Web-based tailored lifestyle programs: exploration of the target group's interests and implications for practice.

PubMed

Verheijden, Marieke W; Jans, Marielle P; Hildebrandt, Vincent H

2008-01-01

An important challenge in Web-based health promotion is to increase the reach of the target audience by taking the target groups' desires into consideration. Data from 505 members of a Dutch Internet panel (representative for Dutch Internet users) were used to asses the target group's interests and needs. 28% participated in Web-based tailored lifestyle programs, 57% expressed an interest in such programs, and 15% expressed no interest. Interest in Web-based programs was predominantly caused by a general interest in lifestyle and online tests. Participation in Web-based tailored lifestyle programs should not take more than 17 minutes per occasion. 84% were interested in follow-up testing after the initial participation. Responders were particularly interested in physical activity and nutrition. Hardly anyone was willing to pay for participation. The results from this study support the use of Web-based tailored lifestyle programs in behavior change efforts.

The relationship between sustained attention and aerobic fitness in a group of young adults.

PubMed

Ciria, Luis F; Perakakis, Pandelis; Luque-Casado, Antonio; Morato, Cristina; Sanabria, Daniel

2017-01-01

A growing set of studies has shown a positive relationship between aerobic fitness and a broad array of cognitive functions. However, few studies have focused on sustained attention, which has been considered a fundamental cognitive process that underlies most everyday activities. The purpose of this study was to investigate the role of aerobic fitness as a key factor in sustained attention capacities in young adults. Forty-four young adults (18-23 years) were divided into two groups as a function of the level of aerobic fitness (high-fit and low-fit). Participants completed the Psychomotor Vigilance Task (PVT) and an oddball task where they had to detect infrequent targets presented among frequent non-targets. The analysis of variance (ANOVA) showed faster responses for the high-fit group than for the low-fit group in the PVT, replicating previous accounts. In the oddball task, the high-fit group maintained their accuracy (ACC) rate of target detection over time, while the low-fit group suffered a significant decline of response ACC throughout the task. Importantly, the results show that the greater sustained attention capacity of high-fit young adults is not specific to a reaction time (RT) sustained attention task like the PVT, but it is also evident in an ACC oddball task. In sum, the present findings point to the important role of aerobic fitness on sustained attention capacities in young adults.

Performance and consistency of indicator groups in two biodiversity hotspots.

PubMed

Trindade-Filho, Joaquim; Loyola, Rafael Dias

2011-01-01

In a world limited by data availability and limited funds for conservation, scientists and practitioners must use indicator groups to define spatial conservation priorities. Several studies have evaluated the effectiveness of indicator groups, but still little is known about the consistency in performance of these groups in different regions, which would allow their a priori selection. We systematically examined the effectiveness and the consistency of nine indicator groups in representing mammal species in two top-ranked Biodiversity Hotspots (BH): the Brazilian Cerrado and the Atlantic Forest. To test for group effectiveness we first found the best sets of sites able to maximize the representation of each indicator group in the BH and then calculated the average representation of different target species by the indicator groups in the BH. We considered consistent indicator groups whose representation of target species was not statistically different between BH. We called effective those groups that outperformed the target-species representation achieved by random sets of species. Effective indicator groups required the selection of less than 2% of the BH area for representing target species. Restricted-range species were the most effective indicators for the representation of all mammal diversity as well as target species. It was also the only group with high consistency. We show that several indicator groups could be applied as shortcuts for representing mammal species in the Cerrado and the Atlantic Forest to develop conservation plans, however, only restricted-range species consistently held as the most effective indicator group for such a task. This group is of particular importance in conservation planning as it captures high diversity of endemic and endangered species.

Performance and Consistency of Indicator Groups in Two Biodiversity Hotspots

PubMed Central

Trindade-Filho, Joaquim; Loyola, Rafael Dias

2011-01-01

Background In a world limited by data availability and limited funds for conservation, scientists and practitioners must use indicator groups to define spatial conservation priorities. Several studies have evaluated the effectiveness of indicator groups, but still little is known about the consistency in performance of these groups in different regions, which would allow their a priori selection. Methodology/Principal Findings We systematically examined the effectiveness and the consistency of nine indicator groups in representing mammal species in two top-ranked Biodiversity Hotspots (BH): the Brazilian Cerrado and the Atlantic Forest. To test for group effectiveness we first found the best sets of sites able to maximize the representation of each indicator group in the BH and then calculated the average representation of different target species by the indicator groups in the BH. We considered consistent indicator groups whose representation of target species was not statistically different between BH. We called effective those groups that outperformed the target-species representation achieved by random sets of species. Effective indicator groups required the selection of less than 2% of the BH area for representing target species. Restricted-range species were the most effective indicators for the representation of all mammal diversity as well as target species. It was also the only group with high consistency. Conclusions/Significance We show that several indicator groups could be applied as shortcuts for representing mammal species in the Cerrado and the Atlantic Forest to develop conservation plans, however, only restricted-range species consistently held as the most effective indicator group for such a task. This group is of particular importance in conservation planning as it captures high diversity of endemic and endangered species. PMID:21637330

Behavioral Modeling for Mental Health using Machine Learning Algorithms.

PubMed

Srividya, M; Mohanavalli, S; Bhalaji, N

2018-04-03

Mental health is an indicator of emotional, psychological and social well-being of an individual. It determines how an individual thinks, feels and handle situations. Positive mental health helps one to work productively and realize their full potential. Mental health is important at every stage of life, from childhood and adolescence through adulthood. Many factors contribute to mental health problems which lead to mental illness like stress, social anxiety, depression, obsessive compulsive disorder, drug addiction, and personality disorders. It is becoming increasingly important to determine the onset of the mental illness to maintain proper life balance. The nature of machine learning algorithms and Artificial Intelligence (AI) can be fully harnessed for predicting the onset of mental illness. Such applications when implemented in real time will benefit the society by serving as a monitoring tool for individuals with deviant behavior. This research work proposes to apply various machine learning algorithms such as support vector machines, decision trees, naïve bayes classifier, K-nearest neighbor classifier and logistic regression to identify state of mental health in a target group. The responses obtained from the target group for the designed questionnaire were first subject to unsupervised learning techniques. The labels obtained as a result of clustering were validated by computing the Mean Opinion Score. These cluster labels were then used to build classifiers to predict the mental health of an individual. Population from various groups like high school students, college students and working professionals were considered as target groups. The research presents an analysis of applying the aforementioned machine learning algorithms on the target groups and also suggests directions for future work.

Health education in the Libyan Arab Jamahiriya: assessment of future needs.

PubMed

Elfituri, A A; Elmahaishi, M S; MacDonald, T H; Sherif, F M

2006-01-01

The aim of this study was to determine priority health issues, target groups and education media for future health education programmes in the Libyan Arab Jamahiriya. A questionnaire was addressed to 2 groups: health officials (n=60) and the general public (n=300). In their lists of health issues to focus on, 7 were the same although prioritization differed. Children and youth were considered the most important target groups and the school setting the most appropriate medium for them. Broadcast media were acknowledged as valuable for health education for the general public. We recommend systematic consultation across official and lay groups as a preliminary requisite for health education initiatives.

Racial and Ethnic Disparities in Services and the Patient Protection and Affordable Care Act

PubMed Central

Abdus, Salam; Mistry, Kamila B.

2015-01-01

Objectives. We examined prereform patterns in insurance coverage, access to care, and preventive services use by race/ethnicity in adults targeted by the coverage expansions of the Patient Protection and Affordable Care Act (ACA). Methods. We used pre-ACA household data from the Medical Expenditure Panel Survey to identify groups targeted by the coverage provisions of the Act (Medicaid expansions and subsidized Marketplace coverage). We examined racial/ethnic differences in coverage, access to care, and preventive service use, across and within ACA relevant subgroups from 2005 to 2010. The study took place at the Agency for Healthcare Research and Quality in Rockville, Maryland. Results. Minorities were disproportionately represented among those targeted by the coverage provisions of the ACA. Targeted groups had lower rates of coverage, access to care, and preventive services use, and racial/ethnic disparities were, in some cases, widest within these targeted groups. Conclusions. Our findings highlighted the opportunity of the ACA to not only to improve coverage, access, and use for all racial/ethnic groups, but also to narrow racial/ethnic disparities in these outcomes. Our results might have particular importance for states that are deciding whether to implement the ACA Medicaid expansions. PMID:26447920

Racial and Ethnic Disparities in Services and the Patient Protection and Affordable Care Act.

PubMed

Abdus, Salam; Mistry, Kamila B; Selden, Thomas M

2015-11-01

We examined prereform patterns in insurance coverage, access to care, and preventive services use by race/ethnicity in adults targeted by the coverage expansions of the Patient Protection and Affordable Care Act (ACA). We used pre-ACA household data from the Medical Expenditure Panel Survey to identify groups targeted by the coverage provisions of the Act (Medicaid expansions and subsidized Marketplace coverage). We examined racial/ethnic differences in coverage, access to care, and preventive service use, across and within ACA relevant subgroups from 2005 to 2010. The study took place at the Agency for Healthcare Research and Quality in Rockville, Maryland. Minorities were disproportionately represented among those targeted by the coverage provisions of the ACA. Targeted groups had lower rates of coverage, access to care, and preventive services use, and racial/ethnic disparities were, in some cases, widest within these targeted groups. Our findings highlighted the opportunity of the ACA to not only to improve coverage, access, and use for all racial/ethnic groups, but also to narrow racial/ethnic disparities in these outcomes. Our results might have particular importance for states that are deciding whether to implement the ACA Medicaid expansions.

Developing a Drawing Task to Differentiate Group Average Time Course vs. Dynamics in the Individual

ERIC Educational Resources Information Center

Blech, Christine; Gaschler, Robert

2017-01-01

Teaching and theorizing in psychology has long been torn between targeting general underlying principles by observing dynamics in the individual or focusing on average behavior. As dealing with group averages is common practice in psychology, it is important for students to understand how individual learning curves relate to group average curves.…

A novel infrared small moving target detection method based on tracking interest points under complicated background

NASA Astrophysics Data System (ADS)

Dong, Xiabin; Huang, Xinsheng; Zheng, Yongbin; Bai, Shengjian; Xu, Wanying

2014-07-01

Infrared moving target detection is an important part of infrared technology. We introduce a novel infrared small moving target detection method based on tracking interest points under complicated background. Firstly, Difference of Gaussians (DOG) filters are used to detect a group of interest points (including the moving targets). Secondly, a sort of small targets tracking method inspired by Human Visual System (HVS) is used to track these interest points for several frames, and then the correlations between interest points in the first frame and the last frame are obtained. Last, a new clustering method named as R-means is proposed to divide these interest points into two groups according to the correlations, one is target points and another is background points. In experimental results, the target-to-clutter ratio (TCR) and the receiver operating characteristics (ROC) curves are computed experimentally to compare the performances of the proposed method and other five sophisticated methods. From the results, the proposed method shows a better discrimination of targets and clutters and has a lower false alarm rate than the existing moving target detection methods.

Unravelling ``off-target'' effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells

NASA Astrophysics Data System (ADS)

Beretta, Giovanni L.; Folini, Marco; Cavalieri, Francesca; Yan, Yan; Fresch, Enrico; Kaliappan, Subramanian; Hasenöhrl, Christoph; Richardson, Joseph J.; Tinelli, Stella; Fery, Andreas; Caruso, Frank; Zaffaroni, Nadia

2015-03-01

Redox-active polymers and carriers are oxidizing nanoagents that can potentially trigger intracellular off-target effects. In the present study, we investigated the occurrence of off-target effects in prostate cancer cells following exposure to redox-active polymer and thin multilayer capsules with different chemical properties. We show that, depending on the intracellular antioxidant capacity, thiol-functionalized poly(methacrylic acid), PMASH triggers cell defense responses/perturbations that result in off-target effects (i.e., induction of autophagy and down-regulation of survivin). Importantly, the conversion of the carboxyl groups of PMASH into the neutral amides of poly(hydroxypropylmetacrylamide) (pHPMASH) nullified the off-target effects and cytotoxicity in tested cell lines. This suggests that the simultaneous action of carboxyl and disulfide groups in PMASH polymer or capsules may play a role in mediating the intracellular off-target effects. Our work provides evidence that the rational design of redox-active carriers for therapeutic-related application should be guided by a careful investigation on potential disturbance of the cellular machineries related to the carrier association.Redox-active polymers and carriers are oxidizing nanoagents that can potentially trigger intracellular off-target effects. In the present study, we investigated the occurrence of off-target effects in prostate cancer cells following exposure to redox-active polymer and thin multilayer capsules with different chemical properties. We show that, depending on the intracellular antioxidant capacity, thiol-functionalized poly(methacrylic acid), PMASH triggers cell defense responses/perturbations that result in off-target effects (i.e., induction of autophagy and down-regulation of survivin). Importantly, the conversion of the carboxyl groups of PMASH into the neutral amides of poly(hydroxypropylmetacrylamide) (pHPMASH) nullified the off-target effects and cytotoxicity in tested cell lines. This suggests that the simultaneous action of carboxyl and disulfide groups in PMASH polymer or capsules may play a role in mediating the intracellular off-target effects. Our work provides evidence that the rational design of redox-active carriers for therapeutic-related application should be guided by a careful investigation on potential disturbance of the cellular machineries related to the carrier association. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07240e

Ganging up or sticking together? Group processes and children's responses to text-message bullying.

PubMed

Jones, Siân E; Manstead, Antony S R; Livingstone, Andrew G

2011-02-01

Drawing on social identity theory and intergroup emotion theory (IET), we examined group processes underlying bullying behaviour. Children were randomly assigned to one of three groups: a perpetrator's group, a target's group, or a third party group. They then read a gender-consistent scenario in which the norm of the perpetrator's group (to be kind or unkind towards others) was manipulated, and an instance of cyberbullying between the perpetrator's group and a member of the target's group was described. It was found that group membership, group norms, and the proposed antecedents of the group-based emotions of pride, shame, and anger (but not guilt) influenced group-based emotions and action tendencies in ways predicted by social identity and IET. The results underline the importance of understanding group-level emotional reactions when it comes to tackling bullying, and show that being part of a group can be helpful in overcoming the negative effects of bullying. ©2010 The British Psychological Society.

Responsive parenting: establishing early foundations for social, communication, and independent problem-solving skills.

PubMed

Landry, Susan H; Smith, Karen E; Swank, Paul R

2006-07-01

Mothers whose infants varied in early biological characteristics (born at term, n = 120; born at very low birth weight [VLBW], n = 144) were randomized to a target group (n = 133) or developmental feedback comparison group (n = 131) to determine whether learning responsive behaviors would facilitate infant development. The target condition included videotaped examples, problem-solving activities, and mothers' critique of their own behaviors through video procedures across 10 home visits. All target versus comparison mothers showed greater increases across multiple responsiveness behaviors observed in 4 assessments conducted across 6-13 months of age; changes in emotionally supportive behaviors were strongest for target mothers of infants born at VLBW. Increased maternal responsiveness facilitated greater growth in target infants' social, emotional, communication, and cognitive competence, supporting a causal role for responsiveness on infant development. Although benefits were generally comparable across risk groups, aspects of social and emotional skills showed greater change for those born at VLBW. Evidence for responsiveness as a multidimensional construct was provided as well as the importance of different aspects of responsiveness mediating the effect of the intervention on different infant skill domains.

Influence of anglers' specializations on catch, harvest, and bycatch of targeted taxa

USGS Publications Warehouse

Pope, Kevin L.; Chizinski, Christopher J.; Wiley, Christopher L.; Martin, Dustin R.

2016-01-01

Fishery managers often use catch per unit effort (CPUE) of a given taxon derived from a group of anglers, those that sought said taxon, to evaluate fishery objectives because managers assume CPUE for this group of anglers is most sensitive to changes in fish taxon density. Further, likelihood of harvest may differ for sought and non-sought taxa if taxon sought is a defining characteristic of anglers’ attitude toward harvest. We predicted that taxon-specific catch across parties and reservoirs would be influenced by targeted taxon after controlling for number of anglers in a party and time spent fishing (combine to quantify fishing effort of party); we also predicted similar trends for taxon-specific harvest. We used creel-survey data collected from anglers that varied in taxon targeted, from generalists (targeting “anything” [no primary target taxa, but rather targeting all fishes]) to target specialists (e.g., anglers targeting largemouth bass Micropterus salmoides) in 19 Nebraska reservoirs during 2009–2011 to test our predictions. Taxon-specific catch and harvest were, in general, positively related to fishing effort. More importantly, we observed differences of catch and harvest among anglers grouped by taxon targeted for each of the eight taxa assessed. Anglers targeting a specific taxon had the greatest catch for that taxon and anglers targeting anything typically had the second highest catch for that taxon. In addition, anglers tended to catch more of closely related taxa and of taxa commonly targeted with similar fishing techniques. We encourage managers to consider taxon-specific objectives of target and non-target catch and harvest.

The Marketing Concept in an Academic Environment

NASA Astrophysics Data System (ADS)

Rešetová, Kvetoslava

2013-01-01

Universities, as subjects of the academic environment, are institutions with the priority of education and research. The task of the marketing concept in the academic field is to communicate with all important target groups to support a stronger position and their perception of the school. The aim of the intervention is to increase the prestige, improve awareness, support positive attitudes, and present successful results in all areas of activity. This means creation and protection of a positive image, which enables higher interest of all target groups and secures better awareness about it.

Trophic structure in the Gulf of Lions marine ecosystem (north-western Mediterranean Sea) and fishing impacts

NASA Astrophysics Data System (ADS)

Bănaru, D.; Mellon-Duval, C.; Roos, D.; Bigot, J.-L.; Souplet, A.; Jadaud, A.; Beaubrun, P.; Fromentin, J.-M.

2013-02-01

The Gulf of Lions ecosystem was described using the Ecopath mass-balance model to characterise its structure and functioning and to examine the effects of the multispecific fisheries operating in this area. The model is composed of 40 compartments, including 1 group of seabirds, 2 groups of cetaceans, 18 groups of fish, 12 groups of invertebrates, 5 groups of primary producers, detritus and discards. Input data were based on several recurrent scientific surveys, two alternative datasets for fishing data, stock assessment outputs, stomach content analyses and published information. Results showed that the functional groups were organised into five trophic levels with the highest one represented by dolphins, anglerfish, Atlantic bluefin tuna, European hake and European conger. European pilchard and European anchovy dominated in terms of fish biomass and catch. Other fish with high biomass such as Atlantic mackerel and blue whiting were highly important in the food web. Seabirds, dolphins and cuttlefish-squids represented keystone species. Important coupled pelagic-demersal-benthic interactions were described. The 7 different fisheries analysed were operating at mean trophic levels situated between 2.6 for small artisanal boats, and 4.1 for purse seines (> 24 m) targeting large pelagic fish, indicating an intensively exploited ecosystem. Large trawlers (24-40 m) had the highest impact on most of the groups considered; while purse seines (12-24 m) targeting small pelagic fish had the lowest impact. Preliminary results highlighted the importance of data sources for further ecosystem and fisheries analyses and management scenarios.

The application of the rapid assessment and response methodology for cannabis prevention research among youth in the Netherlands.

PubMed

Dupont, Hans B; Kaplan, Charles D; Braam, Richard V; Verbraeck, Hans T; de Vries, Nanne K

2015-08-01

Drug prevention methods tailored to specific target groups have become increasingly important. There is a growing need to find ways to rapidly assess and situate target groups in their particular contexts. This need is associated with the implementation of evidence-based interventions (EBIs) for these specific target groups. This article describes the application of Rapid Assessment and Response (RAR) as a necessary first step in designing and implementing a prevention intervention plan for problematic cannabis use among "loitering" youth in the South of the Netherlands. Seven RAR studies were conducted using an innovative stepwise model in which the prevention field worker is central. The normative structure for the use of cannabis was found to vary across the neighborhoods of the RAR studies and emerged as the focal point in designing a suitable response. The RAR studies also identified the need in the prevention toolbox for a tailored, low-threshold, effective, individual brief intervention for youth problematic cannabis use. The RAR was found to provide a powerful methodology for detecting target groups and generating contextual and normative data that enable the prevention field worker to select and adapt from the spectrum of existing Evidence based Interventions (EBIs) or develop the most promising model for implementation with the specific target group. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Radiation pressure acceleration: The factors limiting maximum attainable ion energy

DOE PAGES

Bulanov, S. S.; Esarey, E.; Schroeder, C. B.; ...

2016-04-15

Radiation pressure acceleration (RPA) is a highly efficient mechanism of laser-driven ion acceleration, with near complete transfer of the laser energy to the ions in the relativistic regime. However, there is a fundamental limit on the maximum attainable ion energy, which is determined by the group velocity of the laser. The tightly focused laser pulses have group velocities smaller than the vacuum light speed, and, since they offer the high intensity needed for the RPA regime, it is plausible that group velocity effects would manifest themselves in the experiments involving tightly focused pulses and thin foils. However, in this case,more » finite spot size effects are important, and another limiting factor, the transverse expansion of the target, may dominate over the group velocity effect. As the laser pulse diffracts after passing the focus, the target expands accordingly due to the transverse intensity profile of the laser. Due to this expansion, the areal density of the target decreases, making it transparent for radiation and effectively terminating the acceleration. The off-normal incidence of the laser on the target, due either to the experimental setup, or to the deformation of the target, will also lead to establishing a limit on maximum ion energy.« less

One size does not fit all-qualitative process evaluation of the Healthy School Start parental support programme to prevent overweight and obesity among children in disadvantaged areas in Sweden.

PubMed

Norman, Åsa; Nyberg, Gisela; Elinder, Liselotte Schäfer; Berlin, Anita

2016-01-14

Parental support interventions have shown some effectiveness in improving children's dietary and physical activity habits and preventing overweight and obesity. To date, there is limited research on barriers and facilitators of school-based parental support interventions targeting overweight and obesity. This study aimed to describe barriers and facilitators influencing implementation of the Healthy School Start (HSS) intervention in disadvantaged areas in Stockholm, Sweden, from the perspective of parents and teachers. Focus groups and individual interviews with teachers (n = 10) and focus groups with parents (n = 14) in the intervention group of the HSS were undertaken, guided by the Consolidated Framework for Implementation Research (CFIR). Transcriptions were analysed using qualitative content analysis in two steps: deductive sorting in two domains of the CFIR (intervention characteristics and process), and subsequent inductive analysis. The overarching theme "tailoring the intervention to increase participant engagement" was found. Among teachers, barriers and facilitators were related to how the intervention was introduced, perceptions of the usefulness of the classroom material, preparation ahead of the start of the intervention, cooperation between home and school and children's and parents' active engagement in the intervention activities. For parents, barriers and facilitators were related to the perceived relevance of the intervention, usefulness of the material, experiences of the Motivational Interviewing (MI) sessions, the family member targeted by the intervention, cooperation between home and school and parents' ability to act as good role models. It seems important to tailor the intervention to the abilities of the target group in order to increase participant engagement. Including activities that focus on parents as role models and cooperation between parents seems important to bring about changes in the home environment. It also appears important to include activities that target cooperation between home and school.

Evidence for the importance of personalized molecular profiling in pancreatic cancer.

PubMed

Lili, Loukia N; Matyunina, Lilya V; Walker, L DeEtte; Daneker, George W; McDonald, John F

2014-03-01

There is a growing body of evidence that targeted gene therapy holds great promise for the future treatment of cancer. A crucial step in this therapy is the accurate identification of appropriate candidate genes/pathways for targeted treatment. One approach is to identify variant genes/pathways that are significantly enriched in groups of afflicted individuals relative to control subjects. However, if there are multiple molecular pathways to the same cancer, the molecular determinants of the disease may be heterogeneous among individuals and possibly go undetected by group analyses. In an effort to explore this question in pancreatic cancer, we compared the most significantly differentially expressed genes/pathways between cancer and control patient samples as determined by group versus personalized analyses. We found little to no overlap between genes/pathways identified by gene expression profiling using group analyses relative to those identified by personalized analyses. Our results indicate that personalized and not group molecular profiling is the most appropriate approach for the identification of putative candidates for targeted gene therapy of pancreatic and perhaps other cancers with heterogeneous molecular etiology.

Chemoselective Hydroxyl Group Transformation: An Elusive Target‡

PubMed Central

Trader, Darci J.; Carlson, Erin E.

2012-01-01

The selective reaction of one functional group in the presence of others is not a trivial task. A noteworthy amount of research has been dedicated to the chemoselective reaction of the hydroxyl moiety. This group is prevalent in many biologically important molecules including natural products and proteins. However, targeting the hydroxyl group is difficult for many reasons including its relatively low nucleophilicity in comparison to other ubiquitous functional groups such as amines and thiols. Additionally, many of the developed chemoselective reactions cannot be used in the presence of water. Despite these complications, chemoselective transformation of the hydroxyl moiety has been utilized in the synthesis of complex natural product derivatives, the reaction of tyrosine residues in proteins, the isolation of natural products and is the mechanism of action of myriad drugs. Here, methods for selective targeting of this group, as well as applications of several devised methods, are described. PMID:22695722

Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features

PubMed Central

Shi, Xiao-He; Hu, Le-Le; Kong, Xiangyin; Cai, Yu-Dong; Chou, Kuo-Chen

2010-01-01

Background Study of drug-target interaction networks is an important topic for drug development. It is both time-consuming and costly to determine compound-protein interactions or potential drug-target interactions by experiments alone. As a complement, the in silico prediction methods can provide us with very useful information in a timely manner. Methods/Principal Findings To realize this, drug compounds are encoded with functional groups and proteins encoded by biological features including biochemical and physicochemical properties. The optimal feature selection procedures are adopted by means of the mRMR (Maximum Relevance Minimum Redundancy) method. Instead of classifying the proteins as a whole family, target proteins are divided into four groups: enzymes, ion channels, G-protein- coupled receptors and nuclear receptors. Thus, four independent predictors are established using the Nearest Neighbor algorithm as their operation engine, with each to predict the interactions between drugs and one of the four protein groups. As a result, the overall success rates by the jackknife cross-validation tests achieved with the four predictors are 85.48%, 80.78%, 78.49%, and 85.66%, respectively. Conclusion/Significance Our results indicate that the network prediction system thus established is quite promising and encouraging. PMID:20300175

Targeting gender: A content analysis of alcohol advertising in magazines.

PubMed

Jung, A-Reum; Hovland, Roxanne

2016-01-01

Creating target specific advertising is fundamental to maximizing advertising effectiveness. When crafting an advertisement, message and creative strategies are considered important because they affect target audiences' attitudes toward advertised products. This study endeavored to find advertising strategies that are likely to have special appeal for men or women by examining alcohol advertising in magazines. The results show that the substance of the messages is the same for men and women, but they only differ in terms of presentation. However, regardless of gender group, the most commonly used strategies in alcohol advertising are appeals to the target audience's emotions.

Interaction between object-based attention and pertinence values shapes the attentional priority map of a multielement display.

PubMed

Gillebert, Celine R; Petersen, Anders; Van Meel, Chayenne; Müller, Tanja; McIntyre, Alexandra; Wagemans, Johan; Humphreys, Glyn W

2016-06-01

Previous studies have shown that the perceptual organization of the visual scene constrains the deployment of attention. Here we investigated how the organization of multiple elements into larger configurations alters their attentional weight, depending on the "pertinence" or behavioral importance of the elements' features. We assessed object-based effects on distinct aspects of the attentional priority map: top-down control, reflecting the tendency to encode targets rather than distracters, and the spatial distribution of attention weights across the visual scene, reflecting the tendency to report elements belonging to the same rather than different objects. In 2 experiments participants had to report the letters in briefly presented displays containing 8 letters and digits, in which pairs of characters could be connected with a line. Quantitative estimates of top-down control were obtained using Bundesen's Theory of Visual Attention (1990). The spatial distribution of attention weights was assessed using the "paired response index" (PRI), indicating responses for within-object pairs of letters. In Experiment 1, grouping along the task-relevant dimension (targets with targets and distracters with distracters) increased top-down control and enhanced the PRI; in contrast, task-irrelevant grouping (targets with distracters) did not affect performance. In Experiment 2, we disentangled the effect of target-target and distracter-distracter grouping: Pairwise grouping of distracters enhanced top-down control whereas pairwise grouping of targets changed the PRI. We conclude that object-based perceptual representations interact with pertinence values (of the elements' features and location) in the computation of attention weights, thereby creating a widespread pattern of attentional facilitation across the visual scene. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Nonimaging solar concentrator with uniform irradiance

NASA Astrophysics Data System (ADS)

Winston, Roland; O'Gallagher, Joseph J.; Gee, Randy C.

2004-09-01

We report results of a study our group has undertaken under NREL/DOE auspices to design a solar concentrator with uniform irradiance on a planar target. This attribute is especially important for photovoltaic concentrators.

Social exclusion impairs distractor suppression but not target enhancement in selective attention.

PubMed

Xu, Mengsi; Li, Zhiai; Diao, Liuting; Fan, Lingxia; Zhang, Lijie; Yuan, Shuge; Yang, Dong

2017-11-01

Social exclusion has been thought to weaken one's ability to exert inhibitory control. Existing studies have primarily focused on the relationship between exclusion and behavioral inhibition, and have reported that exclusion impairs behavioral inhibition. However, whether exclusion also affects selective attention, another important aspect of inhibitory control, remains unknown. Therefore, the current study aimed to explore whether social exclusion impairs selective attention, and to specifically examine its effect on two hypothesized mechanisms of selective attention: target enhancement and distractor suppression. The Cyberball game was used to manipulate social exclusion. Participants then performed a visual search task while event-related potentials were recorded. In the visual search task, target and salient distractor were either both presented laterally or one was presented on the vertical midline and the other laterally. Results showed that social exclusion differentially affected target and distractor processing. While exclusion impaired distractor suppression, reflected as smaller distractor-positivity (Pd) amplitudes for the exclusion group compared to the inclusion group, it did not affect target enhancement, reflected as similar target-negativity (Nt) amplitudes for both the exclusion and inclusion groups. Together, these results extend our understanding of the relationship between exclusion and inhibitory control, and suggest that social exclusion affects selective attention in a more complex manner than previously thought. Copyright © 2017. Published by Elsevier B.V.

Pointing at targets by children with congenital and transient blindness.

PubMed

Gaunet, Florence; Ittyerah, Miriam; Rossetti, Yves

2007-04-01

The study investigated pointing at memorized targets in reachable space in congenitally blind (CB) and blindfolded sighted (BS) children (6, 8, 10 and 12 years; ten children in each group). The target locations were presented on a sagittal plane by passive positioning of the left index finger. A go signal for matching the target location with the right index finger was provided 0 or 4 s after demonstration. An age effect was found only for absolute distance errors and the surface area of pointing was smaller for the CB children. Results indicate that early visual experience and age are not predictive factors for pointing in children. The delay was an important factor at all ages and for both groups, indicating distinct spatial representations such as egocentric and allocentric frames of reference, for immediate and delayed pointing, respectively. Therefore, the CB like the BS children are able to use both ego- and allocentric frames of reference.

Friendship quality and social information processing in clinically anxious children.

PubMed

Baker, J R; Hudson, J L

2014-02-01

The association between perceived friendship quality (FQ) and social information processing (SIP) was examined in three groups of children and their close friends aged 7-12 years: 16 anxiety disordered children with social phobia (SP); 12 anxiety disordered children without SP (No-SP); and 32 nonclinical children. Positive and negative FQ positively associated with target children's positive and negative responding on a vignette measure of SIP. SP children reported lower positive SIP than No-SP but not nonclinical children; and this was the only group difference in SIP. Target children and their friends were similar in negative but not positive SIP. Following discussion about the vignette with a close friend, all target children increased in positive SIP; negative SIP did not change. Lower FQ and a more socially anxious friend predicted higher negative target child SIP postdiscussion. Close friendships play an important role in the SIP of both clinical and nonclinical children.

Nano-sized metabolic precursors for heterogeneous tumor-targeting strategy using bioorthogonal click chemistry in vivo.

PubMed

Lee, Sangmin; Jung, Seulhee; Koo, Heebeom; Na, Jin Hee; Yoon, Hong Yeol; Shim, Man Kyu; Park, Jooho; Kim, Jong-Ho; Lee, Seulki; Pomper, Martin G; Kwon, Ick Chan; Ahn, Cheol-Hee; Kim, Kwangmeyung

2017-12-01

Herein, we developed nano-sized metabolic precursors (Nano-MPs) for new tumor-targeting strategy to overcome the intrinsic limitations of biological ligands such as the limited number of biological receptors and the heterogeneity in tumor tissues. We conjugated the azide group-containing metabolic precursors, triacetylated N-azidoacetyl-d-mannosamine to generation 4 poly(amidoamine) dendrimer backbone. The nano-sized dendrimer of Nano-MPs could generate azide groups on the surface of tumor cells homogeneously regardless of cell types via metabolic glycoengineering. Importantly, these exogenously generated 'artificial chemical receptors' containing azide groups could be used for bioorthogonal click chemistry, regardless of phenotypes of different tumor cells. Furthermore, in tumor-bearing mice models, Nano-MPs could be mainly localized at the target tumor tissues by the enhanced permeation and retention (EPR) effect, and they successfully generated azide groups on tumor cells in vivo after an intravenous injection. Finally, we showed that these azide groups on tumor tissues could be used as 'artificial chemical receptors' that were conjugated to bioorthogonal chemical group-containing liposomes via in vivo click chemistry in heterogeneous tumor-bearing mice. Therefore, overall results demonstrated that our nano-sized metabolic precursors could be extensively applied to new alternative tumor-targeting technique for molecular imaging and drug delivery system, regardless of the phenotype of heterogeneous tumor cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improving the Cost-Effectiveness of Visual Devices for the Control of Riverine Tsetse Flies, the Major Vectors of Human African Trypanosomiasis

PubMed Central

Esterhuizen, Johan; Rayaisse, Jean Baptiste; Tirados, Inaki; Mpiana, Serge; Solano, Philippe; Vale, Glyn A.; Lehane, Michael J.; Torr, Stephen J.

2011-01-01

Control of the Riverine (Palpalis) group of tsetse flies is normally achieved with stationary artificial devices such as traps or insecticide-treated targets. The efficiency of biconical traps (the standard control device), 1×1 m black targets and small 25×25 cm targets with flanking nets was compared using electrocuting sampling methods. The work was done on Glossina tachinoides and G. palpalis gambiensis (Burkina Faso), G. fuscipes quanzensis (Democratic Republic of Congo), G. f. martinii (Tanzania) and G. f. fuscipes (Kenya). The killing effectiveness (measured as the catch per m2 of cloth) for small targets plus flanking nets is 5.5–15X greater than for 1 m2 targets and 8.6–37.5X greater than for biconical traps. This has important implications for the costs of control of the Riverine group of tsetse vectors of sleeping sickness. PMID:21829743

Structural biology of antibody recognition of carbohydrate epitopes and potential uses for targeted cancer immunotherapies.

PubMed

Dingjan, Tamir; Spendlove, Ian; Durrant, Lindy G; Scott, Andrew M; Yuriev, Elizabeth; Ramsland, Paul A

2015-10-01

Monoclonal antibodies represent the most successful class of biopharmaceuticals for the treatment of cancer. Mechanisms of action of therapeutic antibodies are very diverse and reflect their ability to engage in antibody-dependent effector mechanisms, internalize to deliver cytotoxic payloads, and display direct effects on cells by lysis or by modulating the biological pathways of their target antigens. Importantly, one of the universal changes in cancer is glycosylation and carbohydrate-binding antibodies can be produced to selectively recognize tumor cells over normal tissues. A promising group of cell surface antibody targets consists of carbohydrates presented as glycolipids or glycoproteins. In this review, we outline the basic principles of antibody-based targeting of carbohydrate antigens in cancer. We also present a detailed structural view of antibody recognition and the conformational properties of a series of related tissue-blood group (Lewis) carbohydrates that are being pursued as potential targets of cancer immunotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Using focus groups in the consumer research phase of a social marketing program to promote moderate-intensity physical activity and walking trail use in Sumter County, South Carolina.

PubMed

Burroughs, Ericka; Peck, Lara E; Sharpe, Patricia A; Granner, Michelle L; Bryant, Carol A; Fields, Regina

2006-01-01

The use of social marketing approaches in public health practice is increasing. Using marketing concepts such as the "four Ps" (product, price, place, and promotion), social marketing borrows from the principles of commercial marketing but promotes beneficial health behaviors. Consumer research is used to segment the population and develop a strategy based on those marketing concepts. In a community-based participatory research study, 17 focus groups were used in consumer research to develop a social marketing program to promote walking and other moderate-intensity physical activities. Two phases of focus groups were conducted. Phase 1 groups, which included both men and women, were asked to respond to questions that would guide the development of a social marketing program based on social marketing concepts. Phase 1 also determined the intervention's target audience, which was irregularly active women aged 35 to 54. Phase 2 groups, composed of members of the target audience, were asked to further define the product and discuss specific promotion strategies. Phase 1 participants determined that the program product, or target behavior, should be walking. In addition, they identified price, place, and promotion strategies. Phase 2 participants determined that moderate-intensity physical activity is best promoted using the term exercise and offered suggestions for marketing walking, or exercise, to the target audience. There have been few published studies of social marketing campaigns to promote physical activity. In this study, focus groups were key to understanding the target audience in a way that would not have been accomplished with quantitative data alone. The group discussions generated important insights into values and motivations that affect consumers' decisions to adopt a product or behavior. The focus group results guided the development of a social marketing program to promote physical activity in the target audience in Sumter County, South Carolina.

I saw where you have been--The topography of human demonstration affects dogs' search patterns and perseverative errors.

PubMed

Péter, András; Topál, József; Miklósi, Ádám; Pongrácz, Péter

2016-04-01

Performance in object search tasks is not only influenced by the subjects' object permanence ability. For example, ostensive cues of the human manipulating the target markedly affect dogs' choices. However, the interference between the target's location and the spatial cues of the human hiding the object is still unknown. In a five-location visible displacement task, the experimental groups differed in the hiding route of the experimenter. In the 'direct' condition he moved straight towards the actual location, hid the object and returned to the dog. In the 'indirect' conditions, he additionally walked behind each screen before returning. The two 'indirect' conditions differed from each other in that the human either visited the previously baited locations before (proactive interference) or after (retroactive interference) hiding the object. In the 'indirect' groups, dogs' performance was significantly lower than in the 'direct' group, demonstrating that for dogs, in an ostensive context, spatial cues of the hider are as important as the observed location of the target. Based on their incorrect choices, dogs were most attracted to the previously baited locations that the human visited after hiding the object in the actual trial. This underlines the importance of retroactive interference in multiple choice tasks. Copyright © 2016 Elsevier B.V. All rights reserved.

Target tracking system based on preliminary and precise two-stage compound cameras

NASA Astrophysics Data System (ADS)

Shen, Yiyan; Hu, Ruolan; She, Jun; Luo, Yiming; Zhou, Jie

2018-02-01

Early detection of goals and high-precision of target tracking is two important performance indicators which need to be balanced in actual target search tracking system. This paper proposed a target tracking system with preliminary and precise two - stage compound. This system using a large field of view to achieve the target search. After the target was searched and confirmed, switch into a small field of view for two field of view target tracking. In this system, an appropriate filed switching strategy is the key to achieve tracking. At the same time, two groups PID parameters are add into the system to reduce tracking error. This combination way with preliminary and precise two-stage compound can extend the scope of the target and improve the target tracking accuracy and this method has practical value.

Why Do They Want to Teach? The Multiple Reasons of Different Groups of Students for Undertaking Teacher Education

ERIC Educational Resources Information Center

Struyven, Katrien; Jacobs, Karen; Dochy, Filip

2013-01-01

In times of teacher shortage, well-considered, goal-oriented teacher recruitment is important. An understanding of the reasons why different groups of students undertake teacher training would be useful in developing targeted campaigns. Against this background, the research question is as follows: what are the motivations prompting students to…

Radiative Decay Width of Neutral non-Strange Baryons from PWA

NASA Astrophysics Data System (ADS)

Strakovsky, Igor I.; Briscoe, William J.; Kudryavtsev, Alexander E.; Kulikov, Viacheslav V.; Martemyanov, Maxim A.; Tarasov, Vladimir E.

2015-06-01

An overview of the GW SAID and ITEP groups effort to analyze pion photoproduction on the neutron-target will be given. The disentanglement the isoscalar and isovector EM couplings of N∗ and Δ∗ resonances does require compatible data on both proton and neutron targets. The final-state interaction plays a critical role in the state-of-the-art analysis in extraction of the γn → πN data from the deuteron target experiments. It is important component of the current JLab, MAMI-C, SPring-8, ELSA, and ELPH programs.

Romantic partners in a market perspective: expectations about what ensures a highly desirable partner.

PubMed

Castro, Felipe N; Hattori, Wallisen T; Yamamoto, Maria Emília; Lopes, Fívia A

2013-10-01

This study used the biological market perspective and influential statistical models from the marketing field to investigate males' and females' expectations regarding which combination of characteristics are most relevant in ensuring desirable partnerships for same-sex individuals. Thus, 358 Brazilian undergraduates assessed eight descriptions of same-gender stimulus targets (formulated with different levels of physical attractiveness, social skills, and current or prospective social status) and evaluated the overall desirability of the targets' expected or probable partners. From the possible combinations, three groups emerged: for one group, mainly composed of men, status characteristics were the most important attributes; for the others, mostly composed of women, social skills or physical characteristics were identified as most important in appealing to a desirable partner. This work expands the understanding of variability in male and female romantic expectations, and its implications are discussed from an evolutionary perspective.

Age-Related Changes in the Ability to Switch between Temporal and Spatial Attention.

PubMed

Callaghan, Eleanor; Holland, Carol; Kessler, Klaus

2017-01-01

Background : Identifying age-related changes in cognition that contribute towards reduced driving performance is important for the development of interventions to improve older adults' driving and prolong the time that they can continue to drive. While driving, one is often required to switch from attending to events changing in time, to distribute attention spatially. Although there is extensive research into both spatial attention and temporal attention and how these change with age, the literature on switching between these modalities of attention is limited within any age group. Methods : Age groups (21-30, 40-49, 50-59, 60-69 and 70+ years) were compared on their ability to switch between detecting a target in a rapid serial visual presentation (RSVP) stream and detecting a target in a visual search display. To manipulate the cost of switching, the target in the RSVP stream was either the first item in the stream (Target 1st), towards the end of the stream (Target Mid), or absent from the stream (Distractor Only). Visual search response times and accuracy were recorded. Target 1st trials behaved as no-switch trials, as attending to the remaining stream was not necessary. Target Mid and Distractor Only trials behaved as switch trials, as attending to the stream to the end was required. Results : Visual search response times (RTs) were longer on "Target Mid" and "Distractor Only" trials in comparison to "Target 1st" trials, reflecting switch-costs. Larger switch-costs were found in both the 40-49 and 60-69 years group in comparison to the 21-30 years group when switching from the Target Mid condition. Discussion : Findings warrant further exploration as to whether there are age-related changes in the ability to switch between these modalities of attention while driving. If older adults display poor performance when switching between temporal and spatial attention while driving, then the development of an intervention to preserve and improve this ability would be beneficial.

High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial.

PubMed

Vedel, Anne G; Holmgaard, Frederik; Rasmussen, Lars S; Langkilde, Annika; Paulson, Olaf B; Lange, Theis; Thomsen, Carsten; Olsen, Peter Skov; Ravn, Hanne Berg; Nilsson, Jens C

2018-04-24

Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients. In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min -1 ·m -2 . The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total number of new ischemic lesions. Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group ( P =0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm 3 (interquartile range, 0-118 mm 3 ; range, 0-25 261 mm 3 ) in the low-target group versus 29 mm 3 (interquartile range, 0-143 mm 3 ; range, 0-22 116 mm 3 ) in the high-target group (median difference estimate, 0; 95% confidence interval, -25 to 0.028; P =0.99), as was the secondary outcome of number of new lesions (1 [interquartile range, 0-2; range, 0-24] versus 1 [interquartile range, 0-2; range, 0-29] respectively; median difference estimate, 0; 95% confidence interval, 0-0; P =0.71). No significant difference was observed in frequency of severe adverse events. Among patients undergoing on-pump cardiac surgery, targeting a higher versus a lower mean arterial pressure during cardiopulmonary bypass did not seem to affect the volume or number of new cerebral infarcts. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02185885. © 2018 American Heart Association, Inc.

Introductory Talk: Adding Up Chemicals: Component-Based Risk Assessment of Chemical Mixturesand Primary Talk: Grouping Chemicals for Assessment and Conducting Assessments with the Hazard Index and Related Methods

EPA Science Inventory

Dr. Simmons will provide a concise overview of established and emerging methods to group chemicals for component-based mixture risk assessments. This will be followed by introduction to several important component-based methods, the Hazard Index, Target Organ Hazard Index, Multi...

Training in Basic Internet Skills for Special Target Groups in Non-Formal Educational Settings--Conclusions from Three Pilot Projects

ERIC Educational Resources Information Center

Berger, Andrea; Croll, Jutta

2012-01-01

With the progress of Digital Inclusion, it becomes important to address marginalised groups that face specific barriers in being part of the information society. From 2009 to 2011 within the framework of the nation-wide Initiative "Internet erfahren", funded by the German Federal Ministry of Economics, Stiftung Digitale Chancen has…

Phylum- and Class-Specific PCR Primers for General Microbial Community Analysis

PubMed Central

Blackwood, Christopher B.; Oaks, Adam; Buyer, Jeffrey S.

2005-01-01

Amplification of a particular DNA fragment from a mixture of organisms by PCR is a common first step in methods of examining microbial community structure. The use of group-specific primers in community DNA profiling applications can provide enhanced sensitivity and phylogenetic detail compared to domain-specific primers. Other uses for group-specific primers include quantitative PCR and library screening. The purpose of the present study was to develop several primer sets targeting commonly occurring and important groups. Primers specific for the 16S ribosomal sequences of Alphaproteobacteria, Betaproteobacteria, Bacilli, Actinobacteria, and Planctomycetes and for parts of both the 18S ribosomal sequence and the internal transcribed spacer region of Basidiomycota were examined. Primers were tested by comparison to sequences in the ARB 2003 database, and chosen primers were further tested by cloning and sequencing from soil community DNA. Eighty-five to 100% of the sequences obtained from clone libraries were found to be placed with the groups intended as targets, demonstrating the specificity of the primers under field conditions. It will be important to reevaluate primers over time because of the continual growth of sequence databases and revision of microbial taxonomy. PMID:16204538

Therapeutic potential of targeting group III metabotropic glutamate receptors in the treatment of Parkinson's disease

PubMed Central

Duty, Susan

2010-01-01

Current drugs used in the treatment of Parkinson's disease (PD), for example, L-DOPA and dopamine agonists, are very effective at reversing the motor symptoms of the disease. However, they do little to combat the underlying degeneration of dopaminergic neurones in the substantia nigra pars compacta (SNc) and their long-term use is associated with the appearance of adverse effects such as L-DOPA-induced dyskinesia. Much emphasis has therefore been placed on finding alternative non-dopaminergic drugs that may circumvent some or all of these problems. Group III metabotropic glutamate (mGlu) receptors were first identified in the basal ganglia a decade ago. One or more of these receptors (mGlu4, mGlu7 or mGlu8) is found on pre-synaptic terminals of basal ganglia pathways whose overactivity is implicated not only in the generation of motor symptoms in PD, but also in driving the progressive SNc degeneration. The finding that drugs which activate group III mGlu receptors can inhibit transmission across these overactive synapses has lead to the proposal that group III mGlu receptors are promising targets for drug discovery in PD. This paper provides a comprehensive review of the role and target potential of group III mGlu receptors in the basal ganglia. Overwhelming evidence obtained from in vitro studies and animal models of PD supports group III mGlu receptors as potentially important drug targets for providing both symptom relief and neuroprotection in PD. PMID:20735415

Comparison between imported versus domestic drug-eluting stents in China: A large single-center data.

PubMed

Liu, Ru; Gao, Zhan; Chen, Jue; Gao, Lijian; Song, Lei; Qiao, Shubin; Yang, Yuejin; Gao, Runlin; Xu, Bo; Yuan, Jinqing

2017-08-01

In recent years, most drug-eluting stents (DESs) were domestically produced in China, but how domestic DESs perform compared to imported DESs was still unknown. A total of 9011 consecutive cases with DESs implantation in a single center throughout 2013 were prospectively collected. Two-year clinical outcomes were evaluated between patients implanted with imported and domestic DESs. During 2-year follow-up, the rates of all-cause death, cardiac death, myocardial infarction, stroke, and stent thrombosis were not significantly different between two groups. However, the rate of revascularization was significantly higher in domestic DES group, shown as higher rates of overall revascularization, target vessel revascularization (TVR), and target lesion revascularization (TLR) (9.7% vs 6.4%, P < 0.001; 5.6% vs 3.2%, P < 0.001; 4.5% vs 2.2%, P < 0.001, respectively). Accordingly, major adverse cardiac events (MACE) rate was significantly higher in domestic DES group (12.1% vs 8.5%, P < 0.001). Multivariable Cox regression analysis indicated that domestic DES was an independent risk factor of MACE (HR [95%CI]: 1.22 [1.05-1.41]), overall revascularization (HR [95%CI]: 1.29 [1.09-1.53]), TVR (HR [95%CI]: 1.54 [1.22-1.94]), and TLR (HR [95%CI]: 1.85 [1.41-2.42]). After propensity score matching, the rates of overall revascularization, TVR, and TLR were still significantly higher in domestic DES group, and domestic DES was still predictive of overall revascularization, TVR, and TLR in multivariate Cox regression analysis. Domestic DESs showed the same safety as imported DESs in this real-world cohort. But, patients implanted with domestic DESs had a higher risk of revascularization than imported DESs. © 2017, Wiley Periodicals, Inc.

