhesion molecule (EpCAM) ... Half LIM domain protein2), and the transcription factor Lef1 that is cleaved by presenilin-2 ..... and self-renewal capability, producing a rapidly dividing tumor mass.

Delimitation of the Earliness per se D1 (Eps-D1) flowering gene to a subtelomeric chromosomal deletion in bread wheat (Triticum aestivum)

Science.gov (United States)

Zikhali, Meluleki; Wingen, Luzie U.; Griffiths, Simon

2016-01-01

Earliness per se (Eps) genes account for the variation in flowering time when vernalization and photoperiod requirements are satisfied. Genomics and bioinformatics approaches were used to describe allelic variation for 40 Triticum aestivum genes predicted, by synteny with Brachypodium distachyon, to be in the 1DL Eps region. Re-sequencing 1DL genes revealed that varieties carrying early heading alleles at this locus, Spark and Cadenza, carry a subtelomeric deletion including several genes. The equivalent region in Rialto and Avalon is intact. A bimodal distribution in the segregating Spark X Rialto single seed descent (SSD) populations enabled the 1DL QTL to be defined as a discrete Mendelian factor, which we named Eps-D1. Near isogenic lines (NILs) and NIL derived key recombinants between markers flanking Eps-D1 suggest that the 1DL deletion contains the gene(s) underlying Eps-D1. The deletion spans the equivalent of the Triticum monoccocum Eps-A m 1 locus, and hence includes MODIFIER OF TRANSCRIPTION 1 (MOT1) and FTSH PROTEASE 4 (FTSH4), the candidates for Eps-A m 1. The deletion also contains T. aestivum EARLY FLOWERING 3-D1 (TaELF3-D1) a homologue of the Arabidopsis thaliana circadian clock gene EARLY FLOWERING 3. Eps-D1 is possibly a homologue of Eps-B1 on chromosome 1BL. NILs carrying the Eps-D1 deletion have significantly reduced total TaELF3 expression and altered TaGIGANTEA (TaGI) expression compared with wild type. Altered TaGI expression is consistent with an ELF3 mutant, hence we propose TaELF3-D1 as the more likely candidate for Eps-D1. This is the first direct fine mapping of Eps effect in bread wheat. PMID:26476691

Delimitation of the Earliness per se D1 (Eps-D1) flowering gene to a subtelomeric chromosomal deletion in bread wheat (Triticum aestivum).

Science.gov (United States)

Zikhali, Meluleki; Wingen, Luzie U; Griffiths, Simon

2016-01-01

Earliness per se (Eps) genes account for the variation in flowering time when vernalization and photoperiod requirements are satisfied. Genomics and bioinformatics approaches were used to describe allelic variation for 40 Triticum aestivum genes predicted, by synteny with Brachypodium distachyon, to be in the 1DL Eps region. Re-sequencing 1DL genes revealed that varieties carrying early heading alleles at this locus, Spark and Cadenza, carry a subtelomeric deletion including several genes. The equivalent region in Rialto and Avalon is intact. A bimodal distribution in the segregating Spark X Rialto single seed descent (SSD) populations enabled the 1DL QTL to be defined as a discrete Mendelian factor, which we named Eps-D1. Near isogenic lines (NILs) and NIL derived key recombinants between markers flanking Eps-D1 suggest that the 1DL deletion contains the gene(s) underlying Eps-D1. The deletion spans the equivalent of the Triticum monoccocum Eps-A (m) 1 locus, and hence includes MODIFIER OF TRANSCRIPTION 1 (MOT1) and FTSH PROTEASE 4 (FTSH4), the candidates for Eps-A (m) 1. The deletion also contains T. aestivum EARLY FLOWERING 3-D1 (TaELF3-D1) a homologue of the Arabidopsis thaliana circadian clock gene EARLY FLOWERING 3. Eps-D1 is possibly a homologue of Eps-B1 on chromosome 1BL. NILs carrying the Eps-D1 deletion have significantly reduced total TaELF3 expression and altered TaGIGANTEA (TaGI) expression compared with wild type. Altered TaGI expression is consistent with an ELF3 mutant, hence we propose TaELF3-D1 as the more likely candidate for Eps-D1. This is the first direct fine mapping of Eps effect in bread wheat. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes.

Science.gov (United States)

Hassouneh, Ramzi; Nasrallah, Rania; Zimpelmann, Joe; Gutsol, Alex; Eckert, David; Ghossein, Jamie; Burns, Kevin D; Hébert, Richard L

2016-06-01

The first clinical manifestation of diabetes is polyuria. The prostaglandin E2 (PGE2) receptor EP3 antagonises arginine vasopressin (AVP)-mediated water reabsorption and its expression is increased in the diabetic kidney. The purpose of this work was to study the contribution of EP3 to diabetic polyuria and renal injury. Male Ep 3 (-/-) (also known as Ptger3 (-/-)) mice were treated with streptozotocin (STZ) to generate a mouse model of diabetes and renal function was evaluated after 12 weeks. Isolated collecting ducts (CDs) were microperfused to study the contribution of EP3 to AVP-mediated fluid reabsorption. Ep 3 (-/-)-STZ mice exhibited attenuated polyuria and increased urine osmolality compared with wild-type STZ (WT-STZ) mice, suggesting enhanced water reabsorption. Compared with WT-STZ mice, Ep 3 (-/-)-STZ mice also had increased protein expression of aquaporin-1, aquaporin-2, and urea transporter A1, and reduced urinary AVP excretion, but increased medullary V2 receptors. In vitro microperfusion studies indicated that Ep 3 (-/-) and WT-STZ CDs responded to AVP stimulation similarly to those of wild-type mice, with a 60% increase in fluid reabsorption. In WT non-injected and WT-STZ mice, EP3 activation with sulprostone (PGE2 analogue) abrogated AVP-mediated water reabsorption; this effect was absent in mice lacking EP3. A major finding of this work is that Ep 3 (-/-)-STZ mice showed blunted renal cyclooxygenase-2 protein expression, reduced renal hypertrophy, reduced hyperfiltration and reduced albuminuria, as well as diminished tubular dilation and nuclear cysts. Taken together, the data suggest that EP3 contributes to diabetic polyuria by inhibiting expression of aquaporins and that it promotes renal injury during diabetes. EP3 may prove to be a promising target for more selective management of diabetic kidney disease.

Selective inhibition of prostaglandin E2 receptors EP2 and EP4 induces apoptosis of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and beta-catenin pathways and activation of intrinsic apoptotic mechanisms.

Science.gov (United States)

Banu, Sakhila K; Lee, JeHoon; Speights, V O; Starzinski-Powitz, Anna; Arosh, Joe A

2009-08-01

Endometriosis is a benign chronic gynecological disease of reproductive-age women characterized by the presence of functional endometrial tissues outside the uterine cavity. It is an estrogen-dependent disease. Current treatment modalities to inhibit biosynthesis and actions of estrogen compromise menstruation, pregnancy, and the reproductive health of women and fail to prevent reoccurrence of disease. There is a critical need to identify new specific signaling modules for non-estrogen-targeted therapies for endometriosis. In our previous study, we reported that selective inhibition of cyclooxygenase-2 prevented survival, migration, and invasion of human endometriotic epithelial and stromal cells, which was due to decreased prostaglandin E(2) (PGE(2)) production. In this study, we determined mechanisms through which PGE(2) promoted survival of human endometriotic cells. Results of the present study indicate that 1) PGE(2) promotes survival of human endometriotic cells through EP2 and EP4 receptors by activating ERK1/2, AKT, nuclear factor-kappaB, and beta-catenin signaling pathways; 2) selective inhibition of EP2 and EP4 suppresses these cell survival pathways and augments interactions between proapoptotic proteins (Bax and Bad) and antiapoptotic proteins (Bcl-2/Bcl-XL), facilitates the release of cytochrome c, and thus activates caspase-3/poly (ADP-ribose) polymerase-mediated intrinsic apoptotic pathways; and 3) these PGE(2) signaling components are more abundantly expressed in ectopic endometriosis tissues compared with eutopic endometrial tissues during the menstrual cycle in women. These novel findings may provide an important molecular framework for further evaluation of selective inhibition of EP2 and EP4 as potential therapy, including nonestrogen target, to expand the spectrum of currently available treatment options for endometriosis in women.

Oral Pre-Exposure Prophylaxis (PrEP) for Prevention of HIV in Serodiscordant Heterosexual Couples in the United States: Opportunities and Challenges

Science.gov (United States)

Myers, Julie E.; Kurth, Ann E.; Cohen, Stephanie E.; Mannheimer, Sharon B.; Simmons, Janie; Pouget, Enrique R.; Trabold, Nicole; Haberer, Jessica E.

2014-01-01

Abstract Oral HIV pre-exposure prophylaxis (PrEP) is a promising new biomedical prevention approach in which HIV-negative individuals are provided with daily oral antiretroviral medication for the primary prevention of HIV-1. Several clinical trials have demonstrated efficacy of oral PrEP for HIV prevention among groups at high risk for HIV, with adherence closely associated with level of risk reduction. In the United States (US), three groups have been prioritized for initial implementation of PrEP—injection drug users, men who have sex with men at substantial risk for HIV, and HIV-negative partners within serodiscordant heterosexual couples. Numerous demonstration projects involving PrEP implementation among MSM are underway, but relatively little research has been devoted to study PrEP implementation in HIV-serodiscordant heterosexual couples in the US. Such couples face a unique set of challenges to PrEP implementation at the individual, couple, and provider level with regard to PrEP uptake and maintenance, adherence, safety and toxicity, clinical monitoring, and sexual risk behavior. Oral PrEP also provides new opportunities for serodiscordant couples and healthcare providers for primary prevention and reproductive health. This article provides a review of the critical issues, challenges, and opportunities involved in the implementation of oral PrEP among HIV-serodiscordant heterosexual couples in the US. PMID:25045996

Composition of Extracellular Polymeric Substances (EPS) produced by Flavobacterium columnare isolated from tropical fish in Brazil.

Science.gov (United States)

de Alexandre Sebastião, Fernanda; Pilarski, Fabiana; Lemos, Manoel Victor Franco

2013-01-01

Thirty nine isolates of Flavobacterium columnare from Brazilian fish farms had their carbohydrate composition of EPS evaluated by high efficiency liquid chromatography, using the phenol-sulfuric acid method of EPS. The occurrence of capsules on F. columnare cells was not directly related to biofilm formation, and the predominant monosaccharide is glucose.

Networks of conforming or nonconforming individuals tend to reach satisfactory decisions.

Science.gov (United States)

Ramazi, Pouria; Riehl, James; Cao, Ming

2016-11-15

Binary decisions of agents coupled in networks can often be classified into two types: "coordination," where an agent takes an action if enough neighbors are using that action, as in the spread of social norms, innovations, and viral epidemics, and "anticoordination," where too many neighbors taking a particular action causes an agent to take the opposite action, as in traffic congestion, crowd dispersion, and division of labor. Both of these cases can be modeled using linear-threshold-based dynamics, and a fundamental question is whether the individuals in such networks are likely to reach decisions with which they are satisfied. We show that, in the coordination case, and perhaps more surprisingly, also in the anticoordination case, the agents will indeed always tend to reach satisfactory decisions, that is, the network will almost surely reach an equilibrium state. This holds for every network topology and every distribution of thresholds, for both asynchronous and partially synchronous decision-making updates. These results reveal that irregular network topology, population heterogeneity, and partial synchrony are not sufficient to cause cycles or nonconvergence in linear-threshold dynamics; rather, other factors such as imitation or the coexistence of coordinating and anticoordinating agents must play a role.

Lepidopteran larva consumption of soybean foliage: basis for developing multiple-species economic thresholds for pest management decisions.

Science.gov (United States)

Bueno, Regiane Cristina Oliveira de Freitas; Bueno, Adeney de Freitas; Moscardi, Flávio; Parra, José Roberto Postali; Hoffmann-Campo, Clara Beatriz

2011-02-01

Defoliation by Anticarsia gemmatalis (Hübner), Pseudoplusia includens (Walker), Spodoptera eridania (Cramer), S. cosmioides (Walker) and S. frugiperda (JE Smith) (Lepidoptera: Noctuidae) was evaluated in four soybean genotypes. A multiple-species economic threshold (ET), based upon the species' feeding capacity, is proposed with the aim of improving growers' management decisions on when to initiate control measures for the species complex. Consumption by A. gemmatalis, S. cosmioides or S. eridania on different genotypes was similar. The highest consumption of P. includens was 92.7 cm(2) on Codetec 219RR; that of S. frugiperda was 118 cm(2) on Codetec 219RR and 115.1 cm(2) on MSoy 8787RR. The insect injury equivalent for S. cosmoides, calculated on the basis of insect consumption, was double the standard consumption by A. gemmatalis, and statistically different from the other species tested, which were similar to each other. As S. cosmioides always defoliated nearly twice the leaf area of the other species, the injury equivalent would be 2 for this lepidopteran species and 1 for the other species. The recommended multiple-species ET to trigger the beginning of insect control would then be 20 insect equivalents per linear metre. Copyright © 2010 Society of Chemical Industry.

Highlights from e-EPS: Physics league… for kick-ass students

CERN Multimedia

Bénédicte Huchet

2013-01-01

e-EPS News is an addition to the CERN Bulletin line-up, showcasing articles from e-EPS – the European Physical Society newsletter – as part of a collaboration between the two publications.   The International Association of Physics Students (IAPS), the Dutch umbrella organisation for physics study associations (SPIN) and the physics students association in Utrecht (A–Eskwadraat) have launched a new contest challenging physics undergraduate students. The first edition of the Physics League Across Numerous Countries for Kick-ass Students (PLANCKS) will be organised in April 2014 in Utrecht, the Netherlands. The competition focuses on theoretical physics problems to be solved by participating teams. Some sample exercises are already available on the PLANCKS website. The goal of the competition is to increase the international collaboration, social activities and personal development of individual contestants. By bringing together physics students from dif...

Beam-helicity associated electroproduction of real photons ep {yields} e{gamma}{pi}N in the {Delta}-resonance region

Energy Technology Data Exchange (ETDEWEB)

Airapetian, A. [Giessen Univ. (Germany). 2. Physikalisches Inst.; Michigan Univ., Ann Arbor, MI (United States). Randall Laboratory of Physics; Akopov, N. [Yerevan Physics Institute (Argentina); Aschenauer, E.C. [DESY Zeuthen (Germany)] [and others; Collaboration: HERMES Collaboration

2013-10-15

The beam-helicity asymmetry in associated electroproduction of real photons, ep {yields} e{gamma}{pi}N, in the {Delta}(1232)-resonance region is measured using the longitudinally polarized HERA positron beam and an unpolarized hydrogen target. Azimuthal Fourier amplitudes of this asymmetry are extracted separately for two channels, ep {yields} e{gamma}{pi}{sup 0}p and ep {yields} e{gamma}{pi}{sup +}n, from a data set collected with a recoil detector. All asymmetry amplitudes are found to be consistent with zero.

Comparing the impact of increasing condom use or HIV pre-exposure prophylaxis (PrEP use among female sex workers

Directory of Open Access Journals (Sweden)

Zindoga Mukandavire

2016-03-01

Full Text Available In many settings, interventions targeting female sex workers (FSWs could significantly reduce the overall transmission of HIV. To understand the role HIV pre-exposure prophylaxis (PrEP could play in controlling HIV transmission amongst FSWs, it is important to understand how its impact compares with scaling-up condom use—one of the proven HIV prevention strategies for FSWs. It is important to remember that condoms also have other benefits such as reducing the incidence of sexually transmitted infections and preventing pregnancy. A dynamic deterministic model of HIV transmission amongst FSWs, their clients and other male partners (termed ‘pimps’ was used to compare the protection provided by PrEP for HIV-negative FSWs with FSWs increasing their condom use with clients and/or pimps. For different HIV prevalence scenarios, levels of pimp interaction, and baseline condom use, we estimated the coverage of PrEP that gives the same reduction in endemic FSW HIV prevalence or HIV infections averted as different increases in condom use. To achieve the same impact on FSW HIV prevalence as increasing condom use by 1%, the coverage of PrEP has to increase by >2%. The relative impact of PrEP increases for scenarios where pimps contribute to HIV transmission, but not greatly, and decreases with higher baseline condom use. In terms of HIV infections averted over 10 years, the relative impact of PrEP compared to condoms was reduced, with a >3% increase in PrEP coverage achieving the same impact as a 1% increase in condom use. Condom promotion interventions should remain the mainstay HIV prevention strategy for FSWs, with PrEP only being implemented once condom interventions have been maximised or to fill prevention gaps where condoms cannot be used.

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

Science.gov (United States)

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.

Inhibition of Pre-Supplementary Motor Area by Continuous Theta Burst Stimulation Leads to More Cautious Decision-making and More Efficient Sensory Evidence Integration.

Science.gov (United States)

Tosun, Tuğçe; Berkay, Dilara; Sack, Alexander T; Çakmak, Yusuf Ö; Balcı, Fuat

2017-08-01

Decisions are made based on the integration of available evidence. The noise in evidence accumulation leads to a particular speed-accuracy tradeoff in decision-making, which can be modulated and optimized by adaptive decision threshold setting. Given the effect of pre-SMA activity on striatal excitability, we hypothesized that the inhibition of pre-SMA would lead to higher decision thresholds and an increased accuracy bias. We used offline continuous theta burst stimulation to assess the effect of transient inhibition of the right pre-SMA on the decision processes in a free-response two-alternative forced-choice task within the drift diffusion model framework. Participants became more cautious and set higher decision thresholds following right pre-SMA inhibition compared with inhibition of the control site (vertex). Increased decision thresholds were accompanied by an accuracy bias with no effects on post-error choice behavior. Participants also exhibited higher drift rates as a result of pre-SMA inhibition compared with the vertex inhibition. These results, in line with the striatal theory of speed-accuracy tradeoff, provide evidence for the functional role of pre-SMA activity in decision threshold modulation. Our results also suggest that pre-SMA might be a part of the brain network associated with the sensory evidence integration.