From Bioengineering to CRISPR/Cas9 – A Personal Retrospective of 20 Years of Research in Programmable Genome Targeting

PubMed Central

Jeltsch, Albert

2018-01-01

Genome targeting of restriction enzymes and DNA methyltransferases has many important applications including genome and epigenome editing. 15–20 years ago, my group was involved in the development of approaches for programmable genome targeting, aiming to connect enzymes with an oligodeoxynucleotide (ODN), which could form a sequence-specific triple helix at the genomic target site. Importantly, the target site of such enzyme-ODN conjugate could be varied simply by altering the ODN sequence promising great applicative values. However, this approach was facing many problems including the preparation and purification of the enzyme-ODN conjugates, their efficient delivery into cells, slow kinetics of triple helix formation and the requirement of a poly-purine target site sequence. Hence, for several years genome and epigenome editing approaches mainly were based on Zinc fingers and TAL proteins as targeting devices. More recently, CRISPR/Cas systems were discovered, which use a bound RNA for genome targeting that forms an RNA/DNA duplex with one DNA strand of the target site. These systems combine all potential advantages of the once imagined enzyme-ODN conjugates and avoid all main disadvantageous. Consequently, the application of CRISPR/Cas in genome and epigenome editing has exploded in recent years. We can draw two important conclusions from this example of research history. First, evolution still is the better bioengineer than humans and, whenever tested in parallel, natural solutions outcompete engineered ones. Second, CRISPR/Cas system were discovered in pure, curiosity driven, basic research, highlighting that it is basic, bottom-up research paving the way for fundamental innovation. PMID:29434619

Ignition of combustible/air mixtures by small radiatively heated surfaces.

PubMed

Welzel, M M; Schenk, S; Hau, M; Cammenga, H K; Bothe, H

2000-02-01

Optical radiation as an ignition source in potentially explosive atmospheres was investigated for a number of explosive mixtures with respect to the most important case occurring in practice, i.e., absorption of the radiation by a solid target. Iron oxide was used as the target material. The combustibles were selected in compliance with the well-known temperature classes and apparatus groups to allow a useful graduation of the power limits to be applied.

Genetics of rare mesenchymal tumors: implications for targeted treatment in DFSP, ASPS, CCS, GCTB and PEComa.

PubMed

Rutkowski, Piotr; Przybył, Joanna; Świtaj, Tomasz

2014-08-01

Soft tissue and bone sarcomas comprise a heterogeneous group of mesenchymal tumors that include roughly 130 distinct diagnostic entities. Many of them are exceptionally rare, with only few cases diagnosed worldwide each year. Development of novel targeted treatment in this group of tumors is of special importance since many sarcoma subtypes are resistant to conventional chemotherapy and the effective therapeutic options are limited. In this review we aim to discuss the molecular implications for targeted therapy in selected rare soft tissue and bone sarcoma subtypes, including dermatofibrosarcoma protuberans (DFSP), alveolar soft part sarcoma (ASPS), clear cell sarcoma (CCS), giant cell tumor of bone (GCTB) and perivascular epithelioid cell neoplasms (PEComas). This article is part of a Directed Issue entitled: Rare cancers. Copyright © 2014 Elsevier Ltd. All rights reserved.

Global assessment of the status of coral reef herbivorous fishes: evidence for fishing effects.

PubMed

Edwards, C B; Friedlander, A M; Green, A G; Hardt, M J; Sala, E; Sweatman, H P; Williams, I D; Zgliczynski, B; Sandin, S A; Smith, J E

2014-01-07

On coral reefs, herbivorous fishes consume benthic primary producers and regulate competition between fleshy algae and reef-building corals. Many of these species are also important fishery targets, yet little is known about their global status. Using a large-scale synthesis of peer-reviewed and unpublished data, we examine variability in abundance and biomass of herbivorous reef fishes and explore evidence for fishing impacts globally and within regions. We show that biomass is more than twice as high in locations not accessible to fisheries relative to fisheries-accessible locations. Although there are large biogeographic differences in total biomass, the effects of fishing are consistent in nearly all regions. We also show that exposure to fishing alters the structure of the herbivore community by disproportionately reducing biomass of large-bodied functional groups (scraper/excavators, browsers, grazer/detritivores), while increasing biomass and abundance of territorial algal-farming damselfishes (Pomacentridae). The browser functional group that consumes macroalgae and can help to prevent coral-macroalgal phase shifts appears to be most susceptible to fishing. This fishing down the herbivore guild probably alters the effectiveness of these fishes in regulating algal abundance on reefs. Finally, data from remote and unfished locations provide important baselines for setting management and conservation targets for this important group of fishes.

A new method of identifying target groups for pronatalist policy applied to Australia.

PubMed

Chen, Mengni; Lloyd, Chris J; Yip, Paul S F

2018-01-01

A country's total fertility rate (TFR) depends on many factors. Attributing changes in TFR to changes of policy is difficult, as they could easily be correlated with changes in the unmeasured drivers of TFR. A case in point is Australia where both pronatalist effort and TFR increased in lock step from 2001 to 2008 and then decreased. The global financial crisis or other unobserved confounders might explain both the reducing TFR and pronatalist incentives after 2008. Therefore, it is difficult to estimate causal effects of policy using econometric techniques. The aim of this study is to instead look at the structure of the population to identify which subgroups most influence TFR. Specifically, we build a stochastic model relating TFR to the fertility rates of various subgroups and calculate elasticity of TFR with respect to each rate. For each subgroup, the ratio of its elasticity to its group size is used to evaluate the subgroup's potential cost effectiveness as a pronatalist target. In addition, we measure the historical stability of group fertility rates, which measures propensity to change. Groups with a high effectiveness ratio and also high propensity to change are natural policy targets. We applied this new method to Australian data on fertility rates broken down by parity, age and marital status. The results show that targeting parity 3+ is more cost-effective than lower parities. This study contributes to the literature on pronatalist policies by investigating the targeting of policies, and generates important implications for formulating cost-effective policies.

Hepatocellular carcinoma-targeted effect of configurations and groups of glycyrrhetinic acid by evaluation of its derivative-modified liposomes

PubMed Central

Sun, Yuqi; Dai, Chunmei; Yin, Meilin; Lu, Jinghua; Hu, Haiyang; Chen, Dawei

2018-01-01

Background There are abundant glycyrrhetinic acid (GA) receptors on the cellular membrane of hepatocytes and hepatocellular carcinoma (HCC) cells. The receptor binding effect might be related to the structure of the guiding molecule. GA exists in two stereoisomers with C3-hydroxyl and C11-carbonyl active groups. Purpose The objective of this study was to investigate the relationship between the HCC-targeted effect and the configurations and groups of GA. Methods and results Different GA derivatives (18β-GA, 18α-GA, 3-acetyl-18β-GA [3-Ace-GA] and 11-deoxy-18β-GA [11-Deo-GA]) were used to investigate the targeting effect of GA’s configurations and groups on HCC cells. The EC50 values of competition to binding sites and the ratio of specific binding in HepG2 cells showed that 18β-GA and 3-Ace-GA demonstrated significant competitive effect with fluorescein isothiocyanate (FITC)-labeled GA. Then, the GA derivatives were distearoyl-phosphatidylethanolamine (DSPE)-PEGylated. 18β-GA-, 18α-GA-, 3-Ace-GA-and 11-Deo-GA-modified liposomes were prepared and characterized by size, zeta potential, encapsulation efficiency, loading capacity, leakage and membrane stability. Evaluation on the cellular location in vitro and tumor targeting in vivo was carried out. Compared to common long-circulation liposome (PEG-Lip), more 18β-GA- and 3-Ace-GA-modified liposomes aggregated around HepG2 cells in vitro in short time and transferred into HCC tumors in vivo for a longer time. Conclusion The β-configuration hydrogen atom on C18 position of GA played the most important role on the targeting effect. C11-carbonyl and C3-hydroxy groups of GA have certain and little influence on targeting action to HCC, respectively. In general, GA might be a promising targeting molecule for the research on liver diseases and hepatoma therapy. PMID:29588589

Hepatocellular carcinoma-targeted effect of configurations and groups of glycyrrhetinic acid by evaluation of its derivative-modified liposomes.

PubMed

Sun, Yuqi; Dai, Chunmei; Yin, Meilin; Lu, Jinghua; Hu, Haiyang; Chen, Dawei

2018-01-01

There are abundant glycyrrhetinic acid (GA) receptors on the cellular membrane of hepatocytes and hepatocellular carcinoma (HCC) cells. The receptor binding effect might be related to the structure of the guiding molecule. GA exists in two stereoisomers with C3-hydroxyl and C11-carbonyl active groups. The objective of this study was to investigate the relationship between the HCC-targeted effect and the configurations and groups of GA. Different GA derivatives (18β-GA, 18α-GA, 3-acetyl-18β-GA [3-Ace-GA] and 11-deoxy-18β-GA [11-Deo-GA]) were used to investigate the targeting effect of GA's configurations and groups on HCC cells. The EC 50 values of competition to binding sites and the ratio of specific binding in HepG2 cells showed that 18β-GA and 3-Ace-GA demonstrated significant competitive effect with fluorescein isothiocyanate (FITC)-labeled GA. Then, the GA derivatives were distearoyl-phosphatidylethanolamine (DSPE)-PEGylated. 18β-GA-, 18α-GA-, 3-Ace-GA-and 11-Deo-GA-modified liposomes were prepared and characterized by size, zeta potential, encapsulation efficiency, loading capacity, leakage and membrane stability. Evaluation on the cellular location in vitro and tumor targeting in vivo was carried out. Compared to common long-circulation liposome (PEG-Lip), more 18β-GA- and 3-Ace-GA-modified liposomes aggregated around HepG2 cells in vitro in short time and transferred into HCC tumors in vivo for a longer time. The β-configuration hydrogen atom on C18 position of GA played the most important role on the targeting effect. C11-carbonyl and C3-hydroxy groups of GA have certain and little influence on targeting action to HCC, respectively. In general, GA might be a promising targeting molecule for the research on liver diseases and hepatoma therapy.

Upgrading Existing Buildings to Universal Design. What Cost-Benefit Analyses Can Tell Us.

PubMed

Aslaksen, Finn

2016-01-01

This article is based on a project aimed at finding the benefits of different measures to upgrade existing public buildings and outdoor areas to be accessible for all. The study was initiated by The Ministry of Children and Equality. The ministry asked for a study of benefits based on a stated preferences (SP) method and an easy-to-complete calculation tool for CBA. In the project 18 commonly used measures and their typical costs were identified. The benefits of each measure were analysed in a stated preference study. The SP analyses included 9 multiple choices in 4 different sequences in an Internet based survey with 800 respondents. The project concluded that it is possible to use stated preferences survey to identify the respondent's valuation of measures to improve accessibility in existing buildings. Some of the measures have a high cost-/benefit ratio. The project report including the calculation manual is based on the average valuation for each measure. But in the background analyses (not referred in the report) there are also some analyses of valuations for target groups for the various measures. The target groups were defined for each measure based on information about the respondents' abilities and use of technical aids. The analyses presented in this paper indicate how valuation varies between the target groups and the average population. This is named the measures profile. Some measures have benefits for the target group that are only twice as high as for the average citizen while another type of measures has high benefits only the target group. The first type which has a wide profile often has high overall socioeconomic benefits, while the last group with a narrow profile more often has low overall socioeconomic benefits, but may be very important for certain user groups and therefore essential for the elimination of discrimination and exclusion of those groups.

A small-molecule fragment that emulates binding of receptor and broadly neutralizing antibodies to influenza A hemagglutinin.

PubMed

Kadam, Rameshwar U; Wilson, Ian A

2018-04-17

The influenza virus hemagglutinin (HA) glycoprotein mediates receptor binding and membrane fusion during viral entry in host cells. Blocking these key steps in viral infection has applications for development of novel antiinfluenza therapeutics as well as vaccines. However, the lack of structural information on how small molecules can gain a foothold in the small, shallow receptor-binding site (RBS) has hindered drug design against this important target on the viral pathogen. Here, we report on the serendipitous crystallization-based discovery of a small-molecule N -cyclohexyltaurine, commonly known as the buffering agent CHES, that is able to bind to both group-1 and group-2 HAs of influenza A viruses. X-ray structural characterization of group-1 H5N1 A/Vietnam/1203/2004 (H5/Viet) and group-2 H3N2 A/Hong Kong/1/1968 (H3/HK68) HAs at 2.0-Å and 2.57-Å resolution, respectively, revealed that N -cyclohexyltaurine binds to the heart of the conserved HA RBS. N -cyclohexyltaurine mimics the binding mode of the natural receptor sialic acid and RBS-targeting bnAbs through formation of similar hydrogen bonds and CH-π interactions with the HA. In H3/HK68, N -cyclohexyltaurine also binds to a conserved pocket in the stem region, thereby exhibiting a dual-binding mode in group-2 HAs. These long-awaited structural insights into RBS recognition by a noncarbohydrate-based small molecule enhance our knowledge of how to target this important functional site and can serve as a template to guide the development of novel broad-spectrum small-molecule therapeutics against influenza virus.

Identifying pathways affected by cancer mutations.

PubMed

Iengar, Prathima

2017-12-16

Mutations in 15 cancers, sourced from the COSMIC Whole Genomes database, and 297 human pathways, arranged into pathway groups based on the processes they orchestrate, and sourced from the KEGG pathway database, have together been used to identify pathways affected by cancer mutations. Genes studied in ≥15, and mutated in ≥10 samples of a cancer have been considered recurrently mutated, and pathways with recurrently mutated genes have been considered affected in the cancer. Novel doughnut plots have been presented which enable visualization of the extent to which pathways and genes, in each pathway group, are targeted, in each cancer. The 'organismal systems' pathway group (including organism-level pathways; e.g., nervous system) is the most targeted, more than even the well-recognized signal transduction, cell-cycle and apoptosis, and DNA repair pathway groups. The important, yet poorly-recognized, role played by the group merits attention. Pathways affected in ≥7 cancers yielded insights into processes affected. Copyright © 2017 Elsevier Inc. All rights reserved.

Age differences in visual search for compound patterns: long- versus short-range grouping.

PubMed

Burack, J A; Enns, J T; Iarocci, G; Randolph, B

2000-11-01

Visual search for compound patterns was examined in observers aged 6, 8, 10, and 22 years. The main question was whether age-related improvement in search rate (response time slope over number of items) was different for patterns defined by short- versus long-range spatial relations. Perceptual access to each type of relation was varied by using elements of same contrast (easy to access) or mixed contrast (hard to access). The results showed large improvements with age in search rate for long-range targets; search rate for short-range targets was fairly constant across age. This pattern held regardless of whether perceptual access to a target was easy or hard, supporting the hypothesis that different processes are involved in perceptual grouping at these two levels. The results also point to important links between ontogenic and microgenic change in perception (H. Werner, 1948, 1957).

Tissue ablation accelerated by peripheral scanning mode with high-intensity focused ultrasound: a study on isolated porcine liver perfusion.

PubMed

Bu, Rui; Yin, Li; Yang, Han; Wang, Qi; Wu, Feng; Zou, Jian Zhong

2013-08-01

The aims of this study were to investigate the feasibility of accelerated tissue ablation using a peripheral scanning mode with high-intensity focused ultrasound (HIFU) and to explore the effect of flow rate on total energy consumption of the target tissues. Using a model of isolated porcine liver perfusion via the portal vein and hepatic artery, we conducted a scanning protocol along the periphery of the target tissues using linear-scanned HIFU to carefully adjust the varying focal depth, generator power, scanning velocity and line-by-line interval over the entire ablation range. Porcine livers were divided into four ablation groups: group 1, n = 12, with dual-vessel perfusion; group 2, n = 11, with portal vein perfusion alone; group 3, n = 10, with hepatic artery perfusion alone; and group 4, n = 11, control group with no-flow perfusion. The samples were cut open consecutively at a thickness of 3 mm, and the actual ablation ranges were calculated along the periphery of the target tissues after triphenyl tetrazolium chloride staining. Total energy consumption was calculated as the sum of the energy requirements at various focal depths in each group. On the basis of the pre-supposed scanning protocol, the peripheral region of the target tissue formed a complete coagulation necrosis barrier in each group with varying dose combinations, and the volume of the peripheral necrotic area did not differ significantly among the four groups (p > 0.05). Furthermore, total energy consumption in each group significantly decreased with the corresponding decrease in flow rate (p < 0.01). This study revealed that the complete peripheral necrosis barrier within the target tissues can defined using linear-scanned HIFU in an isolated porcine liver perfusion model. Additionally, the flow rate in the major hepatic vessels may play an important role in the use of the peripheral ablation mode, and this novel mode of ablation may enhance the therapeutic efficacy and tolerability of the treatment of large tumors using HIFU ablation. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Diverse Actions and Target-Site Selectivity of Neonicotinoids: Structural Insights

PubMed Central

Matsuda, Kazuhiko; Kanaoka, Satoshi; Akamatsu, Miki; Sattelle, David B.

2009-01-01

The nicotinic acetylcholine receptors (nAChRs) are targets for human and veterinary medicines as well as insecticides. Subtype-selectivity among the diverse nAChR family members is important for medicines targeting particular disorders, and pest-insect selectivity is essential for the development of safer, environmentally acceptable insecticides. Neonicotinoid insecticides selectively targeting insect nAChRs have important applications in crop protection and animal health. Members of this class exhibit strikingly diverse actions on their nAChR targets. Here we review the chemistry and diverse actions of neonicotinoids on insect and mammalian nAChRs. Electrophysiological studies on native nAChRs and on wild-type and mutagenized recombinant nAChRs have shown that basic residues particular to loop D of insect nAChRs are likely to interact electrostatically with the nitro group of neonicotinoids. In 2008, the crystal structures were published showing neonicotinoids docking into the acetylcholine binding site of molluscan acetylcholine binding proteins with homology to the ligand binding domain (LBD) of nAChRs. The crystal structures showed that 1) glutamine in loop D, corresponding to the basic residues of insect nAChRs, hydrogen bonds with the NO2 group of imidacloprid and 2) neonicotinoid-unique stacking and CH-π bonds at the LBD. A neonicotinoid-resistant strain obtained by laboratory-screening has been found to result from target site mutations, and possible reasons for this are also suggested by the crystal structures. The prospects of designing neonicotinoids that are safe not only for mammals but also for beneficial insects such as honey bees (Apis mellifera) are discussed in terms of interactions with non-α nAChR subunits. PMID:19321668

Distractor ratio and grouping processes in visual conjunction search.

PubMed

Poisson, M E; Wilkinson, F

1992-01-01

According to feature integration theory, conjunction search is conducted via a serial self-terminating search. However, effects attributed to search processes operating on the entire display may actually reflect search restricted to elements defined by a single feature. In experiment 1 this question is addressed in a reaction-time (RT) paradigm by varying distractor ratios within an array of fixed size. For trials in which the target was present in the array, RT functions were roughly symmetric, the shortest RTs being for extreme distractor ratios, and the longest RTs being for arrays in which there were an equal number of each distractor type. This result is superficially consistent with Zohary and Hochstein's interpretation that subjects search for only one distractor type and are able to switch search strategy from trial to trial. However, negative-trial data from experiment 1 case doubt on this interpretation. In experiment 2 the possible role of 'pop out' and of distractor grouping in visual conjunction search is investigated. Results of experiment 2 suggest that grouping may play a more important role than does distractor ratio, and point to the importance of the spatial layout of the target and of the distractor elements in visual conjunction search. Results of experiment 2 also provide clear evidence that groups of spatially adjacent homogeneous elements may be processed as a unit.

Importance of sustained and "tight" blood pressure control in patients with high cardiovascular risk.

PubMed

Meredith, Peter A; Lloyd, Suzanne M; Ford, Ian; Elliott, Henry L

2016-01-01

A retrospective further analysis of the ACTION database evaluated the relationship between cardiovascular outcomes and the "quality" of the control of blood pressure (BP). The study population (n = 6287) comprised those patients with four BP measurements during year 1 subdivided according to the proportion of visits in which BP was controlled in relation to two BP targets: < 140/90mmHg and < 130/80 mmHg. Differences between the BP control groups for the major prespecified ACTION outcomes were investigated with Cox proportional hazards models. For all the prespecified cardiovascular endpoints the incidence declined as the proportion of visits with BP control increased. The greatest differences in outcomes between the different BP control groups were observed for the risk of stroke but were still apparent for all the other endpoints. For example, the risks for the primary outcome [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.67 to 0.90] were significantly less in the group with >_75% of visits with BP control than in the group with < 25% of visits with BP control. There were no significant treatment-related differences. Retrospective analyses are not definitive but these results highlight the importance of the attainment of BP control targets and the consistency of BP control during long-term follow-up.

Genomic organization, phylogenetic comparison, and expression profiles of the SPL family genes and their regulation in soybean.

PubMed

Tripathi, Rajiv K; Goel, Ridhi; Kumari, Sweta; Dahuja, Anil

2017-03-01

SQUAMOSA Promoter-Binding Protein-Like (SPL) genes form a major family of plant-specific transcription factors and play an important role in plant growth and development. In this study, we report the identification of 41 SPL genes (GmSPLs) in the soybean genome. Phylogenetic analysis revealed that these genes were divided into five groups (groups 1-5). Further, exon/intron structure and motif composition revealed that the GmSPL genes are conserved within their same group. The N-terminal zinc finger 1 (Zn1) of the SBP domain was a CCCH (Cys3His1) and the C terminus zinc finger 2 (Zn2) was a CCHC (Cys2HisCys) type. The 41 GmSPL genes were distributed unevenly on 17 of the 20 chromosomes, with tandem and segmental duplication events. We found that segmental duplication has made an important contribution to soybean SPL gene family expansion. The Ka/Ks ratios revealed that the duplicated GmSPL genes evolved under the effect of purifying selection. In addition, 17 of the 41 GmSPLs were found as targets of miR156; these might be involved in their posttranscriptional regulation through miR156. Importantly, RLM-RACE analysis confirmed the GmmiR156-mediated cleavage of GmSPL2a transcript in 2-4 mm stage of soybean seed. Alternative splicing events in 9 GmSPLs were detected which produces transcripts and proteins of different lengths that may modulate protein signaling, binding, localization, stability, and other properties. Expression analysis of the soybean SPL genes in various tissues and different developmental stages of seed suggested distinct spatiotemporal patterns. Differences in the expression patterns of miR156-targeted and miR156-non-targeted soybean SPL genes suggest that miR156 plays key functions in soybean development. Our results provide an important foundation for further uncovering the crucial roles of GmSPLs in the development of soybean and other biological processes.

Age-Related Changes in the Ability to Switch between Temporal and Spatial Attention

PubMed Central

Callaghan, Eleanor; Holland, Carol; Kessler, Klaus

2017-01-01

Background: Identifying age-related changes in cognition that contribute towards reduced driving performance is important for the development of interventions to improve older adults’ driving and prolong the time that they can continue to drive. While driving, one is often required to switch from attending to events changing in time, to distribute attention spatially. Although there is extensive research into both spatial attention and temporal attention and how these change with age, the literature on switching between these modalities of attention is limited within any age group. Methods: Age groups (21–30, 40–49, 50–59, 60–69 and 70+ years) were compared on their ability to switch between detecting a target in a rapid serial visual presentation (RSVP) stream and detecting a target in a visual search display. To manipulate the cost of switching, the target in the RSVP stream was either the first item in the stream (Target 1st), towards the end of the stream (Target Mid), or absent from the stream (Distractor Only). Visual search response times and accuracy were recorded. Target 1st trials behaved as no-switch trials, as attending to the remaining stream was not necessary. Target Mid and Distractor Only trials behaved as switch trials, as attending to the stream to the end was required. Results: Visual search response times (RTs) were longer on “Target Mid” and “Distractor Only” trials in comparison to “Target 1st” trials, reflecting switch-costs. Larger switch-costs were found in both the 40–49 and 60–69 years group in comparison to the 21–30 years group when switching from the Target Mid condition. Discussion: Findings warrant further exploration as to whether there are age-related changes in the ability to switch between these modalities of attention while driving. If older adults display poor performance when switching between temporal and spatial attention while driving, then the development of an intervention to preserve and improve this ability would be beneficial. PMID:28261088

Target Identification Support and Location Support Among Teams of Unmanned Systems Operators

DTIC Science & Technology

2008-12-01

effectiveness and performance, many studies have highlighted the importance of attending to team process (Campion, Medsker, & Higgs, 1993, Campion, Papper ...work groups. Personnel Psychology, 46, 823-850. Campion, M., Papper , E., & Medsker, G., 1996: Relations between work team characteristics and

Marketers hone their skills to reach target markets.

PubMed

White, D; Christensen, M

1990-08-05

New challenges lie ahead for health care marketers. Marketers must communicate with several important groups: their own administration, the general public, employers, hospital employees, and, of course, physicians. And as budgets tighten, the methods used to communicate must become more creative and more efficient.

Annual public health and economic benefits of seasonal influenza vaccination: a European estimate.

PubMed

Preaud, Emmanuelle; Durand, Laure; Macabeo, Bérengère; Farkas, Norbert; Sloesen, Brigitte; Palache, Abraham; Shupo, Francis; Samson, Sandrine I

2014-08-07

Vaccination is currently the most effective means of preventing influenza infection. Yet evidence of vaccine performance, and the impact and value of seasonal influenza vaccination across risk groups and between seasons, continue to generate much discussion. Moreover, vaccination coverage is below recommended levels. A model was generated to assess the annual public health benefits and economic importance of influenza vaccination in 5 WHO recommended vaccination target groups (children 6 - 23 months of age; persons with underlying chronic health conditions; pregnant women; health care workers; and, the elderly, 65 years of age) in 27 countries of the European Union. Model estimations were based on standard calculation methods, conservative assumptions, age-based and country-specific data. Out of approximately 180 million Europeans for whom influenza vaccination is recommended, only about 80 million persons are vaccinated. Seasonal influenza vaccination currently prevents an annual average of between 1.6 million and 2.1 million cases of influenza, 45,300 to 65,600 hospitalizations, and 25,200 to 37,200 deaths. To reach the 75% vaccination coverage target set by the EU Council Recommendation in 2009, an additional 57.4 million person would need to be vaccinated in the elderly and other risk groups. By achieving the 75% target rate set in EU-27 countries, average annual influenza- related events averted would increase from current levels to an additional +1.6 to +1.7 million cases, +23,800 to +31,400 hospitalization, +9,800 to +14,300 deaths, +678,500 to +767,800 physician visits, and +883,800 to +1,015,100 lost days of work yearly. Influenza-related costs averted because of vaccination would increase by an additional + €190 to + €226 million yearly, in vaccination target groups. Full implementation of current influenza vaccination recommendations of 75% vaccination coverage rate (VCR) in Europe by the 2014-2015 influenza season could immediately reduce an important public health and economic burden.

The cognitive consequences of envy: attention, memory, and self-regulatory depletion.

PubMed

Hill, Sarah E; DelPriore, Danielle J; Vaughan, Phillip W

2011-10-01

In a series of 4 experiments, we provide evidence that--in addition to having an affective component--envy may also have important consequences for cognitive processing. Our first experiment (N = 69) demonstrated that individuals primed with envy better attended to and more accurately recalled information about fictitious peers than did a control group. Studies 2 (N = 187) and 3 (N = 65) conceptually replicated these results, demonstrating that envy elicited by targets predicts attention and later memory for information about them. We demonstrate that these effects cannot be accounted for by admiration or changes in negative affect or arousal elicited by the targets. Study 4 (N = 152) provides evidence that greater memory for envied--but not neutral--targets leads to diminished perseverance on a difficult anagram task. Findings demonstrate that envy may play an important role in attention and memory systems and deplete limited self-regulatory resources available for acts of volition. 2011 APA, all rights reserved

Interventions Targeting Mental Health Self-Stigma: A Review and Comparison

PubMed Central

Yanos, Philip T.; Lucksted, Alicia; Drapalski, Amy L.; Roe, David; Lysaker, Paul

2014-01-01

Objective With growing awareness of the impact of mental illness self-stigma, interest has arisen in the development of interventions to combat it. The present article briefly reviews and compares interventions targeting self-stigma to clarify the similarities and important differences between the interventions. Methods We conducted a narrative review of published literature on interventions targeting self-stigma. Results Six intervention approaches (Healthy Self-Concept, Self-Stigma Reduction Program, Ending Self-Stigma, Narrative Enhancement and Cognitive Therapy, Coming Out Proud, and Anti-Stigma Photo-Voice Intervention) were identified and are discussed, and data is reviewed on format, group-leader backgrounds, languages, number of sessions, primary mechanisms of action, and the current state of data on their efficacy. Conclusions and Implications for Practice We conclude with a discussion of common elements and important distinctions between the interventions and a consideration of which interventions might be best suited to particular populations or settings. PMID:25313530

Interventions targeting mental health self-stigma: A review and comparison.

PubMed

Yanos, Philip T; Lucksted, Alicia; Drapalski, Amy L; Roe, David; Lysaker, Paul

2015-06-01

With growing awareness of the impact of mental illness self-stigma, interest has arisen in the development of interventions to combat it. The present article briefly reviews and compares interventions targeting self-stigma to clarify the similarities and important differences between the interventions. We conducted a narrative review of published literature on interventions targeting self-stigma. Six intervention approaches (Healthy Self-Concept, Self-Stigma Reduction Program, Ending Self-Stigma, Narrative Enhancement and Cognitive Therapy, Coming Out Proud, and Anti-Stigma Photo-Voice Intervention) were identified and are discussed, and data is reviewed on format, group-leader backgrounds, languages, number of sessions, primary mechanisms of action, and the current state of data on their efficacy. We conclude with a discussion of common elements and important distinctions between the interventions and a consideration of which interventions might be best suited to particular populations or settings. (c) 2015 APA, all rights reserved).

Automatic feature-based grouping during multiple object tracking.

PubMed

Erlikhman, Gennady; Keane, Brian P; Mettler, Everett; Horowitz, Todd S; Kellman, Philip J

2013-12-01

Contour interpolation automatically binds targets with distractors to impair multiple object tracking (Keane, Mettler, Tsoi, & Kellman, 2011). Is interpolation special in this regard or can other features produce the same effect? To address this question, we examined the influence of eight features on tracking: color, contrast polarity, orientation, size, shape, depth, interpolation, and a combination (shape, color, size). In each case, subjects tracked 4 of 8 objects that began as undifferentiated shapes, changed features as motion began (to enable grouping), and returned to their undifferentiated states before halting. We found that intertarget grouping improved performance for all feature types except orientation and interpolation (Experiment 1 and Experiment 2). Most importantly, target-distractor grouping impaired performance for color, size, shape, combination, and interpolation. The impairments were, at times, large (>15% decrement in accuracy) and occurred relative to a homogeneous condition in which all objects had the same features at each moment of a trial (Experiment 2), and relative to a "diversity" condition in which targets and distractors had different features at each moment (Experiment 3). We conclude that feature-based grouping occurs for a variety of features besides interpolation, even when irrelevant to task instructions and contrary to the task demands, suggesting that interpolation is not unique in promoting automatic grouping in tracking tasks. Our results also imply that various kinds of features are encoded automatically and in parallel during tracking.

Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated μ opioid receptor (MOR-1) splice variants.

PubMed

Majumdar, Susruta; Subrath, Joan; Le Rouzic, Valerie; Polikar, Lisa; Burgman, Maxim; Nagakura, Kuni; Ocampo, Julie; Haselton, Nathan; Pasternak, Anna R; Grinnell, Steven; Pan, Ying-Xian; Pasternak, Gavril W

2012-07-26

3-Iodobenzoylnaltrexamide 1 (IBNtxA) is a potent analgesic acting through a novel receptor target that lack many side-effects of traditional opiates composed, in part, of exon 11-associated truncated six transmembrane domain MOR-1 (6TM/E11) splice variants. To better understand the SAR of this drug target, a number of 4,5-epoxymorphinan analogues were synthesized. Results show the importance of a free 3-phenolic group, a phenyl ring at the 6 position, an iodine at the 3'or 4' position of the phenyl ring, and an N-allyl or c-propylmethyl group to maintain high 6TM/E11 affinity and activity. 3-Iodobenzoylnaloxamide 15 (IBNalA) with a N-allyl group displayed lower δ opioid receptor affinity than its naltrexamine analogue, was 10-fold more potent an analgesic than morphine, elicited no respiratory depression or physical dependence, and only limited inhibition of gastrointestinal transit. Thus, the aryl-naloxamide scaffold can generate a potent analgesic acting through the 6TM/E11 sites with advantageous side-effect profile and greater selectivity.

A new method of identifying target groups for pronatalist policy applied to Australia

PubMed Central

Chen, Mengni; Lloyd, Chris J.

2018-01-01

A country’s total fertility rate (TFR) depends on many factors. Attributing changes in TFR to changes of policy is difficult, as they could easily be correlated with changes in the unmeasured drivers of TFR. A case in point is Australia where both pronatalist effort and TFR increased in lock step from 2001 to 2008 and then decreased. The global financial crisis or other unobserved confounders might explain both the reducing TFR and pronatalist incentives after 2008. Therefore, it is difficult to estimate causal effects of policy using econometric techniques. The aim of this study is to instead look at the structure of the population to identify which subgroups most influence TFR. Specifically, we build a stochastic model relating TFR to the fertility rates of various subgroups and calculate elasticity of TFR with respect to each rate. For each subgroup, the ratio of its elasticity to its group size is used to evaluate the subgroup’s potential cost effectiveness as a pronatalist target. In addition, we measure the historical stability of group fertility rates, which measures propensity to change. Groups with a high effectiveness ratio and also high propensity to change are natural policy targets. We applied this new method to Australian data on fertility rates broken down by parity, age and marital status. The results show that targeting parity 3+ is more cost-effective than lower parities. This study contributes to the literature on pronatalist policies by investigating the targeting of policies, and generates important implications for formulating cost-effective policies. PMID:29425220

Cultural affiliation and the importance of health care attributes. Marketers can develop segmentation strategies for targeted patient groups.

PubMed

Dolinsky, A L; Stinerock, R

1998-01-01

Culturally based values are known to influence consumer purchase decisions, but little is known about how those values affect health care choices. To rectify that situation and provide health care marketers with a framework for developing culturally based segmentation strategies, the authors undertook an exploratory research project in which Hispanic-, African-, and Anglo-Americans were asked to rate the importance of 16 different health care attributes. Those attributes can be grouped under five categories: quality of physician, quality of nurses and other medical staff, economic issues, access to health care, and nonmedically related experiential aspects. Survey responses identified distinct differences in the importance attached to the various attributes by the three cultural groups. The study also looks at the impact of six demographic and social characteristics on the evaluations made by each cultural group. Those characteristics are educational level, gender, age, health status, marital status, and number of people living in the household.

Progress in neutron electromagnetic couplings

NASA Astrophysics Data System (ADS)

Strakovsky, Igor; Briscoe, William; Kudryavtsev, Alexander; Kulikov, Viacheslav; Martemianov, Maxim; Tarasov, Vladimir; Workman, Ron

2016-05-01

An overview of the GW SAID and ITEP groups' effort to analyze pion photoproduction on the neutron-target will be given. The disentangling of the isoscalar and isovector EM couplings of N* and Δ* resonances does require compatible data on both proton and neutron targets. The final-state interactions play a critical role in the state-of-the-art analysis in extraction of the γn → πN data from the deuteron target experiments. Then resonance couplings determined by the SAID PWA technique are compared to previous findings. The neutron program is an important component of the current JLab, MAMI-C, SPring-8, ELSA, and ELPH studies.

Exclusive Meson Photoproduction off Bound Nucleons

NASA Astrophysics Data System (ADS)

Strakovsky, Igor; Briscoe, William

2017-09-01

An overview of the GW SAID group effort to analyze pion photoproduction on the neutron-target will be given. The disentangling of the isoscalar and isovector EM couplings of N * and Δ * resonances does require compatible data on both proton and neutron targets. The final-state interactions play a critical role in the state-of-the-art analysis in extraction of the γn -> π N data from the deuteron target experiments. Then resonance couplings determined by the SAID PWA technique are compared to previous findings. The neutron program is an important component of the current JLab, MAMI-C, SPring-8, ELSA, and ELPH studies. DOE Research Grant DE``SC0016583.

Effects of colour on preview search: anticipatory and inhibitory biases for colour.

PubMed

Braithwaite, Jason J; Humphreys, Glyn W; Hodsoll, John

2004-01-01

Two experiments are reported examining the effects of colour grouping, colour change and target colour foreknowledge under preview search conditions (Watson and Humphreys, 1997). In Experiment 1 we manipulated the colour homogeneity of the old items at initial presentation, and the colour these items subsequently changed into. In all cases participants knew the colour of the target. We found that when the old items changed into the same colour as the new search set, search performance was affected. In Experiment 2 participants did not know the colour of the target. Here we found evidence for a negative colour-based carry-over effect that slowed search for new targets carrying the colour of the old items. This occurred even when the old items changed their original colour and the new target was a singleton. Collectively the results suggest an important role for both colour grouping and colour-based inhibition in the successful rejection of old distractors. The consequence of this, however, is that new stimuli that may carry the critical attribute may take longer to detect. We discuss the results in relation to prior 'feature-blind' accounts of preview effects on visual search.

Teacher Effectiveness and Causal Inference in Observational Studies

ERIC Educational Resources Information Center

Rose, Roderick A.

2013-01-01

An important target of education policy is to improve overall teacher effectiveness using evidence-based policies. Randomized control trials (RCTs), which randomly assign study participants or groups of participants to treatment and control conditions, are not always practical or possible and observational studies using rigorous quasi-experimental…

[Prevention of skin cancer: considerations on strategic communication].

PubMed

Anders, M P; Baumann, E; Breitbart, E W

2014-03-01

In recent decades the numbers of cases of skin cancer have been increasing worldwide in light skinned populations. In Germany skin cancer is the most common form of cancer. To reduce the burden of skin cancer protection from ultraviolet radiation (primary prevention) and early detection (secondary prevention) of the disease play a decisive role. In this context information to the population about preventive behavior and the support of informed decision-making in skin cancer screening are important aspects in communication. This paper gives an overview about communicational aspects in the promotion of skin cancer prevention. In the development of communicational interventions it is important to identify the relevant target groups. Relevant key opinion leaders have to be included in the information process. Additionally, interventions should be based on a theoretical framework and be designed for the respective target group. Furthermore, different forms of communication and communication tools are provided for the realization of an information intervention. To appraise the intervention elements of summative and formal evaluation are available. The current results provide important findings about different effects of communicational aspects on knowledge and behavior of the population; however, due to the complexity of information interventions a particular effect cannot be explained by a single communicational element.

Impact of Family Planning and Business Trainings on Private-Sector Health Care Providers in Nigeria.

PubMed

Ugaz, Jorge; Leegwater, Anthony; Chatterji, Minki; Johnson, Doug; Baruwa, Sikiru; Toriola, Modupe; Kinnan, Cynthia

2017-06-01

Private health care providers are an important source of modern contraceptives in Sub-Saharan Africa, yet they face many challenges that might be addressed through targeted training. This study measures the impact of a package of trainings and supportive supervision activities targeted to private health care providers in Lagos State, Nigeria, on outcomes including range of contraceptive methods offered, providers' knowledge and quality of counseling, recordkeeping practices, access to credit and revenue. A total of 965 health care facilities were randomly assigned to treatment and control groups. Facilities in the treatment group-but not those in the control group-were offered a training package that included a contraceptive technology update and interventions to improve counseling and clinical skills and business practices. Multivariate regression analysis of data collected through facility and mystery client surveys was used to estimate effects. The training program had a positive effect on the range of contraceptive methods offered, with facilities in the treatment group providing more methods than facilities in the control group. The training program also had a positive impact on the quality of counseling services, especially on the range of contraceptive methods discussed by providers, their interpersonal skills and overall knowledge. Facilities in the treatment group were more likely than facilities in the control group to have good recordkeeping practices and to have obtained loans. No effect was found on revenue generation. Targeted training programs can be effective tools to improve the provision of family planning services through private providers.

HDAC Inhibitors Target Replication Forks to Take a Stab at Cancer | Center for Cancer Research

Cancer.gov

The stability and function of many proteins within the cell can be altered with the addition or removal of certain chemical groups, including acetyl groups. Therefore, the enzymes that regulate these modifications have an important impact on the cell. One class of such enzymes—histone deacetylases, or HDACs—has been implicated in cancer and has become a target for cancer therapy. One HDAC inhibitor, called SAHA, has been approved for use against cutaneous T-cell lymphoma, and more than 60 ongoing clinical trials are continuing to test this class of drugs in various forms of cancer. However, the mechanisms by which SAHA and other HDAC inhibitors undermine the viability of tumor cells are not completely understood.

The structure of ethnic attitudes: the effects of target group, region, gender, and national identity.

PubMed

Verkuyten, M

1997-08-01

The present study was an assessment of attitudes of 410 ethnically Dutch adolescents toward three ethnic minority groups living in the Netherlands. Stereotypes, symbolic beliefs, affective associations, and the evaluation of possible interactions were used to predict the global evaluation of ethnic outgroups and accounted for much of the variance in ethnic attitudes. The relative importance of the four predictors varied by target group and location. Gender differences were found in the structure of attitudes; symbolic beliefs played a greater role in the attitudes of boys, whereas emotions played a more central role in the attitudes of girls. The evaluation of Dutch identity was related to the favorability of ethnic attitudes and also to the underlying structure. Respondents with a positive national identity had less favorable ethnic attitudes, and emotions were more predictive of their attitudes, whereas symbolic beliefs were most predictive among respondents with a less positive national identity.

Developing clinical practice guidelines: target audiences, identifying topics for guidelines, guideline group composition and functioning and conflicts of interest

PubMed Central

2012-01-01

Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the target audience(s) for guidelines and their use of guidelines; identifying topics for guidelines; guideline group composition (including consumer involvement) and the processes by which guideline groups function and the important procedural issue of managing conflicts of interest in guideline development. PMID:22762776

Developing clinical practice guidelines: target audiences, identifying topics for guidelines, guideline group composition and functioning and conflicts of interest.

PubMed

Eccles, Martin P; Grimshaw, Jeremy M; Shekelle, Paul; Schünemann, Holger J; Woolf, Steven

2012-07-04

Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the target audience(s) for guidelines and their use of guidelines; identifying topics for guidelines; guideline group composition (including consumer involvement) and the processes by which guideline groups function and the important procedural issue of managing conflicts of interest in guideline development.

Outskirts of Local Group Dwarf Galaxies Revealed by Subaru Hyper Suprime-Cam

NASA Astrophysics Data System (ADS)

Komiyama, Yutaka

2017-03-01

Local Group galaxies are important targets since their stellar populations can be resolved, and their properties can be investigated in detail with the help of stellar evolutionary models. The newly-built instrument for the 8.2m Subaru Telescope, Hyper Suprime-Cam (HSC), which has a 1 Giga pixel CCD camera with 1.5 degrees field of view, is the best instrument for observing Local Group galaxies. We have carried out a survey for Local Group dwarf galaxies using HSC aiming to shed light on the outskirts of these galaxies. The survey covers target galaxies out beyond the tidal radii down to a depth unexplored by previous surveys. Thanks to the high spatial resolution and high sensitivity provided by the Subaru Telescope, we are able to investigate properties such as spatial distribution and stellar population from the very center of galaxies to the outskirts. In this article, I will show results for the dwarf irregular galaxy NGC 6822 and the dwarf spheroidal galaxy Ursa Minor.

The context and practice of handwashing among new mothers in Serang, Indonesia: a formative research study.

PubMed

Greenland, Katie; Iradati, Endang; Ati, Abigael; Maskoen, Yanti Yulianti; Aunger, Robert

2013-09-11

This article reports on formative research into the context and practice of handwashing with soap by new mothers, which can substantially impact child morbidity and mortality. New mothers are an important target group for handwashing interventions: they are considered particularly susceptible to behaviour change and their actions can directly affect a child's health. Twenty-seven mothers of infants (including neonates) from urban and rural sub-districts of Serang were recruited and filmed over a period of eight hours. Video footage was used to identify handwashing occasions and to understand the context in which behaviour took place. Each woman was subsequently interviewed. Handwashing with soap was found to be infrequent, typically occurring after eating, cooking and household chores or after cleaning a child's bottom. Handwashing before preparing food or eating was rare. Pre-pregnancy routines were reported to have been disrupted. Advice on child care comes from many sources, particularly the midwife and new child's grandmother. Developing interventions to change perceptions and practice of handwashing would seed an important behaviour and could save lives. New mothers represent an ideal target group for such an intervention. We suggest that interventions target an increase in handwashing with soap after contact with own and a baby's faecal matter as part of the post-defecation hygiene routines. As the child's grandmother is an authoritative source of information about parenting, interventions focussed on improving newborn care could target grandmothers as well as midwives.

Stereotypes of Black American Women Related to Sexuality and Motherhood.

PubMed

Rosenthal, Lisa; Lobel, Marci

2016-09-01

Intersectionality theorists and researchers suggest the importance of examining unique stereotypes associated with intersecting group identities. We focus on the unique stereotypes of Black women in the United States related to sexuality and motherhood. In an online experimental study, 435 undergraduates from a Northeastern U.S. university were randomly assigned to one of the four conditions in which they viewed a photograph and read a description of a target young woman. The target's race (Black vs. White) and pregnancy status (pregnant vs. no pregnancy information) were varied. A Black female target (pregnant or not) was perceived more negatively on items related to historically rooted societal stereotypes about sexual activity, sexual risk, motherhood status, and socioeconomic status than was a White female target, but there were no differences on items unrelated to societal stereotypes. A Black target described as pregnant was also perceived as more likely to be a single mother and to need public assistance than was a White target described as pregnant. Current findings, along with evidence that societal stereotypes have damaging effects, underscore the importance of diversifying images of Black women and increasing awareness of how stereotypes affect perceptions of Black women. Findings also highlight the value of research employing intersectionality to understand stereotypes.

Development of Y-shaped peptide for constructing nanoparticle systems targeting tumor-associated macrophages in vitro and in vivo

NASA Astrophysics Data System (ADS)

Yan, Lu; Gao, Yunxiang; Pierce, Ryan; Dai, Liming; Kim, Julian; Zhang, Mei

2014-04-01

Tumor-associated macrophage (TAM) is increasingly being viewed as a target of great interest in tumor microenvironment due to its important role in the progression and metastasis of cancers. It has been shown that TAM indeed overexpresses unique surface marker legumain. In this study, we designed and synthesized a Y-shaped legumain-targeting peptide (Y-Leg) with functional groups allowing for further conjugation with imaging and therapeutic moieties (vide infra). The in vitro cell experiments using FITC-conjugated Y-Leg revealed its specific and selective interaction with M2-polarized macrophages (i.e., TAMs) with preference to M1 macrophages, and that the interaction was not interfered with by conjugating FITC to its functional group. Further, we constructed a nanotube system by grafting Y-Leg onto oxidized carbon nanotubes (OCNTs) loaded with paramagnetic Fe3O4 nanoparticles. The intravenous injection of the resultant Y-Leg-OCNT/Fe3O4 nanotubes to 4T1 mammary tumor-bearing mouse led to the magnetic resonance imaging (MRI) of TAM-infiltrated tumor microenvironment, revealing the targeting specificity of Y-Leg-conjugated nanotubes in vivo. The Y shape of peptide and its functional groups containing amines and imidazole can protonate at different pHs, contributing to the in vitro and in vivo targeting specificity. This study represents the first development of novel peptide and peptide-grafted nanotube system targeting M2-polarized TAMs in vivo. The methodology developed in this study is applicable to the construction of various multifunctional nanoparticle systems for selectively targeting, imaging and manipulating of TAMs for the diagnosis and treatment of cancers and inflammatory diseases identified with macrophage-infiltrated disease tissue.

Barriers and facilitators towards implementing the Sepsis Six care bundle (BLISS-1): a mixed methods investigation using the theoretical domains framework.

PubMed

Roberts, Neil; Hooper, Guy; Lorencatto, Fabiana; Storr, Wendell; Spivey, Michael

2017-09-19

The 'Sepsis 6', a care bundle of basic, but vital, measures (e.g. intravenous fluid, antibiotics) has been implemented to improve sepsis treatment. However, uptake has been variable. Tools from behavioral sciences, such as the Theoretical Domains Framework (TDF) may be used to understand and address such implementation issues. This study used a behavioral science approach to identify barriers and facilitators towards Sepsis Six implementation at a case study hospital. Semi-structured interviews based on the TDF were conducted with a sample group of consultants, junior doctors and nurses from Emergency Department, Medical and Surgical Admissions, to explore barriers/facilitators to Sepsis Six performance. Transcripts were analyzed following the combined principles of content and framework analysis. Emerging themes informed a questionnaire to explore generalizability and importance across a sample of 261 stakeholders. Median importance and agreement ratings for each theme were calculated overall and for each role and clinical area. These were used to identify important barriers and important facilitators as targets for performance improvement. No new belief statements were discovered and data saturation was deemed achieved after 10 interviews. 1699 utterances were coded into 64 belief statements, then collated into a 51-item questionnaire. 113 questionnaire responses were obtained (44.3% response rate). Important barriers included insufficient audit and feedback, poor teamwork and communication, concerns about using the Sepsis Six in certain patients, insufficient training, and resource concerns. Facilitators included confidence in knowledge and skills, beliefs in overall benefits of the bundle, beliefs that identification and management of septic patients fell within everyone's role, and that regular use of the bundle made it easier to remember. Some beliefs were applicable for the entire group, others were specific to particular staff groups. A range of barriers and facilitators towards Sepsis Six performance across different staff groups were systematically identified using a theoretically-informed approach. This can inform development of targeted performance improvement interventions.