Automated, simple, and efficient influenza RNA extraction from clinical respiratory swabs using TruTip and epMotion.

Science.gov (United States)

Griesemer, Sara B; Holmberg, Rebecca; Cooney, Christopher G; Thakore, Nitu; Gindlesperger, Alissa; Knickerbocker, Christopher; Chandler, Darrell P; St George, Kirsten

2013-09-01

Rapid, simple and efficient influenza RNA purification from clinical samples is essential for sensitive molecular detection of influenza infection. Automation of the TruTip extraction method can increase sample throughput while maintaining performance. To automate TruTip influenza RNA extraction using an Eppendorf epMotion robotic liquid handler, and to compare its performance to the bioMerieux easyMAG and Qiagen QIAcube instruments. Extraction efficacy and reproducibility of the automated TruTip/epMotion protocol was assessed from influenza-negative respiratory samples spiked with influenza A and B viruses. Clinical extraction performance from 170 influenza A and B-positive respiratory swabs was also evaluated and compared using influenza A and B real-time RT-PCR assays. TruTip/epMotion extraction efficacy was 100% in influenza virus-spiked samples with at least 745 influenza A and 370 influenza B input gene copies per extraction, and exhibited high reproducibility over four log10 concentrations of virus (extraction were also positive following TruTip extraction. Overall Ct value differences obtained between TruTip/epMotion and easyMAG/QIAcube clinical extracts ranged from 1.24 to 1.91. Pairwise comparisons of Ct values showed a high correlation of the TruTip/epMotion protocol to the other methods (R2>0.90). The automated TruTip/epMotion protocol is a simple and rapid extraction method that reproducibly purifies influenza RNA from respiratory swabs, with comparable efficacy and efficiency to both the easyMAG and QIAcube instruments. Copyright © 2013 Elsevier B.V. All rights reserved.

How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact.

Directory of Open Access Journals (Sweden)

Dobromir T Dimitrov

Full Text Available Randomized controlled trials reported that pre-exposure prophylaxis (PrEP with tenofovir and emtricitabine rarely selects for drug resistance. However, drug resistance due to PrEP is not completely understood. In daily practice, PrEP will not be used under the well-controlled conditions available in the trials, suggesting that widespread use of PrEP can result in increased drug resistance.We surveyed expert virologists with questions about biological assumptions regarding drug resistance due to PrEP use. The influence of these assumptions on the prevalence of drug resistance and the fraction of HIV transmitted resistance was studied with a mathematical model. For comparability, 50% PrEP-coverage of and 90% per-act efficacy of PrEP in preventing HIV acquisition are assumed in all simulations.Virologists disagreed on the following: the time until resistance emergence (range: 20-180 days in infected PrEP users with breakthrough HIV infections; the efficacy of PrEP against drug-resistant HIV (25%-90%; and the likelihood of resistance acquisition upon transmission (10%-75%. These differences translate into projections of 0.6%- 1% and 3.5%-6% infected individuals with detectable resistance 10 years after introducing PrEP, assuming 100% and 50% adherence, respectively. The rate of resistance emergence following breakthrough HIV infection and the rate of resistance reversion after PrEP use is discontinued, were the factors identified as most influential on the expected resistance associated with PrEP. Importantly, 17-23% infected individuals could virologically fail treatment as a result of past PrEP use or transmitted resistance to PrEP with moderate adherence.There is no broad consensus on quantification of key biological processes that underpin the emergence of PrEP-associated drug resistance. Despite this, the contribution of PrEP use to the prevalence of the detectable drug resistance is expected to be small. However, individuals who become

Biological Motion induced mu suppression is reduced in Early Psychosis (EP) patients with active negative symptoms and Autism Spectrum Disorders (ASD).

Science.gov (United States)

Minichino, Amedeo; Singh, Fiza; Pineda, Jaime; Friederich, Elisabeth; Cadenhead, Kristin S

2016-04-30

There is evidence of genetic and neural system overlap in Autism Spectrum Disorder (ASD) and Early Psychosis (EP). Five datasets were pooled to compare mu suppression index (MSI), a proxy of mirror neuron activity, in EP, high functioning ASD, and healthy subjects (HS). ASDs and EPs with "active" negative symptoms showed significant differences in mu suppression, in response to Biological Motion/point-light display animation, compared to HS. Preliminary findings suggest that similar neural network deficits in ASD and EP could be driven by the expression of negative symptoms in the latter group of patients. These findings may aid future studies on EP and ASD and facilitate the formulation of new hypotheses regarding their pathophysiology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Preferences for Injectable PrEP Among Young U.S. Cisgender Men and Transgender Women and Men Who Have Sex with Men.

Science.gov (United States)

Biello, Katie B; Hosek, Sybil; Drucker, Morgan T; Belzer, Marvin; Mimiaga, Matthew J; Marrow, Elliot; Coffey-Esquivel, Julia; Brothers, Jennifer; Mayer, Kenneth H

2017-09-19

Young men who have sex with men account for approximately 20% of incident HIV infections in the U.S. Antiretroviral pre-exposure prophylaxis (PrEP) administered as a daily pill has been shown to decrease HIV acquisition in at-risk individuals. New modalities for PrEP are being developed and tested, including injectable PrEP; however, acceptability of these emerging modalities has not yet been examined in youth. We conducted six focus groups with 36 young men and transgender men and women who have sex with men in Boston, Chicago, and Los Angeles in 2016 to assess interest in and preference for different PrEP modalities. Youth were purposively recruited based on diversity of age, race/ethnicity, and prior PrEP experience. Data were coded using content coding based on key domains of the interview guide, in particular around the central themes of interest in and barriers and facilitators to injectable PrEP use. Participants were knowledgeable about oral PrEP but suggested barriers to broader uptake, including stigma, marginalization, and access to information. While participants were split on preference for injectable versus oral PrEP, they agreed quarterly injections may be more manageable and better for those who have adherence difficulties and for those who engage in sex more frequently. Concerns specific to injectable PrEP included: severity/duration of side effects, pain, level of protection prior to next injection, distrust of medical system and injections, and cost. Understanding barriers to and preferences for diverse prevention modalities will allow for more HIV prevention options, improved products, and better interventions, thus allowing individuals to make informed HIV prevention choices.

PMU Placement Based on Heuristic Methods, when Solving the Problem of EPS State Estimation

OpenAIRE

I. N. Kolosok; E. S. Korkina; A. M. Glazunova

2014-01-01

Creation of satellite communication systems gave rise to a new generation of measurement equipment – Phasor Measurement Unit (PMU). Integrated into the measurement system WAMS, the PMU sensors provide a real picture of state of energy power system (EPS). The issues of PMU placement when solving the problem of EPS state estimation (SE) are discussed in many papers. PMU placement is a complex combinatorial problem, and there is not any analytical function to optimize its variables. Therefore,...

Los epónimos en las ciencias médicas: errores históricos que originan injusticias

OpenAIRE

Duque-Parra, Jorge Eduardo; Barco-Ríos, John; Dávila-Alzate, Natalia

2018-01-01

Resumen Introducción. A lo largo del tiempo, en las ciencias médicas se han usado epónimos para designar estructuras anatómicas, aunque no proporcionan ninguna información descriptiva ni funcional, lo que equivale a un desatino en la lógica del pensamiento actual. Se usan incluso dobles y triples epónimos para nombrar una misma estructura, lo cual crea una confusión que hace pensar que su descubrimiento o descripción fue realizada por varios personajes al mismo tiempo. Pese a que los epónimo...

Active feedback control of kink modes in tokamaks: 3D VALEN modeling and HBT-EP experiments

International Nuclear Information System (INIS)

Maurer, D.A.

2002-01-01

Significant progress in the development of active feedback control as a robust technique for the suppression of the wall stabilized external kink or resistive wall mode (RWM) in tokamaks has been achieved through a combination of modeling and experiments. Results from the 3D feedback modeling code VALEN, which serves as the primary analysis and feedback control design tool for RWM studies on the HBT-EP and DIII-D experiments, are in good agreement with observations. VALEN modeling of proposed advanced control system designs on HBT-EP, DIII-D, NSTX, and FIRE are predicted to approach the ideal wall beta limit in agreement with design principles based on simple single mode analytic theory of RWM feedback control. Benchmark experiments on HBT-EP have shown suppression of plasma disruption at rational edge q values using active feedback control in agreement with model predictions. In addition, the observation in HBT-EP of the plasma amplification of static resonant magnetic fields in plasmas marginally stable to the RWM is in agreement with theory. (author)

Ultrasensitivity of the Bacillus subtilis sporulation decision.