Suicide Prevention in a Diverse Campus Community

ERIC Educational Resources Information Center

Shadick, Richard; Akhter, Sarah

2013-01-01

As the college population in the United States rapidly diversifies, leaders of successful campus suicide prevention programs are recognizing the importance of targeting specific groups of students. Recent estimates from the National Center for Education Statistics indicated that in 2008 more than one-third (36.7 percent) of college students…

Potent Neutralization of Vaccinia Virus by Divergent Murine Antibodies Targeting a Common Site of Vulnerability in L1 Protein

PubMed Central

Kaever, Thomas; Meng, Xiangzhi; Matho, Michael H.; Schlossman, Andrew; Li, Sheng; Sela-Culang, Inbal; Ofran, Yanay; Buller, Mark; Crump, Ryan W.; Parker, Scott; Frazier, April; Crotty, Shane; Zajonc, Dirk M.; Peters, Bjoern

2014-01-01

ABSTRACT Vaccinia virus (VACV) L1 is an important target for viral neutralization and has been included in multicomponent DNA or protein vaccines against orthopoxviruses. To further understand the protective mechanism of the anti-L1 antibodies, we generated five murine anti-L1 monoclonal antibodies (MAbs), which clustered into 3 distinct epitope groups. While two groups of anti-L1 failed to neutralize, one group of 3 MAbs potently neutralized VACV in an isotype- and complement-independent manner. This is in contrast to neutralizing antibodies against major VACV envelope proteins, such as H3, D8, or A27, which failed to completely neutralize VACV unless the antibodies are of complement-fixing isotypes and complement is present. Compared to nonneutralizing anti-L1 MAbs, the neutralization antibodies bound to the recombinant L1 protein with a significantly higher affinity and also could bind to virions. By using a variety of techniques, including the isolation of neutralization escape mutants, hydrogen/deuterium exchange mass spectrometry, and X-ray crystallography, the epitope of the neutralizing antibodies was mapped to a conformational epitope with Asp35 as the key residue. This epitope is similar to the epitope of 7D11, a previously described potent VACV neutralizing antibody. The epitope was recognized mainly by CDR1 and CDR2 of the heavy chain, which are highly conserved among antibodies recognizing the epitope. These antibodies, however, had divergent light-chain and heavy-chain CDR3 sequences. Our study demonstrates that the conformational L1 epitope with Asp35 is a common site of vulnerability for potent neutralization by a divergent group of antibodies. IMPORTANCE Vaccinia virus, the live vaccine for smallpox, is one of the most successful vaccines in human history, but it presents a level of risk that has become unacceptable for the current population. Studying the immune protection mechanism of smallpox vaccine is important for understanding the basic principle of successful vaccines and the development of next-generation, safer vaccines for highly pathogenic orthopoxviruses. We studied antibody targets in smallpox vaccine by developing potent neutralizing antibodies against vaccinia virus and comprehensively characterizing their epitopes. We found a site in vaccinia virus L1 protein as the target of a group of highly potent murine neutralizing antibodies. The analysis of antibody-antigen complex structure and the sequences of the antibody genes shed light on how these potent neutralizing antibodies are elicited from immunized mice. PMID:25031354

Visual Search in the Real World: Color Vision Deficiency Affects Peripheral Guidance, but Leaves Foveal Verification Largely Unaffected.

PubMed

Kugler, Günter; 't Hart, Bernard M; Kohlbecher, Stefan; Bartl, Klaus; Schumann, Frank; Einhäuser, Wolfgang; Schneider, Erich

2015-01-01

People with color vision deficiencies report numerous limitations in daily life, restricting, for example, their access to some professions. However, they use basic color terms systematically and in a similar manner as people with normal color vision. We hypothesize that a possible explanation for this discrepancy between color perception and behavioral consequences might be found in the gaze behavior of people with color vision deficiency. A group of participants with color vision deficiencies and a control group performed several search tasks in a naturalistic setting on a lawn. All participants wore a mobile eye-tracking-driven camera with a high foveal image resolution (EyeSeeCam). Search performance as well as fixations of objects of different colors were examined. Search performance was similar in both groups in a color-unrelated search task as well as in a search for yellow targets. While searching for red targets, participants with color vision deficiencies exhibited a strongly degraded performance. This was closely matched by the number of fixations on red objects shown by the two groups. Importantly, once they fixated a target, participants with color vision deficiencies exhibited only few identification errors. In contrast to controls, participants with color vision deficiencies are not able to enhance their search for red targets on a (green) lawn by an efficient guiding mechanism. The data indicate that the impaired guiding is the main influence on search performance, while foveal identification (verification) is largely unaffected by the color vision deficiency.

Negligible import of enteric pathogens by newly-arrived asylum seekers and no impact on incidence of notified Salmonella and Shigella infections and outbreaks in Rhineland-Palatinate, Germany, January 2015 to May 2016.

PubMed

Ehlkes, Lutz; George, Maja; Knautz, Donald; Burckhardt, Florian; Jahn, Klaus; Vogt, Manfred; Zanger, Philipp

2018-05-01

IntroductionThe 2015 refugee crisis raised concerns about an import of infectious diseases affecting the German population. Aims: To evaluate public and individual health benefits of stool screening, and explore whether importation of enteric pathogens by newly-arrived asylum seekers impacts on the host population. Methods : We used data from mandatory stool screening to determine the overall, age, sex, and country-specific prevalence of enteric bacteria and helminths. We used surveillance data to assess whether the number of incoming asylum seekers influenced notifications of salmonellosis and shigellosis in Rhineland-Palatinate. Results : Salmonella were found in 0.2% (95% confidence interval (CI) 0.2-0.3%) of 23,410 samples collected from January 2015 to May 2016. Prevalence was highest in children under 5 years (0.8%; 95% CI: 0.5-1.3%). No Shigella or invasive Salmonella spp. were detected. In a subset of 14,511 samples, the prevalence of helminth infestation was 2.4% (95% CI: 2.1-2.6%), with highest proportions detected in adolescents (4.6%; 95% CI 3.8-5.4%) and among Eritreans (9.3%; 95% CI: 7.0-12.0%); in the latter particularly Schistosoma mansoni and Taenia spp. The increase in asylum applications did not increase notifications of salmonellosis and shigellosis. No transmission from asylum seekers to German residents was notified. Conclusion : Public health risk associated with imported enteric pathogens is very low overall. Addressing individual and public health risks, we recommend replacing stool screening of all newly-arrived asylum seekers by a targeted approach, with target groups and approaches being adapted if necessary. Target groups supported by our data are children, adolescents, and Eritreans.

Outcome Uncertainty and Brain Activity Aberrance in the Insula and Anterior Cingulate Cortex Are Associated with Dysfunctional Impulsivity in Borderline Personality Disorder

PubMed Central

Mortensen, Jørgen Assar; Evensmoen, Hallvard Røe; Klensmeden, Gunilla; Håberg, Asta Kristine

2016-01-01

Uncertainty is recognized as an important component in distress, which may elicit impulsive behavior in patients with borderline personality disorder (BPD). These patients are known to be both impulsive and distress intolerant. The present study explored the connection between outcome uncertainty and impulsivity in BPD. The prediction was that cue primes, which provide incomplete information of subsequent target stimuli, led BPD patients to overrate the predictive value of these cues in order to reduce distress related to outcome uncertainty. This would yield dysfunctional impulsive behavior detected as commission errors to incorrectly primed targets. We hypothesized that dysfunctional impulsivity would be accompanied by aberrant brain activity in the right insula and anterior cingulate cortex (ACC), previously described to be involved in uncertainty processing, attention-/cognitive control and BPD pathology. 14 female BPD patients and 14 healthy matched controls (HCs) for comparison completed a Posner task during fMRI at 3T. The task was modified to limit the effect of spatial orientation and enhance the effect of conscious expectations. Brain activity was monitored in the priming phase where the effects of cue primes and neutral primes were compared. As predicted, the BPD group made significantly more commission errors to incorrectly primed targets than HCs. Also, the patients had faster reaction times to correctly primed targets relative to targets preceded by neutral primes. The BPD group had decreased activity in the right mid insula and increased activity in bilateral dorsal ACC during cue primes. The results indicate that strong expectations induced by cue primes led to reduced uncertainty, increased response readiness, and ultimately, dysfunctional impulsivity in BPD patients. We suggest that outcome uncertainty may be an important component in distress related impulsivity in BPD. PMID:27199724

Targeting Future Customers: An Introductory Biobanking Course for Undergraduate Students of Life Sciences.

PubMed

Abdelhafiz, Ahmed Samir; Fouda, Merhan Ahmed; El-Jaafary, Shaimaa Ibrahim; Farghly, Maysa Ibrahim; Salem, Mazen; Tammam, Ahmed; Gabr, Hala

2017-08-01

Biobanking is a relatively new concept in the Arab region. Targeting different stakeholders to introduce the concept of biobanking and develop an acceptance of it among them is important for the growth of biobanking in the region. Undergraduate students of life sciences represent an important segment of stakeholders, since they constitute potential future biobank customers. Limited funding, lack of awareness of the existence of the term "biobanking" itself among these students, and questions regarding best marketing strategies presented challenges to planning for the most effective message delivery to this target group. A specific course was designed for undergraduate students of life sciences, which was conducted at the Faculty of Medicine, Cairo University, Egypt. The course was conducted twice in 2016 and included lectures covering biobanking, quality, ethics, information technology, and translational research. Facebook and word-of-mouth were used for marketing and advertising. A total number of 125 participants attended both courses cumulatively. Facebook appeared to have been an effective marketing outlet, especially when paid advertisements were used. Evaluation of knowledge, measured using a pretest and posttest, demonstrated some improvement in knowledge of participants. Evaluation forms filled after the course showed positive attitude toward content and message delivery by a majority of participants. Facebook was also used as an evaluation method through analysis of engagement with posts created after course completion. Biobanking education can be carried out effectively with limited resources. Understanding the needs of the target group and using appropriate methods of communication are essential prerequisites to a well-tailored curriculum and effective message delivery. Using Facebook appears to be an effective and affordable method of communication and advertising. Targeting undergraduate students of life sciences interested in research is a good investment and can be very effective in increasing awareness about biobanking inside the research community.

Docking and scoring protein interactions: CAPRI 2009.

PubMed

Lensink, Marc F; Wodak, Shoshana J

2010-11-15

Protein docking algorithms are assessed by evaluating blind predictions performed during 2007-2009 in Rounds 13-19 of the community-wide experiment on critical assessment of predicted interactions (CAPRI). We evaluated the ability of these algorithms to sample docking poses and to single out specific association modes in 14 targets, representing 11 distinct protein complexes. These complexes play important biological roles in RNA maturation, G-protein signal processing, and enzyme inhibition and function. One target involved protein-RNA interactions not previously considered in CAPRI, several others were hetero-oligomers, or featured multiple interfaces between the same protein pair. For most targets, predictions started from the experimentally determined structures of the free (unbound) components, or from models built from known structures of related or similar proteins. To succeed they therefore needed to account for conformational changes and model inaccuracies. In total, 64 groups and 12 web-servers submitted docking predictions of which 4420 were evaluated. Overall our assessment reveals that 67% of the groups, more than ever before, produced acceptable models or better for at least one target, with many groups submitting multiple high- and medium-accuracy models for two to six targets. Forty-one groups including four web-servers participated in the scoring experiment with 1296 evaluated models. Scoring predictions also show signs of progress evidenced from the large proportion of correct models submitted. But singling out the best models remains a challenge, which also adversely affects the ability to correctly rank docking models. With the increased interest in translating abstract protein interaction networks into realistic models of protein assemblies, the growing CAPRI community is actively developing more efficient and reliable docking and scoring methods for everyone to use. © 2010 Wiley-Liss, Inc.

HIV testing in Europe: Evaluating the impact, added value, relevance and usability of the European Centre for Disease Prevention and Control (ECDC)'s 2010 HIV testing guidance.

PubMed

Sullivan, Ann K; Sperle, Ida; Raben, Dorthe; Amato-Gauci, Andrew J; Lundgren, Jens Dilling; Yazdanpanah, Yazdan; Jakobsen, Stine Finne; Tavoschi, Lara

2017-11-01

An evaluation of the 2010 ECDC guidance on HIV testing, conducted in October 2015-January 2016, assessed its impact, added value, relevance and usability and the need for updated guidance. Data sources were two surveys: one for the primary target audience (health policymakers and decision makers, national programme managers and ECDC official contact points in the European Union/European Economic Area (EU/EEA) countries and one for a broader target audience (clinicians, civil society organisations and international public health agencies); two moderated focus group discussions  (17 participants each); webpage access data; a literature citation review; and an expert consultation (18 participants) to discuss the evaluation findings. Twenty-three of 28 primary target audience and 31 of 51 broader target audience respondents indicated the guidance was the most relevant when compared with other international guidance. Primary target audience respondents in 11 of 23 countries reported that they had used the guidance in development, monitoring and/or evaluation of their national HIV testing policy, guidelines, programme and/or strategy, and 29 of 51 of the broader target audience respondents reported having used the guidance in their work. Both the primary and broader target audience considered it important or very important to have an EU/EEA-level HIV testing guidance (23/28 and 46/51, respectively). The guidance has been widely used to develop policies, guidelines, programmes and strategies in the EU/EEA and should be regularly updated due to continuous developments in the field in order to continue to serve as an important reference guidance in the region.

HIV testing in Europe: Evaluating the impact, added value, relevance and usability of the European Centre for Disease Prevention and Control (ECDC)’s 2010 HIV testing guidance

PubMed Central

Sullivan, Ann K; Sperle, Ida; Raben, Dorthe; Amato-Gauci, Andrew J; Lundgren, Jens Dilling; Yazdanpanah, Yazdan; Jakobsen, Stine Finne; Tavoschi, Lara

2017-01-01

Background: An evaluation of the 2010 ECDC guidance on HIV testing, conducted in October 2015–January 2016, assessed its impact, added value, relevance and usability and the need for updated guidance. Methods: Data sources were two surveys: one for the primary target audience (health policymakers and decision makers, national programme managers and ECDC official contact points in the European Union/European Economic Area (EU/EEA) countries and one for a broader target audience (clinicians, civil society organisations and international public health agencies); two moderated focus group discussions  (17 participants each); webpage access data; a literature citation review; and an expert consultation (18 participants) to discuss the evaluation findings. Results: Twenty-three of 28 primary target audience and 31 of 51 broader target audience respondents indicated the guidance was the most relevant when compared with other international guidance. Primary target audience respondents in 11 of 23 countries reported that they had used the guidance in development, monitoring and/or evaluation of their national HIV testing policy, guidelines, programme and/or strategy, and 29 of 51 of the broader target audience respondents reported having used the guidance in their work. Both the primary and broader target audience considered it important or very important to have an EU/EEA-level HIV testing guidance (23/28 and 46/51, respectively). Conclusion: The guidance has been widely used to develop policies, guidelines, programmes and strategies in the EU/EEA and should be regularly updated due to continuous developments in the field in order to continue to serve as an important reference guidance in the region. PMID:29208158

1,4-Dihydropyridine Derivatives: Dihydronicotinamide Analogues—Model Compounds Targeting Oxidative Stress

PubMed Central

Velena, Astrida; Zarkovic, Neven; Gall Troselj, Koraljka; Bisenieks, Egils; Krauze, Aivars; Poikans, Janis; Duburs, Gunars

2016-01-01

Many 1,4-dihydropyridines (DHPs) possess redox properties. In this review DHPs are surveyed as protectors against oxidative stress (OS) and related disorders, considering the DHPs as specific group of potential antioxidants with bioprotective capacities. They have several peculiarities related to antioxidant activity (AOA). Several commercially available calcium antagonist, 1,4-DHP drugs, their metabolites, and calcium agonists were shown to express AOA. Synthesis, hydrogen donor properties, AOA, and methods and approaches used to reveal biological activities of various groups of 1,4-DHPs are presented. Examples of DHPs antioxidant activities and protective effects of DHPs against OS induced damage in low density lipoproteins (LDL), mitochondria, microsomes, isolated cells, and cell cultures are highlighted. Comparison of the AOA of different DHPs and other antioxidants is also given. According to the data presented, the DHPs might be considered as bellwether among synthetic compounds targeting OS and potential pharmacological model compounds targeting oxidative stress important for medicinal chemistry. PMID:26881016

Grouping and trajectory storage in multiple object tracking: impairments due to common item motions.

PubMed

Suganuma, Mutsumi; Yokosawa, Kazuhiko

2006-01-01

In our natural viewing, we notice that objects change their locations across space and time. However, there has been relatively little consideration of the role of motion information in the construction and maintenance of object representations. We investigated this question in the context of the multiple object tracking (MOT) paradigm, wherein observers must keep track of target objects as they move randomly amid featurally identical distractors. In three experiments, we observed impairments in tracking ability when the motions of the target and distractor items shared particular properties. Specifically, we observed impairments when the target and distractor items were in a chasing relationship or moved in a uniform direction. Surprisingly, tracking ability was impaired by these manipulations even when observers failed to notice them. Our results suggest that differentiable trajectory information is an important factor in successful performance of MOT tasks. More generally, these results suggest that various types of common motion can serve as cues to form more global object representations even in the absence of other grouping cues.

Importance of public relations in recycling strategies: principles and case studies.

PubMed

Salhofer, Stefan; Isaac, Nicole A

2002-07-01

The separate collection of waste, and especially of recyclables with specific collection systems, would not be possible without the involvement of the users. Apart from the physical installations such as collection containers, collection points, etc., the motivation of the users is an essential component. Motivation can be reinforced through public relations work. In addition to the underlying technical considerations, this paper describes the difference between communication in general and public relations and specifically examines public involvement in recycling. Through the use of examples, we look at the targeted users and typical media employed. Furthermore, we analyzes the development of public involvement. The examples show that public relations for recycling strategies relies to a great extent on attitudes, habits, and access to the target group. Thus, standardized procedures cannot be developed. For these reasons, public relation activities must be planned carefully and professionally and include an analysis of the target group, choice of media, and verification of success.

Ubiquitin chain specificities of E6AP E3 ligase and its HECT domain.

PubMed

Kobayashi, Fuminori; Nishiuchi, Takumi; Takaki, Kento; Konno, Hiroki

2018-02-05

Ubiquitination of target proteins is accomplished by isopeptide bond formation between the carboxy group of the C-terminal glycine (Gly) residue of ubiquitin (Ub) and the ɛ-amino group of lysine (Lys) on the target proteins. The formation of an isopeptide bond between Ubs that gives rise to a poly-Ub chain on the target proteins and the types of poly-Ub chains formed depend on which of the seven Lys residues or N-terminal methionine (Met) residue on Ub is used for chain elongation. To understand the linkage specificity mechanism of Ub chains on E3, the previous study established an assay to monitor the formation of a free diubiquitin chain (Ub 2 chain synthesis assay) by HECT type E3 ligase. In this study, we investigated Ub 2 chain specificity using E6AP HECT domain. We here demonstrate the importance of the N-terminal domain of full length E6AP for Ub 2 chain specificity. Copyright © 2017 Elsevier Inc. All rights reserved.

Decolorization pathways of anthraquinone dye Disperse Blue 2BLN by Aspergillus sp. XJ-2 CGMCC12963.

PubMed

Pan, Huiran; Xu, Xiaolin; Wen, Zhu; Kang, Yanshun; Wang, Xinhao; Ren, Youshan; Huang, Danqi

2017-09-03

Anthraquinone dye represents an important group of recalcitrant pollutants in dye wastewater. Aspergillus sp XJ-2 CGMCC12963 showed broad-spectrum decolorization ability, which could efficiently decolorize and degrade various anthraquinone dyes (50 mg L -1 ) under microaerophilic condition. And the decolorization rate of 93.3% was achieved at 120 h with Disperse Blue 2BLN (the target dye). Intermediates of degradation were detected by FTIR and GC-MS, which revealed the cleavage of anthraquinone chromophoric group and partial mineralization of target dye. In addition, extracellular manganese peroxidase showed the most closely related to the increasing of decolorization rate and biomass among intracellular and extracellular ligninolytic enzymes. Given these results, 2 possible degraded pathways of target dye by Aspergillus sp XJ-2 CGMCC12963 were proposed first in this work. The degradation of Disperse Blue 2BLN and broad spectrum decolorization ability provided the potential for Aspergillus sp XJ-2 CGMCC12963 in the treatment of wastewater containing anthraquinone dyes.

[Employees health education--challenges according to the educational level].

PubMed

Korzeniowska, Elzbieta; Puchalski, Krzysztof

2012-01-01

Article addresses the problem of increasing Polish employees health education effectiveness according to the differences in educational level. Research model assume that effective method of developing recommendations improving the health education will synthesise scientific findings regarding methodology of conducting such education and knowledge about needs of two target groups: low and high educated employees. Educational solutions were searched in publications related to: health education, andragogy, propaganda and direct marketing. The empirical material used to characterize two target groups came from four research (qualitative and quantitative) conducted by the National Centre for Workplace Health Promotion (Nofer Institute of Occupational Medicine) in 2007-2010. Low educated employees' health education should be focused on increasing responsibility for health and strengthening their self-confidence according to the introduction of healthy lifestyle changes. To achieve these goals, important issue is to build their motivation to develop knowledge about taking care of health. In providing such information we should avoid the methods associated with school. Another important issue is creating an appropriate infrastructure and conditions facilitating the change of harmful behaviors undertaken at home and in the workplace. According to high-educated employees a challenge is to support taking health behaviors--although they are convinced it is important for their health, such behaviors are perceived as a difficult and freedom restriction. Promoting behavior change techniques, avoiding prohibitions in the educational messages and creating favorable climate for taking care of health in groups they participate are needed.

Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated mu opioid receptor (MOR-1) splice variants

PubMed Central

Majumdar, Susruta; Subrath, Joan; Le Rouzic, Valerie; Polikar, Lisa; Burgman, Maxim; Nagakura, Kuni; Ocampo, Julie; Haselton, Nathan; Pasternak, Anna R.; Grinnell, Steven; Pan, Ying-Xian; Pasternak, Gavril W.

2012-01-01

3-Iodobenzoylnaltrexamide 1 (IBNtxA) is a potent analgesic acting through a novel receptor target that lack many side-effects of traditional opiates composed, in part, of exon 11-associated truncated six transmembrane domain MOR-1 (6TM/E11) splice variants. To better understand the SAR of this drug target, a number of 4,5-epoxymorphinan analogs were synthesized. Results show the importance of a free 3-phenolic group, a phenyl ring at the 6 position, an iodine at the 3′ or 4′ position of the phenyl ring and an N-allyl or c-propylmethyl group to maintain high 6TM/E11 affinity and activity. 3-Iodobenzoylnaloxamide 15 (IBNalA) with a N-allyl group displayed lower delta opioid receptor affinity than its naltrexamine analog, was 10-fold more potent an analgesic than morphine, elicited no respiratory depression or physical dependence and only limited inhibition of gastrointestinal transit. Thus, the aryl-naloxamide scaffold can generate a potent analgesic acting through the 6TM/E11 sites with advantageous side-effect profile and greater selectivity. PMID:22734622

Distribution and conservation of three important bird groups of the Atlantic Forest in north-east Brazil.

PubMed

Pereira, G A; Araújo, H F P; Azevedo-Júnior, S M

2016-01-01

The Pernambuco Endemism Center in north-east Brazil has the most fragmented forest cover and the largest number of threatened birds of the whole Atlantic Forest. We analyzed the distribution of three groups of bird species: forest-dependent, endemic and/or threatened using the interpolation method of Inverse Distance Weighting. We also checked the concentration of these birds in protected and unprotected areas, suggesting new sites that need to be protected. The richness concentration of forest-dependent, endemic and/or threatened birds in 123 sites were analysed. There was a greater concentration of the three groups in north Alagoas, south and north Pernambuco, and north and west Paraíba. The distribution of the three groups was almost regular in different vegetation types, although a lower concentration was found in the pioneer formation. There was a greater concentration of birds from all three groups between Pernambuco and Alagoas, and this must be due to the presence of more forest fragments with better structure and vegetation heterogeneity. The protected and unprotected areas hosted important records of endemic and/or threatened birds. We suggested some important places for implementation of new protected areas due to the larger concentrations of the target birds and because they are located within the boundaries of the Important Bird Areas.

Aligning the SEA's Compliance Responsibilities and Performance Objectives. Benchmark. No. 3

ERIC Educational Resources Information Center

Nafziger, D.; Jochim, A.

2013-01-01

Assuring that state and local agencies comply with the requirements of Federal and state programs has been a central feature of SEAs. The purposes of compliance requirements--ensuring both fiscal integrity and that targeted groups receive intended benefits--are important. While such requirements are often well-intentioned, too often they can act…

75 FR 81233 - Nomination of Existing Marine Protected Areas to the National System of Marine Protected Areas

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-27

... to fill key conservation gaps in important ocean areas. DATES: Comments on the nominations to the... and management initiatives (such as integrated ocean observing systems, systematic monitoring and evaluation, targeted outreach to key user groups, and helping to identify and address MPA research needs). In...

76 FR 6119 - Nomination of Existing Marine Protected Areas to the National System of Marine Protected Areas...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-03

... that may be established by managing agencies to fill key conservation gaps in important ocean areas... systems, systematic monitoring and evaluation, targeted outreach to key user groups, and helping to identify and address MPA research needs). In addition, the national system provides a forum for coordinated...

Importance of Hierarchy Content in the Self-Control of Anxiety

ERIC Educational Resources Information Center

Goldfried, Marvin R.; Goldfried, Anita Powers

1977-01-01

Using speech anxiety as the target behavior, this study compared two self-control desensitization procedures. Speech-anxious community residents (N=42) volunteered for participation in the program and were seen within a group context for a total of seven therapy sessions. No differential effectiveness was found between the two desensitization…

Developing Research Skills for Undergraduate Business Students: Experiential Learning on Introduction to Personnel Administration and Industrial Relations Course

ERIC Educational Resources Information Center

Figueroa, Carmen I.; González, Cándida

2014-01-01

This paper reports on research into developing research skills in human resources management of apprentices through experiential learning. The target groups were undergraduate business students registered in the Introduction to Personnel and Industrial Relations course. The research identified the appreciation level of importance and satisfaction…

Effect of intensive structured care on individual blood pressure targets in primary care: multicentre randomised controlled trial.

PubMed

Stewart, Simon; Carrington, Melinda J; Swemmer, Carla H; Anderson, Craig; Kurstjens, Nicol P; Amerena, John; Brown, Alex; Burrell, Louise M; de Looze, Ferdinandus J; Harris, Mark; Hung, Joseph; Krum, Henry; Nelson, Mark; Schlaich, Markus; Stocks, Nigel P; Jennings, Garry L

2012-11-20

To determine the effectiveness of intensive structured care to optimise blood pressure control based on individual absolute risk targets in primary care. Pragmatic multicentre randomised controlled trial. General practices throughout Australia, except Northern Territory, 2009-11. Of 2185 patients from 119 general practices who were eligible for drug treatment for hypertension according to national guidelines 416 (19.0%) achieved their individual blood pressure target during a 28 day run-in period of monotherapy. After exclusions, 1562 participants not at target blood pressure (systolic 150 (SD 17) mm Hg, diastolic 88 (SD 11) mm Hg) were randomised (1:2 ratio) to usual care (n=524) or the intervention (n=1038). Computer assisted clinical profiling and risk target setting (all participants) with intensified follow-up and stepwise drug titration (initial angiotensin receptor blocker monotherapy or two forms of combination therapy using angiotensin receptor blockers) for those randomised to the intervention. The control group received usual care. The primary outcome was individual blood pressure target achieved at 26 weeks. Secondary outcomes were change in mean sitting systolic and diastolic blood pressure, absolute risk for cardiovascular disease within five years based on the Framingham risk score, and proportion and rate of adverse events. On an intention to treat basis, there was an 8.8% absolute difference in individual blood pressure target achieved at 26 weeks in favour of the intervention group compared with usual care group (358/988 (36.2%) v 138/504 (27.4%)): adjusted relative risk 1.28 (95% confidence interval 1.10 to 1.49, P=0.0013). There was also a 9.5% absolute difference in favour of the intervention group for achieving the classic blood pressure target of ≤ 140/90 mm Hg (627/988 (63.5%) v 272/504 (54.0%)): adjusted relative risk 1.18 (1.07 to 1.29, P<0.001). The intervention group achieved a mean adjusted reduction in systolic blood pressure of 13.2 mm Hg (95% confidence interval -12.3 to -14.2 mm Hg) and diastolic blood pressure of 7.7 mm Hg (-7.1 to -8.3 mm Hg) v 10.1 mm Hg (-8.8 to 11.3 mm Hg) and 5.5 mm Hg (-4.7 to -6.2 mm Hg) in the usual care group (P<0.001). Among 1141 participants in whom five year absolute cardiovascular risk scores were calculated from baseline to the 26 week follow-up, the reduction in risk scores was greater in the intervention group than usual care group (14.7% (SD 9.3%) to 10.9% (SD 8.0%); difference -3.7% (SD 4.5%) and 15.0% (SD 10.1%) to 12.4% (SD 9.4%); -2.6% (SD 4.5%): adjusted mean difference -1.13% (95% confidence interval -0.69% to -1.63%; P<0.001). Owing to adverse events 82 (7.9%) participants in the intervention group and 10 (1.9%) in the usual care group had their drug treatment modified. In a primary care setting intensive structured care resulted in higher levels of blood pressure control, with clinically lower blood pressure and absolute risk of future cardiovascular events overall and with more people achieving their target blood pressure. An important gap in treatment remains though and applying intensive management and achieving currently advocated risk based blood pressure targets is challenging.

Educational Effectiveness, Target, and Content for Prudent Antibiotic Use

PubMed Central

Lee, Chang-Ro; Lee, Jung Hun; Kang, Lin-Woo; Jeong, Byeong Chul; Lee, Sang Hee

2015-01-01

Widespread antimicrobial use and concomitant resistance have led to a significant threat to public health. Because inappropriate use and overuse of antibiotics based on insufficient knowledge are one of the major drivers of antibiotic resistance, education about prudent antibiotic use aimed at both the prescribers and the public is important. This review investigates recent studies on the effect of interventions for promoting prudent antibiotics prescribing. Up to now, most educational efforts have been targeted to medical professionals, and many studies showed that these educational efforts are significantly effective in reducing antibiotic prescribing. Recently, the development of educational programs to reduce antibiotic use is expanding into other groups, such as the adult public and children. The investigation of the contents of educational programs for prescribers and the public demonstrates that it is important to develop effective educational programs suitable for each group. In particular, it seems now to be crucial to develop appropriate curricula for teaching medical and nonmedical (pharmacy, dentistry, nursing, veterinary medicine, and midwifery) undergraduate students about general medicine, microbial virulence, mechanism of antibiotic resistance, and judicious antibiotic prescribing. PMID:25945327

p21 Activated Kinase 5 Activates Raf-1 and Targets it to Mitochondria

PubMed Central

Wu, Xiaochong; Carr, Heather S.; Dan, Ippeita; Ruvolo, Peter P.; Frost, Jeffrey A.

2008-01-01

Raf-1 is an important effector of Ras mediated signaling and is a critical regulator of the ERK/MAPK pathway. Raf-1 activation is controlled in part by phosphorylation on multiple residues, including an obligate phosphorylation site at serine 338. Previously PAK1 and casein kinase II have been implicated as serine 338 kinases. To identify novel kinases that phosphorylate this site, we tested the ability of group II PAKs (PAKs 4-6) to control serine 338 phosphorylation. We observed that all group II PAKs were efficient serine 338 kinases, although only PAK1 and PAK5 significantly stimulated Raf-1 kinase activity. We also showed that PAK5 forms a tight complex with Raf-1 in the cell, but not A-Raf or B-Raf. Importantly, we also demonstrated that the association of Raf-1 with PAK5 targets a subpopulation of Raf-1 to mitochondria. These data indicate that PAK5 is a potent regulator of Raf-1 activity and may control Raf-1 dependent signaling at the mitochondria. PMID:18465753

Pilot study demonstrating effectiveness of targeted education to improve informed consent understanding in AIDS clinical trials.

PubMed

Sengupta, Sohini; Lo, Bernard; Strauss, Ronald P; Eron, Joseph; Gifford, Allen L

2011-11-01

Assessing and improving informed consent understanding is equally important as obtaining consent from participants in clinical trial research, but developing interventions to target gaps in participants' informed consent understanding remains a challenge. We used a randomized controlled study design to pilot test an educational intervention to improve actual informed consent understanding of new enrollees in the Adult AIDS Clinical Trial Group (AACTG). Questionnaires were administered to 24 enrollees to assess their baseline understanding on eight elements of informed consent associated with AIDS clinical trials. Enrollees who scored 18/21(85%) or less were randomly assigned to in-person, targeted education (intervention), or delayed education (control). Two follow-up assessments were administered. Repeated measures ANOVA was performed to determine intervention effectiveness in improving actual informed consent understanding over time. Actual understanding improved at the immediate post-intervention time point with a significant score difference of 2.5 when comparing the intervention and delayed groups. In addition, there was a significant score difference of 3.2 when comparing baseline to three-month follow-up for the two groups, suggesting a statistically significant intervention effect to improve actual understanding of the basic elements of informed consent. The findings demonstrated that one-time targeted education can improve actual informed consent understanding one week after the intervention, but retention of these concepts may require periodic monitoring to ensure comprehension throughout the course of a clinical trial.

Self-organizing team formation for target observation

NASA Astrophysics Data System (ADS)

Bowyer, Richard S.; Bogner, Robert E.

2001-08-01

Target observation is a problem where the application of multiple sensors can improve the probability of detection and observation of the target. Team formation is one method by which seemingly unsophisticated heterogeneous sensors may be organized to achieve a coordinated observation system. The sensors, which we shall refer to as agents, are situated in an area of interest with the goal of observing a moving target. We apply a team approach to this problem, which combines the strengths of individual agents into a cohesive entity - the team. In autonomous systems, the mechanisms that underlie the formation of a team are of interest. Teams may be formed by various mechanisms, which include an externally imposed grouping of agents, or an internally, self-organized (SO) grouping of agents. Internally motivated mechanisms are particularly challenging, but offer the benefit of being unsupervised, an important quality for groups of autonomous cooperating machines. This is the focus of our research. By studying natural systems such as colonies of ants, we obtain insight into these mechanisms of self organization. We propose that the team is an expression of a distributed agent-self, and that a particular realization of the agent-self exists, whilst the environmental conditions are conducive to that existence. We describe an algorithms for agent team formation that is inspired by the self-organizing behavior of ants, and describe simulation results for team formation amongst a lattice of networked sensors.

Membrane Transporters: Structure, Function and Targets for Drug Design

NASA Astrophysics Data System (ADS)

Ravna, Aina W.; Sager, Georg; Dahl, Svein G.; Sylte, Ingebrigt

Current therapeutic drugs act on four main types of molecular targets: enzymes, receptors, ion channels and transporters, among which a major part (60-70%) are membrane proteins. This review discusses the molecular structures and potential impact of membrane transporter proteins on new drug discovery. The three-dimensional (3D) molecular structure of a protein contains information about the active site and possible ligand binding, and about evolutionary relationships within the protein family. Transporters have a recognition site for a particular substrate, which may be used as a target for drugs inhibiting the transporter or acting as a false substrate. Three groups of transporters have particular interest as drug targets: the major facilitator superfamily, which includes almost 4000 different proteins transporting sugars, polyols, drugs, neurotransmitters, metabolites, amino acids, peptides, organic and inorganic anions and many other substrates; the ATP-binding cassette superfamily, which plays an important role in multidrug resistance in cancer chemotherapy; and the neurotransmitter:sodium symporter family, which includes the molecular targets for some of the most widely used psychotropic drugs. Recent technical advances have increased the number of known 3D structures of membrane transporters, and demonstrated that they form a divergent group of proteins with large conformational flexibility which facilitates transport of the substrate.

Targeting Cardiac Fibroblasts to Treat Fibrosis of the Heart: Focus on HDACs

PubMed Central

Schuetze, Katherine B.; McKinsey, Timothy A.; Long, Carlin S.

2014-01-01

Cardiac fibrosis is implicated in numerous physiologic and pathologic conditions, including scar formation, heart failure and cardiac arrhythmias. However the specific cells and signaling pathways mediating this process are poorly understood. Lysine acetylation of nucleosomal histone tails is an important mechanism for the regulation of gene expression. Additionally, proteomic studies have revealed that thousands of proteins in all cellular compartments are subject to reversible lysine acetylation, and thus it is becoming clear that this post-translational modification will rival phosphorylation in terms of biological import. Acetyl groups are conjugated to lysine by histone acetyltransferases (HATs) and removed from lysine by histone deacetylases (HDACs). Recent studies have shown that pharmacologic agents that alter lysine acetylation by targeting HDACs have the remarkable ability to block pathological fibrosis. Here, we review the current understanding of cardiac fibroblasts and the fibrogenic process with respect to the roles of lysine acetylation in the control of disease-related cardiac fibrosis. Potential for small molecule HDAC inhibitors as antifibrotic therapeutics that target cardiac fibroblasts is highlighted. PMID:24631770

The Neural Bases of Directed and Spontaneous Mental State Attributions to Group Agents

PubMed Central

Jenkins, Adrianna C.; Dodell-Feder, David; Saxe, Rebecca; Knobe, Joshua

2014-01-01

In daily life, perceivers often need to predict and interpret the behavior of group agents, such as corporations and governments. Although research has investigated how perceivers reason about individual members of particular groups, less is known about how perceivers reason about group agents themselves. The present studies investigate how perceivers understand group agents by investigating the extent to which understanding the ‘mind’ of the group as a whole shares important properties and processes with understanding the minds of individuals. Experiment 1 demonstrates that perceivers are sometimes willing to attribute a mental state to a group as a whole even when they are not willing to attribute that mental state to any of the individual members of the group, suggesting that perceivers can reason about the beliefs and desires of group agents over and above those of their individual members. Experiment 2 demonstrates that the degree of activation in brain regions associated with attributing mental states to individuals—i.e., brain regions associated with mentalizing or theory-of-mind, including the medial prefrontal cortex (MPFC), temporo-parietal junction (TPJ), and precuneus—does not distinguish individual from group targets, either when reading statements about those targets' mental states (directed) or when attributing mental states implicitly in order to predict their behavior (spontaneous). Together, these results help to illuminate the processes that support understanding group agents themselves. PMID:25140705

Preventing Childhood Malaria in Africa by Protecting Adults from Mosquitoes with Insecticide-Treated Nets

PubMed Central

Killeen, Gerry F; Smith, Tom A; Ferguson, Heather M; Mshinda, Hassan; Abdulla, Salim; Lengeler, Christian; Kachur, Steven P

2007-01-01

Background Malaria prevention in Africa merits particular attention as the world strives toward a better life for the poorest. Insecticide-treated nets (ITNs) represent a practical means to prevent malaria in Africa, so scaling up coverage to at least 80% of young children and pregnant women by 2010 is integral to the Millennium Development Goals (MDG). Targeting individual protection to vulnerable groups is an accepted priority, but community-level impacts of broader population coverage are largely ignored even though they may be just as important. We therefore estimated coverage thresholds for entire populations at which individual- and community-level protection are equivalent, representing rational targets for ITN coverage beyond vulnerable groups. Methods and Findings Using field-parameterized malaria transmission models, we show that high (80% use) but exclusively targeted coverage of young children and pregnant women (representing <20% of the population) will deliver limited protection and equity for these vulnerable groups. In contrast, relatively modest coverage (35%–65% use, with this threshold depending on ecological scenario and net quality) of all adults and children, rather than just vulnerable groups, can achieve equitable community-wide benefits equivalent to or greater than personal protection. Conclusions Coverage of entire populations will be required to accomplish large reductions of the malaria burden in Africa. While coverage of vulnerable groups should still be prioritized, the equitable and communal benefits of wide-scale ITN use by older children and adults should be explicitly promoted and evaluated by national malaria control programmes. ITN use by the majority of entire populations could protect all children in such communities, even those not actually covered by achieving existing personal protection targets of the MDG, Roll Back Malaria Partnership, or the US President's Malaria Initiative. PMID:17608562

Comparing pseudo-absences generation techniques in Boosted Regression Trees models for conservation purposes: A case study on amphibians in a protected area.

PubMed

Cerasoli, Francesco; Iannella, Mattia; D'Alessandro, Paola; Biondi, Maurizio

2017-01-01

Boosted Regression Trees (BRT) is one of the modelling techniques most recently applied to biodiversity conservation and it can be implemented with presence-only data through the generation of artificial absences (pseudo-absences). In this paper, three pseudo-absences generation techniques are compared, namely the generation of pseudo-absences within target-group background (TGB), testing both the weighted (WTGB) and unweighted (UTGB) scheme, and the generation at random (RDM), evaluating their performance and applicability in distribution modelling and species conservation. The choice of the target group fell on amphibians, because of their rapid decline worldwide and the frequent lack of guidelines for conservation strategies and regional-scale planning, which instead could be provided through an appropriate implementation of SDMs. Bufo bufo, Salamandrina perspicillata and Triturus carnifex were considered as target species, in order to perform our analysis with species having different ecological and distributional characteristics. The study area is the "Gran Sasso-Monti della Laga" National Park, which hosts 15 Natura 2000 sites and represents one of the most important biodiversity hotspots in Europe. Our results show that the model calibration ameliorates when using the target-group based pseudo-absences compared to the random ones, especially when applying the WTGB. Contrarily, model discrimination did not significantly vary in a consistent way among the three approaches with respect to the tree target species. Both WTGB and RDM clearly isolate the highly contributing variables, supplying many relevant indications for species conservation actions. Moreover, the assessment of pairwise variable interactions and their three-dimensional visualization further increase the amount of useful information for protected areas' managers. Finally, we suggest the use of RDM as an admissible alternative when it is not possible to individuate a suitable set of species as a representative target-group from which the pseudo-absences can be generated.

Structural Insights into Membrane Targeting by the Flagellar Calcium-binding Protein (FCaBP) a Myristoylated and Palmitoylated Calcium Sensor in Trypanosoma cruzi

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

J Wingard; J Ladner; M Vanarotti

2011-12-31

The flagellar calcium-binding protein (FCaBP) of the protozoan Trypanosoma cruzi is targeted to the flagellar membrane where it regulates flagellar function and assembly. As a first step toward understanding the Ca{sup 2+}-induced conformational changes important for membrane-targeting, we report here the x-ray crystal structure of FCaBP in the Ca{sup 2+}-free state determined at 2.2{angstrom} resolution. The first 17 residues from the N terminus appear unstructured and solvent-exposed. Residues implicated in membrane targeting (Lys-19, Lys-22, and Lys-25) are flanked by an exposed N-terminal helix (residues 26-37), forming a patch of positive charge on the protein surface that may interact electrostatically withmore » flagellar membrane targets. The four EF-hands in FCaBP each adopt a 'closed conformation' similar to that seen in Ca{sup 2+}-free calmodulin. The overall fold of FCaBP is closest to that of grancalcin and other members of the penta EF-hand superfamily. Unlike the dimeric penta EF-hand proteins, FCaBP lacks a fifth EF-hand and is monomeric. The unstructured N-terminal region of FCaBP suggests that its covalently attached myristoyl group at the N terminus may be solvent-exposed, in contrast to the highly sequestered myristoyl group seen in recoverin and GCAP1. NMR analysis demonstrates that the myristoyl group attached to FCaBP is indeed solvent-exposed in both the Ca{sup 2+}-free and Ca{sup 2+}-bound states, and myristoylation has no effect on protein structure and folding stability. We propose that exposed acyl groups at the N terminus may anchor FCaBP to the flagellar membrane and that Ca{sup 2+}-induced conformational changes may control its binding to membrane-bound protein targets..« less

Glycaemic control and cardiovascular risk factor management in patients with diabetes with and without coronary artery disease: insights from the diabetes mellitus status in Canada survey.

PubMed

Grenier, Jasmine; Leiter, Lawrence A; Langer, Anatoly; Goldin, Lianne; Teoh, Hwee; Connelly, Kim A; Cheng, Alice Y Y; Tan, Mary K; Fitchett, David; McGuire, Darren K; Goodman, Shaun G; Yan, Andrew T

2016-10-01

Current diabetes guidelines recommend an individualized approach to glycaemic control. There are limited data on the contemporary and comprehensive management of patients with diabetes in relation to coronary artery disease (CAD). The Diabetes Mellitus Status in Canada (DM-SCAN) survey included 5123 patients with type 2 diabetes seen in primary care in November 2012. Primary care physicians (PCPs) collected clinical data and specified the A1C target for each patient on standardized forms. We compared management strategies and achievement of treatment targets in patients with and without CAD. Among the 4994 patients with data on CAD history, 22.5% had CAD. Primary care physicians were more likely to select a higher A1C target for patients with CAD (≤7.5 or ≤8.0%) versus without (≤7.0%). There was no difference in median A1C or in the proportion of patients with A1C ≤7.0% between the two groups. Compared with the group without known CAD, patients with CAD had a higher reported prevalence of hypoglycaemia in the preceding 6 months; more frequently received aspirin, statins, ACE inhibitors, or angiotensin receptor blockers, and were more likely to achieve blood pressure and low-density lipoprotein-cholesterol targets. Only 15.4 and 12.0% of patients with and without CAD (P = 0.002), respectively, achieved all three guideline-recommended targets. Compared with patients with diabetes without CAD, those with CAD more frequently had a less stringent A1C target selected by their PCPs but achieved similar glycaemic control. Overall, risk factor management remained suboptimal in both groups. There remains an important opportunity to improve the care and outcome of patients with diabetes.

SEEDS Moving Group Status Update

NASA Technical Reports Server (NTRS)

McElwain, Michael

2011-01-01

I will summarize the current status of the SEEDS Moving Group category and describe the importance of this sub-sample for the entire SEEDS survey. This presentation will include analysis of the sensitivity for the Moving Groups with general a comparison to other the other sub-categories. I will discuss the future impact of the Subaru SCExAO system for these targets and the advantage of using a specialized integral field spectrograph. Finally, I will present the impact of a pupil grid mask in order to produce fiducial spots in the focal plane that can be used for both photometry and astrometry.

Lead generation and examples opinion regarding how to follow up hits.

PubMed

Orita, Masaya; Ohno, Kazuki; Warizaya, Masaichi; Amano, Yasushi; Niimi, Tatsuya

2011-01-01

In fragment-based drug discovery (FBDD), not only identifying the starting fragment hit to be developed but also generating a drug lead from that starting fragment hit is important. Converting fragment hits to leads is generally similar to a high-throughput screening (HTS) hits-to-leads approach in that properties associated with activity for a target protein, such as selectivity against other targets and absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox), and physicochemical properties should be taken into account. However, enhancing the potency of the fragment hit is a key requirement in FBDD, unlike HTS, because initial fragment hits are generally weak. This enhancement is presently achieved by adding additional chemical groups which bind to additional parts of the target protein or by joining or combining two or more hit fragments; however, strategies for effecting greater improvements in effective activity are needed. X-ray analysis is a key technology attractive for converting fragments to drug leads. This method makes it clear whether a fragment hit can act as an anchor and provides insight regarding introduction of functional groups to improve fragment activity. Data on follow-up chemical synthesis of fragment hits has allowed for the differentiation of four different strategies: fragment optimization, fragment linking, fragment self-assembly, and fragment evolution. Here, we discuss our opinion regarding how to follow up on fragment hits, with a focus on the importance of fragment hits as an anchor moiety to so-called hot spots in the target protein using crystallographic data. Copyright © 2011 Elsevier Inc. All rights reserved.

The context and practice of handwashing among new mothers in Serang, Indonesia: a formative research study

PubMed Central

2013-01-01

Background This article reports on formative research into the context and practice of handwashing with soap by new mothers, which can substantially impact child morbidity and mortality. New mothers are an important target group for handwashing interventions: they are considered particularly susceptible to behaviour change and their actions can directly affect a child’s health. Methods Twenty-seven mothers of infants (including neonates) from urban and rural sub-districts of Serang were recruited and filmed over a period of eight hours. Video footage was used to identify handwashing occasions and to understand the context in which behaviour took place. Each woman was subsequently interviewed. Results Handwashing with soap was found to be infrequent, typically occurring after eating, cooking and household chores or after cleaning a child’s bottom. Handwashing before preparing food or eating was rare. Pre-pregnancy routines were reported to have been disrupted. Advice on child care comes from many sources, particularly the midwife and new child’s grandmother. Conclusions Developing interventions to change perceptions and practice of handwashing would seed an important behaviour and could save lives. New mothers represent an ideal target group for such an intervention. We suggest that interventions target an increase in handwashing with soap after contact with own and a baby’s faecal matter as part of the post-defecation hygiene routines. As the child’s grandmother is an authoritative source of information about parenting, interventions focussed on improving newborn care could target grandmothers as well as midwives. PMID:24020804

Stereotypes of Black American Women Related to Sexuality and Motherhood

PubMed Central

Rosenthal, Lisa; Lobel, Marci

2016-01-01

Intersectionality theorists and researchers suggest the importance of examining unique stereotypes associated with intersecting group identities. We focus on the unique stereotypes of Black women in the United States related to sexuality and motherhood. In an online experimental study, 435 undergraduates from a Northeastern U.S. university were randomly assigned to one of the four conditions in which they viewed a photograph and read a description of a target young woman. The target’s race (Black vs. White) and pregnancy status (pregnant vs. no pregnancy information) were varied. A Black female target (pregnant or not) was perceived more negatively on items related to historically rooted societal stereotypes about sexual activity, sexual risk, motherhood status, and socioeconomic status than was a White female target, but there were no differences on items unrelated to societal stereotypes. A Black target described as pregnant was also perceived as more likely to be a single mother and to need public assistance than was a White target described as pregnant. Current findings, along with evidence that societal stereotypes have damaging effects, underscore the importance of diversifying images of Black women and increasing awareness of how stereotypes affect perceptions of Black women. Findings also highlight the value of research employing intersectionality to understand stereotypes. PMID:27821904

Targeting as a Mode of Science Communication: Principles, Issues and a Practical Example

NASA Astrophysics Data System (ADS)

Holland, G. J.; Vigh, J. L.