Science.gov (United States)

Narula, Jatin; Devi, Seram N; Fujita, Masaya; Igoshin, Oleg A

2012-12-11

Starving Bacillus subtilis cells execute a gene expression program resulting in the formation of stress-resistant spores. Sporulation master regulator, Spo0A, is activated by a phosphorelay and controls the expression of a multitude of genes, including the forespore-specific sigma factor σ(F) and the mother cell-specific sigma factor σ(E). Identification of the system-level mechanism of the sporulation decision is hindered by a lack of direct control over Spo0A activity. This limitation can be overcome by using a synthetic system in which Spo0A activation is controlled by inducing expression of phosphorelay kinase KinA. This induction results in a switch-like increase in the number of sporulating cells at a threshold of KinA. Using a combination of mathematical modeling and single-cell microscopy, we investigate the origin and physiological significance of this ultrasensitive threshold. The results indicate that the phosphorelay is unable to achieve a sufficiently fast and ultrasensitive response via its positive feedback architecture, suggesting that the sporulation decision is made downstream. In contrast, activation of σ(F) in the forespore and of σ(E) in the mother cell compartments occurs via a cascade of coherent feed-forward loops, and thereby can produce fast and ultrasensitive responses as a result of KinA induction. Unlike σ(F) activation, σ(E) activation in the mother cell compartment only occurs above the KinA threshold, resulting in completion of sporulation. Thus, ultrasensitive σ(E) activation explains the KinA threshold for sporulation induction. We therefore infer that under uncertain conditions, cells initiate sporulation but postpone making the sporulation decision to average stochastic fluctuations and to achieve a robust population response.

Threshold quantum cryptography

International Nuclear Information System (INIS)

Tokunaga, Yuuki; Okamoto, Tatsuaki; Imoto, Nobuyuki

2005-01-01

We present the concept of threshold collaborative unitary transformation or threshold quantum cryptography, which is a kind of quantum version of threshold cryptography. Threshold quantum cryptography states that classical shared secrets are distributed to several parties and a subset of them, whose number is greater than a threshold, collaborates to compute a quantum cryptographic function, while keeping each share secretly inside each party. The shared secrets are reusable if no cheating is detected. As a concrete example of this concept, we show a distributed protocol (with threshold) of conjugate coding

Sex, PrEP, and Stigma: Experiences with HIV Pre-exposure Prophylaxis Among New York City MSM Participating in the HPTN 067/ADAPT Study.

Science.gov (United States)

Franks, Julie; Hirsch-Moverman, Yael; Loquere, Avelino S; Amico, K Rivet; Grant, Robert M; Dye, Bonnie J; Rivera, Yan; Gamboa, Robert; Mannheimer, Sharon B

2018-04-01

The HPTN 067/Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT) study evaluated daily and non-daily dosing schedules for oral pre-exposure prophylaxis (PrEP) to prevent HIV. A qualitative sub-study including focus groups and in-depth interviews was conducted among men who have sex with men participating in New York City to understand their experience with PrEP and study dosing schedules. The 37 sub-study participants were 68% black, 11% white, and 8% Asian; 27% were of Hispanic/Latino ethnicity. Mean age was 34 years. Themes resulting from qualitative analysis include: PrEP is a significant advance for HIV prevention; non-daily dosing of PrEP is congruent with HIV risk; and pervasive stigma connected to HIV and risk behavior is a barrier to PrEP adherence, especially for non-daily dosing schedules. The findings underscore how PrEP intersects with other HIV prevention practices and highlight the need to understand and address multidimensional stigma related to PrEP use.

Competitive adsorption of heavy metal by extracellular polymeric substances (EPS) extracted from sulfate reducing bacteria.

Science.gov (United States)

Wang, Jin; Li, Qing; Li, Ming-Ming; Chen, Tian-Hu; Zhou, Yue-Fei; Yue, Zheng-Bo

2014-07-01

Competitive adsorption of heavy metals by extracellular polymeric substances (EPS) extracted from Desulfovibrio desulfuricans was investigated. Chemical analysis showed that different EPS compositions had different capacities for the adsorption of heavy metals which was investigated using Cu(2+) and Zn(2+). Batch adsorption tests indicated that EPS had a higher combined ability with Zn(2+) than Cu(2+). This was confirmed and explained by Fourier transform infrared (FTIR) and excitation-emission matrix (EEM) spectroscopy analysis. FTIR analysis showed that both polysaccharides and protein combined with Zn(2+) while only protein combined with Cu(2+). EEM spectra further revealed that tryptophan-like substances were the main compositions reacted with the heavy metals. Moreover, Zn(2+) had a higher fluorescence quenching ability than Cu(2+). Copyright © 2014 Elsevier Ltd. All rights reserved.

Decision Making under Uncertainty: A Neural Model based on Partially Observable Markov Decision Processes

Directory of Open Access Journals (Sweden)

Rajesh P N Rao

2010-11-01

Full Text Available A fundamental problem faced by animals is learning to select actions based on noisy sensory information and incomplete knowledge of the world. It has been suggested that the brain engages in Bayesian inference during perception but how such probabilistic representations are used to select actions has remained unclear. Here we propose a neural model of action selection and decision making based on the theory of partially observable Markov decision processes (POMDPs. Actions are selected based not on a single optimal estimate of state but on the posterior distribution over states (the belief state. We show how such a model provides a unified framework for explaining experimental results in decision making that involve both information gathering and overt actions. The model utilizes temporal difference (TD learning for maximizing expected reward. The resulting neural architecture posits an active role for the neocortex in belief computation while ascribing a role to the basal ganglia in belief representation, value computation, and action selection. When applied to the random dots motion discrimination task, model neurons representing belief exhibit responses similar to those of LIP neurons in primate neocortex. The appropriate threshold for switching from information gathering to overt actions emerges naturally during reward maximization. Additionally, the time course of reward prediction error in the model shares similarities with dopaminergic responses in the basal ganglia during the random dots task. For tasks with a deadline, the model learns a decision making strategy that changes with elapsed time, predicting a collapsing decision threshold consistent with some experimental studies. The model provides a new framework for understanding neural decision making and suggests an important role for interactions between the neocortex and the basal ganglia in learning the mapping between probabilistic sensory representations and actions that maximize

The Insignificance of Thresholds in Environmental Impact Assessment: An Illustrative Case Study in Canada

Science.gov (United States)

Murray, Cathryn Clarke; Wong, Janson; Singh, Gerald G.; Mach, Megan; Lerner, Jackie; Ranieri, Bernardo; Peterson St-Laurent, Guillaume; Guimaraes, Alice; Chan, Kai M. A.

2018-06-01

Environmental assessment is the process that decision-makers rely on to predict, evaluate, and prevent biophysical, social, and economic impacts of potential project developments. The determination of significance in environmental assessment is central to environmental management in many nations. We reviewed ten recent environmental impact assessments from British Columbia, Canada and systematically reviewed and scored significance determination and the approaches used by assessors, the use of thresholds in significance determination, threshold exceedances, and the outcomes. Findings of significant impacts were exceedingly rare and practitioners used a combination of significance determination approaches, most commonly relying upon reasoned argumentation. Quantitative thresholds were rarely employed, with less than 10% of the valued components evaluated using thresholds. Even where quantitative thresholds for significance were exceeded, in every case practitioners used a variety of rationales to demote negative impacts to non-significance. These reasons include combinations of scale (temporal and spatial) of impacts, an already exceeded baseline, model uncertainty and/or substituting less stringent thresholds. Governments and agencies can better protect resources by requiring clear and defensible significance determinations, by making government-defined thresholds legally enforceable and accountable, and by requiring or encouraging significance determination through inclusive and collaborative approaches.

Intensity modulation of cutaneous electrical stimulation: : EPs and subjective ratings

NARCIS (Netherlands)

van der Heide, E.M.; Buitenweg, Jan R.; Marani, Enrico; Rutten, Wim

2006-01-01

Chronic pain research is increasingly focused on the neuroplastic mechanisms underlying subjective pain experience. The latter is often measured using reported pain intensity, e.g. using a numeric rating scale (NRS). Evoked Potentials (EPs) reflect the cortical representation of applied stimuli and

Conflict Resolution as Near-Threshold Decision-Making: A Spiking Neural Circuit Model with Two-Stage Competition for Antisaccadic Task.

Directory of Open Access Journals (Sweden)

Chung-Chuan Lo

2016-08-01

Full Text Available Automatic responses enable us to react quickly and effortlessly, but they often need to be inhibited so that an alternative, voluntary action can take place. To investigate the brain mechanism of controlled behavior, we investigated a biologically-based network model of spiking neurons for inhibitory control. In contrast to a simple race between pro- versus anti-response, our model incorporates a sensorimotor remapping module, and an action-selection module endowed with a "Stop" process through tonic inhibition. Both are under the modulation of rule-dependent control. We tested the model by applying it to the well known antisaccade task in which one must suppress the urge to look toward a visual target that suddenly appears, and shift the gaze diametrically away from the target instead. We found that the two-stage competition is crucial for reproducing the complex behavior and neuronal activity observed in the antisaccade task across multiple brain regions. Notably, our model demonstrates two types of errors: fast and slow. Fast errors result from failing to inhibit the quick automatic responses and therefore exhibit very short response times. Slow errors, in contrast, are due to incorrect decisions in the remapping process and exhibit long response times comparable to those of correct antisaccade responses. The model thus reveals a circuit mechanism for the empirically observed slow errors and broad distributions of erroneous response times in antisaccade. Our work suggests that selecting between competing automatic and voluntary actions in behavioral control can be understood in terms of near-threshold decision-making, sharing a common recurrent (attractor neural circuit mechanism with discrimination in perception.