2011-12-01

Today's media landscape contains a rich and diverse range of communications opportunities. New media, such as the internet, blogosphere and social networks, are complementing, supplementing and also replacing the traditional mass media communications through print, radio and television. This diversification certainly contains pitfalls and difficulties as has been demonstrated in the Climategate affair. But there are also real opportunities for utilizing the diversity to provide targeted science communications that are framed in the context of the specific group of interest. That such targeting of audience attitudes and beliefs is an important key to effective science communications has been demonstrated by, for example, Leiserowitz, Maibach et al (2009). This approach does require an understanding of the audience and a careful framing of the message in terms familiar to the targeted group. Here many factors come into play, including: including immediacy, economics, culture, community leaders, emotional framing, and ideological filters. In this talk we shall elaborate on the principles, issues and opportunities. A practical example of working with the religious community on communicating the science of climate change will also be presented. This will include the approach adopted, progress to date and the lessons learnt.

Development of targeted messages to promote smoking cessation among construction trade workers

PubMed Central

Strickland, J. R.; Smock, N.; Casey, C.; Poor, T.; Kreuter, M. W.; Evanoff, B. A.

2015-01-01

Blue-collar workers, particularly those in the construction trades, are more likely to smoke and have less success in quitting when compared with white-collar workers. Little is known about health communication strategies that might influence this priority population. This article describes our formative work to develop targeted messages to increase participation in an existing smoking cessation program among construction workers. Using an iterative and sequential mixed-methods approach, we explored the culture, health attitudes and smoking behaviors of unionized construction workers. We used focus group and survey data to inform message development, and applied audience segmentation methods to identify potential subgroups. Among 144 current smokers, 65% reported wanting to quit smoking in the next 6 months and only 15% had heard of a union-sponsored smoking cessation program, despite widespread advertising. We tested 12 message concepts and 26 images with the target audience to evaluate perceived relevance and effectiveness. Participants responded most favorably to messages and images that emphasized family and work, although responses varied by audience segments based on age and parental status. This study is an important step towards integrating the culture of a high-risk group into targeted messages to increase participation in smoking cessation activities. PMID:25231165

Children's identification of graphic symbols representing four basic emotions: comparison of Afrikaans-speaking and Sepedi-speaking children.

PubMed

DeKlerk, Hester M; Dada, Shakila; Alant, Erna

2014-01-01

Speech language pathologists recommend graphic symbols for AAC users to facilitate communication, including labelling and expressing emotions. The purpose of the current study was to describe and compare how 5- to 6-year-old Afrikaans- and Sepedi-speaking children identify and choose graphic symbols to depict four basic emotions, specifically happy, sad, afraid, and angry. Ninety participants were asked to select the graphic symbol from a 16-matrix communication overlay that would represent the emotion in response to 24 vignettes. The results of the t-tests indicated that the differences between the two groups' selection of target symbols to represent the four emotions are statistically significant. The results of the study indicate that children from different language groups may not perceive graphic symbols in the same way. The Afrikaans-speaking participants more often choose target symbols to represent target basic emotions than did the Sepedi-speaking participants. The most preferred symbols per emotion were identified and these different symbols were analysed in terms of facial features that distinguish them. Readers of this article will (1) recognise the importance of expressing basic emotions for children, particularly those that use AAC, (2) identify the possible limitations of line drawings for expressing and labelling basic emotions in typically developing children and (3) recognise the importance of cultural influences on recognition of basic emotions. Copyright © 2014 Elsevier Inc. All rights reserved.

Appreciation and implementation of the Krachtvoer healthy diet promotion programme for 12- to 14- year-old students of prevocational schools

PubMed Central

2011-01-01

Background Krachtvoer is a school-based healthy diet programme, developed in 2001 and revised in 2007 to meet the needs of particular segments of the target population as well as a wider target group. The main aims of the present process evaluation of the revised programme were to examine student and teacher appreciation of the programme, completeness of and adherence to its implementation, and relations between appreciation and completeness of implementation. Methods Data were collected among 22 teachers and 1117 students of 13 schools, using student evaluation forms, teacher logbooks, telephone interviews, and classroom observations. Results Results indicate favourable levels of teacher and student appreciation for the programme in general and the revised elements. Girls, first-year students and students with more favourable dietary intakes particularly appreciated individual programme elements. Levels of completeness of implementation were high, but several teachers did not adhere to the intended implementation period. Some moderately strong relations were found between teacher appreciation and completeness of implementation scores. Conclusion We conclude that the revisions have resulted in a programme that was appreciated well, also by the extended target group, and was implemented with a high degree of completeness. Teacher appreciation proved potentially important for completeness of implementation. We identified several aspects requiring improvement, indicating the importance of continued programme updates and repeated evaluation. PMID:22151954

Gasotransmitter Heterocellular Signaling

PubMed Central

Kolluru, Gopi K.; Shen, Xinggui; Yuan, Shuai; Kevil, Christopher G.

2017-01-01

Abstract Significance: The family of gasotransmitter molecules, nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), has emerged as an important mediator of numerous cellular signal transduction and pathophysiological responses. As such, these molecules have been reported to influence a diverse array of biochemical, molecular, and cell biology events often impacting one another. Recent Advances: Discrete regulation of gasotransmitter molecule formation, movement, and reaction is critical to their biological function. Due to the chemical nature of these molecules, they can move rapidly throughout cells and tissues acting on targets through reactions with metal groups, reactive chemical species, and protein amino acids. Critical Issues: Given the breadth and complexity of gasotransmitter reactions, this field of research is expanding into exciting, yet sometimes confusing, areas of study with significant promise for understanding health and disease. The precise amounts of tissue and cellular gasotransmitter levels and where they are formed, as well as how they react with molecular targets or themselves, all remain poorly understood. Future Directions: Elucidation of specific molecular targets, characteristics of gasotransmitter molecule heterotypic interactions, and spatiotemporal formation and metabolism are all important to better understand their true pathophysiological importance in various organ systems. Antioxid. Redox Signal. 26, 936–960. PMID:28068782

Visual Search in the Real World: Color Vision Deficiency Affects Peripheral Guidance, but Leaves Foveal Verification Largely Unaffected

PubMed Central

Kugler, Günter; 't Hart, Bernard M.; Kohlbecher, Stefan; Bartl, Klaus; Schumann, Frank; Einhäuser, Wolfgang; Schneider, Erich

2015-01-01

Background: People with color vision deficiencies report numerous limitations in daily life, restricting, for example, their access to some professions. However, they use basic color terms systematically and in a similar manner as people with normal color vision. We hypothesize that a possible explanation for this discrepancy between color perception and behavioral consequences might be found in the gaze behavior of people with color vision deficiency. Methods: A group of participants with color vision deficiencies and a control group performed several search tasks in a naturalistic setting on a lawn. All participants wore a mobile eye-tracking-driven camera with a high foveal image resolution (EyeSeeCam). Search performance as well as fixations of objects of different colors were examined. Results: Search performance was similar in both groups in a color-unrelated search task as well as in a search for yellow targets. While searching for red targets, participants with color vision deficiencies exhibited a strongly degraded performance. This was closely matched by the number of fixations on red objects shown by the two groups. Importantly, once they fixated a target, participants with color vision deficiencies exhibited only few identification errors. Conclusions: In contrast to controls, participants with color vision deficiencies are not able to enhance their search for red targets on a (green) lawn by an efficient guiding mechanism. The data indicate that the impaired guiding is the main influence on search performance, while foveal identification (verification) is largely unaffected by the color vision deficiency. PMID:26733851

Disadvantaged persons' participation in health promotion projects: some structural dimensions.

PubMed

Boyce, W F

2001-05-01

A structural perspective was used in studying community participation of disadvantaged groups (poor women, street youth, and disabled persons) in health promotion projects. Five community projects in the Canadian Health Promotion Contribution Program were examined in a comparative case study utilizing in-depth interviews, documents, and secondary sources. Analysis revealed relatively low numbers and restricted range of participants, difficulties in recruiting and maintaining participants, declining rates of active participation over time, and limited target group influence and power. This paper reports on the relationship between various dimensions of structure (social-cultural, organizational, political-legal-economic) and the community participation process. Participation was influenced by structural factors such as bureaucratic rules and regulators, perceived minority group rights and relations, agency reputations and responsibilities, available resources, and organizational roles. Control of projects by target group members, rather than by service agencies, was an important overall organizational structural factor which allowed community members to achieve influence in projects. The study concludes that a conceptual model based on structural factors is useful in explaining how key factors from federal and local levels can restrict or facilitate the community participation process.

Standardizing Naming Conventions in Radiation Oncology

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

Santanam, Lakshmi; Hurkmans, Coen; Mutic, Sasa

2012-07-15

Purpose: The aim of this study was to report on the development of a standardized target and organ-at-risk naming convention for use in radiation therapy and to present the nomenclature for structure naming for interinstitutional data sharing, clinical trial repositories, integrated multi-institutional collaborative databases, and quality control centers. This taxonomy should also enable improved plan benchmarking between clinical institutions and vendors and facilitation of automated treatment plan quality control. Materials and Methods: The Advanced Technology Consortium, Washington University in St. Louis, Radiation Therapy Oncology Group, Dutch Radiation Oncology Society, and the Clinical Trials RT QA Harmonization Group collaborated in creatingmore » this new naming convention. The International Commission on Radiation Units and Measurements guidelines have been used to create standardized nomenclature for target volumes (clinical target volume, internal target volume, planning target volume, etc.), organs at risk, and planning organ-at-risk volumes in radiation therapy. The nomenclature also includes rules for specifying laterality and margins for various structures. The naming rules distinguish tumor and nodal planning target volumes, with correspondence to their respective tumor/nodal clinical target volumes. It also provides rules for basic structure naming, as well as an option for more detailed names. Names of nonstandard structures used mainly for plan optimization or evaluation (rings, islands of dose avoidance, islands where additional dose is needed [dose painting]) are identified separately. Results: In addition to its use in 16 ongoing Radiation Therapy Oncology Group advanced technology clinical trial protocols and several new European Organization for Research and Treatment of Cancer protocols, a pilot version of this naming convention has been evaluated using patient data sets with varying treatment sites. All structures in these data sets were satisfactorily identified using this nomenclature. Conclusions: Use of standardized naming conventions is important to facilitate comparison of dosimetry across patient datasets. The guidelines presented here will facilitate international acceptance across a wide range of efforts, including groups organizing clinical trials, Radiation Oncology Institute, Dutch Radiation Oncology Society, Integrating the Healthcare Enterprise, Radiation Oncology domain (IHE-RO), and Digital Imaging and Communication in Medicine (DICOM).« less

Needs and Preferences for the Prevention of Intimate Partner Violence among Hispanics: A Community’s Perspective

PubMed Central

Gonzalez-Guarda, R.M.; Cummings, A.M.; Becerra, M.; Fernandez, M.C.; Mesa, I.

2013-01-01

Research suggest that Hispanics in the U.S. are disproportionately affected by the consequences of intimate partner violence. Nevertheless, few intimate partner violence prevention interventions have been developed to address the unique needs and preferences of this population. The Partnership for Domestic Violence Prevention is a community-based participatory research project that assessed the needs and preferences for prevention programs for Hispanics in Miami-Dade County. Nine focus groups with domestic violence service providers, victims and general community members were conducted (N= 76). Four major themes emerged from the focus groups. These included immigrants and teens as the highest priority groups to target in prevention efforts, culture as a double-edged sword, the system that helps and hurts the victim, and the need for wide-scale prevention programs that would reach Hispanics systematically. The results from this study have important implications for the development of intimate violence prevention interventions targeting Hispanics in the U.S. PMID:23843106

Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method

PubMed Central

Niks, Irene; Gevers, Josette

2018-01-01

Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care. PMID:29438350

Needs and preferences for the prevention of intimate partner violence among Hispanics: a community's perspective.

PubMed

Gonzalez-Guarda, R M; Cummings, A M; Becerra, M; Fernandez, M C; Mesa, I

2013-08-01

Research suggest that Hispanics in the U.S. are disproportionately affected by the consequences of intimate partner violence. Nevertheless, few intimate partner violence prevention interventions have been developed to address the unique needs and preferences of this population. The Partnership for Domestic Violence Prevention is a community-based participatory research project that assessed the needs and preferences for prevention programs for Hispanics in Miami-Dade County. Nine focus groups with domestic violence service providers, victims and general community members were conducted (N = 76). Four major themes emerged from the focus groups. These included immigrants and teens as the highest priority groups to target in prevention efforts, culture as a double-edged sword, the system that helps and hurts the victim, and the need for wide-scale prevention programs that would reach Hispanics systematically. The results from this study have important implications for the development of intimate violence prevention interventions targeting Hispanics in the U.S.

Work Stress Interventions in Hospital Care: Effectiveness of the DISCovery Method.

PubMed

Niks, Irene; de Jonge, Jan; Gevers, Josette; Houtman, Irene

2018-02-13

Effective interventions to prevent work stress and to improve health, well-being, and performance of employees are of the utmost importance. This quasi-experimental intervention study presents a specific method for diagnosis of psychosocial risk factors at work and subsequent development and implementation of tailored work stress interventions, the so-called DISCovery method. This method aims at improving employee health, well-being, and performance by optimizing the balance between job demands, job resources, and recovery from work. The aim of the study is to quantitatively assess the effectiveness of the DISCovery method in hospital care. Specifically, we used a three-wave longitudinal, quasi-experimental multiple-case study approach with intervention and comparison groups in health care work. Positive changes were found for members of the intervention groups, relative to members of the corresponding comparison groups, with respect to targeted work-related characteristics and targeted health, well-being, and performance outcomes. Overall, results lend support for the effectiveness of the DISCovery method in hospital care.

Interferon-targeted therapy in systemic lupus erythematosus: Is this an alternative to targeting B and T cells?

PubMed

Kalunian, K C

2016-09-01

Clinical trials of investigational agents in systemic lupus erythematosus (SLE) have focused on targeting dysregulated B and T cells; however, recent translational research findings of the importance of the dysregulation of the innate immune system in SLE have led to clinical trials that target interferon. Three biologics that target type I interferons have been tested for their efficacy and safety in active SLE patients; these phase II trials have tested the hypothesis that down-regulation of interferon-regulated gene expression (the interferon signature) lessen the clinical burden of SLE. Rontalizumab, an anti-interferon-α monoclonal antibody, was studied in patients who had discontinued immunosuppressants. This study failed to show efficacy as assessed by both two outcome assessments; however, in low interferon signature patients, response was higher and corticosteroid usage was less in rontalizumab-treated patients. Sifalimumab, another anti-interferon-α monoclonal antibody, was studied in patients who remained on standard of care therapy. This study showed significantly better efficacy in patients treated with two sifalimumab dosages; significant differences were seen in the high interferon signature group. In a similar design and in a similar population as the sifalimumab study, anifrolumab, a monoclonal antibody that binds to a type I interferon receptor, was studied in patients who remained on standard of care therapy. In this study, one dosage group demonstrated efficacy and statistically significant effects were achieved in both tested dosage groups with secondary end points. Oral corticosteroid reduction to ≤7.5 mg daily was achieved in one of the tested dosage groups and organ-specific outcomes were significantly improved in that same group. For all studies, no significant differences in serious adverse effects were seen; although, herpes zoster infections were increased in sifalimumab- and anifrolumab-treated patients and influenza rates were increased in anifrolumab-treated patients. Anifrolumab is currently in pivotal phase III studies. Data appear to support the concept that targeting type I interferon in SLE patients associates with clinical efficacy and safety. Further data are forthcoming from ongoing phase III clinical trials of anifrolumab. Other drug development efforts should be considered that target plasmacytoid dendritic cells and toll like receptors given the effects these components have on interferon production. © The Author(s) 2016.

Family Literacy in Cultural Context: Lessons from Two Case Studies.

ERIC Educational Resources Information Center

Puchner, Laurel D.

A study examined the literature to determine the veracity of the criticism of some educators who say that family literacy programs in the United States fail to take into account important cultural issues when dealing with certain target groups. Issues invoked included the need to take traditional cultural values and practices into account in…

Psi Chi/APA Edwin B. Newman Graduate Research Award: Joseph H. Hammer

ERIC Educational Resources Information Center

American Psychologist, 2009

2009-01-01

Joseph H. Hammer, recipient of the Psi Chi/APA Edwin B. Newman Graduate Research Award, is cited for an outstanding research paper whose findings provide important evidence regarding the promise of a male-sensitive approach to mental health marketing and empirically support the inclusion of theory-driven enhancements in group-targeted mental…

Nonimaging solar concentrator with near-uniform irradiance for photovoltaic arrays

NASA Astrophysics Data System (ADS)

O'Gallagher, Joseph J.; Winston, Roland; Gee, Randy

2001-11-01

We report results of a study our group has undertaken to design a solar concentrator with uniform irradiance on a planar target. This attribute is especially important for photovoltaic concentrators. We find that a variety of optical mixers, some incorporating a moderate level of concentration, can be quite effective in achieving near uniform irradiance.

A Family-Based Intervention for Preschoolers: Evaluating Sibling Outcomes. Data Trends #130

ERIC Educational Resources Information Center

Research and Training Center on Family Support and Children's Mental Health, 2006

2006-01-01

"Data Trends" reports present summaries of research on mental health services for children and adolescents and their families. The article summarized in this "Data Trends" discusses family-based interventions and how they may have both direct and indirect effects. While the measurement of direct outcomes for a targeted group is important, a…

Genetic relationships in Cucurbita pepo (pumpkin, squash, gourd) as viewed with high frequency oligonucleotide–targeting active gene (HFO–TAG) markers

USDA-ARS?s Scientific Manuscript database

Cucurbita pepo is a highly diverse, economically important member of the Cucurbitaceae. C. pepo encompasses hundreds of cultivars of pumpkins, squash, and gourds. Although C. pepo has been scrutinized with various types of DNA markers, the relationships among the cultivar-groups of C. pepo subsp. p...

The impacts of fear and disgust on the perceived effectiveness of smoking warning labels: a study on Turkish university students.

PubMed

Tugrul, Tugba Orten

2015-03-01

This study investigated the perceived effectiveness of pictorial warning labels on cigarette packages on Turkish university students. In particular, the impacts of fear and disgust elicited by these labels were examined using the smoking decision process model. A survey was conducted with 344 undergraduate students at a private university in Izmir, the third largest city of Turkey. The findings showed differences in levels of fear and disgust evoked by pictorial warning labels for each stage in the smoking decision process, which in turn led to differences in the perceived effectiveness of the labels. Thus, this study underlines the importance of tailoring antismoking messages according to specific target groups and also suggests considering the smoking-decision-process model as segments and targeting groups in creating effective messages. © 2013 APJPH.

Stretchable surfaces with programmable 3D texture morphing for synthetic camouflaging skins

NASA Astrophysics Data System (ADS)

Pikul, J. H.; Li, S.; Bai, H.; Hanlon, R. T.; Cohen, I.; Shepherd, R. F.

2017-10-01

Technologies that use stretchable materials are increasingly important, yet we are unable to control how they stretch with much more sophistication than inflating balloons. Nature, however, demonstrates remarkable control of stretchable surfaces; for example, cephalopods can project hierarchical structures from their skin in milliseconds for a wide range of textural camouflage. Inspired by cephalopod muscular morphology, we developed synthetic tissue groupings that allowed programmable transformation of two-dimensional (2D) stretchable surfaces into target 3D shapes. The synthetic tissue groupings consisted of elastomeric membranes embedded with inextensible textile mesh that inflated to within 10% of their target shapes by using a simple fabrication method and modeling approach. These stretchable surfaces transform from flat sheets to 3D textures that imitate natural stone and plant shapes and camouflage into their background environments.

Targeted Fluoro Positioning for the Discovery of a Potent and Highly Selective Matrix Metalloproteinase Inhibitor.

PubMed

Fischer, Thomas; Riedl, Rainer

2017-04-01

Invited for this month's cover picture is the group of Professor Rainer Riedl from the Institute of Chemistry and Biotechnology at the Zurich University of Applied Sciences (ZHAW), Switzerland. The cover picture depicts the structure-based design of a drug-like small molecule inhibitor of matrix metalloproteinase-13 (MMP-13) with a combined dual binding motif. The targeted introduction of a single fluoro atom was of vital importance for the optimization of the inhibitor. For more details, read the full text of the Communication at 10.1002/open.201600158.

Amateur Astronomers: Secret Agents of EPO

NASA Astrophysics Data System (ADS)

Berendsen, M.; White, V.; Devore, E.; Reynolds, M.

2008-06-01

Amateur astronomers prime the public to be more interested, receptive, and excited about space science, missions, and programs. Through recent research and targeted programs, amateur astronomy outreach is being increasingly recognized by professional astronomers, educators, and other amateurs as a valued and important service. The Night Sky Network program, administered by the ASP, is the first nationwide research-based program specifically targeted to support outreach by amateur astronomers. This Network of trained and informed amateur astronomers can provide a stimulating introduction to your EPO programs as Network members share the night sky with families, students, and youth groups.

4D imaging for target definition in stereotactic radiotherapy for lung cancer.

PubMed

Slotman, Ben J; Lagerwaard, Frank J; Senan, Suresh

2006-01-01

Stereotactic radiotherapy of Stage I lung tumors has been reported to result in high local control rates that are far superior to those obtained with conventional radiotherapy techniques, and which approach those achieved with primary surgery. Breathing-induced motion of tumor and target tissues is an important issue in this technique and careful attention should be paid to the contouring and the generation of individualized margins. We describe our experience with the use of 4DCT scanning for this group of patients, the use of post-processing tools and the potential benefits of respiratory gating.

A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

PubMed Central

Choi, K. Yeon; Root, Matthew

2016-01-01

ABSTRACT Congenital cytomegalovirus (CMV) infection is a leading cause of mental retardation and deafness in newborns. The guinea pig is the only small animal model for congenital CMV infection. A novel CMV vaccine was investigated as an intervention strategy against congenital guinea pig cytomegalovirus (GPCMV) infection. In this disabled infectious single-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (the UL85 homolog GP85) except when grown on a complementing cell line. In vaccinated animals, the GP85 mutant virus (GP85 DISC) induced an antibody response to important glycoprotein complexes considered neutralizing target antigens (gB, gH/gL/gO, and gM/gN). The vaccine also generated a T cell response to the pp65 homolog (GP83), determined via a newly established guinea pig gamma interferon enzyme-linked immunosorbent spot assay. In a congenital infection protection study, GP85 DISC-vaccinated animals and a nonvaccinated control group were challenged during pregnancy with wild-type GPCMV (105 PFU). The pregnant animals carried the pups to term, and viral loads in target organs of pups were analyzed. Based on live pup births in the vaccinated and control groups (94.1% versus 63.6%), the vaccine was successful in reducing mortality (P = 0.0002). Additionally, pups from the vaccinated group had reduced CMV transmission, with 23.5% infected target organs versus 75.9% in the control group. Overall, these preliminary studies indicate that a DISC CMV vaccine strategy has the ability to induce an immune response similar to that of natural virus infection but has the increased safety of a non-replication-competent virus, which makes this approach attractive as a CMV vaccine strategy. IMPORTANCE Congenital CMV infection is a leading cause of mental retardation and deafness in newborns. An effective vaccine against CMV remains an elusive goal despite over 50 years of CMV research. The guinea pig, with a placenta structure similar to that in humans, is the only small animal model for congenital CMV infection and recapitulates disease symptoms (e.g., deafness) in newborn pups. In this report, a novel vaccine strategy against congenital guinea pig cytomegalovirus (GPCMV) infection was developed, characterized, and tested for efficacy. This disabled infectious single-cycle (DISC) vaccine strategy induced a neutralizing antibody or a T cell response to important target antigens. In a congenital infection protection study, animals were protected against CMV in comparison to the nonvaccinated group (52% reduction of transmission). This novel vaccine was more effective than previously tested gB-based vaccines and most other strategies involving live virus vaccines. Overall, the DISC vaccine is a safe and promising approach against congenital CMV infection. PMID:27334585

Ethnic Disparities in Diabetes Management and Pay-for-Performance in the UK: The Wandsworth Prospective Diabetes Study

PubMed Central

Millett, Christopher; Gray, Jeremy; Saxena, Sonia; Netuveli, Gopalakrishnan; Khunti, Kamlesh; Majeed, Azeem

2007-01-01

Background Pay-for-performance rewards health-care providers by paying them more if they succeed in meeting performance targets. A new contract for general practitioners in the United Kingdom represents the most radical shift towards pay-for-performance seen in any health-care system. The contract provides an important opportunity to address disparities in chronic disease management between ethnic and socioeconomic groups. We examined disparities in management of people with diabetes and intermediate clinical outcomes within a multiethnic population in primary care before and after the introduction of the new contract in April 2004. Methods and Findings We conducted a population-based longitudinal survey, using electronic general practice records, in an ethnically diverse part of southwest London. Outcome measures were prescribing levels and achievement of national treatment targets (HbA1c ≤ 7.0%; blood pressure [BP] < 140/80 mm Hg; total cholesterol ≤ 5 mmol/l or 193 mg/dl). The proportion of patients reaching treatment targets for HbA1c, BP, and total cholesterol increased significantly after the implementation of the new contract. The extents of these increases were broadly uniform across ethnic groups, with the exception of the black Caribbean patient group, which had a significantly lower improvement in HbA1c (adjusted odds ratio [AOR] 0.75, 95% confidence interval [CI] 0.57–0.97) and BP control (AOR 0.65, 95% CI 0.53–0.81) relative to the white British patient group. Variations in prescribing and achievement of treatment targets between ethnic groups present in 2003 were not attenuated in 2005. Conclusions Pay-for-performance incentives have not addressed disparities in the management and control of diabetes between ethnic groups. Quality improvement initiatives must place greater emphasis on minority communities to avoid continued disparities in mortality from cardiovascular disease and the other major complications of diabetes. PMID:17564486

Ethnic disparities in diabetes management and pay-for-performance in the UK: the Wandsworth Prospective Diabetes Study.

PubMed

Millett, Christopher; Gray, Jeremy; Saxena, Sonia; Netuveli, Gopalakrishnan; Khunti, Kamlesh; Majeed, Azeem

2007-06-01

Pay-for-performance rewards health-care providers by paying them more if they succeed in meeting performance targets. A new contract for general practitioners in the United Kingdom represents the most radical shift towards pay-for-performance seen in any health-care system. The contract provides an important opportunity to address disparities in chronic disease management between ethnic and socioeconomic groups. We examined disparities in management of people with diabetes and intermediate clinical outcomes within a multiethnic population in primary care before and after the introduction of the new contract in April 2004. We conducted a population-based longitudinal survey, using electronic general practice records, in an ethnically diverse part of southwest London. Outcome measures were prescribing levels and achievement of national treatment targets (HbA1c < or = 7.0%; blood pressure [BP] < 140/80 mm Hg; total cholesterol < or = 5 mmol/l or 193 mg/dl). The proportion of patients reaching treatment targets for HbA1c, BP, and total cholesterol increased significantly after the implementation of the new contract. The extents of these increases were broadly uniform across ethnic groups, with the exception of the black Caribbean patient group, which had a significantly lower improvement in HbA1c (adjusted odds ratio [AOR] 0.75, 95% confidence interval [CI] 0.57-0.97) and BP control (AOR 0.65, 95% CI 0.53-0.81) relative to the white British patient group. Variations in prescribing and achievement of treatment targets between ethnic groups present in 2003 were not attenuated in 2005. Pay-for-performance incentives have not addressed disparities in the management and control of diabetes between ethnic groups. Quality improvement initiatives must place greater emphasis on minority communities to avoid continued disparities in mortality from cardiovascular disease and the other major complications of diabetes.

Changes to online control and eye-hand coordination with healthy ageing.

PubMed

O'Rielly, Jessica L; Ma-Wyatt, Anna

2018-06-01

Goal directed movements are typically accompanied by a saccade to the target location. Online control plays an important part in correction of a reach, especially if the target or goal of the reach moves during the reach. While there are notable changes to visual processing and motor control with healthy ageing, there is limited evidence about how eye-hand coordination during online updating changes with healthy ageing. We sought to quantify differences between older and younger people for eye-hand coordination during online updating. Participants completed a double step reaching task implemented under time pressure. The target perturbation could occur 200, 400 and 600 ms into a reach. We measured eye position and hand position throughout the trials to investigate changes to saccade latency, movement latency, movement time, reach characteristics and eye-hand latency and accuracy. Both groups were able to update their reach in response to a target perturbation that occurred at 200 or 400 ms into the reach. All participants demonstrated incomplete online updating for the 600 ms perturbation time. Saccade latencies, measured from the first target presentation, were generally longer for older participants. Older participants had significantly increased movement times but there was no significant difference between groups for touch accuracy. We speculate that the longer movement times enable the use of new visual information about the target location for online updating towards the end of the movement. Interestingly, older participants also produced a greater proportion of secondary saccades within the target perturbation condition and had generally shorter eye-hand latencies. This is perhaps a compensatory mechanism as there was no significant group effect on final saccade accuracy. Overall, the pattern of results suggests that online control of movements may be qualitatively different in older participants. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

A Meta-Analysis: Identification of Common Mir-145 Target Genes that have Similar Behavior in Different GEO Datasets.

PubMed

Pashaei, Elnaz; Guzel, Esra; Ozgurses, Mete Emir; Demirel, Goksun; Aydin, Nizamettin; Ozen, Mustafa

MicroRNAs, which are small regulatory RNAs, post-transcriptionally regulate gene expression by binding 3'-UTR of their mRNA targets. Their deregulation has been shown to cause increased proliferation, migration, invasion, and apoptosis. miR-145, an important tumor supressor microRNA, has shown to be downregulated in many cancer types and has crucial roles in tumor initiation, progression, metastasis, invasion, recurrence, and chemo-radioresistance. Our aim is to investigate potential common target genes of miR-145, and to help understanding the underlying molecular pathways of tumor pathogenesis in association with those common target genes. Eight published microarray datasets, where targets of mir-145 were investigated in cell lines upon mir-145 over expression, were included into this study for meta-analysis. Inter group variabilities were assessed by box-plot analysis. Microarray datasets were analyzed using GEOquery package in Bioconducter 3.2 with R version 3.2.2 and two-way Hierarchical Clustering was used for gene expression data analysis. Meta-analysis of different GEO datasets showed that UNG, FUCA2, DERA, GMFB, TF, and SNX2 were commonly downregulated genes, whereas MYL9 and TAGLN were found to be commonly upregulated upon mir-145 over expression in prostate, breast, esophageal, bladder cancer, and head and neck squamous cell carcinoma. Biological process, molecular function, and pathway analysis of these potential targets of mir-145 through functional enrichments in PPI network demonstrated that those genes are significantly involved in telomere maintenance, DNA binding and repair mechanisms. As a conclusion, our results indicated that mir-145, through targeting its common potential targets, may significantly contribute to tumor pathogenesis in distinct cancer types and might serve as an important target for cancer therapy.

The genome and life-stage specific transcriptomes of Globodera pallida elucidate key aspects of plant parasitism by a cyst nematode.

PubMed

Cotton, James A; Lilley, Catherine J; Jones, Laura M; Kikuchi, Taisei; Reid, Adam J; Thorpe, Peter; Tsai, Isheng J; Beasley, Helen; Blok, Vivian; Cock, Peter J A; Eves-van den Akker, Sebastian; Holroyd, Nancy; Hunt, Martin; Mantelin, Sophie; Naghra, Hardeep; Pain, Arnab; Palomares-Rius, Juan E; Zarowiecki, Magdalena; Berriman, Matthew; Jones, John T; Urwin, Peter E

2014-03-03

Globodera pallida is a devastating pathogen of potato crops, making it one of the most economically important plant parasitic nematodes. It is also an important model for the biology of cyst nematodes. Cyst nematodes and root-knot nematodes are the two most important plant parasitic nematode groups and together represent a global threat to food security. We present the complete genome sequence of G. pallida, together with transcriptomic data from most of the nematode life cycle, particularly focusing on the life cycle stages involved in root invasion and establishment of the biotrophic feeding site. Despite the relatively close phylogenetic relationship with root-knot nematodes, we describe a very different gene family content between the two groups and in particular extensive differences in the repertoire of effectors, including an enormous expansion of the SPRY domain protein family in G. pallida, which includes the SPRYSEC family of effectors. This highlights the distinct biology of cyst nematodes compared to the root-knot nematodes that were, until now, the only sedentary plant parasitic nematodes for which genome information was available. We also present in-depth descriptions of the repertoires of other genes likely to be important in understanding the unique biology of cyst nematodes and of potential drug targets and other targets for their control. The data and analyses we present will be central in exploiting post-genomic approaches in the development of much-needed novel strategies for the control of G. pallida and related pathogens.

Parental Perspectives on a Behavioral Health Music Intervention for Adolescent/Young Adult Resilience during Cancer Treatment: Report from the Children’s Oncology Group

PubMed Central

Docherty, Sharron L.; Robb, Sheri L.; Phillips-Salimi, Celeste; Cherven, Brooke; Stegenga, Kristin; Hendricks-Ferguson, Verna; Roll, Lona; Stickler, Molly Donovan; Haase, Joan

2012-01-01

Purpose This paper describes parental perspectives on the helpfulness and meaningfulness of a behavioral health music therapy intervention targeted to adolescents/young adults (AYA) with cancer undergoing stem cell transplantation. We demonstrate how qualitative methods may be used to understand critical aspects of an intervention and mechanisms by which the intervention impacts the target AYA outcomes resilience and quality of life. Methods A qualitative descriptive design was used to obtain parents’ perspectives. Maximum variation purposive sampling was used to sample 16 parents whose AYA had been randomized to the intervention group. A semi-structured, open-ended interview was conducted between 100 and 160 days following their AYA’s transplant. Results Results are grouped into three categories: (1) helpfulness and meaningfulness of the intervention to AYA adjustment to the transplantation experience; (2) helpfulness and meaningfulness of the intervention for parents; and (3) AYA ability to participate in the intervention during acute phase of transplantation. Conclusions Parents observed and interacted with their AYA who participated in a targeted, behavioral intervention. Thus parents were able to describe mechanisms through which the intervention was helpful and meaningful for the AYA and indirect personal benefits for themselves. The results suggest the importance of the targeted outcomes identified in the Resilience in Illness Model and mechanisms of action in the Contextual Support Model of Music Therapy and identifies approaches for future study. PMID:23332481

Parental perspectives on a behavioral health music intervention for adolescent/young adult resilience during cancer treatment: report from the children's oncology group.

PubMed

Docherty, Sharron L; Robb, Sheri L; Phillips-Salimi, Celeste; Cherven, Brooke; Stegenga, Kristin; Hendricks-Ferguson, Verna; Roll, Lona; Donovan Stickler, Molly; Haase, Joan

2013-02-01

This article describes parental perspectives on the helpfulness and meaningfulness of a behavioral health music therapy intervention targeted to adolescents/young adults (AYA) with cancer undergoing stem cell transplantation. We demonstrate how qualitative methods may be used to understand critical aspects of an intervention and mechanisms by which the intervention impacts the target AYA outcomes of resilience and quality of life. A qualitative descriptive design was used to obtain parents' perspectives. A maximum-variation purposive sampling technique was used to sample 16 parents whose AYA had been randomized to the intervention group. A semistructured open-ended interview was conducted between 100 and 160 days after the AYA's transplant. Results were grouped into three categories: (1) helpfulness and meaningfulness of the intervention to AYA adjustment to the transplantation experience; (2) helpfulness and meaningfulness of the intervention for parents; and (3) AYA ability to participate in the intervention during the acute phase of transplant. Parents observed and interacted with their AYA who participated in a targeted behavioral intervention. Thus, parents were able to describe mechanisms through which the intervention was helpful and meaningful for the AYA and indirect personal benefits for themselves. The results suggest the importance of the targeted outcomes identified in the Resilience in Illness Model and mechanisms of action in the Contextual Support Model of Music Therapy, and identify approaches for future study. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Validating regulatory predictions from diverse bacteria with mutant fitness data

DOE PAGES

Sagawa, Shiori; Price, Morgan N.; Deutschbauer, Adam M.; ...

2017-05-24

Although transcriptional regulation is fundamental to understanding bacterial physiology, the targets of most bacterial transcription factors are not known. Comparative genomics has been used to identify likely targets of some of these transcription factors, but these predictions typically lack experimental support. Here, we used mutant fitness data, which measures the importance of each gene for a bacterium's growth across many conditions, to test regulatory predictions from RegPrecise, a curated collection of comparative genomics predictions. Because characterized transcription factors often have correlated fitness with one of their targets (either positively or negatively), correlated fitness patterns provide support for the comparative genomicsmore » predictions. At a false discovery rate of 3%, we identified significant cofitness for at least one target of 158 TFs in 107 ortholog groups and from 24 bacteria. Thus, high-throughput genetics can be used to identify a high-confidence subset of the sequence-based regulatory predictions.« less

Validating regulatory predictions from diverse bacteria with mutant fitness data

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

Sagawa, Shiori; Price, Morgan N.; Deutschbauer, Adam M.

Although transcriptional regulation is fundamental to understanding bacterial physiology, the targets of most bacterial transcription factors are not known. Comparative genomics has been used to identify likely targets of some of these transcription factors, but these predictions typically lack experimental support. Here, we used mutant fitness data, which measures the importance of each gene for a bacterium's growth across many conditions, to test regulatory predictions from RegPrecise, a curated collection of comparative genomics predictions. Because characterized transcription factors often have correlated fitness with one of their targets (either positively or negatively), correlated fitness patterns provide support for the comparative genomicsmore » predictions. At a false discovery rate of 3%, we identified significant cofitness for at least one target of 158 TFs in 107 ortholog groups and from 24 bacteria. Thus, high-throughput genetics can be used to identify a high-confidence subset of the sequence-based regulatory predictions.« less

Dual-Responsive Molecular Probe for Tumor Targeted Imaging and Photodynamic Therapy

PubMed Central

Meng, Xiaoqing; Yang, Yueting; Zhou, Lihua; Zhang, li; Lv, Yalin; Li, Sanpeng; Wu, Yayun; Zheng, Mingbin; Li, Wenjun; Gao, Guanhui; Deng, Guanjun; Jiang, Tao; Ni, Dapeng; Gong, Ping; Cai, Lintao

2017-01-01

The precision oncology significantly relies on the development of multifunctional agents to integrate tumor targeting, imaging and therapeutics. In this study, a first small-molecule theranostic probe, RhoSSCy is constructed by conjugating 5′-carboxyrhodamines (Rho) and heptamethine cyanine IR765 (Cy) using a reducible disulfide linker and pH tunable amino-group to realize thiols/pH dual sensing. In vitro experiments verify that RhoSSCy is highly sensitive for quantitative analysis and imaging intracellular pH gradient and biothiols. Furthermore, RhoSSCy shows superb tumor targeted dual-modal imaging via near-infrared fluorescence (NIRF) and photoacoustic (PA). Importantly, RhoSSCy also induces strongly reactive oxygen species for tumor photodynamic therapy (PDT) with robust antitumor activity both in vitro and in vivo. Such versatile small-molecule theranostic probe may be promising for tumor targeted imaging and precision therapy. PMID:28638467

The health information literacy research project.

PubMed

Shipman, Jean P; Kurtz-Rossi, Sabrina; Funk, Carla J

2009-10-01

This research studied hospital administrators' and hospital-based health care providers' (collectively, the target group) perceived value of consumer health information resources and of librarians' roles in promoting health information literacy in their institutions. A web-based needs survey was developed and administered to hospital administrators and health care providers. Multiple health information literacy curricula were developed. One was pilot-tested by nine hospital libraries in the United States and Canada. Quantitative and qualitative methods were used to evaluate the curriculum and its impact on the target group. A majority of survey respondents believed that providing consumer health information resources was critically important to fulfilling their institutions' missions and that their hospitals could improve health information literacy by increasing awareness of its impact on patient care and by training staff to become more knowledgeable about health literacy barriers. The study showed that a librarian-taught health information literacy curriculum did raise awareness about the issue among the target group and increased both the use of National Library of Medicine consumer health resources and referrals to librarians for health information literacy support. It is hoped that many hospital administrators and health care providers will take the health information literacy curricula and recognize that librarians can educate about the topic and that providers will use related consumer health services and resources.

The Health Information Literacy Research Project*

PubMed Central

Kurtz-Rossi, Sabrina; Funk, Carla J.

2009-01-01

Objectives: This research studied hospital administrators' and hospital-based health care providers' (collectively, the target group) perceived value of consumer health information resources and of librarians' roles in promoting health information literacy in their institutions. Methods: A web-based needs survey was developed and administered to hospital administrators and health care providers. Multiple health information literacy curricula were developed. One was pilot-tested by nine hospital libraries in the United States and Canada. Quantitative and qualitative methods were used to evaluate the curriculum and its impact on the target group. Results: A majority of survey respondents believed that providing consumer health information resources was critically important to fulfilling their institutions' missions and that their hospitals could improve health information literacy by increasing awareness of its impact on patient care and by training staff to become more knowledgeable about health literacy barriers. The study showed that a librarian-taught health information literacy curriculum did raise awareness about the issue among the target group and increased both the use of National Library of Medicine consumer health resources and referrals to librarians for health information literacy support. Conclusions: It is hoped that many hospital administrators and health care providers will take the health information literacy curricula and recognize that librarians can educate about the topic and that providers will use related consumer health services and resources. PMID:19851494

Polarized Solid State Target

NASA Astrophysics Data System (ADS)

Dutz, Hartmut; Goertz, Stefan; Meyer, Werner

2017-01-01

The polarized solid state target is an indispensable experimental tool to study single and double polarization observables at low intensity particle beams like tagged photons. It was one of the major components of the Crystal-Barrel experiment at ELSA. Besides the operation of the 'CB frozen spin target' within the experimental program of the Crystal-Barrel collaboration both collaborative groups of the D1 project, the polarized target group of the Ruhr Universität Bochum and the Bonn polarized target group, have made significant developments in the field of polarized targets within the CRC16. The Bonn polarized target group has focused its work on the development of technically challenging polarized solid target systems towards the so called '4π continuous mode polarized target' to operate them in combination with 4π-particle detection systems. In parallel, the Bochum group has developed various highly polarized deuterated target materials and high precision NMR-systems, in the meantime used for polarization experiments at CERN, JLAB and MAMI, too.

A Novel c-VEP BCI Paradigm for Increasing the Number of Stimulus Targets Based on Grouping Modulation With Different Codes.

PubMed

Wei, Qingguo; Liu, Yonghui; Gao, Xiaorong; Wang, Yijun; Yang, Chen; Lu, Zongwu; Gong, Huayuan

2018-06-01

In an existing brain-computer interface (BCI) based on code modulated visual evoked potentials (c-VEP), a method with which to increase the number of targets without increasing code length has not yet been established. In this paper, a novel c-VEP BCI paradigm, namely, grouping modulation with different codes that have good autocorrelation and crosscorrelation properties, is presented to increase the number of targets and information transfer rate (ITR). All stimulus targets are divided into several groups and each group of targets are modulated by a distinct pseudorandom binary code and its circularly shifting codes. Canonical correlation analysis is applied to each group for yielding a spatial filter and templates for all targets in a group are constructed based on spatially filtered signals. Template matching is applied to each group and the attended target is recognized by finding the maximal correlation coefficients of all groups. Based on the paradigm, a BCI with a total of 48 targets divided into three groups was implemented; 12 and 10 subjects participated in an off-line and a simulated online experiments, respectively. Data analysis of the offline experiment showed that the paradigm can massively increase the number of targets from 16 to 48 at the cost of slight compromise in accuracy (95.49% vs. 92.85%). Results of the simulated online experiment suggested that although the averaged accuracy across subjects of all three groups of targets was lower than that of a single group of targets (91.67% vs. 94.9%), the average ITR of the former was substantially higher than that of the later (181 bits/min vs. 135.6 bit/min) due to the large increase of the number of targets. The proposed paradigm significantly improves the performance of the c-VEP BCI, and thereby facilitates its practical applications such as high-speed spelling.

The effect of concurrent bandwidth feedback on learning the lane-keeping task in a driving simulator.

PubMed

de Groot, Stefan; de Winter, Joost C F; López García, José Manuel; Mulder, Max; Wieringa, Peter A

2011-02-01

The aim of this study was to investigate whether concurrent bandwidth feedback improves learning of the lane-keeping task in a driving simulator. Previous research suggests that bandwidth feedback improves learning and that off-target feedback is superior to on-target feedback. This study aimed to extend these findings for the lane-keeping task. Participants without a driver's license drove five 8-min lane-keeping sessions in a driver training simulator: three practice sessions, an immediate retention session, and a delayed retention session I day later. There were four experimental groups (n=15 per group): (a) on-target, receiving seat vibrations when the center of the car was within 0.5 m of the lane center; (b) off-target, receiving seat vibrations when the center of the car was more than 0.5 m away from the lane center; (c) control, receiving no vibrations; and (d) realistic, receiving seat vibrations depending on engine speed. During retention, all groups were provided with the realistic vibrations. During practice, on-target and off-target groups had better lane-keeping performance than the nonaugmented groups, but this difference diminished in the retention phase. Furthermore, during late practice and retention, the off-target group outperformed the on-target group.The off-target group had a higher rate of steering reversal and higher steering entropy than the nonaugmented groups, whereas no clear group differences were found regarding mean speed, mental workload, or self-reported measures. Off-target feedback is superior to on-target feedback for learning the lane-keeping task. This research provides knowledge to researchers and designers of training systems about the value of feedback in simulator-based training of vehicular control.

Cancer metabolism: strategic diversion from targeting cancer drivers to targeting cancer suppliers.

PubMed

Kim, Soo-Youl

2015-03-01

Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through the identification of more pharmaceutically viable targets, and yet major problems and risks associated with late-phase cancer therapy remain. Presently, a growing number of reports have initiated a discussion about the benefits of metabolic regulation in cancers. The Warburg effect, a great discovery approximately 70 years ago, addresses the "universality" of cancer characteristics. For instance, most cancer cells prefer aerobic glycolysis instead of mitochondrial respiration. Recently, cancer metabolism has been explained not only by metabolites but also through modern molecular and chemical biological techniques. Scientists are seeking context-dependent universality among cancer types according to metabolic and enzymatic pathway signatures. This review presents current cancer metabolism studies and discusses future directions in cancer therapy targeting bio-energetics, bio-anabolism, and autophagy, emphasizing the important contribution of cancer metabolism in cancer therapy.

Reliabilities of mental rotation tasks: limits to the assessment of individual differences.

PubMed

Hirschfeld, Gerrit; Thielsch, Meinald T; Zernikow, Boris

2013-01-01

Mental rotation tasks with objects and body parts as targets are widely used in cognitive neuropsychology. Even though these tasks are well established to study between-groups differences, the reliability on an individual level is largely unknown. We present a systematic study on the internal consistency and test-retest reliability of individual differences in mental rotation tasks comparing different target types and orders of presentations. In total n = 99 participants (n = 63 for the retest) completed the mental rotation tasks with hands, feet, faces, and cars as targets. Different target types were presented in either randomly mixed blocks or blocks of homogeneous targets. Across all target types, the consistency (split-half reliability) and stability (test-retest reliabilities) were good or acceptable both for intercepts and slopes. At the level of individual targets, only intercepts showed acceptable reliabilities. Blocked presentations resulted in significantly faster and numerically more consistent and stable responses. Mental rotation tasks-especially in blocked variants-can be used to reliably assess individual differences in global processing speed. However, the assessment of the theoretically important slope parameter for individual targets requires further adaptations to mental rotation tests.

α5-GABAA receptors negatively regulate MYC-amplified medulloblastoma growth

PubMed Central

Sengupta, Soma; Weeraratne, Shyamal Dilhan; Sun, Hongyu; Phallen, Jillian; Rallapalli, Sundari K.; Teider, Natalia; Kosaras, Bela; Amani, Vladimir; Pierre-Francois, Jessica; Tang, Yujie; Nguyen, Brian; Yu, Furong; Schubert, Simone; Balansay, Brianna; Mathios, Dimitris; Lechpammer, Mirna; Archer, Tenley C.; Tran, Phuoc; Reimer, Richard J.; Cook, James M.; Lim, Michael; Jensen, Frances E.; Pomeroy, Scott L.; Cho, Yoon-Jae

2013-01-01

Neural tumors often express neurotransmitter receptors as markers of their developmental lineage. Although these receptors have been well characterized in electrophysiological, developmental and pharmacological settings, their importance in the maintenance and progression of brain tumors, and importantly, the effect of their targeting in brain cancers remains obscure. Here, we demonstrate high levels of GABR5, which encodes the α-subunit of the GABAA receptor complex, in aggressive MYC-driven, “Group 3” medulloblastomas. We hypothesized that modulation of α-GABAA receptors alters medulloblastoma cell survival and monitored biological and electrophysiological responses of GABR5-expressing medulloblastoma cells upon pharmacological targeting of the GABAA receptor. While antagonists, inverse agonists and non-specific positive allosteric modulators had limited effects on medulloblastoma cells, a highly specific and potent α5-GABAA receptor agonist, QHii066, resulted in marked membrane depolarization and a significant decrease in cell survival. This effect was GABR5 dependent and mediated through the induction of apoptosis as well as accumulation of cells in S and G2 phases of the cell cycle. Chemical genomic profiling of QHii066-treated medulloblastoma cells confirmed inhibition of MYC-related transcriptional activity and revealed an enrichment of HOX5 target gene expression. siRNA-mediated knockdown of HOX5 markedly blunted the response of medulloblastoma cells to QHii066. Furthermore, QHii066 sensitized GABR5 positive medulloblastoma cells to radiation and chemotherapy consistent with the role of HOX5 in directly regulating p53 expression and inducing apoptosis. Thus, our results provide novel insights into the synthetic lethal nature of α5-GABAA receptor activation in MYC-driven/Group 3 medulloblastomas and propose its targeting as a novel strategy for the management of this highly aggressive tumor. PMID:24196163

Genetic landscape and deregulated pathways in B-cell lymphoid malignancies.