Contributions to Integral Nuclear Data in ICSBEP and IRPhEP since ND 2013

Energy Technology Data Exchange (ETDEWEB)

Bess, John D.; Briggs, J. Blair; Gulliford, Jim

2016-09-01

The status of the International Criticality Safety Benchmark Evaluation Project (ICSBEP) and the International Reactor Physics Experiment Evaluation Project (IRPhEP) was last discussed directly with the international nuclear data community at ND2013. Since ND2013, integral benchmark data that are available for nuclear data testing has continued to increase. The status of the international benchmark efforts and the latest contributions to integral nuclear data for testing is discussed. Select benchmark configurations that have been added to the ICSBEP and IRPhEP Handbooks since ND2013 are highlighted. The 2015 edition of the ICSBEP Handbook now contains 567 evaluations with benchmark specifications for 4,874 critical, near-critical, or subcritical configurations, 31 criticality alarm placement/shielding configuration with multiple dose points apiece, and 207 configurations that have been categorized as fundamental physics measurements that are relevant to criticality safety applications. The 2015 edition of the IRPhEP Handbook contains data from 143 different experimental series that were performed at 50 different nuclear facilities. Currently 139 of the 143 evaluations are published as approved benchmarks with the remaining four evaluations published in draft format only. Measurements found in the IRPhEP Handbook include criticality, buckling and extrapolation length, spectral characteristics, reactivity effects, reactivity coefficients, kinetics, reaction-rate distributions, power distributions, isotopic compositions, and/or other miscellaneous types of measurements for various types of reactor systems. Annual technical review meetings for both projects were held in April 2016; additional approved benchmark evaluations will be included in the 2016 editions of these handbooks.

Two-stage decision approach to material accounting

International Nuclear Information System (INIS)

Opelka, J.H.; Sutton, W.B.

1982-01-01

The validity of the alarm threshold 4sigma has been checked for hypothetical large and small facilities using a two-stage decision model in which the diverter's strategic variable is the quantity diverted, and the defender's strategic variables are the alarm threshold and the effectiveness of the physical security and material control systems in the possible presence of a diverter. For large facilities, the material accounting system inherently appears not to be a particularly useful system for the deterrence of diversions, and essentially no improvement can be made by lowering the alarm threshold below 4sigma. For small facilities, reduction of the threshold to 2sigma or 3sigma is a cost effective change for the accounting system, but is probably less cost effective than making improvements in the material control and physical security systems

Wnt Signalling Promotes Actin Dynamics during Axon Remodelling through the Actin-Binding Protein Eps8.

Directory of Open Access Journals (Sweden)

Eleanna Stamatakou

Full Text Available Upon arrival at their synaptic targets, axons slow down their growth and extensively remodel before the assembly of presynaptic boutons. Wnt proteins are target-derived secreted factors that promote axonal remodelling and synaptic assembly. In the developing spinal cord, Wnts secreted by motor neurons promote axonal remodelling of NT-3 responsive dorsal root ganglia neurons. Axon remodelling induced by Wnts is characterised by growth cone pausing and enlargement, processes that depend on the re-organisation of microtubules. However, the contribution of the actin cytoskeleton has remained unexplored. Here, we demonstrate that Wnt3a regulates the actin cytoskeleton by rapidly inducing F-actin accumulation in growth cones from rodent DRG neurons through the scaffold protein Dishevelled-1 (Dvl1 and the serine-threonine kinase Gsk3β. Importantly, these changes in actin cytoskeleton occurs before enlargement of the growth cones is evident. Time-lapse imaging shows that Wnt3a increases lamellar protrusion and filopodia velocity. In addition, pharmacological inhibition of actin assembly demonstrates that Wnt3a increases actin dynamics. Through a yeast-two hybrid screen, we identified the actin-binding protein Eps8 as a direct interactor of Dvl1, a scaffold protein crucial for the Wnt signalling pathway. Gain of function of Eps8 mimics Wnt-mediated axon remodelling, whereas Eps8 silencing blocks the axon remodelling activity of Wnt3a. Importantly, blockade of the Dvl1-Eps8 interaction completely abolishes Wnt3a-mediated axonal remodelling. These findings demonstrate a novel role for Wnt-Dvl1 signalling through Eps8 in the regulation of axonal remodeling.

TOMS/EP UV Reflectivity Daily and Monthly Zonal Means V008

Data.gov (United States)

National Aeronautics and Space Administration — This data product contains TOMS/EP UV Reflectivity Daily and Monthly Zonal Means Version 8 data in ASCII format. (The shortname for this Level-3 Earth Probe TOMS...

The Impact of Heterogeneity on Threshold-Limited Social Contagion, and on Crowd Decision-Making

Science.gov (United States)

Karampourniotis, Panagiotis Dimitrios

Recent global events and their poor predictability are often attributed to the complexity of the world event dynamics. A key factor generating the turbulence is human diversity. Here, we study the impact of heterogeneity of individuals on opinion formation and emergence of global biases. In the case of opinion formation, we focus on the heterogeneity of individuals' susceptibility to new ideas. In the case of global biases, we focus on the aggregated heterogeneity of individuals in a country. First, to capture the complex nature of social influencing we use a simple but classic model of contagion spreading in complex social systems, namely the threshold model. We investigate numerically and analytically the transition in the behavior of threshold-limited cascades in the presence of multiple initiators as the distribution of thresholds is varied between the two extreme cases of identical thresholds and a uniform distribution. We show that individuals' heterogeneity of susceptibility governs the dynamics, resulting in different sizes of initiators needed for consensus. Furthermore, given the impact of heterogeneity on the cascade dynamics, we investigate selection strategies for accelerating consensus. To this end, we introduce two new selection strategies for Influence Maximization. One of them focuses on finding the balance between targeting nodes which have high resistance to adoptions versus nodes positioned in central spots in networks. The second strategy focuses on the combination of nodes for reaching consensus, by targeting nodes which increase the group's influence. Our strategies outperform other existing strategies regardless of the susceptibility diversity and network degree assortativity. Finally, we study the aggregated biases of humans in a global setting. The emergence of technology and globalization gives raise to the debate on whether the world moves towards becoming flat, a world where preferential attachment does not govern economic growth. By

Does Pre-exposure prophylaxis (PrEP) for HIV prevention in men who have sex with men (MSM) change risk behavior? A systematic review.

Science.gov (United States)

Freeborn, Kellie; Portillo, Carmen J

2017-08-03

Pre-exposure prophylaxis (PrEP) for HIV has been available since 2012. Even so, PrEP has not been widely accepted among healthcare providers and MSM some of whom are convinced that PrEP decreases condom use, and increases sexually transmitted infections (STIs). A systematic review of the state of the evidence regarding the association of PrEP with condom use, STI incidence and change in sexual risk behaviors in MSM. A structured search of databases resulted in 142 potential citations, but only ten publications met inclusion criteria and underwent data abstraction and critical appraisal. An adapted Cochrane Collaboration domain based assessment tool was used to critically appraise the methodological components of each quantitative study, and the Mixed Methods Appraisal Tool (MMAT) was used to critically appraise qualitative and mixed-methods studies. Condom use in MSM utilizing PrEP is influenced by multiple factors. Studies indicate rates of STIs in treatment and placebo groups were high. PrEP did not significantly change STI rates between baseline and follow-up. Reporting of sexual risk improved when questionnaires were completed in private by clients. Our review found that PrEP may provide an opportunity for MSM to access sexual health care, testing, treatment and counselling services. We did not find any conclusive evidence that PrEP users increase sexual risk behaviors. The perception among healthcare providers that PrEP leads to increased sexual risk behaviors has yet to be confirmed. In order to provide effective sexual health services, clinicians need to be knowledgeable about PrEP as an HIV prevention tool. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Distinguishing hypothetical willingness from behavioral intentions to initiate HIV pre-exposure prophylaxis (PrEP): Findings from a large cohort of gay and bisexual men in the U.S.

Science.gov (United States)

Rendina, H Jonathon; Whitfield, Thomas H F; Grov, Christian; Starks, Tyrel J; Parsons, Jeffrey T

2017-01-01

Much of the data on the acceptability of HIV Pre-Exposure Prophylaxis (PrEP) is based on willingness to take PrEP (i.e., hypothetical receptivity) rather than actual intentions (i.e., planned behavioral action) to do so. We sought to examine differences between hypothetical willingness and behavioral intentions to begin PrEP in a national sample of gay and bisexual men (GBM) across the U.S. We utilized data collected in 2015 to examine differences between those Unwilling (42.6% n = 375), Willing but not intending (41.4%, n = 365), and willing and Intending to take PrEP (15.9%, n = 140) in a multivariable, multinomial logistic regression. Men with less education had higher odds of Intending to take PrEP. Compared to men unsure about PrEP's efficacy, those who believed PrEP was at least 90% efficacious had higher odds of Intending to take PrEP. Those who saw themselves as appropriate candidates for PrEP had higher odds of Intending to take PrEP while those who saw themselves as inappropriate candidates for PrEP had lower odds of Intending to take PrEP in comparison to men unsure if they were appropriate candidates. Increased motivation for condom non-use because of perceived sexual pressure by partners was associated with higher odds of Intending to take PrEP. The groups did not differ by risk behavior nor recent STI diagnosis. Overall, the distinction between willingness and intentions to take PrEP was meaningful and may help explain disparities between PrEP acceptability and uptake. While much of the literature has focused on hypothetical willingness to take PrEP, these results highlight the importance of simultaneously assessing willingness and intentions when examining correspondence with uptake and developing interventions to increase PrEP uptake. Copyright © 2016 Elsevier Ltd. All rights reserved.

'WTF is PrEP?': attitudes towards pre-exposure prophylaxis among men who have sex with men and transgender women in New York City.

Science.gov (United States)

Thomann, Matthew; Grosso, Ashley; Zapata, Richard; Chiasson, Mary Ann

2017-10-06

In the USA, gay and other men who have sex with men and transgender women are disproportionately affected by HIV. Uptake of pre-exposure prophylaxis (PrEP), anti-retroviral therapy to prevent HIV-negative individuals from seroconverting if exposed to HIV, by members of this population remains low, particularly among African-Americans. We conducted two focus groups to assess responses to an online social media campaign focusing on PrEP use in New York City. We designed, produced and disseminated the campaign to address knowledge of PrEP; its physical and psychological side effects; and psychosocial barriers related to PrEP adherence and sex shaming. Focus group participants demonstrated a relatively high knowledge of PrEP, although considerable concern remained about side effects, particularly among Black participants. Participants suggested that stigma against PrEP users was declining as PrEP use became more common, but stigma remained, particularly for those not using condoms. Many focus group participants reported distrust of medical providers and were critical of the commodification of HIV prevention by the pharmaceutical industry. Participants reported that those in romantic relationships confronted unique issues regarding PrEP, namely suspicions of infidelity. Finally, Black participants spoke of the need for more tailored and sensitive representations of Black gay men in future programmes and interventions.

Limits on the effective quark radius from inclusive $ep$ scattering at HERA

CERN Document Server

Abramowicz, H; Adamczyk, L; Adamus, M; Antonelli, S; Aushev, V; Behnke, O; Behrens, U; Bertolin, A; Bloch, I; Boos, EG; Brock, I; Brook, NH; Brugnera, R; Bruni, A; Bussey, PJ; Caldwell, A; Capua, M; Catterall, CD; Chwastowski, J; Ciborowski, J; Ciesielski, R; Cooper-Sarkar, AM; Corradi, M; Dementiev, RK; Devenish, RCE; Dusini, S; Foster, B; Gach, G; Gallo, E; Garfagnini, A; Geiser, A; Gizhko, A; Gladilin, LK; Golubkov, Yu A; Grzelak, G; Guzik, M; Hain, W; Hochman, D; Hori, R; Ibrahim, ZA; Iga, Y; Ishitsuka, M; Januschek, F; Jomhari, NZ; Kadenko, I; Kananov, S; Karshon, U; Kaur, P; Kisielewska, D; Klanner, R; Klein, U; Korzhavina, IA; Kotański, A; Kötz, U; Kovalchuk, N; Kowalski, H; Krupa, B; Kuprash, O; Kuze, M; Levchenko, BB; Levy, A; Limentani, S; Lisovyi, M; Lobodzinska, E; Löhr, B; Lohrmann, E; Longhin, A; Lontkovskyi, D; Lukina, OYu; Makarenko, I; Malka, J; Mohamad Idris, F; Mohammad Nasir, N; Myronenko, V; Nagano, K; Nobe, T; Nowak, RJ; Onishchuk, Yu; Paul, E; Perlański, W; Pokrovskiy, NS; Przybycien, M; Roloff, P; Ruspa, M; Saxon, DH; Schioppa, M; Schneekloth, U; Schörner-Sadenius, T; Shcheglova, LM; Shevchenko, R; Shkola, O; Shyrma, Yu; Singh, I; Skillicorn, IO; Słomiński, W; Solano, A; Stanco, L; Stefaniuk, N; Stern, A; Stopa, P; Sztuk-Dambietz, J; Tassi, E; Tokushuku, K; Tomaszewska, J; Tsurugai, T; Turcato, M; Turkot, O; Tymieniecka, T; Verbytskyi, A; Wan Abdullah, WAT; Wichmann, K; Wing, M; Yamada, S; Yamazaki, Y; Zakharchuk, N; Żarnecki, AF; Zawiejski, L; Zenaiev, O; Zhautykov, BO; Zotkin, DS; Bhadra, S; Gwenlan, C; Hlushchenko, O; Polini, A; Mastroberardino, A; Sukhonos, D

2016-01-01

The high-precision HERA data allows searches up to TeV scales for Beyond the Standard Model contributions to electron-quark scattering. Combined measurements of the inclusive deep inelastic cross sections in neutral and charged current $ep$ scattering corresponding to a luminosity of around 1 fb$^{-1}$ have been used in this analysis. A new approach to the beyond the Standard Model analysis of the inclusive $ep$ data is presented; simultaneous fits of parton distribution functions together with contributions of "new physics" processes were performed. Results are presented considering a finite radius of quarks within the quark form-factor model. The resulting 95% C.L. upper limit on the effective quark radius is $0.43\\cdot 10^{-16}$ cm.

Precipitation thresholds for landslide occurrence near Seattle, Mukilteo, and Everett, Washington

Science.gov (United States)

Scheevel, Caroline R.; Baum, Rex L.; Mirus, Benjamin B.; Smith, Joel B.

2017-04-27

Shallow landslides along coastal bluffs frequently occur in the railway corridor between Seattle and Everett, Washington. These slides disrupt passenger rail service, both because of required track maintenance and because the railroad owner, Burlington Northern Santa Fe Railway, does not allow passenger travel for 48 hours after a disruptive landslide. Sound Transit, which operates commuter trains in the corridor, is interested in a decision-making tool to help preemptively cancel passenger railway service in dangerous conditions and reallocate resources to alternative transportation.Statistical analysis showed that a majority of landslides along the Seattle-Everett Corridor are strongly correlated with antecedent rainfall, but that 21-37 percent of recorded landslide dates experienced less than 1 inch of precipitation in the 3 days preceding the landslide and less than 4 inches of rain in the 15 days prior to the preceding 3 days. We developed two empirical thresholds to identify precipitation conditions correlated with landslide occurrence. The two thresholds are defined as P3 = 2.16-0.44P15 and P3 = 2.16-0.22P32, where P3 is the cumulative precipitation in the 3 days prior to the considered date and P15 or P32 is the cumulative precipitation in the 15 days or 32 days prior to P3 (all measurements given in inches). The two thresholds, when compared to a previously developed threshold, quantitatively improve the prediction rate.We also investigated rainfall intensity-duration (ID) thresholds to determine whether revision would improve identification of moderate-intensity, landslide-producing storms. New, optimized ID thresholds evaluate rainstorms lasting at least 12 hours and identify landslide-inducing storms that were typically missed by previously published ID thresholds. The main advantage of the ID thresholds appears when they are combined with recent-antecedent thresholds because rainfall conditions that exceed both threshold types are more likely to induce

Probing Anomalous WW γ and WWZ Couplings with Polarized Electron Beam at the LHeC and FCC-Ep Collider

CERN Document Server

Turk Cakir, I; Tasci, A T; Cakir, O

2016-01-01

We study the anomalous WWγ and WWZ couplings by calculating total cross sections of two processes at the LHeC with electron beam energy Ee=140 GeV and the proton beam energy Ep=7 TeV, and at the FCC-ep collider with the polarized electron beam energy Ee=80 GeV and the proton beam energy Ep=50 TeV. At the LHeC with electron beam polarization, we obtain the results for the difference of upper and lower bounds as (0.975, 0.118) and (0.285, 0.009) for the anomalous (∆κγ, λγ) and (∆κz, λz) couplings, respectively. As for FCC-ep collider, these bounds are obtained as (1.101, 0.065) and (0.320, 0.002) at an integrated luminosity of Lint=100 fb-1.

Newly Available Reactor Physics Benchmark data in the March 2011 Edition of the IRPhEP Handbook

International Nuclear Information System (INIS)

Bess, John D.; Briggs, J. Blair; Gulliford, Jim

2011-01-01

The International Reactor Physics Experiment Evaluation Project (IRPhEP) was established to preserve integral reactor physics experimental data, including separate or special effects data for nuclear energy and technology applications. Numerous experiments that have been performed worldwide, represent a large investment of infrastructure, expertise, and cost, and are valuable resources of data for present and future research. These valuable assets provide the basis for recording, development, and validation of methods. If the data are compromised, it is unlikely that any of these measurements would be repeated in the future. The purpose of the IRPhEP is to provide an extensively peer-reviewed set of reactor physics-related integral data that can be used by reactor designers and safety analysts to validate the analytical tools used to design next-generation reactors and establish the safety basis for operation of these reactors. Contributors from around the world collaborate in the evaluation and review of selected benchmark experiments for inclusion in the International Handbook of Evaluated Reactor Physics Benchmark Experiments (IRPhEP Handbook). Several new evaluations have been prepared for inclusion in the March 2011 edition of the IRPhEP Handbook.