PubMed

Rosenquist, R; Beà, S; Du, M-Q; Nadel, B; Pan-Hammarström, Q

2017-11-01

With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma. We will detail recurrent alterations affecting important signalling pathways, that is the B-cell receptor/NF-κB pathway, NOTCH signalling, JAK-STAT signalling, p53/DNA damage response, apoptosis and cell cycle regulation, as well as other perhaps unexpected cellular processes, such as immune regulation, cell migration, epigenetic regulation and RNA processing. Whilst many of these pathways/processes are commonly altered in different lymphoid tumors, albeit at varying frequencies, others are preferentially targeted in selected B-cell malignancies. Some of these genetic lesions are either involved in disease ontogeny or linked to the evolution of each disease and/or specific clinicobiological features, and some of them have been demonstrated to have prognostic and even predictive impact. Future work is especially needed to understand the therapy-resistant disease, particularly in patients treated with targeted therapy, and to identify novel targets and therapeutic strategies in order to realize true precision medicine in this clinically heterogeneous patient group. © 2017 The Association for the Publication of the Journal of Internal Medicine.

MiR-422a as a Potential Cellular MicroRNA Biomarker for Postmenopausal Osteoporosis

PubMed Central

Cao, Zheng; Moore, Benjamin T.; Wang, Yang; Peng, Xian-Hao; Lappe, Joan M.; Recker, Robert R.; Xiao, Peng

2014-01-01

Background MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis. Methodology/Principal Findings We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression. Conclusions/Significance Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis. PMID:24820117

MiR-422a as a potential cellular microRNA biomarker for postmenopausal osteoporosis.

PubMed

Cao, Zheng; Moore, Benjamin T; Wang, Yang; Peng, Xian-Hao; Lappe, Joan M; Recker, Robert R; Xiao, Peng

2014-01-01

MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis. We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression. Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis.

Placing and preserving priorities: projects, productivity, progress and people

PubMed Central

Babiak, John

1998-01-01

High throughput screening (HTS) involves using automated equipment to test a large number of samples against a defined molecular target to identify a reasonable number of active molecules in a timely fashion. Major factors which can influence priorities for the limited resources of the HTS group are projects, productivity, progress and people. The challenge to the HTS group is to provide excellent and timely screening services, but still devote efforts to new technologies and personnel development. This article explains why these factors are so important. PMID:18924829

Computational exploration of zinc binding groups for HDAC inhibition.

PubMed

Chen, Kai; Xu, Liping; Wiest, Olaf

2013-05-17

Histone deacetylases (HDACs) have emerged as important drug targets in epigenetics. The most common HDAC inhibitors use hydroxamic acids as zinc binding groups despite unfavorable pharmacokinetic properties. A two-stage protocol of M05-2X calculations of a library of 48 fragments in a small model active site, followed by QM/MM hybrid calculations of the full enzyme with selected binders, is used to prospectively select potential bidentate zinc binders. The energetics and interaction patterns of several zinc binders not previously used for the inhibition of HDACs are discussed.

Representing target motion: the role of the right hemisphere in the forward displacement bias.

PubMed

McGeorge, Peter; Beschin, Nicoletta; Della Sala, Sergio

2006-11-01

Patients with left spatial neglect, patients with right hemisphere damage but no neglect, and a control group were asked to judge the final position of a series of moving targets. Both patient groups showed attentional deficits. All 3 groups demonstrated a forward displacement bias, overestimating the final target position along the object trajectory. However, in both patient groups the size of this forward displacement bias decreased as the distance the target traveled before vanishing increased. For horizontally moving targets, at the maximum distance only the control group showed significant forward displacement. For all 3 groups, the direction in which the target traveled had no influence, but the size of the forward displacement increased as target speed increased. Several attentional explanations of these results are considered, including the differential allocation of spatial attention between central and peripheral locations, differences between exogenous and endogenous attention, and deficits in sustained attention.

Intercepting moving targets: does memory from practice in a specific condition of target displacement affect movement timing?

PubMed

de Azevedo Neto, Raymundo Machado; Teixeira, Luis Augusto

2011-05-01

This investigation aimed at assessing the extent to which memory from practice in a specific condition of target displacement modulates temporal errors and movement timing of interceptive movements. We compared two groups practicing with certainty of future target velocity either in unchanged target velocity or in target velocity decrease. Following practice, both experimental groups were probed in the situations of unchanged target velocity and target velocity decrease either under the context of certainty or uncertainty about target velocity. Results from practice showed similar improvement of temporal accuracy between groups, revealing that target velocity decrease did not disturb temporal movement organization when fully predictable. Analysis of temporal errors in the probing trials indicated that both groups had higher timing accuracy in velocity decrease in comparison with unchanged velocity. Effect of practice was detected by increased temporal accuracy of the velocity decrease group in situations of decreased velocity; a trend consistent with the expected effect of practice was observed for temporal errors in the unchanged velocity group and in movement initiation at a descriptive level. An additional point of theoretical interest was the fast adaptation in both groups to a target velocity pattern different from that practiced. These points are discussed under the perspective of integration of vision and motor control by means of an internal forward model of external motion.

Beta oscillatory responses in healthy subjects and subjects with mild cognitive impairment☆

PubMed Central

Güntekin, Bahar; Emek-Savaş, Derya Durusu; Kurt, Pınar; Yener, Görsev Gülmen; Başar, Erol

2013-01-01

The aim of the present study was to investigate the role of beta oscillatory responses upon cognitive load in healthy subjects and in subjects with mild cognitive impairment (MCI). The role of beta oscillations upon cognitive stimulation is least studied in comparison to other frequency bands. The study included 17 consecutive patients with MCI (mean age = 70.8 ± 5.6 years) according to Petersen's criteria, and 17 age- and education-matched normal elderly controls (mean age = 68.5 ± 5.5 years). The experiments used a visual oddball paradigm. EEG was recorded at 30 cortical locations. EEG-evoked power, inter-trial phase synchronization, and event-related beta responses filtered in 15–20 Hz were obtained in response to target and non-target stimuli for both groups of subjects. In healthy subjects, EEG-evoked beta power, inter-trial phase synchronization of beta responses and event-related filtered beta responses were significantly higher in responses to target than non-target stimuli (p < 0.05). In MCI patients, there were no differences in evoked beta power between target and non-target stimuli. Furthermore, upon presentation of visual oddball paradigm, occipital electrodes depict higher beta response in comparison to other electrode sites. The increased beta response upon presentation of target stimuli in healthy subjects implies that beta oscillations could shift the system to an attention state, and had important function in cognitive activity. This may, in future, open the way to consider beta activity as an important operator in brain cognitive processes. PMID:24179847

Using Social Cognitive Theory to Predict Safer Sex Behaviors in African American College Students

ERIC Educational Resources Information Center

Kanekar, Amar; Sharma, Manoj

2009-01-01

Safer sex is important for protection against STDs and HIV/AIDS. Most of the HIV-related research is targeted towards high-risk groups such as prostitutes, gays and substance abusers there is evidence that HIV/AIDS is increasing in college students particularly among African-American college students. The purpose of this study was to study…

Centro de Biologia Molecular "Severo Ochoa": a center for basic research into Alzheimer's disease.

PubMed

Avila, Jesus; Hernandez, Felix; Wandosell, Francisco; Lucas, Jose J; Esteban, Jose A; Ledesma, M Dolores; Bullido, Maria J

2010-01-01

One important aspect of studies carried out at the Center for Molecular Biology "Severo Ochoa" is focused on basic aspects of Alzheimer's disease, mainly the search for suitable therapeutic targets for this disorder. Several groups at the Center are involved in these studies, and, in this spotlight, the work they are carrying out will be described.

Social Participation and Health among Ageing People in East-Central Europe

ERIC Educational Resources Information Center

Makai, Alexandra; Prémusz, Viktória; Füge, Kata; Figler, Mária; Lampek, Kinga

2015-01-01

In this study we examined the health of the ageing population of East-Central Europe. Data derived from the 6th round of the European Social Survey. The aim of our research was to examine the most important factors that determine ageing people's health status. We paid particular attention to the social ties of our target group.

Substance Use: Determinants and Opportunities for Prevention in the Family and School Context

ERIC Educational Resources Information Center

Kleinjan, Marloes; Engels, Rutger C. M. E.

2014-01-01

During adolescence, teenagers try a range of risk behaviors including smoking, drinking, and the use of soft drugs. Because substance use contributes to an unhealthy lifestyle of teenagers on the short term and can lead to serious health problems on the longer term, prevention in this target group is important. This chapter provides an overview of…

Planning Continuing Education to Meet the Needs of Nurses: Diabetes Mellitus Programs.

ERIC Educational Resources Information Center

Heller, Debbie Ransom; Brown, Sylvia J.

1983-01-01

It is critical for nurses to be aware of changing treatment strategies and new research developments in the field of diabetes. This is important so that nurses can respond to patient questions as well as, in some cases, modify their actual patient care approach. Thus, nurses are a vital target group for diabetes continuing education programs. (SSH)

Therapeutic hypothermia for out-of-hospital ventricular fibrillation survivors: a feasibility study comparing time to achieve target core temperature using conventional conductive cooling versus combined conductive plus pericranial convective cooling.

PubMed

Wass, C Thomas; White, Roger D; Schroeder, Darrell R; Mirzoyev, Sultan A; Warfield, Karen T

2013-04-01

Mild to moderate therapeutic hypothermia (TH) has been shown to improve survival and neurologic outcome, as well as to reduce healthcare costs in patients resuscitated from out-of-hospital cardiac arrest (OHCA) with ventricular fibrillation. Accordingly, the American Heart Association has categorized this as a Class IB intervention. The therapeutic window for initiating TH is narrow, and thus, achieving target temperature expeditiously is of paramount importance to improve postresuscitative neurologic outcome. The present investigation is a feasibility study designed to assess the practicality and efficacy of including pericranial cooling in our postresuscitative TH protocol. Specifically, we compared time required to achieve target temperature (33°C) using our present standard of TH care (ie, conductive body cooling, conventional TH group) versus combined conductive body cooling plus convective (forced-air) head and neck cooling (combined TH group). Adult patients who experienced OHCA were included in the study provided TH could be initiated within 4 hours of resuscitation from ventricular fibrillation. Patients enrolled in both groups were cooled using the servo-controlled Arctic Sun conductive cooling system (Medivance, Inc, Louisville, CO). However, patients enrolled in the combined TH group also received forced-air pericranial cooling with an ambient temperature of approximately 13°C. In all cases, the target core (bladder) temperature was 33°C. The primary endpoint (ie, time required to achieve a core temperature of 33°C) was analyzed as a continuous variable and compared between groups using the rank sum test, whereas categorical variables were compared between groups using the chi-square test. Cardiac intensive care unit at a major tertiary care teaching center in Rochester, MN. Adult patients who experienced OHCA were included in the study. Patients enrolled in both groups were cooled using the servo-controlled Arctic Sun conductive cooling system (Medivance, Inc, Louisville, CO). However, patients enrolled in the combined TH group also received forced-air pericranial cooling with an ambient temperature of approximately 13°C. Only patients admitted after January 1, 2008, were included in the analysis (28 combined TH group patients v 55 conventional TH group patients). Demographic data were similar between groups. When compared with the conventional TH group, time to achieve 33°C was significantly shorter in the combined TH group: 207 minutes (173 and 286 min) [median (25th, 75th percentile)] v 181 minutes (63 and 247 min). The magnitude and frequency of hypothermia-mediated physiologic perturbations (eg, hypokalemia) were similar for both groups. Both TH cooling paradigms effectively achieved 33°C; however, the combined TH technique significantly decreased the time required to achieve the target temperature. Although not evaluated in this study, such an effect may further improve postresuscitative neurologic outcomes beyond that previously described using conventional TH. Although a positive result (ie, abbreviated time taken to achieve target temperature) was observed, we maintain guarded enthusiasm for this evolving adjunctive technique until corroborative outcome-based evidence is available. Copyright © 2013 Elsevier Inc. All rights reserved.

Sources of perceived responsiveness in family relationships.

PubMed

Cook, William L; Dezangré, Marie; De Mol, Jan

2018-05-10

Perceived responsiveness has become one of the most important constructs in the relationship sciences. It is central to the development of a secure attachment style, the experience of social support, an internal locus of control, and the sense of control in close relationships. Conversely, an unresponsive environment is associated with learned helplessness and depression. Viewed through the lens of the social relations model (SRM), perceived responsiveness in family relationships could have multiple sources: the perceiver; the target or partner; the perceiver-target relationship; and the family group. This study used the SRM to determine the relative importance of these sources of perceived responsiveness in the relationships of 207 two-parent two-child families. Characteristics of the perceiver and the target each accounted for about 25% of the systematic variance in perceived responsiveness, whereas the perceiver-target relationship accounted for approximately 48%. At the individual level of analysis, reciprocity of perceived responsiveness was pervasive in the family relationships of the two children. Regardless of age, young people who generally perceived others as responsive were generally perceived by others as responsive. At the dyadic level of analysis, reciprocity was present in two dyads: mother-father and older child-younger child. Reliable target variances support the view that perceived responsiveness is not just "inside the head" of the perceiver, and reciprocity correlations suggest potentially useful systemic interventions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

16S rRNA beacons for bacterial monitoring during human space missions.

PubMed

Larios-Sanz, Maia; Kourentzi, Katerina D; Warmflash, David; Jones, Jeffrey; Pierson, Duane L; Willson, Richard C; Fox, George E

2007-04-01

Microorganisms are unavoidable in space environments and their presence has, at times, been a source of problems. Concerns about disease during human space missions are particularly important considering the significant changes the immune system incurs during spaceflight and the history of microbial contamination aboard the Mir space station. Additionally, these contaminants may have adverse effects on instrumentation and life-support systems. A sensitive, highly specific system to detect, characterize, and monitor these microbial populations is essential. Herein we describe a monitoring approach that uses 16S rRNA targeted molecular beacons to successfully detect several specific bacterial groupings. This methodology will greatly simplify in-flight monitoring by minimizing sample handling and processing. We also address and provide solutions to target accessibility problems encountered in hybridizations that target 16S rRNA.

Protein S-nitrosylation as a therapeutic target for neurodegenerative diseases

PubMed Central

Nakamura, Tomohiro; Lipton, Stuart A.

2015-01-01

At physiological levels, nitric oxide (NO) contributes to the maintenance of normal neuronal activity and survival, thus serving as an important regulatory mechanism in the central nervous system. In contrast, accumulating evidence suggests that exposure to environmental toxins or the normal aging process can trigger excessive production of reactive oxygen/nitrogen species (such as NO), contributing to the etiology of several neurodegenerative diseases. Here we highlight protein S-nitrosylation, resulting from covalent attachment of an NO group to a cysteine thiol of the target protein, as a ubiquitous effector of NO signaling in both health and disease. We review our current understanding of this redox-dependent posttranslational modification under neurodegenerative conditions, and evaluate how targeting dysregulated protein S-nitrosylation can lead to novel therapeutics. PMID:26707925

Adolescents Can Know Best: Using concept mapping to identify factors and pathways driving adolescent sexuality in Lima, Peru

PubMed Central

Bayer, Angela M.; Cabrera, Lilia Z.; Gilman, Robert H.; Hindin, Michelle J.; Tsui, Amy O.

2011-01-01

The primary objective of this study was to identify and describe individual- and environmental-level factors that Peruvian adolescents perceive to be related to adolescent sexuality. A series of concept mapping sessions were carried out from January-March 2006 with 63 15–17 year olds from a low-income community near Lima in order for adolescents to (1) brainstorm items that they thought were related to sexuality (2) sort, group and rate items to score their importance for sexuality-related outcomes, and (3) create pathways from the groups of items to engaging in sex. Brainstorming resulted in 61 items, which participants grouped into 11 clusters. The highest rated clusters were personal values, respect and confidence in relationships, future achievements and parent-child communication. The pathway of decision-making about having sex primarily contained items rated as only moderately important. This study identified important understudied factors, new perspectives on previously-recognized factors, and possible pathways to sexual behavior. These interesting, provocative findings underscore the importance of directly integrating adolescent voices into future sexual and reproductive health research, policies and programs that target this population. PMID:20382462

High-Throughput Sequencing Identifies MicroRNAs from Posterior Intestine of Loach (Misgurnus anguillicaudatus) and Their Response to Intestinal Air-Breathing Inhibition.

PubMed

Huang, Songqian; Cao, Xiaojuan; Tian, Xianchang; Wang, Weimin

2016-01-01

MicroRNAs (miRNAs) exert important roles in animal growth, immunity, and development, and regulate gene expression at the post-transcriptional level. Knowledges about the diversities of miRNAs and their roles in accessory air-breathing organs (ABOs) of fish remain unknown. In this work, we used high-throughput sequencing to identify known and novel miRNAs from the posterior intestine, an important ABO, in loach (Misgurnus anguillicaudatus) under normal and intestinal air-breathing inhibited conditions. A total of 204 known and 84 novel miRNAs were identified, while 47 miRNAs were differentially expressed between the two small RNA libraries (i.e. between the normal and intestinal air-breathing inhibited group). Potential miRNA target genes were predicted by combining our transcriptome data of the posterior intestine of the loach under the same conditions, and then annotated using COG, GO, KEGG, Swissprot and Nr databases. The regulatory networks of miRNAs and their target genes were analyzed. The abundances of nine known miRNAs were validated by qRT-PCR. The relative expression profiles of six known miRNAs and their eight corresponding target genes, and two novel potential miRNAs were also detected. Histological characteristics of the posterior intestines in both normal and air-breathing inhibited group were further analyzed. This study contributes to our understanding on the functions and molecular regulatory mechanisms of miRNAs in accessory air-breathing organs of fish.

Elective Clinical Target Volumes for Conformal Therapy in Anorectal Cancer: A Radiation Therapy Oncology Group Consensus Panel Contouring Atlas

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

Myerson, Robert J.; Garofalo, Michael C.; El Naqa, Issam

2009-07-01

Purpose: To develop a Radiation Therapy Oncology Group (RTOG) atlas of the elective clinical target volume (CTV) definitions to be used for planning pelvic intensity-modulated radiotherapy (IMRT) for anal and rectal cancers. Methods and Materials: The Gastrointestinal Committee of the RTOG established a task group (the nine physician co-authors) to develop this atlas. They responded to a questionnaire concerning three elective CTVs (CTVA: internal iliac, presacral, and perirectal nodal regions for both anal and rectal case planning; CTVB: external iliac nodal region for anal case planning and for selected rectal cases; CTVC: inguinal nodal region for anal case planning andmore » for select rectal cases), and to outline these areas on individual computed tomographic images. The imaging files were shared via the Advanced Technology Consortium. A program developed by one of the co-authors (I.E.N.) used binomial maximum-likelihood estimates to generate a 95% group consensus contour. The computer-estimated consensus contours were then reviewed by the group and modified to provide a final contouring consensus atlas. Results: The panel achieved consensus CTV definitions to be used as guidelines for the adjuvant therapy of rectal cancer and definitive therapy for anal cancer. The most important difference from similar atlases for gynecologic or genitourinary cancer is mesorectal coverage. Detailed target volume contouring guidelines and images are discussed. Conclusion: This report serves as a template for the definition of the elective CTVs to be used in IMRT planning for anal and rectal cancers, as part of prospective RTOG trials.« less

Region segmentation and contextual cuing in visual search.

PubMed

Conci, Markus; von Mühlenen, Adrian

2009-10-01

Contextual information provides an important source for behavioral orienting. For instance, in the contextual-cuing paradigm, repetitions of the spatial layout of elements in a search display can guide attention to the target location. The present study explored how this contextual-cuing effect is influenced by the grouping of search elements. In Experiment 1, four nontarget items could be arranged collinearly to form an imaginary square. The presence of such a square eliminated the contextual-cuing effect, despite the fact that the square's location still had a predictive value for the target location. Three follow-up experiments demonstrated that other types of grouping abolished contextual cuing in a similar way and that the mere presence of a task-irrelevant singleton had only a diminishing effect (by half) on contextual cuing. These findings suggest that a segmented, salient region can interfere with contextual cuing, reducing its predictive impact on search.

Recommendations from the Spanish Oncology Genitourinary Group for the treatment of metastatic renal cancer.

PubMed

Bellmunt, Joaquim; Calvo, Emiliano; Castellano, Daniel; Climent, Miguel Angel; Esteban, Emilio; García del Muro, Xavier; González-Larriba, José Luis; Maroto, Pablo; Trigo, José Manuel

2009-03-01

For almost the last two decades, interleukin-2 and interferon-alpha have been the only systemic treatment options available for metastatic renal cell carcinoma. However, in recent years, five new targeted therapies namely sunitinib, sorafenib, temsirolimus, everolimus and bevacizumab have demonstrated clinical activity in these patients. With the availability of new targeted agents that are active in this disease, there is a need to continuously update the treatment algorithm of the disease. Due to the important advances obtained, the Spanish Oncology Genitourinary Group (SOGUG) has considered it would be useful to review the current status of the disease, including the genetic and molecular biology factors involved, the current predicting models for development of metastases as well as the role of surgery, radiotherapy and systemic therapies in the early- or late management of the disease. Based on this previous work, a treatment algorithm was developed.

Evidence for a young adult-targeted tobacco control campaign stimulating cessation-related responses among adult smokers and recent quitters.

PubMed

Li, Judy; Guiney, Hayley; Walton, Darren

2016-02-19

Young adults are an important group for tobacco control interventions because of their high smoking prevalence. In 2014, New Zealand launched a young adult-targeted tobacco control campaign: 'Stop Before You Start'. The evaluation undertaken with young adults (aged 18 to 24 years) showed that the campaign exerted positive impacts on this age group. This study aimed to investigate the collateral effects of this campaign on older adults. Data were collected from a fortnightly survey of adult smokers and recent quitters, where respondents were maintained on a panel and interviewed every fortnight, up to six times. This paper reports on data collected over three consecutive fortnights (540 interviews). Ten measures were used to assess campaign effectiveness (eg, felt regret, tried to quit). After adjusting for recent quit attempt status and socio-demographic characteristics, age differences were not found in any of the outcome variables (aged 25-44 years and 45+ years were compared against 18-24 years). Internationally, little is known about the effectiveness of young adult-targeted tobacco control campaigns. Alongside data from the campaign evaluation with young adults, findings from the current study suggest that this young adult-targeted campaign also created a desirable impact on older adults.

Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents.

PubMed

Abed, Dhulfiqar Ali; Goldstein, Melanie; Albanyan, Haifa; Jin, Huijuan; Hu, Longqin

2015-07-01

The Keap1-Nrf2-ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1-Nrf2 protein-protein interaction (PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1-Nrf2 PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1׳s cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1-Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1-Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.

Birth outcomes across ethnic groups of women in Nepal.

PubMed

Acharya, Pratima Poudel; Alpass, Fiona

2004-01-01

This study was conducted at the Western Regional Hospital (WRH), Pokhara, Nepal. We investigated the relationship between selected socioeconomic variables, pregnancy indices, birth weight, and maternal health in women of different ethnic origins. In our cross-sectional data set, 29.8% of infants were born with a low birth weight. Our data analysis showed Indo-Aryan and lower caste ethnic groups had significantly lower weight babies than Tibeto-Burman and Newar groups. Further analysis showed that the Tibeto-Burman group received better care during pregnancy. Similarly, the Newar groups had significantly better nutritional intake than the Indo-Aryan and lower caste groups. The outcome of food restriction and antenatal care during pregnancy in specific ethnic groups has important implications for the health care delivery system. Health policymakers should target those ethnic groups and develop culturally based policies to reduce the incidence of low birth weight in Nepal.

Conducting Ethical Evaluations with Disadvantaged and Minority Target Groups.

ERIC Educational Resources Information Center

English, Brian

1997-01-01

This paper examines issues involved in conducting evaluations when participation by the target groups, typically minorities and disadvantaged groups, may put them in jeopardy. Argues that participation by target groups as cooperative partners throughout the evaluation is a way of addressing this dilemma. (SLD)

Targeted subsidy for malaria control with treated nets using a discount voucher system in Tanzania.

PubMed

Mushi, Adiel K; Schellenberg, Joanna R M Armstrong; Mponda, Haji; Lengeler, Christian

2003-06-01

During the last decade insecticide-treated nets have become a key strategy for malaria control. Social marketing is an appealing tool for getting such nets to poor rural African communities who are most afflicted by malaria. This approach usually involves subsidized prices to make nets and insecticide more affordable and help establish a commercial market. We evaluated a voucher system for targeted subsidy of treated nets in young children and pregnant women in two rural districts of southern Tanzania. Qualitative work involved focus group discussions with community leaders, male and female parents of children under 5 years. In-depth interviews were held with maternal and child health clinic staff and retail agents. Quantitative data were collected through interviewing more than 750 mothers of children under 5 years during a cluster sample survey of child health. The voucher return rate was extremely high at 97% (7720/8000). However, 2 years after the start of the scheme awareness among target groups was only 43% (45/104), and only 12% of women (12/103; 95% CI 4-48%) had used a voucher towards the cost of a net. We found some evidence of increased voucher use among least poor households, compared with the poorest households. On the basis of these results we renewed our information, education and communication (IEC) campaign about vouchers. Discount vouchers are a feasible system for targeted subsidies, although a substantial amount of time and effort may be needed to achieve high awareness and uptake - by which we mean the proportion of eligible women who used the vouchers - among those targeted. Within a poor society, vouchers may not necessarily increase health equity unless they cover a high proportion of the total cost: since some cash is needed when using a voucher as part-payment, poorer women among the target group are likely to have lower uptake than richer women. The vouchers have two important additional functions: strengthening the role of public health services in the context of a social marketing programme and forming an IEC tool to demonstrate the group at most risk of severe malaria.

Origin, evolution and function of the hemipteran perimicrovillar membrane with emphasis on Reduviidae that transmit Chagas disease.

PubMed

Gutiérrez-Cabrera, A E; Córdoba-Aguilar, A; Zenteno, E; Lowenberger, C; Espinoza, B

2016-06-01

The peritrophic matrix is a chitin-protein structure that envelops the food bolus in the midgut of the majority of insects, but is absent in some groups which have, instead, an unusual extra-cellular lipoprotein membrane named the perimicrovillar membrane. The presence of the perimicrovillar membrane (PMM) allows these insects to exploit restricted ecological niches during all life stages. It is found only in some members of the superorder Paraneoptera and many of these species are of medical and economic importance. In this review we present an overview of the midgut and the digestive system of insects with an emphasis on the order Paraneoptera and differences found across phylogenetic groups. We discuss the importance of the PMM in Hemiptera and the apparent conservation of this structure among hemipteran groups, suggesting that the basic mechanism of PMM production is the same for different hemipteran species. We propose that the PMM is intimately involved in the interaction with parasites and as such should be a target for biological and chemical control of hemipteran insects of economic and medical importance.

Assessing the relative importance of correlates of loneliness in later life. Gaining insight using recursive partitioning.

PubMed

Ejlskov, Linda; Wulff, Jesper; Bøggild, Henrik; Kuh, Diana; Stafford, Mai

2017-09-08

Improving the design and targeting of interventions is important for alleviating loneliness among older adults. This requires identifying which correlates are the most important predictors of loneliness. This study demonstrates the use of recursive partitioning in exploring the characteristics and assessing the relative importance of correlates of loneliness in older adults. Using exploratory regression trees and random forests, we examined combinations and the relative importance of 42 correlates in relation to loneliness at age 68 among 2453 participants from the birth cohort study the MRC National Survey of Health and Development. Positive mental well-being, personal mastery, identifying the spouse as the closest confidant, being extrovert and informal social contact were the most important correlates of lower loneliness levels. Participation in organised groups and demographic correlates were poor identifiers of loneliness. The regression tree suggested that loneliness was not raised among those with poor mental wellbeing if they identified their partner as closest confidante and had frequent social contact. Recursive partitioning can identify which combinations of experiences and circumstances characterise high-risk groups. Poor mental wellbeing and sparse social contact emerged as especially important and classical demographic factors as insufficient in identifying high loneliness levels among older adults.

The effects of impairments on employment and wages: estimates from the 1984 and 1990 SIPP.

PubMed

Baldwin, M L

1999-01-01

Unlike the minority groups covered by civil rights laws in the past, the disabled population is a heterogeneous group. Because of differences in the nature and onset of health conditions, it is important to study the labor market experiences of different impairment groups separately, rather than treating "disabled workers" as a single group. This article uses data from the 1984 and the 1990 panels of the Survey of Income and Program Participation to analyze trends in the employment and wages of six impairment groups in the years immediately preceding the ADA. The results confirm the diversity of labor market experiences within the disabled population and suggest that policies designed to improve labor market outcomes for workers with disabilities in response to the ADA should be targeted to the different needs of different impairment groups.

Substance Abuse Prevention.

PubMed

LeNoue, Sean R; Riggs, Paula D

2016-04-01

Substance use disorders account for approximately 6% of deaths worldwide and cost about $700 billion in the United States. Approximately 80% of drug users begin using during adolescence, underscoring the public health importance of effective substance prevention programs for youth and families. Prevention science designates 3 intervention categories: (1) universal prevention, targeting all individuals in the population, (2) selective interventions, targeting high-risk groups, and (3) indicated prevention interventions for youth with risk-taking behaviors. School-based and non-school-based interventions are reviewed, as well as the limitations of existing research, gaps in access and availability, and directions for future research and development. Copyright © 2016 Elsevier Inc. All rights reserved.

Non-compact nonlinear sigma models

NASA Astrophysics Data System (ADS)

de Rham, Claudia; Tolley, Andrew J.; Zhou, Shuang-Yong

2016-09-01

The target space of a nonlinear sigma model is usually required to be positive definite to avoid ghosts. We introduce a unique class of nonlinear sigma models where the target space metric has a Lorentzian signature, thus the associated group being non-compact. We show that the would-be ghost associated with the negative direction is fully projected out by 2 second-class constraints, and there exist stable solutions in this class of models. This result also has important implications for Lorentz-invariant massive gravity: There exist stable nontrivial vacua in massive gravity that are free from any linear vDVZ-discontinuity and a Λ2 decoupling limit can be defined on these vacua.

Beyond the "general public": implications of audience characteristics for promoting species conservation in the Western Ghats hotspot, India.

PubMed

Kanagavel, Arun; Raghavan, Rajeev; Veríssimo, Diogo

2014-03-01

Understanding how different audience groups perceive wildlife is crucial for the promotion of biodiversity conservation, especially given the key role of flagship species in conservation campaigns. Although the heterogeneity in preferences reinforces the need for campaigns tailored to specific target audiences, many conservation education and awareness campaigns still claim to target the "general public". Audiences can be segmented according to social, economic, and cultural criteria across which species perceptions are known to vary. Different studies have investigated the preferences of different groups towards certain wildlife species, but these are largely confined to a single conservation stakeholder group, such as tourists, local communities, or potential donors in western countries. In this study, we seek to determine from a multi-stakeholder perspective, audience characteristics that influence perceptions towards wildlife at Valparai, a fragmented plateau in the Western Ghats region of the Western Ghats-Sri Lanka Hotspot. We found that stakeholder group membership was the most important characteristic followed by gender. While some characteristics had a wide-scale effect others were restricted to a few species. Our results emphasize the need to design conservation campaigns with specific audiences in mind, instead of the very often referred to "general public".

Glycogenomics as a mass spectrometry-guided genome-mining method for microbial glycosylated molecules.

PubMed

Kersten, Roland D; Ziemert, Nadine; Gonzalez, David J; Duggan, Brendan M; Nizet, Victor; Dorrestein, Pieter C; Moore, Bradley S

2013-11-19

Glycosyl groups are an essential mediator of molecular interactions in cells and on cellular surfaces. There are very few methods that directly relate sugar-containing molecules to their biosynthetic machineries. Here, we introduce glycogenomics as an experiment-guided genome-mining approach for fast characterization of glycosylated natural products (GNPs) and their biosynthetic pathways from genome-sequenced microbes by targeting glycosyl groups in microbial metabolomes. Microbial GNPs consist of aglycone and glycosyl structure groups in which the sugar unit(s) are often critical for the GNP's bioactivity, e.g., by promoting binding to a target biomolecule. GNPs are a structurally diverse class of molecules with important pharmaceutical and agrochemical applications. Herein, O- and N-glycosyl groups are characterized in their sugar monomers by tandem mass spectrometry (MS) and matched to corresponding glycosylation genes in secondary metabolic pathways by a MS-glycogenetic code. The associated aglycone biosynthetic genes of the GNP genotype then classify the natural product to further guide structure elucidation. We highlight the glycogenomic strategy by the characterization of several bioactive glycosylated molecules and their gene clusters, including the anticancer agent cinerubin B from Streptomyces sp. SPB74 and an antibiotic, arenimycin B, from Salinispora arenicola CNB-527.

Limited generalization with varied, as compared to specific, practice in short-term motor learning.

PubMed

Willey, Chéla R; Liu, Zili

2018-01-01

The schema theory of learning predicts that varied training in motor learning should give rise to better transfer than specific training. For example, throwing beanbags during practice to targets 5 and 9ft away should better generalize to targets 7 and 11ft away, as compared to only throwing to a target 7ft away. In this study, we tested this prediction in a throwing task, when the pretest, practice, and posttest were all completed within an hour. Participants in the varied group practiced throwing at 5 and 9ft targets, while participants in the specific group practiced throwing at 7ft only. All participants reliably reduced errors from pretest to posttest. The varied group never outperformed the specific group at the 7ft target (the trained target for the specific group). They did not reliably outperform the specific group at 11ft, either. The numerically better performance at 11ft by the varied group was due, as it turned out in a subsequent experiment, to the fact that 11ft was closer to 9ft (one of the two training targets for the varied group) than to 7ft (the training target for the specific group). We conclude that varied training played a very limited role in short-term motor learning. Copyright © 2017 Elsevier B.V. All rights reserved.

Factors affecting acceptability of an email-based intervention to increase fruit and vegetable consumption.

PubMed

Kothe, Emily J; Mullan, Barbara A

2014-09-30

Fresh Facts is a 30-day email-delivered intervention designed to increase the fruit and vegetable consumption of Australian young adults. This study investigated the extent to which the program was acceptable to members of the target audience and examined the relationships between participant and intervention characteristics, attrition, effectiveness, and acceptability ratings. Young adults were randomised to two levels of message frequency: high-frequency (n = 102), low-frequency (n = 173). Individuals in the high-frequency group received daily emails while individuals in the low-frequency group received an email every 3 days. Individuals in the high-frequency group were more likely to indicate that they received too many emails than individuals in the low-frequency group. No other differences in acceptability were observed. Baseline beliefs about fruit and vegetables were an important predictor of intervention acceptability. In turn, acceptability was associated with a number of indicators of intervention success, including change in fruit and vegetable consumption. The findings highlight the importance of considering the relationship between these intervention and participant factors and acceptability in intervention design and evaluation. Results support the ongoing use of email-based interventions to target fruit and vegetable consumption within young adults. However, the relationships between beliefs about fruit and vegetable consumption and acceptability suggest that this intervention may be differentially effective depending on individual's existing beliefs about fruit and vegetable consumption. As such, there is a pressing need to consider these factors in future research in order to minimize attrition and maximize intervention effectiveness when interventions are implemented outside of a research context.

Development of a Brochure for Increasing Awareness of Inherited Breast Cancer in Black Women

PubMed Central

Quinn, Gwendolyn P.; Gjyshi, Anxhela; Pal, Tuya

2011-01-01

Low levels of awareness about hereditary breast cancer and ovarian cancer and underutilization of genetic services combined with the high incidence of early onset breast cancer in the black community underscore the urgent need to provide information about hereditary breast and ovarian cancer to black women. The primary goal of the present study was to develop a culturally targeted brochure designed to increase awareness about inherited breast cancer among black women using the principles of Learner Verification. Three focus groups were conducted with black women, including those with or without a history of breast cancer (n = 46), to evaluate the brochure. Data were analyzed through hand coding using a simple classification system placing participants' responses in the predetermined Learner Verification categories. On the basis of the feedback obtained, the brochure has been modified to improve cultural-targeting, relevance, and clarity and has been made available for dissemination. Our study illustrates the importance of obtaining feedback from the target audience when developing a culturally targeted informational brochure for black women. Further, the complexity of our subject matter (i.e., inherited breast and ovarian cancer) underscores the importance of using inviting visuals and personal vignettes, while maintaining a simple and clear message. PMID:21275654

Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated SARS-CoV vaccine.

PubMed

He, Yuxian; Li, Jingjing; Du, Lanying; Yan, Xuxia; Hu, Guangan; Zhou, Yusen; Jiang, Shibo

2006-06-29

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a major antigen for vaccine design. We previously demonstrated that the receptor-binding domain (RBD: residues 318-510) of S protein contains multiple conformation-dependent neutralizing epitopes (Conf I to VI) and serves as a major target of SARS-CoV neutralization. Here, we further characterized the antigenic structure in the RBD by a panel of novel mAbs isolated from the mice immunized with an inactivated SARS-CoV vaccine. Ten of the RBD-specific mAbs were mapped to four distinct groups of conformational epitopes (designated Group A to D), and all of which had potent neutralizing activity against S protein-pseudotyped SARS viruses. Group A, B, C mAbs target the epitopes that may overlap with the previously characterized Conf I, III, and VI respectively, but they display different capacity to block the receptor binding. Group D mAb (S25) was directed against a unique epitope by its competitive binding. Two anti-RBD mAbs recognizing the linear epitopes (Group E) were mapped to the RBD residues 335-352 and 442-458, respectively, and none of them inhibited the receptor binding and virus entry. Surprisingly, most neutralizing epitopes (Groups A to C) could be completely disrupted by single amino acid substitutions (e.g., D429A, R441A or D454A) or by deletions of several amino acids at the N-terminal or C-terminal region of the RBD; however, the Group D epitope was not sensitive to the mutations, highlighting its importance for vaccine development. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV, and this panel of novel mAbs can be used as tools for studying the structure of S protein and for guiding SARS vaccine design.

Selective attention in an insect visual neuron.

PubMed

Wiederman, Steven D; O'Carroll, David C

2013-01-21

Animals need attention to focus on one target amid alternative distracters. Dragonflies, for example, capture flies in swarms comprising prey and conspecifics, a feat that requires neurons to select one moving target from competing alternatives. Diverse evidence, from functional imaging and physiology to psychophysics, highlights the importance of such "competitive selection" in attention for vertebrates. Analogous mechanisms have been proposed in artificial intelligence and even in invertebrates, yet direct neural correlates of attention are scarce from all animal groups. Here, we demonstrate responses from an identified dragonfly visual neuron that perfectly match a model for competitive selection within limits of neuronal variability (r(2) = 0.83). Responses to individual targets moving at different locations within the receptive field differ in both magnitude and time course. However, responses to two simultaneous targets exclusively track those for one target alone rather than any combination of the pair. Irrespective of target size, contrast, or separation, this neuron selects one target from the pair and perfectly preserves the response, regardless of whether the "winner" is the stronger stimulus if presented alone. This neuron is amenable to electrophysiological recordings, providing neuroscientists with a new model system for studying selective attention. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Ackerman, G; Bale, J; Moran, K

Certain types of infrastructure--critical infrastructure (CI)--play vital roles in underpinning our economy, security, and way of life. One particular type of CI--that relating to chemicals--constitutes both an important element of our nation's infrastructure and a particularly attractive set of potential targets. This is primarily because of the large quantities of toxic industrial chemicals (TICs) it employs in various operations and because of the essential economic functions it serves. This study attempts to minimize some of the ambiguities that presently impede chemical infrastructure threat assessments by providing new insight into the key motivational factors that affect terrorist organizations propensity to attackmore » chemical facilities. Prepared as a companion piece to the Center for Nonproliferation Studies August 2004 study--''Assessing Terrorist Motivations for Attacking Critical Infrastructure''--it investigates three overarching research questions: (1) why do terrorists choose to attack chemical-related infrastructure over other targets; (2) what specific factors influence their target selection decisions concerning chemical facilities; and (3) which, if any, types of groups are most inclined to attack chemical infrastructure targets? The study involved a multi-pronged research design, which made use of four discrete investigative techniques to answer the above questions as comprehensively as possible. These include: (1) a review of terrorism and threat assessment literature to glean expert consensus regarding terrorist interest in targeting chemical facilities; (2) the preparation of case studies to help identify internal group factors and contextual influences that have played a significant role in leading some terrorist groups to attack chemical facilities; (3) an examination of data from the Critical Infrastructure Terrorist Incident Catalog (CrITIC) to further illuminate the nature of terrorist attacks against chemical facilities to date; and (4) the refinement of the DECIDe--the Determinants Effecting Critical Infrastructure Decisions--analytical framework to make the factors and dynamics identified by the study more ''usable'' in future efforts to assess terrorist intentions to target chemical-related infrastructure.« less

Blood Type Biochemistry and Human Disease

PubMed Central

Ewald, D Rose; Sumner, Susan CJ

2016-01-01

Associations between blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. In the 1950s, the chemical identification of the carbohydrate structure of surface antigens led to the understanding of biosynthetic pathways. The blood type is defined by oligosaccharide structures, which are specific to the antigens, thus, blood group antigens are secondary gene products, while the primary gene products are various glycosyltransferase enzymes that attach the sugar molecules to the oligosaccharide chain. Blood group antigens are found on red blood cells, platelets, leukocytes, plasma proteins, certain tissues, and various cell surface enzymes, and also exist in soluble form in body secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions, urine, and amniotic fluid. Recent advances in technology, biochemistry, and genetics have clarified the functional classifications of human blood group antigens, the structure of the A, B, H, and Lewis determinants and the enzymes that produce them, and the association of blood group antigens with disease risks. Further research to identify differences in the biochemical composition of blood group antigens, and the relationship to risks for disease, can be important for the identification of targets for the development of nutritional intervention strategies, or the identification of druggable targets. PMID:27599872

Attentional selection and suppression in children and adults.

PubMed

Sun, Meirong; Wang, Encong; Huang, Jing; Zhao, Chenguang; Guo, Jialiang; Li, Dongwei; Sun, Li; Du, Boqi; Ding, Yulong; Song, Yan

2018-05-15

The fundamental role of covert spatial attention is to enhance the processing of attended items while simultaneously ignoring irrelevant items. However, relatively little is known about how brain electrophysiological activities associated with target selection and distractor suppression are involved as they develop and become fully functional. The current study aimed to identify the neurophysiological bases of the development of covert spatial attention, focusing on electroencephalographic (EEG) markers of attentional selection (N2pc) and suppression (P D ). EEG data were collected from healthy young adults and typically developing children (9-15 years old) as they searched for a shape singleton target in either the absence or the presence of a salient-but-irrelevant color singleton distractor. The ERP results showed that a lateral shape target elicited a smaller N2pc in children compared with adults regardless of whether a distractor was present or not. Moreover, the target-elicited N2pc was always followed by a similar positivity in both age groups. Counterintuitively, a lateral salient-but-irrelevant distractor elicited a large P D in children with low behavioral accuracy, whereas high-accuracy children exhibited a small and "adult-like" P D . More importantly, we found no evidence for a correlation between the target-elicited N2pc and the distractor-elicited P D in either age group. Our results provide neurophysiological evidence for the developmental differences between target selection and distractor suppression. Compared with adults, 9-15-year-old children deploy insufficient attentional selection resources to targets but use "adult-like" or even more attentional suppression resources to resist irrelevant distractors. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=NhWapx0d75I. © 2018 John Wiley & Sons Ltd.

Spontaneous gaze selection and following during naturalistic social interactions in school-aged children and adolescents with autism spectrum disorder.

PubMed

Birmingham, Elina; Johnston, Krista Haley Smith; Iarocci, Grace

2017-09-01

Using a novel naturalistic paradigm allowing participants the freedom to spontaneously select and follow gaze cues in their environment, this study extends previous research conducted with younger children to determine whether school-age children with autism spectrum disorder (ASD, n = 17) demonstrate abnormal gaze following relative to typically developing (TD, n = 15) children. The participant and experimenter played a series of games, during which the experimenter pseudorandomly averted her gaze toward a social target (person) or a nonsocial target (object). A significant finding was that, relative to TD children, children with ASD were slower to follow the experimenter's gaze relative to the start of the trial (social targets d = -.93 [-1.70, -.16], nonsocial targets d = -1.05 [-1.88, -.20]). When we analyzed the duration of glances to the experimenter, we found that the ASD group made longer glances relative to TD children, but only in the nonsocial target condition (social targets d = .01 [-.68, .71], nonsocial targets d = -.81 [-1.53, -.08]). Other analyses revealed patterns of gaze selection and following that may help interpret the main findings. Despite the differences in the timing of gaze selection and following, the most common type of responder in both groups was one who followed the experimenter's gaze on over half of the trials. This pattern of results argues against a clear deficit in social attention in school-age children with ASD and underscores the importance of measuring both the timing of distinct mechanisms of social attention and the context in which these behaviors occur. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Calling Where It Counts: Subordinate Pied Babblers Target the Audience of Their Vocal Advertisements.

PubMed

Humphries, David J; Finch, Fiona M; Bell, Matthew B V; Ridley, Amanda R

2015-01-01

For territorial group-living species, opportunities to reproduce on the natal territory can be limited by a number of factors including the availability of resources within a territory, access to unrelated individuals, and monopolies on reproduction by dominant group members. Individuals looking to reproduce are therefore faced with the options of either waiting for a breeding opportunity to arise in the natal territory, or searching for reproductive opportunities in non-natal groups. In the cooperatively breeding Southern pied babbler, Turdoides bicolor, most individuals who achieve reproductive success do so through taking up dominant breeding positions within non-natal groups. For subordinate pied babblers therefore, searching for breeding opportunities in non-natal groups is of primary importance as this represents the major route to reproductive success. However, prospecting (where individuals leave the group to search for reproductive opportunities within other groups) is costly and individuals rapidly lose weight when not part of a group. Here we demonstrate that subordinate pied babblers adopt an alternative strategy for mate attraction by vocal advertisement from within their natal territories. We show that subordinates focus their calling efforts on the edges of their territory, and specifically near boundaries with neighbouring groups that have potential breeding partners (unrelated individuals of the opposite sex). In contrast to prospecting, calling individuals showed no body mass loss associated with this behaviour, suggesting that calling from within the group may provide a 'cheap' advertisement strategy. Additionally, we show that subordinates use information regarding the composition of neighbouring groups to target the greatest number of potential mating partners.

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

Kirkpatrick, R. C.

Nuclear fusion was discovered experimentally in 1933-34 and other charged particle nuclear reactions were documented shortly thereafter. Work in earnest on the fusion ignition problem began with Edward Teller's group at Los Alamos during the war years. His group quantified all the important basic atomic and nuclear processes and summarized their interactions. A few years later, the success of the early theory developed at Los Alamos led to very successful thermonuclear weapons, but also to decades of unsuccessful attempts to harness fusion as an energy source of the future. The reasons for this history are many, but it seems appropriatemore » to review some of the basics with the objective of identifying what is essential for success and what is not. This tutorial discusses only the conditions required for ignition in small fusion targets and how the target design impacts driver requirements. Generally speaking, the driver must meet the energy, power and power density requirements needed by the fusion target. The most relevant parameters for ignition of the fusion fuel are the minimum temperature and areal density (rhoR), but these parameters set secondary conditions that must be achieved, namely an implosion velocity, target size and pressure, which are interrelated. Despite the apparent simplicity of inertial fusion targets, there is not a single mode of fusion ignition, and the necessary combination of minimum temperature and areal density depends on the mode of ignition. However, by providing a magnetic field of sufficient strength, the conditions needed for fusion ignition can be drastically altered. Magnetized target fusion potentially opens up a vast parameter space between the extremes of magnetic and inertial fusion.« less

Important knowledge for parents of children with heart disease: parent, nurse, and physician views.

PubMed

Daily, Joshua; FitzGerald, Mike; Downing, Kimberly; King, Eileen; del Rey, Javier Gonzalez; Ittenbach, Richard; Marino, Bradley

2016-01-01

Parental understanding of their children's heart disease is inadequate, which may contribute to poor health outcomes. The purpose of this study was to determine what parental knowledge is important in the care of children with heart disease from the perspective of parents, nurses, and physicians. Focus groups were formed with parents of children with single ventricle congenital heart disease (CHD), biventricular CHD, and heart transplantation, and with nurses and physicians who provide care for these children. A nominal group technique was used to identify and prioritise important parental knowledge items and themes. The voting data for each theme were reported by participant type--parent, nurse, and physician--and patient diagnosis--single ventricle CHD, biventricular CHD, and heart transplantation. The following three themes were identified as important by all groups: recognition of and response to clinical deterioration, medications, and prognosis and plan. Additional themes that were unique to specific groups included the following: medical team members and interactions (parents), tests and labs (parents), neurodevelopmental outcomes and interventions (physicians), lifelong disease requiring lifelong follow-up (physicians and nurses), and diagnosis, physiology, and interventions (single ventricle and biventricular CHD). Parents, nurses, and physicians have both common and unique views regarding what parents should know to effectively care for their children with single ventricle CHD, biventricular CHD, or heart transplantation. Specific targeted parental education that incorporates these findings should be provided to each group. Further development of questionnaires regarding parental knowledge with appropriate content validity is warranted.

78 FR 50443 - Notice of Temporary Closure to Target Shooting on Public Lands in Yakima County, WA

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-19

... increased significantly over the past few years and is important to engage these groups to assist in... message or question with the above individual. You will receive a reply during normal hours. SUPPLEMENTARY... provided for by 18 U.S.C. 3571. This 2-year temporary closure will allow the BLM to utilize public input to...