Transitioning to HIV Pre-Exposure Prophylaxis (PrEP) from Non-Occupational Post-Exposure Prophylaxis (nPEP) in a Comprehensive HIV Prevention Clinic: A Prospective Cohort Study.

Science.gov (United States)

Siemieniuk, Reed A C; Sivachandran, Nirojini; Murphy, Pauline; Sharp, Andrea; Walach, Christine; Placido, Tania; Bogoch, Isaac I

2015-08-01

The uptake of pre-exposure prophylaxis (PrEP) for HIV prevention remains low. We hypothesized that a high proportion of patients presenting for HIV non-occupational post-exposure prophylaxis (nPEP) would be candidates for PrEP based on current CDC guidelines. Outcomes from a comprehensive HIV Prevention Clinic are described. We evaluated all patients who attended the HIV Prevention Clinic for nPEP between January 1, 2013 and September 30, 2014. Each patient was evaluated for PrEP candidacy based on current CDC-guidelines and subjectively based on physician opinion. Patients were then evaluated for initiation of PrEP if they met guideline suggestions. Demographic, social, and behavioral factors were then analyzed with logistic regression for associations with PrEP candidacy and initiation. 99 individuals who attended the nPEP clinic were evaluated for PrEP. The average age was 32 years (range, 18-62), 83 (84%) were male, of whom 46 (55%) men who had have sex with men (MSM). 31 (31%) met CDC guidelines for PrEP initiation, which had very good agreement with physician recommendation (kappa=0.88, 0.78-0.98). Factors associated with PrEP candidacy included sexual exposure to HIV, prior nPEP use, and lack of drug insurance (p<0.05 for all comparisons). Combining nPEP and PrEP services in a dedicated clinic can lead to identification of PrEP candidates and may facilitate PrEP uptake. Strategies to ensure equitable access of PrEP should be explored such that those without drug coverage may also benefit from this effective HIV prevention modality.

Highlights from e-EPS: Neutrino Oscillation / DPG President / Outreach Database

CERN Multimedia

2012-01-01

e-EPS News is a monthly addition to the CERN Bulletin line-up, showcasing articles from e-EPS – the European Physical Society newsletter – as part of a collaboration between the two publications.   Asian experiments unlock neutrino oscillation mystery Two reactor experiments, China’s Daya Bay and Korea’s RENO, have made the best measurement of the neutrino mixing angle, θ13, an essential property for neutrino research. The discovery of a non-zero θ13 at approximately 9˚ – which was published in March and April this year – completes our picture of neutrino mixing. This quite large value for the mixing angle will make it easier to conduct future long baseline neutrino experiments. This, in turn, may lead to a better understanding of the matter-antimatter asymmetry seen in the Universe. Neutrino oscillations – the change in flavour&a...

Highlights from e-EPS: Gender Manifesto / Energy Conference / ERASMUS Anniversary

CERN Multimedia

Hendrik Ferdinande and Ian Randall

2012-01-01

e-EPS News is a monthly addition to the CERN Bulletin line-up, showcasing articles from e-EPS – the European Physical Society newsletter – as part of a collaboration between the two publications.   Manifesto on the Gender Dimension in Research Interested parties are encouraged to sign the Manifesto for Integrated Action on the Gender Dimension in Research and Innovation. The manifesto discusses potential actions to enhance research and innovation by addressing gender equality issues. The manifesto follows on from the European Commission public consultation on the green paper “What actions should be taken at EU level to further strengthen the role of women in science and innovation?”, which received 300 responses, and the subsequent 2011 European Gender Summit, which was attended by over 400 stakeholders. To date, over 2,800 people have signed the manifesto. For more information, and to sign the manifesto, please visit the gender summit website. Seco...

Perceptions of pre-exposure prophylaxis (PrEP) among HIV-negative and HIV-positive men who have sex with men.

OpenAIRE

Jaspal, Rusi; Daramilas, C.

2016-01-01

open access article Pre-exposure prophylaxis (PrEP) is a novel bio-medical HIV prevention op- tion for individuals at high risk of HIV exposure. This qualitative interview study ex- plores perceptions and understandings of PrEP among a sample of 20 HIV-negative and HIV-positive men who have sex with men (MSM) in the UK, where there is a debate about the feasibility of o ering PrEP on the NHS. Data were analysed using qualitative thematic analysis and social representations theory from soci...

Cooverexpression of EpCAM and c-myc genes in malignant breast

Indian Academy of Sciences (India)

oncogene, affects progression, treatment, and diagnosis of many adenocarcinomas. C-myc has been shown to be a downstream target of EpCAM and is also one of the most important proto-oncogenes routinely overexpressed in breast cancer.

Threshold models of recognition and the recognition heuristic

Directory of Open Access Journals (Sweden)

Edgar Erdfelder

2011-02-01

Full Text Available According to the recognition heuristic (RH theory, decisions follow the recognition principle: Given a high validity of the recognition cue, people should prefer recognized choice options compared to unrecognized ones. Assuming that the memory strength of choice options is strongly correlated with both the choice criterion and recognition judgments, the RH is a reasonable strategy that approximates optimal decisions with a minimum of cognitive effort (Davis-Stober, Dana, and Budescu, 2010. However, theories of recognition memory are not generally compatible with this assumption. For example, some threshold models of recognition presume that recognition judgments can arise from two types of cognitive states: (1 certainty states in which judgments are almost perfectly correlated with memory strength and (2 uncertainty states in which recognition judgments reflect guessing rather than differences in memory strength. We report an experiment designed to test the prediction that the RH applies to certainty states only. Our results show that memory states rather than recognition judgments affect use of recognition information in binary decisions.

Influence of bacterial exopolymers on cell adhesion of Desulfovibrio vulgaris on high alloyed steel: Corrosion inhibition by extracellular polymeric substances (EPS)

Energy Technology Data Exchange (ETDEWEB)

Stadler, R.; Wei, L.; Fuerbeth, W. [Karl-Winnacker-Institut, DECHEMA e.V., Theodor-Heuss-Allee 25, 60486 Frankfurt am Main (Germany); Grooters, M.; Kuklinski, A. [University of Duisburg-Essen, Biofilm Centre, Geibelstrasse 41, 47057 Duisburg (Germany)

2010-12-15

Extracellular polymeric substances (EPS) were studied with regard to their potential application as inhibitors of biocorrosion. EPS that have been isolated from biofilms of sulphate-reducing bacteria (SRB) were adsorbed on samples of high alloyed steel (type 1.4301) at different temperatures. The samples were exposed to SRB containing solution and afterwards analysed by fluorescence microscopy (FM). The results show that the EPS form an incomplete layer and lead to a smaller amount of cell adhesion when compared to pure surfaces. The results are discussed with regard to the application of EPS for the prevention of biofilm formation. (Copyright copyright 2010 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

"I Did Not Want to Give Birth to a Child Who has HIV": Experiences Using PrEP During Pregnancy Among HIV-Uninfected Kenyan Women in HIV-Serodiscordant Couples.

Science.gov (United States)

Pintye, Jillian; Beima-Sofie, Kristin M; Kimemia, Grace; Ngure, Kenneth; Trinidad, Susan Brown; Heffron, Renee A; Baeten, Jared M; Odoyo, Josephine; Mugo, Nelly; Bukusi, Elizabeth A; Kelley, Maureen C; John-Stewart, Grace C

2017-11-01

The perceptions, motivations, and beliefs of HIV-uninfected women about pre-exposure prophylaxis (PrEP) use during pregnancy can influence its uptake and adherence. This study elicited the views of HIV-uninfected women with personal experience taking PrEP during pregnancy. Qualitative interviews were conducted with HIV-uninfected women who had personal experience taking PrEP while pregnant. Semistructured interviews were conducted with 21 HIV-uninfected Kenyan women in HIV-serodiscordant couples enrolled in an open-label PrEP demonstration project who became pregnant while using PrEP and continued PrEP through their pregnancy. Interviews were audio-recorded and transcribed into English. A qualitative descriptive analysis was performed, using a constant comparison approach to identify key themes related to PrEP use in pregnancy. Desire to remain HIV uninfected and have an HIV-free infant were strong motivators influencing continued use of PrEP during pregnancy. Supporting HIV-infected partners and childbearing within an HIV-serodiscordant relationship were also motivators. Women had challenges distinguishing normal pregnancy symptoms from PrEP side effects and were concerned that observed side effects could be signs of danger for the infant related to PrEP exposure. Health care providers were important conduits of knowledge about PrEP, and continuity of PrEP providers throughout pregnancy facilitated adherence. HIV-uninfected women in HIV-serodiscordant couples were motivated to use PrEP during pregnancy to remain HIV uninfected and to have an HIV-free child but had concerns about side effects. Health care providers will be important for PrEP messaging and adherence support in this unique population.