Conflict transformation, stigma, and HIV-preventive structural change

PubMed Central

Miller, Robin Lin; Reed, Sarah J.; Francisco, Vincent T.; Ellen, Jonathan M.

2012-01-01

Over the prior decade, structural change efforts have become an important component of community-based HIV prevention initiatives. However, these efforts may not succeed when structural change initiatives encounter political resistance or invoke conflicting values, which may be likely when changes are intended to benefit a stigmatized population. The current study sought to examine the impact of target population stigma on the ability of 13 community coalitions to achieve structural change objectives. Results indicated that coalitions working on behalf of highly stigmatized populations had to abandon objectives more often than did coalitions working for less stigmatized populations because of external opposition to coalition objectives and resultant internal conflict over goals. Those coalitions that were most successful in meeting external challenges used opposition and conflict as transformative occasions by targeting conflicts directly and attempting to neutralize oppositional groups or turn them into strategic allies; less successful coalitions working on behalf of stigmatized groups struggled to determine an appropriate response to opposition. The role of conflict transformation as a success strategy for working on behalf of stigmatized groups is discussed. PMID:21805217

Beyond the usual suspects: target group- and behavior-specific factors add to a theory-based sun protection intervention for teenagers.

PubMed

Schüz, Natalie; Eid, Michael

2013-10-01

Sun protection standards among teenagers are low while sun exposure peaks in this age group. Study 1 explores predictors of adolescent protection intentions and exposure behavior. Study 2 tests the effectiveness of an intervention based on these predictors. Study 1(cross-sectional, N = 207, ages 15-18) and Study 2 (RCT, N = 253, ages 13-19) were conducted in schools. Path models were used to analyze data. Self-efficacy (β = .26, p < .001) and time perspective (β = .17, p = .014) were the strongest predictors of intentions; appearance motivation (β = .54, p < .001) and intention (β = -.18, p = .015) predicted behavior. The intervention effected changes in all predictors except self-efficacy. Changes in outcome expectancies (β = .19, p < .001) and time perspective (β = .09, p = .039) predicted changes in intention, while changes in intention (β = -.17, p = .002) and appearance motivation (β = .29, p < .001) predicted behavior changes. Target group- and behavior-specific intervention components are as important for changes in intentions and behavior as components derived from common health behavior theories.

Effects of fluorescent dyes, quenchers, and dangling ends on DNA duplex stability.

PubMed

Moreira, Bernardo G; You, Yong; Behlke, Mark A; Owczarzy, Richard

2005-02-11

Single and dual-labeled fluorescent oligodeoxynucleotides are used in many molecular biology applications. We investigated the effects of commonly used fluorescent dyes and quenchers on the thermodynamic stability of a model probe-target DNA duplex. We demonstrate that those effects can be significant. Fluorescent dyes and quenchers were attached to the probe ends. In certain combinations, these groups stabilized the duplex up to 1.8kcal/mol and increased T(m) up to 4.3 degrees C. None of the groups tested significantly destabilized the duplex. Rank order of potency was, starting with the most stabilizing group: Iowa Black RQ approximately Black Hole 2>Cy5 approximately Cy3>Black Hole 1>QSY7 approximately Iowa Black FQ>Texas Red approximately TAMRA>FAM approximately HEX approximately Dabcyl>TET. Longer linkers decreased stabilizing effects. Hybridizations to targets with various dangling ends were also studied and were found to have only minor effects on thermodynamic stability. Depending on the dye/quencher combination employed, it can be important to include thermodynamic contributions from fluorophore and quencher when designing oligonucleotide probe assays.

Opinions about donating blood among those who never gave and those who stopped: a focus group assessment.

PubMed

Mathew, Sunitha M; King, Melissa R; Glynn, Simone A; Dietz, Stephen K; Caswell, Scott L; Schreiber, George B

2007-04-01

Understanding what prevents people from ever donating blood, or having donated, what influenced them to stop, are both equally important in devising recruitment strategies. Enlisting new donors and encouraging previous donors to return are vital to increasing collections. Six racially homogeneous focus groups of never donors and lapsed donors were conducted. Both sexes and a range of age groups were represented. The importance of blood donation as a volunteer activity, deterrents, motivations, awareness of need, and effective recruitment messages were topics discussed. Never donors do not see blood donation as an important volunteer activity on par with others like volunteering at hospitals, schools, and support groups. Fear and inconvenience were major barriers to donating. Better education campaigns to allay fears about donating and workplace drives were considered important motivators. Participants were unaware of the need for blood. Media messages that combine safety of the process along with who it benefits were considered most effective. Messages that target the specific needs of minority communities were considered good motivators for their recruitment. Blood collection agencies should increase awareness that blood donation is a worthwhile and important volunteer activity. Another strategy would be to capitalize on the existing perception that donating blood is like donating money or used clothing, by focusing on the concept of giving something tangible. Along with providing convenient opportunities to donate, blood centers need to effectively convey the need for blood and allay fears about the donation process to increase the current donor pool.

The relevance of spirituality, religion and personal beliefs to health-related quality of life: themes from focus groups in Britain.

PubMed

O'Connell, Kathryn A; Skevington, Suzanne M

2005-09-01

Generic health-related quality of life (QoL) instruments have not routinely assessed spirituality, religion, and personal beliefs (SRPB) in their measurement. This research addresses the perceived importance of 18 facets (dimensions) of SRPB, for example, inner peace, to QoL that are not specific to a religion, but address the experience of having this belief, in relation to health. Adult focus groups were structured according to beliefs from UK surveys. Quotas targeted gender and health status. Nine focus groups (N = 55, age 51, 47% male) contained sick and well people who were religious, Christians, Buddhists, Quakers (50.1%), agnostic (27.4%), or atheist (21.8%) participants. Qualitative and quantitative analysis showed considerable variability in the importance attributed to some concepts, although spiritual strength, meaning in life and inner peace were relevant to all groups. Spiritual strength (4.42), the meaning of life (4.09), wholeness/integration (4.06), and inner peace (4.02) were most important. Divine love, freedom to practice beliefs, and attachment/detachment were less relevant, conceptually confusing or had religious bias; atheists rated them as unimportant and as less important (p < .04) than agnostics or religious people. SRPB is relevant to health-related QoL and consensually important facets should be included in generic health care assessments. Their inclusion permits a more holistic assessment and improves the case for a biopsychosociospiritual model of health.

Individualized feedback during simulated laparoscopic training: a mixed methods study

PubMed Central

Weurlander, Maria; Hedman, Leif; Nisell, Henry; Lindqvist, Pelle G.; Felländer-Tsai, Li; Enochsson, Lars

2015-01-01

Objectives This study aimed to explore the value of indi-vidualized feedback on performance, flow and self-efficacy during simulated laparoscopy. Furthermore, we wished to explore attitudes towards feedback and simulator training among medical students. Methods Sixteen medical students were included in the study and randomized to laparoscopic simulator training with or without feedback. A teacher provided individualized feedback continuously throughout the procedures to the target group. Validated questionnaires and scales were used to evaluate self-efficacy and flow. The Mann-Whitney U test was used to evaluate differences between groups regarding laparoscopic performance (instrument path length), self-efficacy and flow. Qualitative data was collected by group interviews and interpreted using inductive thematic analyses. Results Sixteen students completed the simulator training and questionnaires. Instrument path length was shorter in the feedback group (median 3.9 m; IQR: 3.3-4.9) as com-pared to the control group (median 5.9 m; IQR: 5.0-8.1), p<0.05. Self-efficacy improved in both groups. Eleven students participated in the focus interviews. Participants in the control group expressed that they had fun, whereas participants in the feedback group were more concentrated on the task and also more anxious. Both groups had high ambitions to succeed and also expressed the importance of getting feedback. The authenticity of the training scenario was important for the learning process. Conclusions This study highlights the importance of individualized feedback during simulated laparoscopy training. The next step is to further optimize feedback and to transfer standardized and individualized feedback from the simulated setting to the operating room. PMID:26223033

If We Build It, Will They Come? A Qualitative Study of Key Stakeholder Opinions on the Implementation of a Videogame Intervention for Risk Reduction in Adolescents.

PubMed

Pendergrass, Tyra M; Hieftje, Kimberly; Crusto, Cindy A; Montanaro, Erika; Fiellin, Lynn E

2016-08-01

Serious games are emerging as important tools that offer an innovative approach to teach adolescents behavioral skills to avoid risky situations. PlayForward: Elm City Stories, an interactive videogame targeting risk reduction, is currently undergoing evaluation. Collecting stakeholder data on its acceptability and real-life implementation strategies is critical for successful dissemination. We collected interview data from four stakeholder groups regarding incorporating PlayForward into settings with adolescents. Transcripts were coded, creating a comprehensive code structure for each stakeholder group. We conducted 40 semi-structured interviews that included 14 adolescents (aged 12-15 years; 10 boys), eight parents/guardians (all women), 12 after-school/school coordinators (nine women), and 14 community partners (13 women). We identified four themes that reflected stakeholders' perceptions about how the videogame might be implemented in real-world settings. (1) Stakeholder groups expressed that the topics of sex, alcohol, and drugs were not being taught in an educational setting. (2) Stakeholder groups saw a videogame as a viable option to teach about sex, alcohol, and drugs. (3) Stakeholder groups thought that the videogame would fit well into other settings, such as after-school programs or community organizations. (4) Some stakeholder groups highlighted additional tools that could help with implementation, such as manuals, homework assignments, and group discussion questions. Stakeholder groups supported the game as a delivery vehicle for targeted content, indicating high acceptability but highlighting additional tools that would aid in implementation.

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

Shen, Wen-jun; Dong, Rui; Chen, Gong, E-mail: chengongzlp@hotmail.com

Highlights: • The RRV infected group showed cholestasis, retardation and extrahepatic biliary atresia. • miR-222 was highly expressed, and PPP2R2A was inhibited in the murine biliary atresia model. • miR-222 profoundly modulated the process of fibrosis in the murine biliary atresia model. • miR-222 might represent a potential target for improving biliary atresia prognosis. - Abstract: microRNA-222 (miR-222) has been shown to initiate the activation of hepatic stellate cells, which plays an important role in the pathogenesis of liver fibrosis. The aim of our study was to evaluate the role of miR-22 in a mouse model of biliary atresia (BA)more » induced by Rhesus Rotavirus (RRV) infection. New-born Balb/c mice were randomized into control and RRV infected groups. The extrahepatic bile ducts were evaluated. The experimental group was divided into BA group and negative group based on histology. The expression of miR-222, protein phosphatase 2 regulatory subunit B alpha (PPP2R2A), proliferating cell nuclear antigen (PCNA) and phospho-Akt were detected. We found that the experimental group showed signs of cholestasis, retardation and extrahepatic biliary atresia. No abnormalities were found in the control group. In the BA group, miR-222, PCNA and Akt were highly expressed, and PPP2R2A expression was significantly inhibited. Our findings suggest that miR-222 profoundly modulated the process of fibrosis in the murine BA model, which might represent a potential target for improving BA prognosis.« less

Neural reactivity to reward in school-age offspring of depressed mothers.

PubMed

Wiggins, Jillian Lee; Schwartz, Karen T G; Kryza-Lacombe, Maria; Spechler, Philip A; Blankenship, Sarah L; Dougherty, Lea R

2017-05-01

Identifying neural profiles predictive of future psychopathology in at-risk individuals is important to efficiently direct preventive care. Alterations in reward processing may be a risk factor for depression. The current study characterized neural substrates of reward processing in children at low- and high-risk for psychopathology due to maternal depression status. Children with (n=27) and without (n=19) maternal depression (ages 5.9-9.6 years) performed a monetary incentive delay task in which they received rewards, if they successfully hit a target, or no reward regardless of performance, during fMRI acquisition. Multiple dorsal prefrontal, temporal, and striatal regions showed significant Group (high- vs. low-risk)×Performance (hit vs. miss)×Condition (no reward vs. reward) interactions in a whole-brain analysis. All regions exhibited similar patterns, whereby the high-risk group showed blunted activation differences between trials with vs. without rewards when participants hit the target. Moreover, high-risk children showed activation differences between trials with vs. without rewards in the opposite direction, compared to the low-risk group, when they missed the target. This study had a modest sample size, though larger than existing studies. Children with maternal depression are at elevated risk for future psychopathology, yet not all experience clinically significant symptoms; longitudinal research is necessary to fully track the pathway from risk to disorder. Children of depressed mothers exhibited attenuated neural activation differences and activation patterns opposite to children without depressed mothers. Our findings may provide targets for hypothesis-driven preventive interventions and lead to earlier identification of individuals at risk. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain activation of semantic category-based grouping in multiple identity tracking task

PubMed Central

Wei, Liuqing; Lyu, Chuang; Hu, Siyuan; Li, Zhen

2017-01-01

Using Multiple Identity Tracking task and the functional magnetic resonance imaging (fMRI) technology, the present study aimed to isolate and visualize the functional anatomy of neural systems involved in the semantic category-based grouping process. Three experiment conditions were selected and compared: the category-based targets grouping (TG) condition, the targets-distractors grouping (TDG) condition and the homogenous condition. In the TG condition, observers could utilize the categorical distinction between targets and distractors, to construct a uniform presentation of targets, that is, to form a group of the targets to facilitate tracking. In the TDG condition, half the targets and half the distractors belonged to the same category. Observers had to inhibit the grouping of targets and distractors in one category to complete tracking. In the homogenous condition, where targets and distractors consisted of the same objects, no grouping could be formed. The “TG-Homogenous” contrast (p<0.01) revealed the activation of the left fusiform and the pars triangularis of inferior frontal gyrus (IFG). The “TG-TDG” contrast only revealed the activation of the left anterior cingulate gyrus (ACC). The fusiform and IFG pars triangularis might participate in the representation of semantic knowledge, IFG pars triangularis might relate intensely with the classification of semantic categories. The ACC might be responsible for the initiation and maintenance of grouping representation. PMID:28505166

Three-layered polyplex as a microRNA targeted delivery system for breast cancer gene therapy

NASA Astrophysics Data System (ADS)

Li, Yan; Dai, Yu; Zhang, Xiaojin; Chen, Jihua

2017-07-01

MicroRNAs (miRNAs), small non-coding RNAs, play an important role in modulating cell proliferation, migration, and differentiation. Since miRNAs can regulate multiple cancer-related genes simultaneously, regulating miRNAs could target a set of related oncogenic genes or pathways. Owing to their reduced immune response and low toxicity, miRNAs with small size and low molecular weight have become increasingly promising therapeutic drugs in cancer therapy. However, one of the major challenges of miRNAs-based cancer therapy is to achieve specific, effective, and safe delivery of therapeutic miRNAs into cancer cells. Here we provide a strategy using three-layered polyplex with folic acid as a targeting group to systemically deliver miR-210 into breast cancer cells, which results in breast cancer growth being inhibited.

Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing

PubMed Central

Chandran, Anandhakumar; Syed, Junetha; Taylor, Rhys D.; Kashiwazaki, Gengo; Sato, Shinsuke; Hashiya, Kaori; Bando, Toshikazu; Sugiyama, Hiroshi

2016-01-01

Chemically engineered small molecules targeting specific genomic sequences play an important role in drug development research. Pyrrole-imidazole polyamides (PIPs) are a group of molecules that can bind to the DNA minor-groove and can be engineered to target specific sequences. Their biological effects rely primarily on their selective DNA binding. However, the binding mechanism of PIPs at the chromatinized genome level is poorly understood. Herein, we report a method using high-throughput sequencing to identify the DNA-alkylating sites of PIP-indole-seco-CBI conjugates. High-throughput sequencing analysis of conjugate 2 showed highly similar DNA-alkylating sites on synthetic oligos (histone-free DNA) and on human genomes (chromatinized DNA context). To our knowledge, this is the first report identifying alkylation sites across genomic DNA by alkylating PIP conjugates using high-throughput sequencing. PMID:27098039

Three-layered polyplex as a microRNA targeted delivery system for breast cancer gene therapy.

PubMed

Li, Yan; Dai, Yu; Zhang, Xiaojin; Chen, Jihua

2017-07-14

MicroRNAs (miRNAs), small non-coding RNAs, play an important role in modulating cell proliferation, migration, and differentiation. Since miRNAs can regulate multiple cancer-related genes simultaneously, regulating miRNAs could target a set of related oncogenic genes or pathways. Owing to their reduced immune response and low toxicity, miRNAs with small size and low molecular weight have become increasingly promising therapeutic drugs in cancer therapy. However, one of the major challenges of miRNAs-based cancer therapy is to achieve specific, effective, and safe delivery of therapeutic miRNAs into cancer cells. Here we provide a strategy using three-layered polyplex with folic acid as a targeting group to systemically deliver miR-210 into breast cancer cells, which results in breast cancer growth being inhibited.

Targeted gene panel sequencing in children with very early onset inflammatory bowel disease--evaluation and prospective analysis.

PubMed

Kammermeier, Jochen; Drury, Suzanne; James, Chela T; Dziubak, Robert; Ocaka, Louise; Elawad, Mamoun; Beales, Philip; Lench, Nicholas; Uhlig, Holm H; Bacchelli, Chiara; Shah, Neil

2014-11-01

Multiple monogenetic conditions with partially overlapping phenotypes can present with inflammatory bowel disease (IBD)-like intestinal inflammation. With novel genotype-specific therapies emerging, establishing a molecular diagnosis is becoming increasingly important. We have introduced targeted next-generation sequencing (NGS) technology as a prospective screening tool in children with very early onset IBD (VEOIBD). We evaluated the coverage of 40 VEOIBD genes in two separate cohorts undergoing targeted gene panel sequencing (TGPS) (n=25) and whole exome sequencing (WES) (n=20). TGPS revealed causative mutations in four genes (IL10RA, EPCAM, TTC37 and SKIV2L) discovered unexpected phenotypes and directly influenced clinical decision making by supporting as well as avoiding haematopoietic stem cell transplantation. TGPS resulted in significantly higher median coverage when compared with WES, fewer coverage deficiencies and improved variant detection across established VEOIBD genes. Excluding or confirming known VEOIBD genotypes should be considered early in the disease course in all cases of therapy-refractory VEOIBD, as it can have a direct impact on patient management. To combine both described NGS technologies would compensate for the limitations of WES for disease-specific application while offering the opportunity for novel gene discovery in the research setting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Crystal structures, in-silico study and anti-microbial potential of synthetic monocarbonyl curcuminoids

NASA Astrophysics Data System (ADS)

Ud Din, Zia; Serrano, N. F. G.; Ademi, Kastriot; Sousa, C. P.; Deflon, Victor Marcelo; Maia, Pedro Ivo da Silva; Rodrigues-Filho, Edson

2017-09-01

In this work the screening of 20 unsymmetrical chalcone and curcuminoids analogues in regard of their antimicrobial properties was conducted. Electron donating groups in the aromatic rings in the chalcone and curcuminoid derivatives produced higher antimicrobial effect. Compounds 1, 9 and 15 exhibited good activity against Escherichia coli and Staphylococcus aureus. These compounds were further evaluated against nine micro-organisms of pathological interest. Pharmmaper was used for target fishing of compounds against important bacterial targets. Molecular Docking helped to verify the results of these compounds against the selected bacterial target D-alanyl-D-alanine carboxypeptidase (PDB ID: 1PW1). The crystal structure of ligand and docked conformers in the active site of 1PW1 were analyzed. As a result structure-activity relationships are proposed. Structures of compounds 14 and 16 were obtained through single crystals X-ray diffraction studies. Compound 14 crystallizes in monoclinic space group P21/c with unit cell dimensions a = 13.1293(3) Å, b = 17.5364(4) Å, c = 15.1433(3) Å, β = 95.6440(10), V = 3469.70(13) Å3 and Z = 8. Compound 16 crystallizes in triclinic space group Pī with unit cell dimensions a = 6.8226(4) Å, b = 7.2256(4) Å, c = 18.1235(12) Å, β = 87.322(4), V = 850.57(9) Å3 and Z = 2.

Improved GGIW-PHD filter for maneuvering non-ellipsoidal extended targets or group targets tracking based on sub-random matrices.

PubMed

Liang, Zhibing; Liu, Fuxian; Gao, Jiale

2018-01-01

For non-ellipsoidal extended targets and group targets tracking (NETT and NGTT), using an ellipsoid to approximate the target extension may not be accurate enough because of the lack of shape and orientation information. In consideration of this, we model a non-ellipsoidal extended target or target group as a combination of multiple ellipsoidal sub-objects, each represented by a random matrix. Based on these models, an improved gamma Gaussian inverse Wishart probability hypothesis density (GGIW-PHD) filter is proposed to estimate the measurement rates, kinematic states, and extension states of the sub-objects for each extended target or target group. For maneuvering NETT and NGTT, a multi-model (MM) approach based GGIW-PHD (MM-GGIW-PHD) filter is proposed. The common and the individual dynamics of the sub-objects belonging to the same extended target or target group are described by means of the combination between the overall maneuver model and the sub-object models. For the merging of updating components, an improved merging criterion and a new merging method are derived. A specific implementation of prediction partition with pseudo-likelihood method is presented. Two scenarios for non-maneuvering and maneuvering NETT and NGTT are simulated. The results demonstrate the effectiveness of the proposed algorithms.

Improved GGIW-PHD filter for maneuvering non-ellipsoidal extended targets or group targets tracking based on sub-random matrices

PubMed Central

Liu, Fuxian; Gao, Jiale

2018-01-01

For non-ellipsoidal extended targets and group targets tracking (NETT and NGTT), using an ellipsoid to approximate the target extension may not be accurate enough because of the lack of shape and orientation information. In consideration of this, we model a non-ellipsoidal extended target or target group as a combination of multiple ellipsoidal sub-objects, each represented by a random matrix. Based on these models, an improved gamma Gaussian inverse Wishart probability hypothesis density (GGIW-PHD) filter is proposed to estimate the measurement rates, kinematic states, and extension states of the sub-objects for each extended target or target group. For maneuvering NETT and NGTT, a multi-model (MM) approach based GGIW-PHD (MM-GGIW-PHD) filter is proposed. The common and the individual dynamics of the sub-objects belonging to the same extended target or target group are described by means of the combination between the overall maneuver model and the sub-object models. For the merging of updating components, an improved merging criterion and a new merging method are derived. A specific implementation of prediction partition with pseudo-likelihood method is presented. Two scenarios for non-maneuvering and maneuvering NETT and NGTT are simulated. The results demonstrate the effectiveness of the proposed algorithms. PMID:29444144

Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application

PubMed Central

Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia

2009-01-01

Background microRNAs (miRNAs) are single-stranded RNA molecules of about 20–23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. Results GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. Conclusion GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA. PMID:19534746

Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application.

PubMed

Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia

2009-06-16

microRNAs (miRNAs) are single-stranded RNA molecules of about 20-23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA.

Global Comparison of Warring Groups in 2002–2007: Fatalities from Targeting Civilians vs. Fighting Battles

PubMed Central

Hicks, Madelyn Hsiao-Rei; Lee, Uih Ran; Sundberg, Ralph; Spagat, Michael

2011-01-01

Background Warring groups that compete to dominate a civilian population confront contending behavioral options: target civilians or battle the enemy. We aimed to describe degrees to which combatant groups concentrated lethal behavior into intentionally targeting civilians as opposed to engaging in battle with opponents in contemporary armed conflict. Methodology/Principal Findings We identified all 226 formally organized state and non-state groups (i.e. actors) that engaged in lethal armed conflict during 2002–2007: 43 state and 183 non-state. We summed civilians killed by an actor's intentional targeting with civilians and combatants killed in battles in which the actor was involved for total fatalities associated with each actor, indicating overall scale of armed conflict. We used a Civilian Targeting Index (CTI), defined as the proportion of total fatalities caused by intentional targeting of civilians, to measure the concentration of lethal behavior into civilian targeting. We report actor-specific findings and four significant trends: 1.) 61% of all 226 actors (95% CI 55% to 67%) refrained from targeting civilians. 2.) Logistic regression showed actors were more likely to have targeted civilians if conflict duration was three or more years rather than one year. 3.) In the 88 actors that targeted civilians, multiple regressions showed an inverse correlation between CTI values and the total number of fatalities. Conflict duration of three or more years was associated with lower CTI values than conflict duration of one year. 4.) When conflict scale and duration were accounted for, state and non-state actors did not differ. We describe civilian targeting by actors in prolonged conflict. We discuss comparable patterns found in nature and interdisciplinary research. Conclusions/Significance Most warring groups in 2002–2007 did not target civilians. Warring groups that targeted civilians in small-scale, brief conflict concentrated more lethal behavior into targeting civilians, and less into battles, than groups in larger-scale, longer conflict. PMID:21915272

Ubiquinol-binding site in the alternative oxidase: mutagenesis reveals features important for substrate binding and inhibition.

PubMed

Albury, Mary S; Elliott, Catherine; Moore, Anthony L

2010-12-01

The alternative oxidase (AOX) is a non-protonmotive ubiquinol oxidase that is found in all plants, some fungi, green algae, bacteria and pathogenic protozoa. The lack of AOX in the mammalian host renders this protein an important potential therapeutic target in the treatment of pathogenic protozoan infections. Bioinformatic searches revealed that, within a putative ubiquinol-binding crevice in AOX, Gln242, Asn247, Tyr253, Ser256, His261 and Arg262 were highly conserved. To confirm that these amino-acid residues are important for ubiquinol-binding and hence activity substitution mutations were generated and characterised. Assessment of AOX activity in isolated Schizosaccharomyces pombe mitochondria revealed that mutation of either Gln242, Ser256, His261 and Arg262 resulted in >90% inhibition of antimycin A-insensitive respiration suggesting that hydroxyl, guanidino, imidazole groups, polar and charged residues in addition to the size of the amino-acid chain are important for ubiquinone-binding. Substitution of Asn247 with glutamine or Tyr253 with phenylalanine had little effect upon the respiratory rate indicating that these residues are not critical for AOX activity. However replacement of Tyr253 by alanine resulted in a 72% loss of activity suggesting that the benzoquinone group and not hydroxyl group is important for quinol binding. These results provide important new insights into the ubiquinol-binding site of the alternative oxidase, the identity of which maybe important for future rational drug design. Copyright © 2010 Elsevier B.V. All rights reserved.

Drug-eluting stents versus bare-metal stents in saphenous vein grafts: a double-blind, randomised trial.

PubMed

Brilakis, Emmanouil S; Edson, Robert; Bhatt, Deepak L; Goldman, Steven; Holmes, David R; Rao, Sunil V; Shunk, Kendrick; Rangan, Bavana V; Mavromatis, Kreton; Ramanathan, Kodangudi; Bavry, Anthony A; Garcia, Santiago; Latif, Faisal; Armstrong, Ehrin; Jneid, Hani; Conner, Todd A; Wagner, Todd; Karacsonyi, Judit; Uyeda, Lauren; Ventura, Beverly; Alsleben, Aaron; Lu, Ying; Shih, Mei-Chiung; Banerjee, Subhash

2018-05-19

Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions. Patients were recruited to our double-blind, randomised controlled trial from 25 US Department of Veterans Affairs centres. Eligible participants were aged at least 18 years and had at least one significant de-novo SVG lesion (50-99% stenosis of a 2·25-4·5 mm diameter SVG) requiring percutaneous coronary intervention with intent to use embolic protection devices. Enrolled patients were randomly assigned, in a 1:1 ratio, by phone randomisation system to receive a DES or BMS. Randomisation was stratified by presence or absence of diabetes and number of target SVG lesions requiring percutaneous coronary intervention (one or two or more) within each participating site by use of an adaptive scheme intended to balance the two stent type groups on marginal totals for the stratification factors. Patients, referring physicians, study coordinators, and outcome assessors were masked to group allocation. The primary endpoint was the 12-month incidence of target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularisation. The DIVA trial is registered with ClinicalTrials.gov, number NCT01121224. Between Jan 1, 2012, and Dec 31, 2015, 599 patients were randomly assigned to the stent groups, and the data for 597 patients were used. The patients' mean age was 68·6 (SD 7·6) years, and 595 (>99%) patients were men. The two stent groups were similar for most baseline characteristics. At 12 months, the incidence of target vessel failure was 17% (51 of 292) in the DES group versus 19% (58 of 305) in the BMS group (adjusted hazard ratio 0·92, 95% CI 0·63-1·34, p=0·70). Between-group differences in the components of the primary endpoint, serious adverse events, or stent thrombosis were not significant. Enrolment was stopped before the revised target sample size of 762 patients was reached. In patients undergoing stenting of de-novo SVG lesions, no significant differences in outcomes between those receiving DES and BMS during 12 months of follow-up were found. The study results have important economic implications in countries with high DES prices such as the USA, because they suggest that the lower-cost BMS can be used in SVG lesions without compromising either safety or efficacy. US Department of Veterans Affairs Cooperative Studies Program. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of a group-specific 16S rRNA-targeted probe set for the identification of Marinobacter by fluorescence in situ hybridization

NASA Astrophysics Data System (ADS)

McKay, Luke J.; Gutierrez, Tony; Teske, Andreas P.

2016-07-01

Members of the Marinobacter genus play an important role in hydrocarbon degradation in the ocean - a topic of special significance in light of the recent Deepwater Horizon oil spill of 2010. The Marinobacter group has thus far lacked a genus level phylogenetic probe that would allow in situ identification of representative members. Here, we developed two new 16S rRNA-targeted oligonucleotide probes (Mrb-0625-a and Mrb-0625-b) to enumerate Marinobacter species by fluorescence in situ hybridization (FISH). In silico analysis of this probe set demonstrated 80% coverage of the Marinobacter genus. A competitor probe was developed to block hybridization by Mrb-0625-a to six Halomonas species with which it shared a one base pair mismatch. The probe set was optimized using pure cultures, and then used in an enrichment experiment with a deep sea oil plume water sample collected from the Deepwater Horizon oil spill. Marinobacter cells rapidly increased as a significant fraction of total microbial abundance in all incubations of original contaminated seawater as well as those amended with n-hexadecane, suggesting this group may be among the first microbial responders to oil pollution in the marine environment. The new probe set will provide a reliable tool for quantifying Marinobacter in the marine environment, particularly at contaminated sites where these organisms can play an important role in the biodegradation of oil pollutants.

Harmonization of urine albumin/creatinine ratio (ACR) results: a study based on an external quality assessment program in Polish laboratories.

PubMed

Ćwiklińska, Agnieszka; Dąbrowska, Hanna; Kowalski, Robert; Kuchta, Agnieszka; Kortas-Stempak, Barbara; Fijałkowska, Aleksandra; Bednarczuk, Gabriela; Jankowski, Maciej

2018-05-11

The ratio of albumin to creatinine (ACR) is an important parameter used for detection of albuminuria in patients with early kidney damage. The aim of the study was to evaluate the harmonization of ACR results among Polish participants in an international external quality assessment (EQA) program, and to evaluate the impact of albumin and creatinine analytical performance on the harmonization of ACR results. We analyzed 182 results of albumin, 202 of creatinine, and 180 of ACR obtained from Polish laboratories in an EQA program organized by Labquality. The dispersion of the results in surveys and percentage differences between the results and target values were calculated. Moreover, differences between method groups were assessed. The inter-laboratory coefficient of variation (CV) for ACR was 36%. Only 74% of results of Polish laboratories were within the target limits; for 11% of the results, an incorrect albuminuria category would have been reported. The inter-laboratory CV for albumin was 20%, 2.6-fold higher than for creatinine. Significant differences between method groups for albumin determination have been observed, even when the same measurement technique was used. The greatest difference between two groups was 23%, 2.5-fold greater in comparison to creatinine. There is an insufficient harmonization of ACR values among Polish laboratories, caused mainly by urine albumin analytical performance. Given the important role of ACR in the classification, monitoring and treatment of kidney damage, the harmonization of albumin measurements is crucial and urgently needed.

Creating demand for foreign brands in a 'home run' market: tobacco company tactics in South Korea following market liberalisation.

PubMed

Lee, Sungkyu; Lee, Kelley; Holden, Chris

2014-05-01

To analyse the tactics transnational tobacco companies (TTCs) used to increase market share in South Korea after market liberalisation in 1988, and the subsequent impact of TTCs' activities on the domestic industry and ultimately public health. Internal tobacco industry documents were searched iteratively and analysed by keyword related to strategies for increasing market share in Korea since liberalisation. Following market liberalisation, TTCs faced entrenched cultural and institutional barriers in Korea which hindered increased sales of cigarette imports. TTCs identified population groups more favourably inclined towards imported brands, developed new distribution channels and used promotional activities targeting these groups. The growth in market share by TTCs suggests that these activities were successful at challenging the Korea Tobacco & Ginseng Corporation (KTGC) monopoly. In response, KTGC shifted to a proactive marketing approach and adopted strategies similar to TTCs. This, in turn, made the Korean market highly competitive. Findings show that, after market liberalisation, there was an upward trend in cigarette consumption and smoking prevalence among the targeted population groups, notably youth and young women. Governments engaging in trade negotiations that may lead to the opening of domestic tobacco markets need a fuller understanding of previous industry activities for expanding into emerging markets as well as how the domestic industry can change accordingly. To protect public health, the adoption of comprehensive tobacco control measures, guided by WHO Framework Convention on Tobacco Control, are needed as part of such negotiations.

Therapeutic effects of Euphorbia Pekinensis and Glycyrrhiza glabra on Hepatocellular Carcinoma Ascites Partially Via Regulating the Frk-Arhgdib-Inpp5d-Avpr2-Aqp4 Signal Axis

NASA Astrophysics Data System (ADS)

Zhang, Yanqiong; Yan, Chen; Li, Yuting; Mao, Xia; Tao, Weiwei; Tang, Yuping; Lin, Ya; Guo, Qiuyan; Duan, Jingao; Lin, Na

2017-02-01

To clarify unknown rationalities of herbaceous compatibility of Euphorbia Pekinensis (DJ) and Glycyrrhiza glabra (GC) acting on hepatocellular carcinoma (HCC) ascites, peritoneum transcriptomics profiling of 15 subjects, including normal control (Con), HCC ascites mouse model (Mod), DJ-alone, DJ/GC-synergy and DJ/GC-antagonism treatment groups were performed on OneArray platform, followed by differentially expressed genes (DEGs) screening. DEGs between Mod and Con groups were considered as HCC ascites-related genes, and those among different drug treatment and Mod groups were identified as DJ/GC-combination-related genes. Then, an interaction network of HCC ascites-related gene-DJ/GC combination-related gene-known therapeutic target gene for ascites was constructed. Based on nodes’ degree, closeness, betweenness and k-coreness, the Frk-Arhgdib-Inpp5d-Avpr2-Aqp4 axis with highly network topological importance was demonstrated to be a candidate target of DJ/GC combination acting on HCC ascites. Importantly, both qPCR and western blot analyses verified this regulatory effects based on HCC ascites mice in vivo and M-1 collecting duct cells in vitro. Collectively, different combination designs of DJ and GC may lead to synergistic or antagonistic effects on HCC ascites partially via regulating the Frk-Arhgdib-Inpp5d-Avpr2-Aqp4 axis, implying that global gene expression profiling combined with network analysis can offer an effective way to understand pharmacological mechanisms of traditional Chinese medicine prescriptions.

The poultry red mite Dermanyssus gallinae as a potential carrier of vector-borne diseases.

PubMed

De Luna, Carlos J; Arkle, Samuel; Harrington, David; George, David R; Guy, Jonathan H; Sparagano, Olivier A E

2008-12-01

The poultry red mite Dermanyssus gallinae is an obligatory blood-sucking parasite that is considered to be one of the most important ectoparasites in the poultry industry, mainly because it is responsible for important economic losses, leads to a reduction of welfare of laying hens, and may pose a disease risk to humans. As a result of these problems, much of the current research on this parasite targets new methods of control. Less attention has been paid to the importance of D. gallinae as a carrier of vector-borne diseases. Some authors have mentioned the possible involvement of D. gallinae in the transmission (both in vitro and directly isolated from the mites) of viral and bacterial agents. Our research group has demonstrated the presence of Mycobacterium spp. within D. gallinae. DNA coding for Mycobacterium spp. was successfully amplified from unfed adult D. gallinae, larvae, and eggs by using reverse transcription-polymerase chain reaction targeting the 16S rRNA gene. The results have suggested the possible transovarial and transstadial transmission of pathogens by D. gallinae.

Impaired Retention of Motor Learning of Writing Skills in Patients with Parkinson's Disease with Freezing of Gait.

PubMed

Heremans, Elke; Nackaerts, Evelien; Vervoort, Griet; Broeder, Sanne; Swinnen, Stephan P; Nieuwboer, Alice

2016-01-01

Patients with Parkinson's disease (PD) and freezing of gait (FOG) suffer from more impaired motor and cognitive functioning than their non-freezing counterparts. This underlies an even higher need for targeted rehabilitation programs in this group. However, so far it is unclear whether FOG affects the ability for consolidation and generalization of motor learning and thus the efficacy of rehabilitation. To investigate the hallmarks of motor learning in people with FOG compared to those without by comparing the effects of an intensive motor learning program to improve handwriting. Thirty five patients with PD, including 19 without and 16 with FOG received six weeks of handwriting training consisting of exercises provided on paper and on a touch-sensitive writing tablet. Writing training was based on single- and dual-task writing and was supported by means of visual target zones. To investigate automatization, generalization and retention of learning, writing performance was assessed before and after training in the presence and absence of cues and dual tasking and after a six-week retention period. Writing amplitude was measured as primary outcome measure and variability of writing and dual-task accuracy as secondary outcomes. Significant learning effects were present on all outcome measures in both groups, both for writing under single- and dual-task conditions. However, the gains in writing amplitude were not retained after a retention period of six weeks without training in the patient group without FOG. Furthermore, patients with FOG were highly dependent on the visual target zones, reflecting reduced generalization of learning in this group. Although short-term learning effects were present in both groups, generalization and retention of motor learning were specifically impaired in patients with PD and FOG. The results of this study underscore the importance of individualized rehabilitation protocols.

Impact of Bt-corn MON88017 in comparison to three conventional lines on Trigonotylus caelestialium (Kirkaldy) (Heteroptera: Miridae) field densities.

PubMed

Rauschen, Stefan; Schultheis, Eva; Pagel-Wieder, Sibylle; Schuphan, Ingolf; Eber, Sabine

2009-04-01

In Europe, Bt-corn resistant against the European Corn Borer has until now been the only genetically modified plant to be grown commercially. With the advent of the Western Corn Rootworm Bt-corn varieties with resistance against Coleoptera will become important. The cultivation of Bt-plants may have negative impacts on non-target organisms, i.e. all species not explicitly targeted by a given Bt-crop. One prominent non-target group in corn are the herbivorous plant bugs (Heteroptera: Miridae). They are common, abundant and exposed to the Cry-protein. We therefore assessed the potential impact of the cultivation of the Cry3Bb1-expressing Bt-corn variety MON88017 and three conventional varieties on this group. Trigonotylus caelestialium (Kirkaldy) was the most abundant plant bug at the experimental field. There was no evidence for a negative impact of MON88017 on this species, despite its considerable exposure to Cry3Bb1 demonstrated with ELISA. The conventional corn varieties, however, had a consistent and significant influence on the field densities of this species over all three growing seasons.

The role of calcium signalling in the chondrogenic response of mesenchymal stem cells to hydrostatic pressure.

PubMed

Steward, A J; Kelly, D J; Wagner, D R

2014-10-28

The object of this study was to elucidate the role of Ca++ signalling in the chondrogenic response of mesenchymal stem cells (MSCs) to hydrostatic pressure (HP). MSCs were seeded into agarose hydrogels, subjected to HP or kept in free swelling conditions, and were cultured either with or without pharmacological inhibitors of Ca++ mobility and downstream targets. Chelating free Ca++, inhibiting voltage-gated calcium channels, and depleting intracellular calcium storessuppressed the beneficial effect of HP on chondrogenesis, indicating that Ca++ mobility may play an important role in the mechanotransduction of HP. However, inhibition of stretch-activated calcium channels in the current experiment yielded similar results to the control group, suggesting that mechanotransduction of HP is distinct from loads that generate cell deformations. Inhibition of the downstream targets calmodulin, calmodulin kinase II, and calcineurin all knocked down the effect of HP on chondrogenesis, implicating these targets in MSCs response to HP. All of the pharmacological inhibitors that abolished the chondrogenic response to HP also maintained a punctate vimentin organisation in the presence of HP, as opposed to the mechanoresponsive groups where the vimentin structure became more diffuse. These results suggest that Ca++ signalling may transduce HP via vimentin adaptation to loading.

Current progress of targetron technology: development, improvement and application in metabolic engineering.

PubMed

Liu, Ya-Jun; Zhang, Jie; Cui, Gu-Zhen; Cui, Qiu

2015-06-01

Targetrons are mobile group II introns that can recognize their DNA target sites by base-pairing RNA-DNA interactions with the aid of site-specific binding reverse transcriptases. Targetron technology stands out from recently developed gene targeting methods because of the flexibility, feasibility, and efficiency, and is particularly suitable for the genetic engineering of difficult microorganisms, including cellulolytic bacteria that are considered promising candidates for biomass conversion via consolidated bioprocessing. Along with the development of the thermotargetron method for thermophiles, targetron technology becomes increasingly important for the metabolic engineering of industrial microorganisms aiming at biofuel/chemical production. To summarize the current progress of targetron technology and provide new insights on the use of the technology, this paper reviews the retrohoming mechanisms of both mesophilic and thermophilic targetron methods based on various group II introns, investigates the improvement of targetron tools for high target efficiency and specificity, and discusses the current applications in the metabolic engineering for bacterial producers. Although there are still intellectual property and technical restrictions in targetron applications, we propose that targetron technology will contribute to both biochemistry research and the metabolic engineering for industrial productions. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MicroRNA Signatures as Biomarkers and Therapeutic Target for CNS Embryonal Tumors: The Pros and the Cons

PubMed Central

Shalaby, Tarek; Fiaschetti, Giulio; Baumgartner, Martin; Grotzer, Michael A.

2014-01-01

Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients’ response to therapy is difficult to predict. They encompass medulloblastoma, atypical teratoid/rhabdoid tumors and a group of primitive neuroectodermal tumors. All are aggressive tumors with the tendency to disseminate throughout the central nervous system. The large amount of genomic and molecular data generated over the last 5–10 years encourages optimism that new molecular targets will soon improve outcomes. Recent neurobiological studies have uncovered the key role of microRNAs (miRNAs) in embryonal tumors biology and their potential use as biomarkers is increasingly being recognized and investigated. However the successful use of microRNAs as reliable biomarkers for the detection and management of pediatric brain tumors represents a substantial challenge. This review debates the importance of miRNAs in the biology of central nervous systemembryonal tumors focusing on medulloblastoma and atypical teratoid/rhabdoid tumors and highlights the advantages as well as the limitations of their prospective application as biomarkers and candidates for molecular therapeutic targets. PMID:25421247

Nucleotide excision repair is a potential therapeutic target in multiple myeloma

PubMed Central

Szalat, R; Samur, M K; Fulciniti, M; Lopez, M; Nanjappa, P; Cleynen, A; Wen, K; Kumar, S; Perini, T; Calkins, A S; Reznichenko, E; Chauhan, D; Tai, Y-T; Shammas, M A; Anderson, K C; Fermand, J-P; Arnulf, B; Avet-Loiseau, H; Lazaro, J-B; Munshi, N C

2018-01-01

Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents and therefore we here evaluate the role of nucleotide excision repair (NER), which is involved in the removal of bulky adducts and DNA crosslinks in MM. We first evaluated NER activity using a novel functional assay and observed a heterogeneous NER efficiency in MM cell lines and patient samples. Using next-generation sequencing data, we identified that expression of the canonical NER gene, excision repair cross-complementation group 3 (ERCC3), significantly impacted the outcome in newly diagnosed MM patients treated with alkylating agents. Next, using small RNA interference, stable knockdown and overexpression, and small-molecule inhibitors targeting xeroderma pigmentosum complementation group B (XPB), the DNA helicase encoded by ERCC3, we demonstrate that NER inhibition significantly increases sensitivity and overcomes resistance to alkylating agents in MM. Moreover, inhibiting XPB leads to the dual inhibition of NER and transcription and is particularly efficient in myeloma cells. Altogether, we show that NER impacts alkylating agents sensitivity in myeloma cells and identify ERCC3 as a potential therapeutic target in MM. PMID:28588253

Evaluation of the Efficiency of the Nursing Care Plan Applied Using NANDA, NOC, and NIC Linkages to Elderly Women with Incontinence Living in a Nursing Home: A Randomized Controlled Study.

PubMed

Gencbas, Dercan; Bebis, Hatice; Cicek, Hatice

2017-05-30

Evaluate the efficiency of the nursing care plan, applied with the use of NANDA-I, NOC, and NIC (NNN) linkages, for elderly women with incontinence who live in nursing homes. A randomized controlled experimental design was applied. NNN linkages were prepared and applied for 12 weeks in an experimental group. NOC scales were evaluated again for two groups. A 0.5 NOC point change targeted in all elderly in the experimental group were provided between pretest-posttest scores. The experimental group had higher life quality and lower incontinence severity/symptoms than the control group. It is important that NNN linkages effective for solving the problems are used in different groups and with larger samples to create further evidence linking NNN. © 2017 NANDA International, Inc.

Applying cognitive training to target executive functions during early development.

PubMed

Wass, Sam V

2015-01-01

Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development.

Applying cognitive training to target executive functions during early development

PubMed Central

Wass, Sam V.

2015-01-01

Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development. PMID:24511910

Belonging and doing: important factors for satisfaction with sexual relations as perceived by people with persistent mental illness.

PubMed

Eklund, Mona; Ostman, Margareta

2010-07-01

It is increasingly acknowledged that satisfaction with sexual relations forms an important aspect of people's lives, but little is known of factors associated with this phenomenon among people with mental illness. This study aimed to investigate how demographic, social, clinical, and health-related factors were related to satisfaction with sexual relations. Patients with persistent mental illness (N = 103), recruited from an outpatient unit, were assessed regarding the target variables. No clinical variable, and only one demographic factor, namely being a cohabitant, was found to be important to satisfaction with sexual relations. Several social factors, pertaining to how everyday occupations were valued and how the social network was perceived, were shown to be of importance. General quality of life, but not self-rated health or interviewer-assessed psychopathology, was also important for satisfaction with sexual relations. A multivariate analysis showed that the most significant factor for satisfaction with sexual relations was how everyday activities were valued, and being a cohabitant explained some additional variation. Previous research indicates that the mental health care services largely neglect sexual problems among people with mental illness, and the findings may provide additional knowledge that may be used in the support of this target group.

Chimeric origins of ochrophytes and haptophytes revealed through an ancient plastid proteome

PubMed Central

Dorrell, Richard G; Gile, Gillian; McCallum, Giselle; Méheust, Raphaël; Bapteste, Eric P; Klinger, Christen M; Brillet-Guéguen, Loraine; Freeman, Katalina D; Richter, Daniel J; Bowler, Chris

2017-01-01

Plastids are supported by a wide range of proteins encoded within the nucleus and imported from the cytoplasm. These plastid-targeted proteins may originate from the endosymbiont, the host, or other sources entirely. Here, we identify and characterise 770 plastid-targeted proteins that are conserved across the ochrophytes, a major group of algae including diatoms, pelagophytes and kelps, that possess plastids derived from red algae. We show that the ancestral ochrophyte plastid proteome was an evolutionary chimera, with 25% of its phylogenetically tractable nucleus-encoded proteins deriving from green algae. We additionally show that functional mixing of host and plastid proteomes, such as through dual-targeting, is an ancestral feature of plastid evolution. Finally, we detect a clear phylogenetic signal from one ochrophyte subgroup, the lineage containing pelagophytes and dictyochophytes, in plastid-targeted proteins from another major algal lineage, the haptophytes. This may represent a possible serial endosymbiosis event deep in eukaryotic evolutionary history. DOI: http://dx.doi.org/10.7554/eLife.23717.001 PMID:28498102

Dacarbazine-Loaded Hollow Mesoporous Silica Nanoparticles Grafted with Folic Acid for Enhancing Antimetastatic Melanoma Response.

PubMed

Liu, Qianqian; Xu, Nan; Liu, Liping; Li, Jun; Zhang, Yamin; Shen, Chen; Shezad, Khurram; Zhang, Lianbin; Zhu, Jintao; Tao, Juan

2017-07-05

Dacarbazine (DTIC) is one of the most important chemotherapeutic agents for the treatment of melanoma; however, its poor solubility, photosensitivity, instability, and serious toxicity to normal cells limit its clinical applications. In this article, we present a rationally designed nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for the encapsulation and targeted release of DTIC for eradicating melanoma. The nanocarrier (DTIC@HMLBFs) is prepared by modifying HMSNs with carboxyl groups to enhance the loading of DTIC, followed by further enveloping of folic acid-grafted liposomes, which act as a melanoma active target for controlled and targeted drug release. In vitro, DTIC@HMLBFs exhibited the strongest cytotoxicity to melanoma cells compared with DTIC@HMSNs and free DTIC. The in vivo investigations demonstrate that the rationally designed nanocarrier loaded with DTIC achieves significant improvement against lung metastasis of melanoma via targeting melanoma cells and tumor-associated macrophages. This study provides a promising platform for the design and fabrication of multifunctional nanomedicines, which are potentially useful for the treatment of melanoma.

The effect of targeted wide age range SIAs in reducing measles incidence in the African Region.