The PGE(2)-EP4 receptor is necessary for stimulation of the renin-angiotensin-aldosterone system in response to low dietary salt intake in vivo

DEFF Research Database (Denmark)

Pöschke, Antje; Kern, Niklas; Maruyama, Takayuki

2012-01-01

, creatinine clearance, and plasma antidiuretic hormone (ADH) concentration. Following salt restriction, plasma renin and aldosterone concentrations and kidney renin mRNA level rose significantly in EP4(+/+) but not in EP4(-/-) and in wild-type mice treated with EP4 antagonist ONO-AE3-208. In the latter two...... groups, the low-salt diet caused a significantly greater rise in PGE(2) excretion. Furthermore, mRNA expression for COX-2 and PGE(2) synthetic activity was significantly greater in EP4(-/-) than in EP4(+/+) mice. We conclude that low dietary salt intake induces expression of COX-2 followed by enhanced...... renal PGE(2) synthesis, which stimulates the renin-angiotensin-aldosterone system by activation of EP4 receptor. Most likely, defects at the step of EP4 receptor block negative feedback mechanisms on the renal COX system, leading to persistently high PGE(2) levels, diuresis, and K(+) loss....

Tufting enteropathy with EpCAM mutation: case report

OpenAIRE

Pêgas,Karla Lais; Cambruzzi,Eduardo; Ferrelli,Regis Schander; Silva,Carolina Soares da; Guedes,Renata Rostirola; Adami,Marina; Dias,Eduardo Montagner; Melere,Melina Utz; Ceza,Marilia Rosso; Steinhaus,Cintia; Epifanio,Matias; Salomon,Julie; Ferreira,Cristina Targa

2014-01-01

Tufting enteropathy (TE), also known as intestinal epithelial dysplasia (IED), is a rare congenital enteropathy related to an earlyonset of severe intractable diarrhea due to specific abnormalities of the intestinal epithelium and mutations of the EpCAM gene. TE is characterized by clinical and histological heterogeneity, such as with low or without mononuclear cell infiltration of the lamina propria, and abnormalities of basement membrane. TE can be associated with malformations, other epith...

CARA Risk Assessment Thresholds

Science.gov (United States)

Hejduk, M. D.

2016-01-01

Warning remediation threshold (Red threshold): Pc level at which warnings are issued, and active remediation considered and usually executed. Analysis threshold (Green to Yellow threshold): Pc level at which analysis of event is indicated, including seeking additional information if warranted. Post-remediation threshold: Pc level to which remediation maneuvers are sized in order to achieve event remediation and obviate any need for immediate follow-up maneuvers. Maneuver screening threshold: Pc compliance level for routine maneuver screenings (more demanding than regular Red threshold due to additional maneuver uncertainty).

Cooverexpression of EpCAM and c-myc genes in malignant breast ...

Indian Academy of Sciences (India)

RT-qPCR method, our results showed that EpCAM was overexpressed in 48% of malignant and 11.1% of benign .... to 45% of patients with breast cancer in different studies ..... in cancer maintenance, development, drug resistance, as well.

Intimacy motivations and pre-exposure prophylaxis (PrEP) adoption intentions among HIV-negative men who have sex with men (MSM) in romantic relationships.

Science.gov (United States)

Gamarel, Kristi E; Golub, Sarit A

2015-04-01

In the USA, men who have sex with men (MSM) in primary partnerships are at elevated risk for human immunodeficiency virus (HIV) infection. Pre-exposure prophylaxis (PrEP), a new biomedical prevention strategy, has potential to reduce HIV transmission. This study examined predictors of PrEP adoption intentions among HIV-negative MSM in primary partnerships. The sample included HIV-negative MSM (n = 164) who participated in an ongoing cross-sectional study with an in-person interview examining PrEP adoption intentions. Higher HIV risk perception, intimacy motivations for condomless sex, recent condomless anal sex with outside partners, education, and age were each independently associated with PrEP adoption intentions. In a multivariate model, only age, education, and intimacy motivations for condomless sex were significantly associated with PrEP adoption intentions. Intimacy motivations may play a central role in PrEP adoption for MSM couples. Incorporating relationship dynamics into biomedical strategies is a promising avenue for research and intervention.

Limits on the effective quark radius from inclusive ep scattering at HERA

Energy Technology Data Exchange (ETDEWEB)

Abramowicz, H. [Tel Aviv Univ. (Israel). School of Physics; Max Planck Institute for Physics, Munich (Germany); Abt, I. [Max Planck Institute for Physics, Munich (Germany); Adamczyk, L. [AGH-Univ. of Science and Technology, Krakow (Poland). Faculty of Physics and Applied Computer Sciences; Collaboration: ZEUS Collaboration; and others

2016-04-15

The high-precision HERA data allows searches up to TeV scales for Beyond the Standard Model contributions to electron-quark scattering. Combined measurements of the inclusive deep inelastic cross sections in neutral and charged current ep scattering corresponding to a luminosity of around 1 fb{sup -1} have been used in this analysis. A new approach to the beyond the Standard Model analysis of the inclusive ep data is presented; simultaneous fits of parton distribution functions together with contributions of ''new physics'' processes were performed. Results are presented considering a finite radius of quarks within the quark form-factor model. The resulting 95% C.L. upper limit on the effective quark radius is 0.43.10{sup -16} cm.

Limits on the effective quark radius from inclusive ep scattering at HERA

International Nuclear Information System (INIS)

Abramowicz, H.; Abt, I.; Adamczyk, L.

2016-04-01

The high-precision HERA data allows searches up to TeV scales for Beyond the Standard Model contributions to electron-quark scattering. Combined measurements of the inclusive deep inelastic cross sections in neutral and charged current ep scattering corresponding to a luminosity of around 1 fb -1 have been used in this analysis. A new approach to the beyond the Standard Model analysis of the inclusive ep data is presented; simultaneous fits of parton distribution functions together with contributions of ''new physics'' processes were performed. Results are presented considering a finite radius of quarks within the quark form-factor model. The resulting 95% C.L. upper limit on the effective quark radius is 0.43.10 -16 cm.

Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2.

Science.gov (United States)

Furness, David N; Johnson, Stuart L; Manor, Uri; Rüttiger, Lukas; Tocchetti, Arianna; Offenhauser, Nina; Olt, Jennifer; Goodyear, Richard J; Vijayakumar, Sarath; Dai, Yuhai; Hackney, Carole M; Franz, Christoph; Di Fiore, Pier Paolo; Masetto, Sergio; Jones, Sherri M; Knipper, Marlies; Holley, Matthew C; Richardson, Guy P; Kachar, Bechara; Marcotti, Walter

2013-08-20

Mechanotransduction in the mammalian auditory system depends on mechanosensitive channels in the hair bundles that project from the apical surface of the sensory hair cells. Individual stereocilia within each bundle contain a core of tightly packed actin filaments, whose length is dynamically regulated during development and in the adult. We show that the actin-binding protein epidermal growth factor receptor pathway substrate 8 (Eps8)L2, a member of the Eps8-like protein family, is a newly identified hair bundle protein that is localized at the tips of stereocilia of both cochlear and vestibular hair cells. It has a spatiotemporal expression pattern that complements that of Eps8. In the cochlea, whereas Eps8 is essential for the initial elongation of stereocilia, Eps8L2 is required for their maintenance in adult hair cells. In the absence of both proteins, the ordered staircase structure of the hair bundle in the cochlea decays. In contrast to the early profound hearing loss associated with an absence of Eps8, Eps8L2 null-mutant mice exhibit a late-onset, progressive hearing loss that is directly linked to a gradual deterioration in hair bundle morphology. We conclude that Eps8L2 is required for the long-term maintenance of the staircase structure and mechanosensory function of auditory hair bundles. It complements the developmental role of Eps8 and is a candidate gene for progressive age-related hearing loss.

Colour thresholding and objective quantification in bioimaging

Science.gov (United States)

Fermin, C. D.; Gerber, M. A.; Torre-Bueno, J. R.

1992-01-01

Computer imaging is rapidly becoming an indispensable tool for the quantification of variables in research and medicine. Whilst its use in medicine has largely been limited to qualitative observations, imaging in applied basic sciences, medical research and biotechnology demands objective quantification of the variables in question. In black and white densitometry (0-256 levels of intensity) the separation of subtle differences between closely related hues from stains is sometimes very difficult. True-colour and real-time video microscopy analysis offer choices not previously available with monochrome systems. In this paper we demonstrate the usefulness of colour thresholding, which has so far proven indispensable for proper objective quantification of the products of histochemical reactions and/or subtle differences in tissue and cells. In addition, we provide interested, but untrained readers with basic information that may assist decisions regarding the most suitable set-up for a project under consideration. Data from projects in progress at Tulane are shown to illustrate the advantage of colour thresholding over monochrome densitometry and for objective quantification of subtle colour differences between experimental and control samples.

Hysteresis as an Implicit Prior in Tactile Spatial Decision Making