PubMed

Masresha, Balcha; Luce, Richard; Katsande, Regis; Fall, Amadou; Eshetu, Meseret; Mihigo, Richard

2017-01-01

Periodic measles supplemental immunisation activities (SIAs) increase population immunity and thereby reduce the pool of accumulated susceptible children. They are typically conducted every 2 - 4 years, and most often target children up to five years of age. Between 2012 and 2015, after surveillance data indicated a shift in the epidemiological profile of measles towards older age groups, 11 countries were supported to conduct wide age range SIAs based on their local epidemiological patterns. Six other countries conducted SIAs with measles-rubella vaccines targeting ages 9 months to 14 years as an initial step of introducing rubella vaccine into the immunization program. In subsequent years, the incidence of confirmed measles dropped significantly in 13 of the 17 countries reviewed. The findings emphasize the importance of well-functioning surveillance systems, and the benefits of using of surveillance data to determine the specific target age-range for periodic SIAs to accelerate progress towards measles elimination.

Gene silencing efficiency and INF-β induction effects of splicing miRNA 155-based artificial miRNA with pre-miRNA stem-loop structures.

PubMed

Sin, Onsam; Mabiala, Prudence; Liu, Ye; Sun, Ying; Hu, Tao; Liu, Qingzhen; Guo, Deyin

2012-02-01

Artificial microRNA (miRNA) expression vectors have been developed and used for RNA interference. The secondary structure of artificial miRNA is important for RNA interference efficacy. We designed two groups of six artificial splicing miRNA 155-based miRNAs (SM155-based miRNAs) with the same target in the coding region or 3' UTR of a target gene and studied their RNA silencing efficiency and interferon β (IFN-β) induction effects. SM155-based miRNA with a mismatch at the +1 position and a bulge at the +11, +12 positions in a miRNA precursor stem-loop structure showed the highest gene silencing efficiency and lowest IFN-β induction effect (increased IFN-β mRNA level by 10% in both target cases), regardless of the specificity of the target sequence, suggesting that pSM155-based miRNA with this design could be a valuable miRNA expression vector.

Apatinib as targeted therapy for sarcoma

PubMed Central

Li, Feng; Liao, Zhichao; Zhang, Chao; Zhao, Jun; Xing, Ruwei; Teng, Sheng; Zhang, Jin; Yang, Yun; Yang, Jilong

2018-01-01

Sarcomas are a group of malignant tumors originating from mesenchymal tissue with a variety of cell subtypes. Despite several major treatment breakthroughs, standard treatment using surgery, radiation, and chemotherapy has failed to improve overall survival. Therefore, there is an urgent need to explore new strategies and innovative therapies to further improve the survival rates of patients with sarcomas. Pathological angiogenesis has an important role in the growth and metastasis of tumors. Vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFRs) play a central role in tumor angiogenesis and represent potential targets for anticancer therapy. As a novel targeted therapy, especially with regard to angiogenesis, apatinib is a new type of small molecule tyrosine kinase inhibitor that selectively targets VEGFR-2 and has shown encouraging anticancer activity in a wide range of malignancies, including gastric cancer, non-small cell lung cancer, breast cancer, hepatocellular carcinoma, and sarcomas. In this review, we summarize the preclinical and clinical data for apatinib, focusing primarily on its use in the treatment of sarcomas. PMID:29849960

The effect of targeted wide age range SIAs in reducing measles incidence in the African Region

PubMed Central

Masresha, Balcha; Luce, Richard; Katsande, Regis; Fall, Amadou; Eshetu, Meseret; Mihigo, Richard

2017-01-01

Periodic measles supplemental immunisation activities (SIAs) increase population immunity and thereby reduce the pool of accumulated susceptible children. They are typically conducted every 2 – 4 years, and most often target children up to five years of age. Between 2012 and 2015, after surveillance data indicated a shift in the epidemiological profile of measles towards older age groups, 11 countries were supported to conduct wide age range SIAs based on their local epidemiological patterns. Six other countries conducted SIAs with measles-rubella vaccines targeting ages 9 months to 14 years as an initial step of introducing rubella vaccine into the immunization program. In subsequent years, the incidence of confirmed measles dropped significantly in 13 of the 17 countries reviewed. The findings emphasize the importance of well-functioning surveillance systems, and the benefits of using of surveillance data to determine the specific target age-range for periodic SIAs to accelerate progress towards measles elimination. PMID:29296148

Ethiopia: hard work for successful AIDS prevention.

PubMed

1992-01-01

An innovative AIDS control program targeting sex workers and clients in Ethiopia has shown that hard work and government support are essential for the success of a program. Serosurveys conducted in 1988 and 1989 had shown that certain groups were particularly vulnerable to HIV infection: women who engage in formal or informal prostitution and their clients -- often migrant workers or truck drivers. So in mid-1990, Ethiopia's Department of AIDS Control (DAC) launched an intervention effort targeting these high-risk groups, a program entitled the Multiple Partner Sexual Contact (MPSC) Female and Male Mobilization and Condom Promotion Project. The program had a 3-layer strategy: 1) establishing a "trickle down" training process, which would create a network of MPSC peer educators and organizers; 2) identifying MPSC men to serve as educators for other men; and 3) ensuring the widespread availability of condoms for both men and women. As site for its pilot project, DAC selected Nazareth, a trading city of more than 30% among MPSC females. After 6 months of operation, the program's effectiveness convinced DAC to expand the project to 9 additional sites. An evaluation of the project has revealed several important findings: 1) retraining and motivation sessions must be constantly maintained; 2) men's resistance to condom use may be diminished by targeting them with education at the same time as the women; 3) interventions that take into account the socioeconomic issues faced by MPSC women make the program more effective; 4) it is important to develop new educational materials periodically; and 5) involving the owners and managers of sex-related businesses makes the program more effective.

PROSPECT: Profiling of Resistance Patterns & Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

DTIC Science & Technology

2012-06-01

neoadjuvant therapies on disease-free, progression-free, and overall survival will vary across prognostically distinct groups. 3. Specific molecular... prognostically distinct subpopulations of patients with resectable NSCLC, and to assess the extent to which these molecular profiles correlate with tumor...overall survival, and will use Cox proportional hazards models and recursive partitioning methods to identify important biomarkers and prognostically

Using fear appeals in advertising for AIDS prevention in the college-age population.

PubMed

LaTour, M S; Pitts, R E

1989-09-01

A multiple-indicator model reveals the impact of AIDS prevention advertising on dimensions of arousal and subsequent cognitive impressions of the advertisement. Exploratory results obtained from a sample of college students indicate that levels of arousal and impressions of the advertisement vary according to emphasis on the deadly consequences of AIDS. These findings have strategic implications for addressing important target groups such as college students.

Variations in accommodation and convergence responses in a minimally controlled photorefractive setting.

PubMed

Horwood, A M; Turner, J E; Houston, S M; Riddell, P M

2001-11-01

A remote haploscopic photorefractor, designed for assessment of accommodation and convergence in infants and clinical groups, was used to determine heterophoria accommodative convergence/accommodation (AC/A) ratios in normal naïve adults. These were compared with conventional clinical measures. Twenty-one naïve subjects were used to compare occluded and unoccluded prism cover test responses with the remote haploscopic photorefractor using a text and picture target. Although luminance was generally low for both targets, binocular vergences were appropriate for target demand in both studies. Binocular accommodation showed greater lag for the highest target accommodative demand and the less demanding target. Occlusion not only reduced vergence response, but also frequently caused a marked reduction in accommodation, especially to the picture target. Normal mean AC/A values were found, but with wide variations between individual subjects. Although mean accommodation, vergence, and AC/A values were comparable with published data, we suggest that in these conditions using naïve subjects, accommodation is frequently inaccurate, especially on occlusion, without concomitant loss of vergence, at least at low light levels. Accommodative convergence may play a less important part in, and other cues contribute more to, the near reflex than has been previously suggested.

Development of targeted messages to promote smoking cessation among construction trade workers.

PubMed

Strickland, J R; Smock, N; Casey, C; Poor, T; Kreuter, M W; Evanoff, B A

2015-02-01

Blue-collar workers, particularly those in the construction trades, are more likely to smoke and have less success in quitting when compared with white-collar workers. Little is known about health communication strategies that might influence this priority population. This article describes our formative work to develop targeted messages to increase participation in an existing smoking cessation program among construction workers. Using an iterative and sequential mixed-methods approach, we explored the culture, health attitudes and smoking behaviors of unionized construction workers. We used focus group and survey data to inform message development, and applied audience segmentation methods to identify potential subgroups. Among 144 current smokers, 65% reported wanting to quit smoking in the next 6 months and only 15% had heard of a union-sponsored smoking cessation program, despite widespread advertising. We tested 12 message concepts and 26 images with the target audience to evaluate perceived relevance and effectiveness. Participants responded most favorably to messages and images that emphasized family and work, although responses varied by audience segments based on age and parental status. This study is an important step towards integrating the culture of a high-risk group into targeted messages to increase participation in smoking cessation activities. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Knowledge-based identification of the ERK2/STAT3 signal pathway as a therapeutic target for type 2 diabetes and drug discovery.

PubMed

Kinoshita, Takayoshi; Doi, Kentaro; Sugiyama, Hajime; Kinoshita, Shuhei; Wada, Mutsuyo; Naruto, Shuji; Tomonaga, Atsushi

2011-09-01

Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which has an important role in the recognition of cognate kinases, phosphatases, scaffold proteins, and substrates. The peptide inhibitor was confirmed to exert effects in vitro and in vivo. The peptide inhibitor conferred a significant decrease in HOMA-IR levels on Day 28 compared with that in the vehicle group. Besides lowering the fasting blood glucose level, the peptide inhibitor also attenuated the blood glucose increment in the fed state, as compared with the vehicle group. © 2011 John Wiley & Sons A/S.

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

Lim, Karen; Small, William; Portelance, Lorraine

Purpose: Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group. Methods and Materials: A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aidmore » in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants. Results: Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate. Conclusions: This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting.« less

An oyster species-specific miRNA scaffold42648_5080 modulates haemocyte migration by targeting integrin pathway.

PubMed

Chen, Hao; Wang, Hao; Jiang, Shuai; Xu, Jiachao; Wang, Lingling; Qiu, Limei; Song, Linsheng

2016-10-01

miRNAs are important gene regulators at post-transcriptional level and can modulate diverse biological processes, including immune response. Dozens of species-specific miRNAs have been identified in oyster Crassostrea gigas while their functions remain largely unknown. In the present study, an oyster species-specific miRNA scaffold42648_5080 was found responsive to LPS stimulation and might target a total of 31 oyster genes possibly involved in cell communication, cellular localization and cellular response to stimulus. Besides, in gain-of-function assay of scaffold42648_5080 in vivo, the phagocytosis (30.90% in miRNA group verse 23.20% in miRNA control group), apoptosis (3.10% in miRNA group verse 5.30% in miRNA control group) and migration rate (13.88% in miRNA group verse 21.03% in miRNA control group) of oyster haemocytes were found significantly altered after the injection of scaffold42648_5080 mimics. Among the target genes, integrin-linked kinase (CgILK) was considered crucial in cell migration and its interaction with scaffold42648_5080 was then verified both in vitro and in vivo. Consequently, a significant decrease of relative luciferase ratio was observed in CgILK 3'-UTR luciferase reporter assay after transfection of scaffold42648_5080 mimics (0.70-fold of that in blank group, p < 0.01). Meanwhile, when scaffold42648_5080 was overexpressed in vivo (5.41-fold of miRNA control group, p < 0.01), the expression of CgILK declined significantly to 0.25-fold of miRNA control group (p < 0.01). Comparatively, a significant decrease of the haemocyte migration rate (19.76% verse 34.82% in siEGFP control group, p < 0.01) was observed after knock-down of CgILK in vivo. The present study, as far as we know, for the first time revealed the immunomodulation role of an oyster species-specific miRNA, which might provide new insights into miRNA-mediated adaptation mechanism of oysters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mapping the Barriers and Facilitators of HCV Treatment Initiation in Methadone Maintenance Therapy Patients: Implications for Intervention Development.

PubMed

Bass, Sarah Bauerle; Jessop, Amy; Maurer, Laurie; Gashat, Muhamed; Al Hajji, Mohammed; Gutierrez, Mercedes

2018-01-01

An estimated 70-90% of current methadone users have Hepatitis C (HCV). Current treatments have few side effects and can cure infection in 8-12 weeks, but less than 10% of methadone patients initiate treatment. Engaging this group in treatment is an important strategy to lower both morbidity and mortality from liver disease and eliminate a significant reservoir of HCV in communities. To understand how to address this treatment gap we used commercial marketing techniques called perceptual mapping and vector message modeling to analyze survey data from 100 HCV+ methadone patients from four centers in Philadelphia. Results were used to understand barriers and facilitators to treatment initiation and to devise targeted message strategies to adapt to a mobile health communication intervention. Results indicate that focusing on how treatment can make one feel "in charge", positive interactions with healthcare providers, the positive attributes of the new vs. old HCV treatments, and providing strategies to address tangible barriers to getting treatment, would be important to address in a communication intervention. These marketing methods allow for focusing on specific variables to "move" the group toward a treatment decision, making them an innovative technique to use in developing highly targeted health communication messages.

Identifying policy target groups with qualitative and quantitative methods: the case of wildfire risk on nonindustrial private forest lands

Treesearch

A. Paige Fischer

2012-01-01

Designing policies to harness the potential of heterogeneous target groups such as nonindustrial private forest owners to contribute to public policy goals can be challenging. The behaviors of such groups are shaped by their diverse motivations and circumstances. Segmenting heterogeneous target groups into more homogeneous subgroups may improve the chances of...

Molecular profiling of sarcomas: new vistas for precision medicine.

PubMed

Al-Zaid, Tariq; Wang, Wei-Lien; Somaiah, Neeta; Lazar, Alexander J

2017-08-01

Sarcoma is a large and heterogeneous group of malignant mesenchymal neoplasms with significant histological overlap. Accurate diagnosis can be challenging yet important for selecting the appropriate treatment approach and prognosis. The currently torrid pace of new genomic discoveries aids our classification and diagnosis of sarcomas, understanding of pathogenesis, development of new medications, and identification of alterations that predict prognosis and response to therapy. Unfortunately, demonstrating effective targets for precision oncology has been elusive in most sarcoma types. The list of potential targets greatly outnumbers the list of available inhibitors at the present time. This review will discuss the role of molecular profiling in sarcomas in general with emphasis on selected entities with particular clinical relevance.

Non-compact nonlinear sigma models

DOE PAGES

de Rham, Claudia; Tolley, Andrew J.; Zhou, Shuang-Yong

2016-07-19

The target space of a nonlinear sigma model is usually required to be positive definite to avoid ghosts. We introduce a unique class of nonlinear sigma models where the target space metric has a Lorentzian signature, thus the associated group being non-compact. We show that the would-be ghost associated with the negative direction is fully projected out by 2 second-class constraints, and there exist stable solutions in this class of models. This result also has important implications for Lorentz–invariant massive gravity: There exist stable nontrivial vacua in massive gravity that are free from any linear vDVZ-discontinuity and a decoupling limitmore » can be defined on these vacua.« less

Non-compact nonlinear sigma models

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

de Rham, Claudia; Tolley, Andrew J.; Zhou, Shuang-Yong

The target space of a nonlinear sigma model is usually required to be positive definite to avoid ghosts. We introduce a unique class of nonlinear sigma models where the target space metric has a Lorentzian signature, thus the associated group being non-compact. We show that the would-be ghost associated with the negative direction is fully projected out by 2 second-class constraints, and there exist stable solutions in this class of models. This result also has important implications for Lorentz–invariant massive gravity: There exist stable nontrivial vacua in massive gravity that are free from any linear vDVZ-discontinuity and a decoupling limitmore » can be defined on these vacua.« less

Tailoring hospital marketing efforts to physicians' needs.

PubMed

Mackay, J M; Lamb, C W

1988-12-01

Marketing has become widely recognized as an important component of hospital management (Kotler and Clarke 1987; Ludke, Curry, and Saywell 1983). Physicians are becoming recognized as an important target market that warrants more marketing attention than it has received in the past (Super 1987; Wotruba, Haas, and Hartman 1982). Some experts predict that hospitals will begin focusing more marketing attention on physicians and less on consumers (Super 1986). Much of this attention is likely to take the form of practice management assistance, such as computer-based information system support or consulting services. The survey results reported here are illustrative only of how one hospital addressed the problem of physician need assessment. Other potential target markets include physicians who admit patients only to competitor hospitals and physicians who admit to multiple hospitals. The market might be segmented by individual versus group practice, area of specialization, or possibly even physician practice life cycle stage (Wotruba, Haas, and Hartman 1982). The questions included on the survey and the survey format are likely to be situation-specific. The key is the process, not the procedure. It is important for hospital marketers to recognize that practice management assistance needs will vary among markets (Jensen 1987). Therefore, hospitals must carefully identify their target physician market(s) and survey them about their specific needs before developing and implementing new physician marketing programs. Only then can they be reasonably confident that their marketing programs match their customers' needs.

Accumulation patterns of lipophilic organic contaminants in surface sediments and in economic important mussel and fish species from Jakarta Bay, Indonesia.

PubMed

Dwiyitno; Dsikowitzky, Larissa; Nordhaus, Inga; Andarwulan, Nuri; Irianto, Hari Eko; Lioe, Hanifah Nuryani; Ariyani, Farida; Kleinertz, Sonja; Schwarzbauer, Jan

2016-09-30

Non-target screening analyses were conducted in order to identify a wide range of organic contaminants in sediment and animal tissue samples from Jakarta Bay. High concentrations of di-iso-propylnaphthalenes (DIPNs), linear alkylbenzenes (LABs) and polycyclic aromatic hydrocarbons (PAHs) were detected in all samples, whereas phenylmethoxynaphthalene (PMN), DDT and DDT metabolites (DDX) were detected at lower concentrations. In order to evaluate the uptake and accumulation by economic important mussel (Perna viridis) and fish species, contaminant patterns of DIPNs, LABs and PAHs in different compartments were compared. Different patterns of these contaminant groups were found in sediment and animal tissue samples, suggesting compound-specific accumulation and metabolism processes. Significantly higher concentrations of these three contaminant groups in mussel tissue as compared to fish tissue from Jakarta Bay were found. Because P. viridis is an important aquaculture species in Asia, this result is relevant for food safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of a road safety educational program for kindergarten children on their parents' behavior and knowledge.

PubMed

Ben-Bassat, Tamar; Avnieli, Shani

2016-10-01

Road safety education for children is one of the most important means for raising awareness of road safety and for educating children to behave safely as pedestrians, bicycle riders, and vehicle passengers. The current research presents a novel attempt to examine the effect of a unique road safety educational program for kindergarten children on a secondary target group-the parents. The program, named the "Zahav Bagan" program (ZBP), is presented at kindergartens once a week during the entire academic year. It is conducted by senior citizen volunteers and is part of the formal education of the children. The main purpose of the current study was to compare the behavior, awareness, and knowledge about child road safety, of two groups of parents-those whose children participated in the ZBP group, and those whose children did not; this latter group was the control group. A telephone-based survey was conducted using a sample of 76 ZBP parents and 59 control group parents. Results of the survey showed no effect of ZBP on parents' knowledge of child road safety law and recommendations, but more importantly, the results did show a significant effect in terms of parents' observance of safe behavior and in their awareness of road safety in everyday life. These results confirm the importance of educational programs on road safety, especially as triggers and reminders to children and to their parents, to act as cautious road users. Copyright © 2016 Elsevier Ltd. All rights reserved.

Constraints on global temperature target overshoot.

PubMed

Ricke, K L; Millar, R J; MacMartin, D G

2017-11-07

In the aftermath of the Paris Agreement, the climate science and policy communities are beginning to assess the feasibility and potential benefits of limiting global warming to 1.5 °C or 2 °C above preindustrial. Understanding the dependence of the magnitude and duration of possible temporary exceedance (i.e., "overshoot") of temperature targets on sustainable energy decarbonization futures and carbon dioxide (CO 2 ) removal rates will be an important contribution to this policy discussion. Drawing upon results from the mitigation literature and the IPCC Working Group 3 (WG3) scenario database, we examine the global mean temperature implications of differing, independent pathways for the decarbonization of global energy supply and the implementation of negative emissions technologies. We find that within the scope of scenarios broadly-consistent with the WG3 database, the magnitude of temperature overshoot is more sensitive to the rate of decarbonization. However, limiting the duration of overshoot to less than two centuries requires ambitious deployment of both decarbonization and negative emissions technology. The dependencies of temperature target overshoot's properties upon currently untested negative emissions technologies suggests that it will be important to consider how climate impacts depend on both the magnitude and duration of overshoot, not just long term residual warming.

Causes of CNS inflammation and potential targets for anticonvulsants.

PubMed

Falip, Mercé; Salas-Puig, Xavier; Cara, Carlos

2013-08-01

Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

Parentally-adjusted deficit of height as a prognostic factor of the effectiveness of growth hormone (GH) therapy in children with GH deficiency.

PubMed

Hilczer, Maciej; Smyczyńska, Joanna; Lewiński, Andrzej

2006-01-01

Parental height is the most important identifiable factor influencing final height (FH) of children with growth hormone (GH) deficiency (GHD), treated with GH. Assessment of FH of patients with GHD--classified into familial short stature (FSS) and non-familial short stature (non-FSS) according to parentally adjusted deficit of height. The analysis comprised 101 patients (76 boys) with childhood-onset GHD. Final height was compared with patients' height before GH therapy, predicted adult height (PAH) and target height (TH). Both GH peak in stimulating tests and height standard deviation score (SDS) before the therapy were significantly lower in non-FSS than in FSS. Target height was significantly lower in FSS than in non-FSS. Parentally-adjusted deficit of height was significantly more profound in non-FSS than in FSS. The prognosis of adult height was very similar in both groups of patients, being significantly worse in non-FSS than in FSS while corrected by TH. The absolute FH was similar in FSS and non-FSS, being, however, significantly lower in non-FSS than in FSS while corrected by TH. Improvement of height was significantly better in non-FSS than in FSS. In both groups, FH SDS was significantly better than height SDS before the therapy (H0SDS). In FSS group, PAH was similar to TH, moreover, FH corresponded to both PAH and TH. In non-FSS group FH was significantly higher than PAH, but both FH and PAH were significantly lower than TH. 1) Growth hormone therapy was more effective in the patients with non-FSS than in those with FSS. 2) Parentally-adjusted deficit of height is an important prognostic factor of GH therapy effectiveness.

Assessing Terrorist Motivations for Attacking Critical Infrastructure

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

Ackerman, G; Abhayaratne, P; Bale, J

Certain types of infrastructure--critical infrastructure (CI)--play vital roles in underpinning our economy, security and way of life. These complex and often interconnected systems have become so ubiquitous and essential to day-to-day life that they are easily taken for granted. Often it is only when the important services provided by such infrastructure are interrupted--when we lose easy access to electricity, health care, telecommunications, transportation or water, for example--that we are conscious of our great dependence on these networks and of the vulnerabilities that stem from such dependence. Unfortunately, it must be assumed that many terrorists are all too aware that CImore » facilities pose high-value targets that, if successfully attacked, have the potential to dramatically disrupt the normal rhythm of society, cause public fear and intimidation, and generate significant publicity. Indeed, revelations emerging at the time of this writing about Al Qaida's efforts to prepare for possible attacks on major financial facilities in New York, New Jersey, and the District of Columbia remind us just how real and immediate such threats to CI may be. Simply being aware that our nation's critical infrastructure presents terrorists with a plethora of targets, however, does little to mitigate the dangers of CI attacks. In order to prevent and preempt such terrorist acts, better understanding of the threats and vulnerabilities relating to critical infrastructure is required. The Center for Nonproliferation Studies (CNS) presents this document as both a contribution to the understanding of such threats and an initial effort at ''operationalizing'' its findings for use by analysts who work on issues of critical infrastructure protection. Specifically, this study focuses on a subsidiary aspect of CI threat assessment that has thus far remained largely unaddressed by contemporary terrorism research: the motivations and related factors that determine whether a terrorist organization will attack critical infrastructure. In other words, this research investigates: (1) why terrorists choose to attack critical infrastructure rather than other targets; (2) how groups make such decisions; (3) what, if any, types of groups are most inclined to attack critical infrastructure targets; and (4) which types of critical infrastructure terrorists prefer to attack and why. In an effort to address the above questions as comprehensively as possible, the project team employed four discrete investigative approaches in its research design. These include: (1) a review of existing terrorism and threat assessment literature to glean expert consensus regarding terrorist target selection, as well as to identify theoretical approaches that might be valuable to analysts and decision-makers who are seeking to understand such terrorist group decision-making processes; (2) the preparation of several concise case studies to help identify internal group factors and contextual influences that have played significant roles in leading some terrorist groups to attack critical infrastructure; (3) the creation of a new database--the Critical Infrastructure Terrorist Incident Catalog (CrITC)--to capture a large sample of empirical CI attack data that might be used to illuminate the nature of such attacks to date; and (4) the development of a new analytical framework--the Determinants Effecting Critical Infrastructure Decisions (DECIDe) Framework--designed to make the factors and dynamics identified by the study more ''usable'' in any future efforts to assess terrorist intentions to target critical infrastructure. Although each is addressed separately in the following chapters, none of the four aspects of this study were developed in isolation. Rather, all the constituent elements of the project informed--and were informed by--the others. For example, the review of the available literature on terrorist target selection made possible the identification of several target selection factors that were both important in the development of the analytical framework and subsequently validated by the case studies. Similarly, statistical analysis of the CrITIC data yielded measurable evidence that supported hypotheses derived from the framework, the case studies, and the writings of various experts. Besides providing an important mechanism of self-reinforcement and validation, the project's multifaceted nature made it possible to discern aspects of CI attack motivations that would likely have been missed if any single approach had been adopted.« less

Morpholine Derivative-Functionalized Carbon Dots-Based Fluorescent Probe for Highly Selective Lysosomal Imaging in Living Cells.

PubMed

Wu, Luling; Li, Xiaolin; Ling, Yifei; Huang, Chusen; Jia, Nengqin

2017-08-30

The development of a suitable fluorescent probe for the specific labeling and imaging of lysosomes through the direct visual fluorescent signal is extremely important for understanding the dysfunction of lysosomes, which might induce various pathologies, including neurodegenerative diseases, cancer, and Alzheimer's disease. Herein, a new carbon dot-based fluorescent probe (CDs-PEI-ML) was designed and synthesized for highly selective imaging of lysosomes in live cells. In this probe, PEI (polyethylenimine) is introduced to improve water solubility and provide abundant amine groups for the as-prepared CDs-PEI, and the morpholine group (ML) serves as a targeting unit for lysosomes. More importantly, passivation with PEI could dramatically increase the fluorescence quantum yield of CDs-PEI-ML as well as their stability in fluorescence emission under different excitation wavelength. Consequently, experimental data demonstrated that the target probe CDs-PEI-ML has low cytotoxicity and excellent photostability. Additionally, further live cell imaging experiment indicated that CDs-PEI-ML is a highly selective fluorescent probe for lysosomes. We speculate the mechanism for selective staining of lysosomes that CDs-PEI-ML was initially taken up by lysosomes through the endocytic pathway and then accumulated in acidic lysosomes. It is notable that there was less diffusion of CDs-PEI-ML into cytoplasm, which could be ascribed to the presence of lysosome target group morpholine on surface of CDs-PEI-ML. The blue emission wavelength combined with the high photo stability and ability of long-lasting cell imaging makes CDs-PEI-ML become an alternative fluorescent probe for multicolor labeling and long-term tracking of lysosomes in live cells and the potential application in super-resolution imaging. To best of our knowledge, there are still limited carbon dots-based fluorescent probes that have been studied for specific lysosomal imaging in live cells. The concept of surface functionality of carbon dots will also pave a new avenue for developing carbon dots-based fluorescent probes for subcellular labeling.

Plasmodium falciparum malaria importation from Africa to China and its mortality: an analysis of driving factors

NASA Astrophysics Data System (ADS)

Lai, Shengjie; Wardrop, Nicola A.; Huang, Zhuojie; Bosco, Claudio; Sun, Junling; Bird, Tomas; Wesolowski, Amy; Zhou, Sheng; Zhang, Qian; Zheng, Canjun; Li, Zhongjie; Tatem, Andrew J.; Yu, Hongjie

2016-12-01

Plasmodium falciparum malaria importation from Africa to China is rising with increasing Chinese overseas investment and international travel. Identifying networks and drivers of this phenomenon as well as the contributors to high case-fatality rate is a growing public health concern to enable efficient response. From 2011-2015, 8653 P. falciparum cases leading to 98 deaths (11.3 per 1000 cases) were imported from 41 sub-Saharan countries into China, with most cases (91.3%) occurring in labour-related Chinese travellers. Four strongly connected groupings of origin African countries with destination Chinese provinces were identified, and the number of imported cases was significantly associated with the volume of air passengers to China (P = 0.006), parasite prevalence in Africa (P < 0.001), and the amount of official development assistance from China (P < 0.001) with investment in resource extraction having the strongest relationship with parasite importation. Risk factors for deaths from imported cases were related to the capacity of malaria diagnosis and diverse socioeconomic factors. The spatial heterogeneity uncovered, principal drivers explored, and risk factors for mortality found in the rising rates of P. falciparum malaria importation to China can serve to refine malaria elimination strategies and the management of cases, and high risk groups and regions should be targeted.

Group cognitive behavioral therapy targeting intolerance of uncertainty: a randomized trial for older Chinese adults with generalized anxiety disorder.

PubMed

Hui, Chen; Zhihui, Yang

2017-12-01

China has entered the aging society, but the social support systems for the elderly are underdeveloped, which may make the elderly feel anxiety about their health and life quality. Given the prevalence of generalized anxiety disorder (GAD) in the elderly, it is very important to pay more attention to the treatment for old adults. Although cognitive behavioral therapy targeting intolerance of uncertainty (CBT-IU) has been applied to different groups of patients with GAD, few studies have been performed to date. In addition, the effects of CBT-IU are not well understood, especially when applied to older adults with GAD. Sixty-three Chinese older adults with a principal diagnosis of GAD were enrolled. Of these, 32 were randomized to receive group CBT-IU (intervention group) and 31 were untreated (control group). GAD and related symptoms were assessed using the Penn State Worry Questionnaire, Intolerance of Uncertainty Scale-Chinese Version, Beck Anxiety Inventory, Beck Depression Inventory, Why Worry-II scale, Cognitive Avoidance Questionnaire, Generalized Anxiety Disorder Questionnaire-IV, and Generalized Anxiety Disorder Severity Scale across the intervention. The changes between pre and after the intervention were collected, as well as the six-month follow-up. F test and repeated-measures ANOVA were conducted to analyze the data. Compared to control group, the measures' scores of experimental group decreased significantly after the intervention and six-month follow-up. Besides the main effects for time and group were significant, the interaction effect for group × time was also significant. These results indicated the improvement of the CBT-IU group and the persistence of effect after six months. Group CBT-IU is effective in Chinese older adults with GAD. The effects of CBT-IU on GAD symptoms persist for at least six months after treatment.

A randomized trial of a community-based approach to dyslipidemia management: Pharmacist prescribing to achieve cholesterol targets (RxACT Study).

PubMed

Tsuyuki, Ross T; Rosenthal, Meagen; Pearson, Glen J

2016-09-01

Dyslipidemia is an important risk factor for cardiovascular disease but is suboptimally managed. Pharmacists are accessible primary care professionals and with expanded scopes of practice (including prescribing), could identify and manage patients with dyslipidemia. We sought to evaluate the effect of pharmacist prescribing of dyslipidemia medications on the proportion of participants achieving target LDL-cholesterol (LDL-c) levels. We conducted a randomized controlled trial in 14 community pharmacies in Alberta, Canada. We enrolled adults with uncontrolled dyslipidemia as defined by the 2009 Canadian Dyslipidemia Guidelines. Intervention was pharmacist-directed dyslipidemia care, including assessment of cardiovascular risk, review of LDL-c, prescribing of medications, health behaviour interventions and follow-up every 6 weeks for 6 months. Usual care patients received their lipid results and a pamphlet on cardiovascular disease and usual care from their physician and pharmacist. Primary outcome was the proportion of participants achieving their target LDL-c (<2 mmol/L or ≥50% reduction) at 6 months between groups. We enrolled 99 patients with a mean (SD) age of 63 (13) years, 49% male and baseline LDL-c of 3.37 mmol/L (0.98). Proportion of patients achieving LDL-c target was 43% intervention versus 18% control ( p = 0.007). Adjusted odds of achieving target LDL-c were 3.3 times higher for the intervention group ( p = 0.031), who also achieved greater reduction in LDL-c (1.12 mmol/L, SE = 0.112) versus control (0.42 mmol/L, SE = 0.109), for an adjusted mean difference of 0.546 mmol/L (SE = 0.157), p < 0.001. Pharmacist prescribing resulted in >3-fold more patients achieving target LDL-c levels. This could have major public health implications.

Heterogeneity effects in visual search predicted from the group scanning model.

PubMed

Macquistan, A D

1994-12-01

The group scanning model of feature integration theory (Treisman & Gormican, 1988) suggests that subjects search visual displays serially by groups, but process items within each group in parallel. The size of these groups is determined by the discriminability of the targets in the background of distractors. When the target is poorly discriminable, the size of the scanned group will be small, and search will be slow. The model predicts that group size will be smallest when targets of an intermediate value on a perceptual dimension are presented in a heterogeneous background of distractors that have higher and lower values on the same dimension. Experiment 1 demonstrates this effect. Experiment 2 controls for a possible confound of decision complexity in Experiment 1. For simple feature targets, the group scanning model provides a good account of the visual search process.

Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer.

PubMed

Lin, Meng-Lay; Patel, Hetal; Remenyi, Judit; Banerji, Christopher R S; Lai, Chun-Fui; Periyasamy, Manikandan; Lombardo, Ylenia; Busonero, Claudia; Ottaviani, Silvia; Passey, Alun; Quinlan, Philip R; Purdie, Colin A; Jordan, Lee B; Thompson, Alastair M; Finn, Richard S; Rueda, Oscar M; Caldas, Carlos; Gil, Jesus; Coombes, R Charles; Fuller-Pace, Frances V; Teschendorff, Andrew E; Buluwela, Laki; Ali, Simak

2015-08-28

The Nuclear Receptor (NR) superfamily of transcription factors comprises 48 members, several of which have been implicated in breast cancer. Most important is estrogen receptor-α (ERα), which is a key therapeutic target. ERα action is facilitated by co-operativity with other NR and there is evidence that ERα function may be recapitulated by other NRs in ERα-negative breast cancer. In order to examine the inter-relationships between nuclear receptors, and to obtain evidence for previously unsuspected roles for any NRs, we undertook quantitative RT-PCR and bioinformatics analysis to examine their expression in breast cancer. While most NRs were expressed, bioinformatic analyses differentiated tumours into distinct prognostic groups that were validated by analyzing public microarray data sets. Although ERα and progesterone receptor were dominant in distinguishing prognostic groups, other NR strengthened these groups. Clustering analysis identified several family members with potential importance in breast cancer. Specifically, RORγ is identified as being co-expressed with ERα, whilst several NRs are preferentially expressed in ERα-negative disease, with TLX expression being prognostic in this subtype. Functional studies demonstrated the importance of TLX in regulating growth and invasion in ERα-negative breast cancer cells.

Effect of different external attention of focus instruction on learning of golf putting skill.

PubMed

Shafizadeh, Mohsen; McMorris, Terry; Sproule, John

2011-10-01

The effect of different sources of external attentional focus on learning a motor skill was assessed in the present study. 30 students (12 men, 18 women) participated voluntarily and were divided, according to type of external focus, into target, club swing, and target-club swing groups. The task was a golf putting skill. The target focus group attended to the target (hole), the club swing focus group attended to the execution of the club's swing, and the target-club swing focus group attended to both. All participants performed 50 trials of the putting skill in the acquisition phase and 10 trials in the 24-hr. delayed retention phase. The dependent variable was the error in the putting skill measured as the distance from the hole to the ball after each strike. Results showed the target-club swing focus group had better scores in the acquisition and retention phases than the other groups. It was concluded that external focus instruction helped the learners to integrate target cue with action cue and is more effective in skill learning than other external-focus instructions. These results support the claims of ecological psychology theorists concerning the effects of external focus of attention.

Target Abundance-Based Fitness Screening (TAFiS) Facilitates Rapid Identification of Target-Specific and Physiologically Active Chemical Probes

PubMed Central

Butts, Arielle; DeJarnette, Christian; Peters, Tracy L.; Parker, Josie E.; Kerns, Morgan E.; Eberle, Karen E.; Kelly, Steve L.

2017-01-01

ABSTRACT Traditional approaches to drug discovery are frustratingly inefficient and have several key limitations that severely constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein are constructed, tagged with spectrally distinct fluorescent proteins (FPs), and pooled. The pooled strains are then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture is compared by measuring the intensity of the corresponding FP tags. Chemical-induced population shifts indicate that the bioactivity of a small molecule is dependent upon the target protein’s abundance and thus establish a specific functional interaction. Here, we describe the molecular tools required to apply this technique in the prevalent human fungal pathogen Candida albicans and validate the approach using two well-characterized drug targets—lanosterol demethylase and dihydrofolate reductase. However, our approach, which we have termed target abundance-based fitness screening (TAFiS), should be applicable to a wide array of molecular targets and in essentially any genetically tractable microbe. IMPORTANCE Conventional drug screening typically employs either target-based or cell-based approaches. The first group relies on biochemical assays to detect modulators of a purified target. However, hits frequently lack drug-like characteristics such as membrane permeability and target specificity. Cell-based screens identify compounds that induce a desired phenotype, but the target is unknown, which severely restricts further development and optimization. To address these issues, we have developed a second-generation target-based whole-cell screening approach that incorporates the principles of both chemical genetics and competitive fitness, which enables the identification of target-specific and physiologically active compounds from a single screen. We have chosen to validate this approach using the important human fungal pathogen Candida albicans with the intention of pursuing novel antifungal targets. However, this approach is broadly applicable and is expected to dramatically reduce the time and resources required to progress from screening hit to lead compound. PMID:28989971

A targeted resequencing gene panel for focal epilepsy.

PubMed

Hildebrand, Michael S; Myers, Candace T; Carvill, Gemma L; Regan, Brigid M; Damiano, John A; Mullen, Saul A; Newton, Mark R; Nair, Umesh; Gazina, Elena V; Milligan, Carol J; Reid, Christopher A; Petrou, Steven; Scheffer, Ingrid E; Berkovic, Samuel F; Mefford, Heather C

2016-04-26

We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies. The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing. We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases. We searched for both germline and somatic mutations in 251 patients with unsolved sporadic or familial focal epilepsy and identified 11 novel or very rare missense variants in 5 different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were predicted to be pathogenic or likely pathogenic, explaining ∼0.8% of the cohort, and 8 were of uncertain significance based on available data. We have developed and validated a targeted resequencing panel for focal epilepsies, the most important clinical class of epilepsies, accounting for about 60% of all cases. Our application of MIP technology is an innovative approach that will be advantageous in the clinical setting because it is highly sensitive, efficient, and cost-effective for screening large patient cohorts. Our findings indicate that mutations in known genes likely explain only a small proportion of focal epilepsy cases. This is not surprising given the established clinical and genetic heterogeneity of these disorders and underscores the importance of further gene discovery studies in this complex syndrome. © 2016 American Academy of Neurology.

Genome-wide identification and characterization of microRNA genes and their targets in flax (Linum usitatissimum): Characterization of flax miRNA genes.

PubMed

Barvkar, Vitthal T; Pardeshi, Varsha C; Kale, Sandip M; Qiu, Shuqing; Rollins, Meaghen; Datla, Raju; Gupta, Vidya S; Kadoo, Narendra Y

2013-04-01

MicroRNAs (miRNAs) are small (20-24 nucleotide long) endogenous regulatory RNAs that play important roles in plant growth and development. They regulate gene expression at the post-transcriptional level by translational repression or target degradation and gene silencing. In this study, we identified 116 conserved miRNAs belonging to 23 families from the flax (Linum usitatissimum L.) genome using a computational approach. The precursor miRNAs varied in length; while most of the mature miRNAs were 21 nucleotide long, intergenic and showed conserved signatures of RNA polymerase II transcripts in their upstream regions. Promoter region analysis of the flax miRNA genes indicated prevalence of MYB transcription factor binding sites. Four miRNA gene clusters containing members of three phylogenetic groups were identified. Further, 142 target genes were predicted for these miRNAs and most of these represent transcriptional regulators. The miRNA encoding genes were expressed in diverse tissues as determined by digital expression analysis as well as real-time PCR. The expression of fourteen miRNAs and nine target genes was independently validated using the quantitative reverse transcription PCR (qRT-PCR). This study suggests that a large number of conserved plant miRNAs are also found in flax and these may play important roles in growth and development of flax.

Community Priorities for Healthy Eating in Older Adults.

PubMed

Jiang, Qianzhi; Cohen, Nancy L; Marra, Melissa Ventura; Woolf, Kathleen; Gilbride, Judith; Francis, Sarah L

2017-01-01

Community planners such as policymakers and health care and nutrition service providers can create an "age-friendly" environment to support healthy eating in older residents by addressing the highest priorities that enable older adults to improve their dietary intake through different food-related community settings. To identify and prioritize these factors that facilitate behavioral change (enablers) and behavioral settings important for older adult nutrition based on the social ecological model, nutrition and aging professionals (n = 30) from two rural (West Virginia, Iowa) and two urban (Massachusetts, New York) city/county regions (communities) participated in an online or live focus group discussion and completed an analytic hierarchy process survey online. Overall, the most important perceived enablers were accessibility and cost, followed by transportation and social support, but their relative importance varied by community. Participants from all communities considered congregate meal sites and food banks among the most important behavioral settings. Participants from most communities considered food stores to be important and also highlighted other settings unique to the area, such as senior housing, neighborhood, and farmers' markets. By targeting interventions to address the most notable enablers and behavioral settings specific to their community, planning groups can enhance their older residents' ability to achieve optimal nutritional health.

Investigation and management of tall stature.

PubMed

Davies, Justin H; Cheetham, Tim

2014-08-01

Referral for an assessment of tall stature is much less common than for short stature. Although the commonest cause is an underlying familial tendency to tallness, there are important disorders that should be considered at the initial assessment. Distinguishing these conditions from normal variations of growth is the key objective when managing the child and family. In some children, further targeted investigations will be needed and in rare instances intervention to limit final height may be appropriate. This article discusses a structured approach to the assessment and management of a child with tall stature. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Opportunity costs and financial incentives for Hispanic youth participating in a family-based HIV and substance use preventive intervention.

PubMed

McCollister, Kathryn E; Freitas, Derek M; Prado, Guillermo; Pantin, Hilda

2014-02-01

This paper presents results from a pilot study of the synergies between the opportunity costs incurred by research participants, participant compensation, and program attendance in a family-based substance use and HIV preventive intervention for Hispanic adolescents in Miami-Dade County, Florida. To estimate parent/caretaker cost per session and cost for the duration of the intervention, we administered the Caretaker Drug Abuse Treatment Cost Analysis Program to a random sample of 34 families who participated in a recent clinical trial of Familias Unidas. The total opportunity cost per parent/caretaker was under $40 per group session, under $30 per family session, and just over $570 for the duration of the intervention. Participants were compensated between $40 and $50 per session and attended more than 79% of family and group sessions. Parents and caretakers incurred a cost of approximately $30-40 per intervention session for which they were adequately compensated. Attendance was very good overall for this group (>79%) and significantly higher than attendance in a comparable uncompensated study group from another recent Familias Unidas trial that targeted similar youth. Findings suggest that incentives should be considered important for future implementations of Familias Unidas and similar family-based interventions that target minority and low-SES populations.

Opportunity Costs and Financial Incentives for Hispanic Youth Participating in a Family-Based HIV and Substance Use Preventive Intervention

PubMed Central

McCollister, Kathryn E.; Freitas, Derek M.; Prado, Guillermo; Pantin, Hilda

2013-01-01

This paper presents results from a pilot study of the synergies between the opportunity costs incurred by research participants, participant compensation, and program attendance in a family-based substance use and HIV preventive intervention for Hispanic adolescents in Miami-Dade County, Florida. To estimate parent/caretaker cost per session and cost for the duration of the intervention, we administered the Caretaker Drug Abuse Treatment Cost Analysis Program (Caretaker DATCAP) to a random sample of 34 families who participated in a recent clinical trial of Familias Unidas. The total opportunity cost per parent/caretaker was under $40 per group session, under $30 per family session, and just over $570 for the duration of the intervention. Participants were compensated between $40 and $50 per session and attended more than 79% of family and group sessions. Parents and caretakers incurred a cost of approximately $30–40 per intervention session for which they were adequately compensated. Attendance was very good overall for this group (>79%) and significantly higher than attendance in a comparable uncompensated study group from another recent Familias Unidas trial that targeted similar youth. Findings suggest that incentives should be considered important for future implementations of Familias Unidas and similar family-based interventions that target minority and low-SES populations. PMID:24162106

Effective reduction of the interleukin-1β transcript in osteoarthritis-prone guinea pig chondrocytes via short hairpin RNA mediated RNA interference influences gene expression of mediators implicated in disease pathogenesis

PubMed Central

Santangeloyz, K.S.; Bertoneyz, A.L.

2011-01-01

summary Objective To ascertain a viral vector-based short hairpin RNA (shRNA) capable of reducing the interleukin-1β (IL-1β) transcript in osteoarthritis (OA)-prone chondrocytes and detect corresponding changes in the expression patterns of several critical disease mediators. Methods Cultured chondrocytes from 2-month-old Hartley guinea pigs were screened for reduction of the IL-1β transcript following plasmid-based delivery of U6-driven shRNA sequences. A successful plasmid/shRNA knockdown combination was identified and used to construct an adeno-associated virus serotype 5 (AAV5) vector for further evaluation. Relative real-time reverse transcription polymerase chain reaction (RTPCR) was used to quantify in vitro transcript changes of IL-1β and an additional nine genes following transduction with this targeting knockdown vector. To validate in vitro findings, this AAV5 vector was injected into one knee, while either an equivalent volume of saline vehicle (three animals) or non-targeting control vector (three animals) were injected into opposite knees. Fold differences and subsequent percent gene expression levels relative to control groups were calculated using the comparative CT (2−ΔΔCT) method. Results Statistically significant decreases in IL-1β expression were achieved by the targeting knockdown vector relative to both the mock-transduced control and non-targeting vector control groups in vitro. Transcript levels of anabolic transforming growth factor-β (TGF-β) were significantly increased by use of this targeting knockdown vector. Transduction with this targeting AAV5 vector also significantly decreased the transcript levels of key inflammatory cytokines [tumor necrosis factor-α (TNF-α), IL-2, IL-8, and IL-12] and catabolic agents [matrix metalloproteinase (MMP)13, MMP2, interferon-γ (IFN-γ), and inducible nitrous oxide synthase (iNOS)] relative to both mock-transduced and non-targeting vector control groups. In vivo application of this targeting knockdown vector resulted in a >50% reduction (P= 0.0045) or >90% (P= 0.0001) of the IL-1β transcript relative to vehicle-only or non-targeting vector control exposed cartilage, respectively. Conclusions Successful reduction of the IL-1β transcript was achieved via RNA interference (RNAi) techniques. Importantly, this alteration significantly influenced the transcript levels of several major players involved in OA pathogenesis in the direction of disease modification. Investigations to characterize additional gene expression changes influenced by targeting knockdown AAV5 vector-based diminution of the IL-1β transcript in vivo are warranted. PMID:21945742

The Ability of Narrative Communication to Address Health-related Social Norms

PubMed Central

Moran, Meghan Bridgid; Murphy, Sheila T.; Frank, Lauren; Baezconde-Garbanati, Lourdes

2013-01-01

Social norms are an important predictor of health behavior and have been targeted by a variety of health communication campaigns. However, these campaigns often encounter challenges related to the socially specific context in which norms exist: specifically, the extent to which the target population identifies with the reference group presented in the ad and the extent to which the target population believes the campaign's message. We argue that because of its capacity to effect identification among viewers, narrative communication is particularly appropriate for impacting social norms and, consequently, behavioral intention. This manuscript presents the results of a randomized trial testing the effectiveness of two films – one narrative, one non-narrative – in changing perceived social norms and behavioral intention regarding Pap testing to detect cervical cancer. Results of the study indicate that the narrative film was in fact more effective at producing positive changes in perceived norm and intention. PMID:24179677

[PLASMALEMMAL ION TRANSPORT IN POLLEN TUBES IS REGULATED BY HYDROGEN PEROXIDE].

PubMed

Maksimov, N M; Breygina, M A; Yermakov, I P

2015-01-01

Pollen tube growth is a key step in the life cycle of seed plants, which defines the success of sexual reproduction. One of the most important contributions to this process is made by ion transport through plasmalemma, which is tightly coordinated in time and space. Different classes of signaling molecules are involved in the regulation of transmembrane ion transport including reactive oxygen species as it has been recently demonstrated. Here, using subprotoplasts isolated from pollen tubes, we have demonstrated a connection between hydrogen peroxide, on one side, and two groups of targets on the plasma membrane, on the other side: nifedipine-sensitive Ca(2+)-permeable channels and transport systems controlling membrane potential. H2O2 interaction with these targets causes the increase in cytoplasmic Ca2+ concentration and plasmalemma hyperpolarization. One of the consequences of target modification was acceleration of cell wall regeneration.

Role of the NFκB-signaling pathway in cancer

PubMed Central

Zhou, Yujuan; Lin, Jingguan; Wang, Heran; Oyang, Linda; Tian, Yutong; Liu, Lu; Su, Min; Wang, Hui; Cao, Deliang; Liao, Qianjin

2018-01-01

Cancer is a group of cells that malignantly grow and proliferate uncontrollably. At present, treatment modes for cancer mainly comprise surgery, chemotherapy, radiotherapy, molecularly targeted therapy, gene therapy, and immunotherapy. However, the curative effects of these treatments have been limited thus far by specific characteristics of tumors. Abnormal activation of signaling pathways is involved in tumor pathogenesis and plays critical roles in growth, progression, and relapse of cancers. Targeted therapies against effectors in oncogenic signaling have improved the outcomes of cancer patients. NFκB is an important signaling pathway involved in pathogenesis and treatment of cancers. Excessive activation of the NFκB-signaling pathway has been documented in various tumor tissues, and studies on this signaling pathway for targeted cancer therapy have become a hot topic. In this review, we update current understanding of the NFκB-signaling pathway in cancer. PMID:29695914

Foucault on targets.

PubMed

Lynch, John

2004-01-01

This paper seeks to gain an insight into the behavior of a large NHS trust, in its attempt to meet a 90 percent patient access target, in a week long national audit in March 2003. Why did individuals act in dramatically different ways to their norm over this period. The work of Michel Foucault is used to explore these issues. The discourses of power, knowledge, discipline and governmentality are identified as key foucaudian themes that offer an alternative interpretation of how individuals behave in their place of work. The importance of the historical context of discourse within the NHS cannot be underestimated in shaping the behavior of individuals and groups today. Power and knowledge permeate NHS organizations through disciplinary practices and dressage. Governmentality seeks to maintain the status quo through disciplinary processes such as national healthcare targets. The natural response of NHS organizations is therefore, to seek order and conformity rather than disorder and conflict.

A comparison of policy and direct practice stakeholder perceptions of factors affecting evidence-based practice implementation using concept mapping

PubMed Central

2011-01-01

Background The goal of this study was to assess potential differences between administrators/policymakers and those involved in direct practice regarding factors believed to be barriers or facilitating factors to evidence-based practice (EBP) implementation in a large public mental health service system in the United States. Methods Participants included mental health system county officials, agency directors, program managers, clinical staff, administrative staff, and consumers. As part of concept mapping procedures, brainstorming groups were conducted with each target group to identify specific factors believed to be barriers or facilitating factors to EBP implementation in a large public mental health system. Statements were sorted by similarity and rated by each participant in regard to their perceived importance and changeability. Multidimensional scaling, cluster analysis, descriptive statistics and t-tests were used to analyze the data. Results A total of 105 statements were distilled into 14 clusters using concept-mapping procedures. Perceptions of importance of factors affecting EBP implementation varied between the two groups, with those involved in direct practice assigning significantly higher ratings to the importance of Clinical Perceptions and the impact of EBP implementation on clinical practice. Consistent with previous studies, financial concerns (costs, funding) were rated among the most important and least likely to change by both groups. Conclusions EBP implementation is a complex process, and different stakeholders may hold different opinions regarding the relative importance of the impact of EBP implementation. Implementation efforts must include input from stakeholders at multiple levels to bring divergent and convergent perspectives to light. PMID:21899754

A comparison of policy and direct practice stakeholder perceptions of factors affecting evidence-based practice implementation using concept mapping.

PubMed

Green, Amy E; Aarons, Gregory A

2011-09-07

The goal of this study was to assess potential differences between administrators/policymakers and those involved in direct practice regarding factors believed to be barriers or facilitating factors to evidence-based practice (EBP) implementation in a large public mental health service system in the United States. Participants included mental health system county officials, agency directors, program managers, clinical staff, administrative staff, and consumers. As part of concept mapping procedures, brainstorming groups were conducted with each target group to identify specific factors believed to be barriers or facilitating factors to EBP implementation in a large public mental health system. Statements were sorted by similarity and rated by each participant in regard to their perceived importance and changeability. Multidimensional scaling, cluster analysis, descriptive statistics and t-tests were used to analyze the data. A total of 105 statements were distilled into 14 clusters using concept-mapping procedures. Perceptions of importance of factors affecting EBP implementation varied between the two groups, with those involved in direct practice assigning significantly higher ratings to the importance of Clinical Perceptions and the impact of EBP implementation on clinical practice. Consistent with previous studies, financial concerns (costs, funding) were rated among the most important and least likely to change by both groups. EBP implementation is a complex process, and different stakeholders may hold different opinions regarding the relative importance of the impact of EBP implementation. Implementation efforts must include input from stakeholders at multiple levels to bring divergent and convergent perspectives to light.

Crowding with conjunctions of simple features.

PubMed

Põder, Endel; Wagemans, Johan

2007-11-20

Several recent studies have related crowding with the feature integration stage in visual processing. In order to understand the mechanisms involved in this stage, it is important to use stimuli that have several features to integrate, and these features should be clearly defined and measurable. In this study, Gabor patches were used as target and distractor stimuli. The stimuli differed in three dimensions: spatial frequency, orientation, and color. A group of 3, 5, or 7 objects was presented briefly at 4 deg eccentricity of the visual field. The observers' task was to identify the object located in the center of the group. A strong effect of the number of distractors was observed, consistent with various spatial pooling models. The analysis of incorrect responses revealed that these were a mix of feature errors and mislocalizations of the target object. Feature errors were not purely random, but biased by the features of distractors. We propose a simple feature integration model that predicts most of the observed regularities.

Mindfulness training and stress reactivity in substance abuse: results from a randomized, controlled stage I pilot study.

PubMed

Brewer, Judson A; Sinha, Rajita; Chen, Justin A; Michalsen, Ravenna N; Babuscio, Theresa A; Nich, Charla; Grier, Aleesha; Bergquist, Keri L; Reis, Deidre L; Potenza, Marc N; Carroll, Kathleen M; Rounsaville, Bruce J

2009-01-01

Stress is important in substance use disorders (SUDs). Mindfulness training (MT) has shown promise for stress-related maladies. No studies have compared MT to empirically validated treatments for SUDs. The goals of this study were to assess MT compared to cognitive behavioral therapy (CBT) in substance use and treatment acceptability, and specificity of MT compared to CBT in targeting stress reactivity. Thirty-six individuals with alcohol and/or cocaine use disorders were randomly assigned to receive group MT or CBT in an outpatient setting. Drug use was assessed weekly. After treatment, responses to personalized stress provocation were measured. Fourteen individuals completed treatment. There were no differences in treatment satisfaction or drug use between groups. The laboratory paradigm suggested reduced psychological and physiological indices of stress during provocation in MT compared to CBT. This pilot study provides evidence of the feasibility of MT in treating SUDs and suggests that MT may be efficacious in targeting stress.

Gender Differences in the Routine Activities Associated With Risks for Larceny in South Korea.

PubMed

Moon, Byongook; Morash, Merry; Jeong, SeokJin; Yoon, Hae-Sung

2016-08-01

The present research uses data from the 2010 Korean National Criminal Victimization Survey to examine gender differences in larceny victimization and in predictors of victimization (i.e., target attractiveness, exposure to potential offenders, target hardening, guardianship, and proximity to crime and social disorder) identified by routine activity theory. The findings show no significant gender difference in general larceny victimization, suggesting that Korean females are just as likely to be victims of theft of personal belongings as males. Consistent with the theory, physical proximity to crime and social disorder are significant predictors of larceny victimization for both males and females. However, public transportation appears to have unexpected protective influences for both gender groups, showing the importance of differences in national context. Overall, the current research provides partial support for routine activity theory's applicability in explaining larceny victimization across gender groups outside of the Western context. It also raises questions about reasons for women's increasing larceny victimization rates in Korea. © The Author(s) 2015.

Heterologous vaccine effects.

PubMed

Saadatian-Elahi, Mitra; Aaby, Peter; Shann, Frank; Netea, Mihai G; Levy, Ofer; Louis, Jacques; Picot, Valentina; Greenberg, Michael; Warren, William

2016-07-25

The heterologous or non-specific effects (NSEs) of vaccines, at times defined as "off-target effects" suggest that they can affect the immune response to organisms other than their pathogen-specific intended purpose. These NSEs have been the subject of clinical, immunological and epidemiological studies and are increasingly recognized as an important biological process by a growing group of immunologists and epidemiologists. Much remain to be learned about the extent and underlying mechanisms for these effects. The conference "Off-target effects of vaccination" held in Annecy-France (June 8-10 2015) intended to take a holistic approach drawing from the fields of immunology, systems biology, epidemiology, bioinformatics, public health and regulatory science to address fundamental questions of immunological mechanisms, as well as translational questions about vaccines NSEs. NSE observations were examined using case-studies on live attenuated vaccines and non-live vaccines followed by discussion of studies of possible biological mechanisms. Some possible pathways forward in the study of vaccines NSE were identified and discussed by the expert group. Copyright © 2016.

Mindfulness Training and Stress Reactivity in Substance Abuse: Results from A Randomized, Controlled Stage I Pilot Study

PubMed Central

Brewer, Judson A.; Sinha, Rajita; Chen, Justin A.; Michalsen, Ravenna N.; Babuscio, Theresa A.; Nich, Charla; Grier, Aleesha; Bergquist, Keri L.; Reis, Deidre L.; Potenza, Marc N.; Carroll, Kathleen M.; Rounsaville, Bruce J.

2011-01-01

Background Stress is important in substance use disorders (SUDs). Mindfulness training (MT) has shown promise for stress-related maladies. No studies have compared MT to empirically-validated treatments for SUDs. Goals to assess MT compared to cognitive behavioral therapy (CBT) in substance use and treatment acceptability, and specificity of MT compared to CBT in targeting stress reactivity. Methods 36 individuals with alcohol and/or cocaine use disorders were randomly assigned to receive group MT or CBT in an outpatient setting. Drug use was assessed weekly. After treatment, responses to personalized stress provocation were measured. Results Fourteen individuals completed treatment. There were no differences in treatment satisfaction, or drug use between groups. The laboratory paradigm suggested reduced psychological and physiological indices of stress during provocation in MT compared to CBT. Conclusions This pilot study provides evidence of the feasibility of MT in treating SUDs and suggests that MT may be efficacious in targeting stress. PMID:19904666

Target size matters: target errors contribute to the generalization of implicit visuomotor learning.

PubMed

Reichenthal, Maayan; Avraham, Guy; Karniel, Amir; Shmuelof, Lior

2016-08-01

The process of sensorimotor adaptation is considered to be driven by errors. While sensory prediction errors, defined as the difference between the planned and the actual movement of the cursor, drive implicit learning processes, target errors (e.g., the distance of the cursor from the target) are thought to drive explicit learning mechanisms. This distinction was mainly studied in the context of arm reaching tasks where the position and the size of the target were constant. We hypothesize that in a dynamic reaching environment, where subjects have to hit moving targets and the targets' dynamic characteristics affect task success, implicit processes will benefit from target errors as well. We examine the effect of target errors on learning of an unnoticed perturbation during unconstrained reaching movements. Subjects played a Pong game, in which they had to hit a moving ball by moving a paddle controlled by their hand. During the game, the movement of the paddle was gradually rotated with respect to the hand, reaching a final rotation of 25°. Subjects were assigned to one of two groups: The high-target error group played the Pong with a small ball, and the low-target error group played with a big ball. Before and after the Pong game, subjects performed open-loop reaching movements toward static targets with no visual feedback. While both groups adapted to the rotation, the postrotation reaching movements were directionally biased only in the small-ball group. This result provides evidence that implicit adaptation is sensitive to target errors. Copyright © 2016 the American Physiological Society.

Which population groups should be targeted for cardiovascular prevention? A modelling study based on the Norwegian Hordaland Health Study (HUSK).

PubMed

Brekke, Mette; Rekdal, Magne; Straand, Jørund

2007-06-01

To assess level of cardiovascular risk factors in a non-selected, middle-aged population. To estimate the proportion target for risk intervention according to present guidelines and according to different cut-off levels for two risk algorithms. Population survey, modelling study. The Norwegian Hordaland Health Study (HUSK) 1997-99. A total of 22 289 persons born in 1950-57. Own and relatives' cardiovascular morbidity, antihypertensive and lipid-lowering treatment, smoking, blood pressure, cholesterol. Framingham and Systematic Coronary Risk Evaluation (SCORE) algorithms. The European guidelines on CVD prevention in clinical practice were applied to estimate size of risk groups. Some 9.7% of men and 7.6% of women had CVD, diabetes mellitus, a high level of one specific risk factor, or received lipid-lowering or antihypertensive treatment. Applying a SCORE (60 years) cut-off level at 5% to the rest of the population selected 52.4% of men and 0.8% of women into a primary prevention group, while a cut-off level at 8% included 22.0% and 0.06% respectively. A cut-off level for the Framingham score (60 years) of 20% selected 43.6% of men and 4.7% of women, while a cut-off level of 25% selected 25.6% of men and 1.8% of women. The findings illustrate how choices regarding risk estimation highly affect the size of the target population. Modelling studies are important when preparing guidelines, to address implications for resource allocation and risk of medicalization. The population share to be targeted for primary prevention ought to be estimated, including the impact of various cut-off points for risk algorithms on the size of the risk population.

If We Build It, Will They Come? A Qualitative Study of Key Stakeholder Opinions on the Implementation of a Videogame Intervention for Risk Reduction in Adolescents

PubMed Central

Hieftje, Kimberly; Crusto, Cindy A.; Montanaro, Erika; Fiellin, Lynn E.

2016-01-01

Abstract Objective: Serious games are emerging as important tools that offer an innovative approach to teach adolescents behavioral skills to avoid risky situations. PlayForward: Elm City Stories, an interactive videogame targeting risk reduction, is currently undergoing evaluation. Collecting stakeholder data on its acceptability and real-life implementation strategies is critical for successful dissemination. Materials and Methods: We collected interview data from four stakeholder groups regarding incorporating PlayForward into settings with adolescents. Transcripts were coded, creating a comprehensive code structure for each stakeholder group. Results: We conducted 40 semi-structured interviews that included 14 adolescents (aged 12–15 years; 10 boys), eight parents/guardians (all women), 12 after-school/school coordinators (nine women), and 14 community partners (13 women). We identified four themes that reflected stakeholders' perceptions about how the videogame might be implemented in real-world settings. (1) Stakeholder groups expressed that the topics of sex, alcohol, and drugs were not being taught in an educational setting. (2) Stakeholder groups saw a videogame as a viable option to teach about sex, alcohol, and drugs. (3) Stakeholder groups thought that the videogame would fit well into other settings, such as after-school programs or community organizations. (4) Some stakeholder groups highlighted additional tools that could help with implementation, such as manuals, homework assignments, and group discussion questions. Conclusion: Stakeholder groups supported the game as a delivery vehicle for targeted content, indicating high acceptability but highlighting additional tools that would aid in implementation. PMID:27336205

Social identity and support for counteracting tobacco company marketing that targets vulnerable populations

PubMed Central

Baig, Sabeeh A.; Pepper, Jessica K.; Morgan, Jennifer C.; Brewer, Noel T.

2017-01-01

Rationale Tobacco companies use advertising to target vulnerable populations, including youth, racial/ethnic minorities, and sexual minorities. Objective We sought to examine how personal identity affects support for population-specific anti-smoking advertisements that could serve as countermeasures to industry practices. Methods In 2014–2015, we surveyed probability phone samples of adults and adolescents (n = 6,139) and an online convenience sample of adults (n = 4,137) in the United States. We experimentally varied the description of tobacco industry marketing practices (no description, general, or specific to a target group). The four prevention target groups were teens; African Americans; Latinos; and gays, lesbians, and bisexuals (GLBs). Participants were either members or non-members of their prevention target group. Results Support was highest for anti-smoking advertisements targeting teens, moderate for Latinos and African Americans, and lowest for GLBs. In-group members expressed higher support than out-group members when anti-smoking advertisements targeted African Americans, Latinos, and GLBs (all p < .05). However, when teens were the target prevention group, in-group members expressed lower support than out-group members (p < .05). The description of industry marketing practices did not have an effect. Results were similar across the phone and online studies. Conclusions Our findings suggest that the public strongly supports advertisements to prevent smoking among teens, but support for similar efforts among other vulnerable populations is comparatively low. Anti-smoking campaigns for vulnerable populations may benefit from a greater understanding of the role of social identity in shaping public support for such campaigns. PMID:28427731

Individual, employment and psychosocial factors influencing walking to work: Implications for intervention design

PubMed Central

Esliger, Dale W.; Taylor, Ian M.; Sherar, Lauren B.

2017-01-01

Background Promoting walking for the journey to and from work (commuter walking) is a potential strategy for increasing physical activity. Understanding the factors influencing commuter walking is important for identifying target groups and designing effective interventions. This study aimed to examine individual, employment-related and psychosocial factors associated with commuter walking and to discuss the implications for targeting and future design of interventions. Methods 1,544 employees completed a baseline survey as part of the ‘Walking Works’ intervention project (33.4% male; 36.3% aged <30 years). Multivariate logistic regression was used to examine the associations of individual (age, ethnic group, educational qualifications, number of children <16 and car ownership), employment-related (distance lived from work, free car parking at work, working hours, working pattern and occupation) and psychosocial factors (perceived behavioural control, intention, social norms and social support from work colleagues) with commuter walking. Results Almost half of respondents (n = 587, 49%) were classified as commuter walkers. Those who were aged <30 years, did not have a car, had no free car parking at work, were confident of including some walking or intended to walk to or from work on a regular basis, and had support from colleagues for walking were more likely to be commuter walkers. Those who perceived they lived too far away from work to walk, thought walking was less convenient than using a car for commuting, did not have time to walk, needed a car for work or had always travelled the same way were less likely to be commuter walkers. Conclusions A number of individual, employment-related and psychosocial factors were associated with commuter walking. Target groups for interventions to promote walking to and from work may include those in older age groups and those who own or have access to a car. Multi-level interventions targeting individual level behaviour change, social support within the workplace and organisational level travel policies may be required in order to promote commuter walking. PMID:28182714

Individual, employment and psychosocial factors influencing walking to work: Implications for intervention design.

PubMed

Adams, Emma J; Esliger, Dale W; Taylor, Ian M; Sherar, Lauren B

2017-01-01

Promoting walking for the journey to and from work (commuter walking) is a potential strategy for increasing physical activity. Understanding the factors influencing commuter walking is important for identifying target groups and designing effective interventions. This study aimed to examine individual, employment-related and psychosocial factors associated with commuter walking and to discuss the implications for targeting and future design of interventions. 1,544 employees completed a baseline survey as part of the 'Walking Works' intervention project (33.4% male; 36.3% aged <30 years). Multivariate logistic regression was used to examine the associations of individual (age, ethnic group, educational qualifications, number of children <16 and car ownership), employment-related (distance lived from work, free car parking at work, working hours, working pattern and occupation) and psychosocial factors (perceived behavioural control, intention, social norms and social support from work colleagues) with commuter walking. Almost half of respondents (n = 587, 49%) were classified as commuter walkers. Those who were aged <30 years, did not have a car, had no free car parking at work, were confident of including some walking or intended to walk to or from work on a regular basis, and had support from colleagues for walking were more likely to be commuter walkers. Those who perceived they lived too far away from work to walk, thought walking was less convenient than using a car for commuting, did not have time to walk, needed a car for work or had always travelled the same way were less likely to be commuter walkers. A number of individual, employment-related and psychosocial factors were associated with commuter walking. Target groups for interventions to promote walking to and from work may include those in older age groups and those who own or have access to a car. Multi-level interventions targeting individual level behaviour change, social support within the workplace and organisational level travel policies may be required in order to promote commuter walking.

Serum Metabolic Alterations upon Zika Infection.

PubMed

Melo, Carlos Fernando O R; Delafiori, Jeany; de Oliveira, Diogo N; Guerreiro, Tatiane M; Esteves, Cibele Z; Lima, Estela de O; Pando-Robles, Victoria; Catharino, Rodrigo R

2017-01-01

Zika virus (ZIKV) infection has recently emerged as a major concern worldwide due to its strong association with nervous system malformation (microcephaly) of fetuses in pregnant women infected by the virus. Signs and symptoms of ZIKV infection are often mistaken with other common viral infections. Since transmission may occur through biological fluids exchange and coitus, in addition to mosquito bite, this condition is an important infectious disease. Thus, understanding the mechanism of viral infection has become an important research focus, as well as providing potential targets for assertive clinical diagnosis and quality screening for hemoderivatives. Within this context, the present work analyzed blood plasma from 79 subjects, divided as a control group and a ZIKV-infected group. Samples underwent direct-infusion mass spectrometry and statistical analysis, where eight markers related to the pathophysiological process of ZIKV infection were elected and characterized. Among these, Angiotensin (1-7) and Angiotensin I were upregulated under infection, showing an attempt to induce autophagy of the infected cells. However, this finding is concerning about hypertensive individuals under treatment with inhibitors of the Renin-Angiotensin System (RAS), which could reduce this response against the virus and exacerbate the symptoms of the infection. Moreover, one of the most abundant glycosphingolipids in the nervous tissue, Ganglioside GM2, was also elected in the present study as an infection biomarker. Considered an important pathogen receptor at membrane's outer layer, this finding represents the importance of gangliosides for ZIKV infection and its association with brain tropism. Furthermore, a series of phosphatidylinositols were also identified as biomarkers, implying a significant role of the PI3K-AKT-mTOR Pathway in this mechanism. Finally, these pathways may also be understood as potential targets to be considered in pharmacological intervention studies on ZIKV infection management.

Serum Metabolic Alterations upon Zika Infection

PubMed Central

Melo, Carlos Fernando O. R.; Delafiori, Jeany; de Oliveira, Diogo N.; Guerreiro, Tatiane M.; Esteves, Cibele Z.; Lima, Estela de O.; Pando-Robles, Victoria; Catharino, Rodrigo R.; Milanez, Guilherme P.

2017-01-01

Zika virus (ZIKV) infection has recently emerged as a major concern worldwide due to its strong association with nervous system malformation (microcephaly) of fetuses in pregnant women infected by the virus. Signs and symptoms of ZIKV infection are often mistaken with other common viral infections. Since transmission may occur through biological fluids exchange and coitus, in addition to mosquito bite, this condition is an important infectious disease. Thus, understanding the mechanism of viral infection has become an important research focus, as well as providing potential targets for assertive clinical diagnosis and quality screening for hemoderivatives. Within this context, the present work analyzed blood plasma from 79 subjects, divided as a control group and a ZIKV-infected group. Samples underwent direct-infusion mass spectrometry and statistical analysis, where eight markers related to the pathophysiological process of ZIKV infection were elected and characterized. Among these, Angiotensin (1-7) and Angiotensin I were upregulated under infection, showing an attempt to induce autophagy of the infected cells. However, this finding is concerning about hypertensive individuals under treatment with inhibitors of the Renin-Angiotensin System (RAS), which could reduce this response against the virus and exacerbate the symptoms of the infection. Moreover, one of the most abundant glycosphingolipids in the nervous tissue, Ganglioside GM2, was also elected in the present study as an infection biomarker. Considered an important pathogen receptor at membrane's outer layer, this finding represents the importance of gangliosides for ZIKV infection and its association with brain tropism. Furthermore, a series of phosphatidylinositols were also identified as biomarkers, implying a significant role of the PI3K-AKT-mTOR Pathway in this mechanism. Finally, these pathways may also be understood as potential targets to be considered in pharmacological intervention studies on ZIKV infection management. PMID:29067015

The use of tools for learning science in small groups

NASA Astrophysics Data System (ADS)

Valdes, Rosa Maria

2000-10-01

"Hands-on" learning through the use of tools or manipulatives representative of science concepts has long been an important component of the middle school science curriculum. However, scarce research exists on the impact of tool use on learning of science concepts, particularly on the processes involved in such learning. This study investigated how the use of tools by students engaged in small group discussion about the concept of electrical resistance and the explanations that accompany such use leads to improved understandings of the concept. Specifically, the main hypothesis of the study was that students who observe explanations by their high-ability peers accompanied by accurate tool use and who are highly engaged in these explanations would show learning gains. Videotaped interactions of students working in small groups to solve tasks on electricity were coded using scales that measured the accuracy of the tool use, the accuracy of the explanations presented, and the level of engagement of target students. The data of 48 students whose knowledge of the concept of resistance was initially low and who also were determined to be low achievers as shown by their scores on a set of pretest, was analyzed. Quantitative and qualitative analyses showed that students who observed their peers give explanations using tools and who were engaged at least moderately made gains in their understandings of resistance. Specifically, the results of regression analyses showed that both the level of accuracy of a high-ability peer's explanation and the target student's level of engagement in the explanation significantly predicted target students' outcome scores. The number of presentations offered by a high-ability peer also significantly predicted outcome scores. Case study analyses of six students found that students who improved their scores the most from pretest to posttest had high-ability peers who tended to be verbal and who gave numerous explanations, whereas students who improved the least had high-ability peers who gave no explanations at all. Important implications of this study for teaching are that (1) teachers should group students heterogeneously and should monitor students' small groups to insure that students are producing content-oriented discussion, and (2) students should be allowed to manipulate tools that allow experimentation as students build understandings and promote communication of abstract ideas.

[Ethnic origin of patients remains important].

PubMed

Stronks, Karien

2013-01-01

The ethnic diversity in medical practices is increasing rapidly. In the Netherlands, ethnic groups are predominantly defined on the basis of their geographical origin, e.g. inhabitants of Turkish, Moroccan or Surinamese origin. The prevalence of health problems and the utilisation of health care differ between ethnic groups. This ethnic variation arises, firstly, from characteristics that are inherent to these groups such as genetic profile and culture, and, secondly, from characteristics that reflect their position in Dutch society such as socio-economic position and discrimination on the other. If we could fully understand which of these specific characteristics leads to a specific pattern of health problems or health care use, the classification of patient into ethnic groups would then become redundant. As long as we do not completely understand this variation, however, ethnic origin is a good entry-point for targeting health care to groups of patients.

Categorical vowel perception enhances the effectiveness and generalization of auditory feedback in human-machine-interfaces.

PubMed

Larson, Eric; Terry, Howard P; Canevari, Margaux M; Stepp, Cara E

2013-01-01

Human-machine interface (HMI) designs offer the possibility of improving quality of life for patient populations as well as augmenting normal user function. Despite pragmatic benefits, utilizing auditory feedback for HMI control remains underutilized, in part due to observed limitations in effectiveness. The goal of this study was to determine the extent to which categorical speech perception could be used to improve an auditory HMI. Using surface electromyography, 24 healthy speakers of American English participated in 4 sessions to learn to control an HMI using auditory feedback (provided via vowel synthesis). Participants trained on 3 targets in sessions 1-3 and were tested on 3 novel targets in session 4. An "established categories with text cues" group of eight participants were trained and tested on auditory targets corresponding to standard American English vowels using auditory and text target cues. An "established categories without text cues" group of eight participants were trained and tested on the same targets using only auditory cuing of target vowel identity. A "new categories" group of eight participants were trained and tested on targets that corresponded to vowel-like sounds not part of American English. Analyses of user performance revealed significant effects of session and group (established categories groups and the new categories group), and a trend for an interaction between session and group. Results suggest that auditory feedback can be effectively used for HMI operation when paired with established categorical (native vowel) targets with an unambiguous cue.

Comparison of Reef Fish Survey Data Gathered by Open and Closed Circuit SCUBA Divers Reveals Differences in Areas With Higher Fishing Pressure

PubMed Central

Stamoulis, Kostantinos A.; Boland, Raymond C.; Lino, Kevin C.; Hauk, Brian B.; Leonard, Jason C.; Asher, Jacob M.; Lopes, Keolohilani H.; Kosaki, Randall K.

2016-01-01

Visual survey by divers using open-circuit (OC) SCUBA is the most widely used approach to survey coral reef fishes. Therefore, it is important to quantify sources of bias in OC surveys, such as the possibility that avoidance of OC divers by fishes can lead to undercounting in areas where targeted species have come to associate divers with a risk of being speared. One potential way to reduce diver avoidance is to utilize closed circuit rebreathers (CCRs), which do not produce the noise and bubbles that are a major source of disturbance associated with OC diving. For this study, we conducted 66 paired OC and CCR fish surveys in the Main Hawaiian Islands at locations with relatively high, moderate, and light fishing pressure. We found no significant differences in biomass estimates between OC and CCR surveys when data were pooled across all sites, however there were differences at the most heavily fished location, Oahu. There, biomass estimates from OC divers were significantly lower for several targeted fish groups, including surgeonfishes, targeted wrasses, and snappers, as well as for all targeted fishes combined, with mean OC biomass between 32 and 68% of mean CCR biomass. There were no clear differences between OC and CCR biomass estimates for these groups at sites with moderate or low fishing pressure, or at any location for other targeted fish groups, including groupers, parrotfishes, and goatfishes. Bias associated with avoidance of OC divers at heavily fished locations could be substantially reduced, or at least calibrated for, by utilization of CCR. In addition to being affected by fishing pressure, the extent to which avoidance of OC divers is problematic for visual surveys varies greatly among taxa, and is likely to be highly influenced by the survey methodology and dimensions used. PMID:27936044

Comparison of Reef Fish Survey Data Gathered by Open and Closed Circuit SCUBA Divers Reveals Differences in Areas With Higher Fishing Pressure.

PubMed

Gray, Andrew E; Williams, Ivor D; Stamoulis, Kostantinos A; Boland, Raymond C; Lino, Kevin C; Hauk, Brian B; Leonard, Jason C; Rooney, John J; Asher, Jacob M; Lopes, Keolohilani H; Kosaki, Randall K

2016-01-01

Visual survey by divers using open-circuit (OC) SCUBA is the most widely used approach to survey coral reef fishes. Therefore, it is important to quantify sources of bias in OC surveys, such as the possibility that avoidance of OC divers by fishes can lead to undercounting in areas where targeted species have come to associate divers with a risk of being speared. One potential way to reduce diver avoidance is to utilize closed circuit rebreathers (CCRs), which do not produce the noise and bubbles that are a major source of disturbance associated with OC diving. For this study, we conducted 66 paired OC and CCR fish surveys in the Main Hawaiian Islands at locations with relatively high, moderate, and light fishing pressure. We found no significant differences in biomass estimates between OC and CCR surveys when data were pooled across all sites, however there were differences at the most heavily fished location, Oahu. There, biomass estimates from OC divers were significantly lower for several targeted fish groups, including surgeonfishes, targeted wrasses, and snappers, as well as for all targeted fishes combined, with mean OC biomass between 32 and 68% of mean CCR biomass. There were no clear differences between OC and CCR biomass estimates for these groups at sites with moderate or low fishing pressure, or at any location for other targeted fish groups, including groupers, parrotfishes, and goatfishes. Bias associated with avoidance of OC divers at heavily fished locations could be substantially reduced, or at least calibrated for, by utilization of CCR. In addition to being affected by fishing pressure, the extent to which avoidance of OC divers is problematic for visual surveys varies greatly among taxa, and is likely to be highly influenced by the survey methodology and dimensions used.

Cultural targeting and tailoring of shared decision making technology: a theoretical framework for improving the effectiveness of patient decision aids in culturally diverse groups.

PubMed

Alden, Dana L; Friend, John; Schapira, Marilyn; Stiggelbout, Anne

2014-03-01

Patient decision aids are known to positively impact outcomes critical to shared decision making (SDM), such as gist knowledge and decision preparedness. However, research on the potential improvement of these and other important outcomes through cultural targeting and tailoring of decision aids is very limited. This is the case despite extensive evidence supporting use of cultural targeting and tailoring to improve the effectiveness of health communications. Building on prominent psychological theory, we propose a two-stage framework incorporating cultural concepts into the design process for screening and treatment decision aids. The first phase recommends use of cultural constructs, such as collectivism and individualism, to differentially target patients whose cultures are known to vary on these dimensions. Decision aid targeting is operationalized through use of symbols and values that appeal to members of the given culture. Content dimensions within decision aids that appear particularly appropriate for targeting include surface level visual characteristics, language, beliefs, attitudes and values. The second phase of the framework is based on evidence that individuals vary in terms of how strongly cultural norms influence their approach to problem solving and decision making. In particular, the framework hypothesizes that differences in terms of access to cultural mindsets (e.g., access to interdependent versus independent self) can be measured up front and used to tailor decision aids. Thus, the second phase in the framework emphasizes the importance of not only targeting decision aid content, but also tailoring the information to the individual based on measurement of how strongly he/she is connected to dominant cultural mindsets. Overall, the framework provides a theory-based guide for researchers and practitioners who are interested in using cultural targeting and tailoring to develop and test decision aids that move beyond a "one-size fits all" approach and thereby, improve SDM in our multicultural world. Copyright © 2014 Elsevier Ltd. All rights reserved.

Beta blockers and chronic heart failure patients: prognostic impact of a dose targeted beta blocker therapy vs. heart rate targeted strategy.

PubMed

Corletto, Anna; Fröhlich, Hanna; Täger, Tobias; Hochadel, Matthias; Zahn, Ralf; Kilkowski, Caroline; Winkler, Ralph; Senges, Jochen; Katus, Hugo A; Frankenstein, Lutz

2018-05-17

Beta blockers improve survival in patients with chronic systolic heart failure (CHF). Whether physicians should aim for target dose, target heart rate (HR), or both is still under debate. We identified 1,669 patients with systolic CHF due to ischemic heart disease or idiopathic dilated cardiomyopathy from the University Hospital Heidelberg and the Clinic of Ludwigshafen, Germany. All patients were treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had a history of CHF known for at least 6 months. Target dose was defined as treatment with ≥ 95% of the respective published guideline-recommended dose. Target HR was defined as 51-69 bpm. All-cause mortality during the median follow-up of 42.8 months was analysed with respect to beta blocker dosing and resting HR. 201 (12%) patients met the dose target (group A), 285 (17.1%) met the HR target (group B), 627 (37.6%) met no target (group C), and 556 (33.3%) did not receive beta blockers (Group D). 5-year mortality was 23.7, 22.7, 37.6, and 55.6% for group A, B, C, and D, respectively (p <  0.001). Survival for group A patients with a HR ≥ 70 bpm was 28.8% but 14.8% if HR was 50-70 bpm (p = 0.054). Achieving guidelines recommended beta blocker dose or to HR control has a similar positive impact on survival. When on target dose, supplemental HR control additionally improves survival.

Visuo-vestibular interaction: predicting the position of a visual target during passive body rotation.

PubMed

Mackrous, I; Simoneau, M

2011-11-10

Following body rotation, optimal updating of the position of a memorized target is attained when retinal error is perceived and corrective saccade is performed. Thus, it appears that these processes may enable the calibration of the vestibular system by facilitating the sharing of information between both reference frames. Here, it is assessed whether having sensory information regarding body rotation in the target reference frame could enhance an individual's learning rate to predict the position of an earth-fixed target. During rotation, participants had to respond when they felt their body midline had crossed the position of the target and received knowledge of result. During practice blocks, for two groups, visual cues were displayed in the same reference frame of the target, whereas a third group relied on vestibular information (vestibular-only group) to predict the location of the target. Participants, unaware of the role of the visual cues (visual cues group), learned to predict the location of the target and spatial error decreased from 16.2 to 2.0°, reflecting a learning rate of 34.08 trials (determined from fitting a falling exponential model). In contrast, the group aware of the role of the visual cues (explicit visual cues group) showed a faster learning rate (i.e. 2.66 trials) but similar final spatial error 2.9°. For the vestibular-only group, similar accuracy was achieved (final spatial error of 2.3°), but their learning rate was much slower (i.e. 43.29 trials). Transferring to the Post-test (no visual cues and no knowledge of result) increased the spatial error of the explicit visual cues group (9.5°), but it did not change the performance of the vestibular group (1.2°). Overall, these results imply that cognition assists the brain in processing the sensory information within the target reference frame. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Cognitive biases toward Internet game-related pictures and executive deficits in individuals with an Internet game addiction.

PubMed

Zhou, Zhenhe; Yuan, Guozhen; Yao, Jianjun

2012-01-01

The cue-related go/no-go switching task provides an experimental approach to study individual's flexibility in changing situations. Because Internet addiction disorder (IAD) belongs to the compulsive-impulsive spectrum of disorders, it should present cognitive bias and executive functioning deficit characteristics of some of these types of disorders. Until now, no studies have been reported on cognitive bias and executive function involving mental flexibility and response inhibition in IAD. A total of 46 subjects who met the criteria of the modified Young's Diagnostic Questionnaire for Internet addiction (YDQ) were recruited as an Internet game addiction (IGA) group, along with 46 healthy control individuals. All participants performed the Internet game-shifting task. Using hit rate, RT, d' and C as the dependent measures, a three-way ANOVA (group × target × condition) was performed. For hit rate, a significant effect of group, type of target and condition were found. The group-target interaction effect was significant. For RT, significant effects were revealed for group and type of target. The group-target interaction effect was significant. Comparisons of the means revealed that the slowing down of IGA relative to NIA was more pronounced when the target stimuli were neutral as opposed to Internet game-related pictures. In addition, the group-condition interaction effect was significant. For d', significant effects of group, type of target and condition were found. The group-target interaction effect was significant. For C, the type of target produced a significant effect. There was a positive correlation between the length of the addiction (number of years) and the severity of the cognitive bias. IGA present cognitive biases towards information related to Internet gaming. These biases, as well as poor executive functioning skills (lower mental flexibility and response inhibition), might be responsible for Internet game addiction. The assessment of cognitive biases in IGA might provide a methodology for evaluation of therapeutic effects.

Insights into the history of a bacterial group II intron remnant from the genomes of the nitrogen-fixing symbionts Sinorhizobium meliloti and Sinorhizobium medicae.

PubMed

Toro, N; Martínez-Rodríguez, L; Martínez-Abarca, F

2014-10-01

Group II introns are self-splicing catalytic RNAs that act as mobile retroelements. In bacteria, they are thought to be tolerated to some extent because they self-splice and home preferentially to sites outside of functional genes, generally within intergenic regions or in other mobile genetic elements, by mechanisms including the divergence of DNA target specificity to prevent target site saturation. RmInt1 is a mobile group II intron that is widespread in natural populations of Sinorhizobium meliloti and was first described in the GR4 strain. Like other bacterial group II introns, RmInt1 tends to evolve toward an inactive form by fragmentation, with loss of the 3' terminus. We identified genomic evidence of a fragmented intron closely related to RmInt1 buried in the genome of the extant S. meliloti/S. medicae species. By studying this intron, we obtained evidence for the occurrence of intron insertion before the divergence of ancient rhizobial species. This fragmented group II intron has thus existed for a long time and has provided sequence variation, on which selection can act, contributing to diverse genetic rearrangements, and to generate pan-genome divergence after strain differentiation. The data presented here suggest that fragmented group II introns within intergenic regions closed to functionally important neighboring genes may have been microevolutionary forces driving adaptive evolution of these rhizobial species.

Insights into the history of a bacterial group II intron remnant from the genomes of the nitrogen-fixing symbionts Sinorhizobium meliloti and Sinorhizobium medicae

PubMed Central

Toro, N; Martínez-Rodríguez, L; Martínez-Abarca, F

2014-01-01

Group II introns are self-splicing catalytic RNAs that act as mobile retroelements. In bacteria, they are thought to be tolerated to some extent because they self-splice and home preferentially to sites outside of functional genes, generally within intergenic regions or in other mobile genetic elements, by mechanisms including the divergence of DNA target specificity to prevent target site saturation. RmInt1 is a mobile group II intron that is widespread in natural populations of Sinorhizobium meliloti and was first described in the GR4 strain. Like other bacterial group II introns, RmInt1 tends to evolve toward an inactive form by fragmentation, with loss of the 3′ terminus. We identified genomic evidence of a fragmented intron closely related to RmInt1 buried in the genome of the extant S. meliloti/S. medicae species. By studying this intron, we obtained evidence for the occurrence of intron insertion before the divergence of ancient rhizobial species. This fragmented group II intron has thus existed for a long time and has provided sequence variation, on which selection can act, contributing to diverse genetic rearrangements, and to generate pan-genome divergence after strain differentiation. The data presented here suggest that fragmented group II introns within intergenic regions closed to functionally important neighboring genes may have been microevolutionary forces driving adaptive evolution of these rhizobial species. PMID:24736785

7 CFR 761.208 - Target participation rates for socially disadvantaged groups.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 7 2011-01-01 2011-01-01 false Target participation rates for socially disadvantaged... Farm Loan Programs Funds to State Offices § 761.208 Target participation rates for socially disadvantaged groups. (a) General. (1) The Agency establishes target participation rates for providing FO, CL...

Race, belief in destiny, and seat belt usage: a pilot study.

PubMed Central

Colón, I

1992-01-01

A survey of 1063 individuals found that when belief in destiny was statistically controlled, differences in seat belt use by race disappeared. Thus, racial differences in seat belt use are statistically accounted for and might be explained by belief in destiny. Efforts to increase seat belt use should target minority groups rather than include them in broadbrush programs. Further, these efforts should take into account this important difference in motivation. PMID:1585969

The Importance of Health Surveys in Workplaces, with Emphasis on the Field of Public Health, in the Target Group of Employees Who Work in Shifts

ERIC Educational Resources Information Center

Vámosiné-Rovó, Gyöngyvér

2016-01-01

In today's world the economic uncertainty, the huge overload of work, the expectations related to the work performance--which are not said--, the monotone work and the risk of violence contribute to the increase of psychosocial risks, which can lead to serious consequences in a company. If we succeed in preventing the negative impact of stress…

Abuse by care professionals. Part 3: Analysis of characteristics and reasons.

PubMed

Barber, Chris

In order to prevent abusive episodes and abusive behaviour from occurring it is important that society, in particular the health and social care sector, identify the individuals who may be at the greatest risk of abuse and those who are or may become abusers. This article attempts to define such behaviour and illustrate some of the reasons as to why particular groups are the targets of abuse and why particular individuals abuse.

Assessing gait adaptability in people with a unilateral amputation on an instrumented treadmill with a projected visual context.

PubMed

Houdijk, Han; van Ooijen, Mariëlle W; Kraal, Jos J; Wiggerts, Henri O; Polomski, Wojtek; Janssen, Thomas W J; Roerdink, Melvyn

2012-11-01

Gait adaptability, including the ability to avoid obstacles and to take visually guided steps, is essential for safe movement through a cluttered world. This aspect of walking ability is important for regaining independent mobility but is difficult to assess in clinical practice. The objective of this study was to investigate the validity of an instrumented treadmill with obstacles and stepping targets projected on the belt's surface for assessing prosthetic gait adaptability. This was an observational study. A control group of people who were able bodied (n=12) and groups of people with transtibial (n=12) and transfemoral (n=12) amputations participated. Participants walked at a self-selected speed on an instrumented treadmill with projected visual obstacles and stepping targets. Gait adaptability was evaluated in terms of anticipatory and reactive obstacle avoidance performance (for obstacles presented 4 steps and 1 step ahead, respectively) and accuracy of stepping on regular and irregular patterns of stepping targets. In addition, several clinical tests were administered, including timed walking tests and reports of incidence of falls and fear of falling. Obstacle avoidance performance and stepping accuracy were significantly lower in the groups with amputations than in the control group. Anticipatory obstacle avoidance performance was moderately correlated with timed walking test scores. Reactive obstacle avoidance performance and stepping accuracy performance were not related to timed walking tests. Gait adaptability scores did not differ in groups stratified by incidence of falls or fear of falling. Because gait adaptability was affected by walking speed, differences in self-selected walking speed may have diminished differences in gait adaptability between groups. Gait adaptability can be validly assessed by use of an instrumented treadmill with a projected visual context. When walking speed is taken into account, this assessment provides unique, quantitative information about walking ability in people with a lower-limb amputation.

HDAC inhibitors: a 2013-2017 patent survey.

PubMed

Faria Freitas, Micaela; Cuendet, Muriel; Bertrand, Philippe

2018-04-19

Zinc-dependent histone deacetylases (HDAC) inhibitors represent an important class of biologically active compounds with four of them approved by the FDA. A wide range of molecules has been reported for applications in several human diseases.Area covered: This review covers recent efforts in the synthesis and applications of HDAC inhibitors from 2013-2017.Expert opinion: HDAC inhibitors represent an important class of biologically active compounds for single or combination therapies. The current synthetic methodologies are oriented towards selective HDAC isoforms to achieve better therapeutic effects. Among the recent patents available, most of them focus on HDAC6 selective inhibitors. Beside this search for isoform selectivity, the quest for zinc binding groups with better pharmacokinetic properties and high potency against HDACs only motivates medicinal chemists, as well as the design of inhibitors targeting HDACs and at the same time another biological target. If the major applications are for anticancer activity, one can note the emerging applications in neurological or metabolic disorders or for the stimulation of the immune system.

Cultural group selection follows Darwin's classic syllogism for the operation of selection.

PubMed

Richerson, Peter; Baldini, Ryan; Bell, Adrian V; Demps, Kathryn; Frost, Karl; Hillis, Vicken; Mathew, Sarah; Newton, Emily K; Naar, Nicole; Newson, Lesley; Ross, Cody; Smaldino, Paul E; Waring, Timothy M; Zefferman, Matthew

2016-01-01

The main objective of our target article was to sketch the empirical case for the importance of selection at the level of groups on cultural variation. Such variation is massive in humans, but modest or absent in other species. Group selection processes acting on this variation is a framework for developing explanations of the unusual level of cooperation between non-relatives found in our species. Our case for cultural group selection (CGS) followed Darwin's classic syllogism regarding natural selection: If variation exists at the level of groups, if this variation is heritable, and if it plays a role in the success or failure of competing groups, then selection will operate at the level of groups. We outlined the relevant domains where such evidence can be sought and characterized the main conclusions of work in those domains. Most commentators agree that CGS plays some role in human evolution, although some were considerably more skeptical. Some contributed additional empirical cases. Some raised issues of the scope of CGS explanations versus competing ones.

A comparison of the effectiveness of an adult nutrition education program for Aboriginal and non-Aboriginal Australians.

PubMed

Pettigrew, Simone; Jongenelis, Michelle I; Moore, Sarah; Pratt, Iain S

2015-11-01

Adult nutrition education is an important component of broader societal efforts to address the high prevalence of nutrition-related diseases. In Australia, Aboriginal people are a critical target group for such programs because of their substantially higher rates of these diseases. The aim of this study was to assess the relative effectiveness of an adult nutrition education program for Aboriginal and non-Aboriginal participants. Pre-and post-course evaluation data were used to assess changes in confidence in ability to buy healthy foods on a budget, nutrition knowledge, and dietary behaviours among individuals attending FOODcents nutrition education courses. The total sample of 875 Western Australians included 169 who self-identified as Aboriginal or Torres Strait Islander. Perceptions of course usefulness were very high and comparable between Aboriginal and non-Aboriginal participants. Significantly larger improvements in confidence, nutrition knowledge, and reported consumption behaviours were evident among Aboriginal participants. The findings suggest that adult nutrition education programs that address specific knowledge and skill deficits that are common among disadvantaged groups can be effective for multiple target groups, and may also assist in reducing nutrition-related inequalities. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Secreted Phospholipases A₂ from Animal Venoms in Pain and Analgesia.

PubMed

Zambelli, Vanessa O; Picolo, Gisele; Fernandes, Carlos A H; Fontes, Marcos R M; Cury, Yara

2017-12-19

Animal venoms comprise a complex mixture of components that affect several biological systems. Based on the high selectivity for their molecular targets, these components are also a rich source of potential therapeutic agents. Among the main components of animal venoms are the secreted phospholipases A₂ (sPLA₂s). These PLA₂ belong to distinct PLA₂s groups. For example, snake venom sPLA₂s from Elapidae and Viperidae families, the most important families when considering envenomation, belong, respectively, to the IA and IIA/IIB groups, whereas bee venom PLA₂ belongs to group III of sPLA₂s. It is well known that PLA₂, due to its hydrolytic activity on phospholipids, takes part in many pathophysiological processes, including inflammation and pain. Therefore, secreted PLA₂s obtained from animal venoms have been widely used as tools to (a) modulate inflammation and pain, uncovering molecular targets that are implicated in the control of inflammatory (including painful) and neurodegenerative diseases; (b) shed light on the pathophysiology of inflammation and pain observed in human envenomation by poisonous animals; and, (c) characterize molecular mechanisms involved in inflammatory diseases. The present review summarizes the knowledge on the nociceptive and antinociceptive actions of sPLA₂s from animal venoms, particularly snake venoms.

Evaluation of free modeling targets in CASP11 and ROLL.

PubMed

Kinch, Lisa N; Li, Wenlin; Monastyrskyy, Bohdan; Kryshtafovych, Andriy; Grishin, Nick V

2016-09-01

We present an assessment of 'template-free modeling' (FM) in CASP11and ROLL. Community-wide server performance suggested the use of automated scores similar to previous CASPs would provide a good system of evaluating performance, even in the absence of comprehensive manual assessment. The CASP11 FM category included several outstanding examples, including successful prediction by the Baker group of a 256-residue target (T0806-D1) that lacked sequence similarity to any existing template. The top server model prediction by Zhang's Quark, which was apparently selected and refined by several manual groups, encompassed the entire fold of target T0837-D1. Methods from the same two groups tended to dominate overall CASP11 FM and ROLL rankings. Comparison of top FM predictions with those from the previous CASP experiment revealed progress in the category, particularly reflected in high prediction accuracy for larger protein domains. FM prediction models for two cases were sufficient to provide functional insights that were otherwise not obtainable by traditional sequence analysis methods. Importantly, CASP11 abstracts revealed that alignment-based contact prediction methods brought about much of the CASP11 progress, producing both of the functionally relevant models as well as several of the other outstanding structure predictions. These methodological advances enabled de novo modeling of much larger domain structures than was previously possible and allowed prediction of functional sites. Proteins 2016; 84(Suppl 1):51-66. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Identifying User Preferences for a Digital Educational Solution for Young Seniors With Diabetes.

PubMed

van der Molen, Pieta; Maas, Anne H; Chen, Wei; van Pul, Carola; Cottaar, Eduardus J E; van Riel, Natal A W; Hilbers, Peter A J; Haak, Harm R

2017-08-01

The Eindhoven Diabetes Education Simulator project was initiated to develop an educational solution that helps diabetes patients understand and learn more about their diabetes. This article describes the identification of user preferences for the development of such solutions. Young seniors (aged 50-65 years) with type 2 diabetes were chosen as the target group because they are likely to have more affinity with digital devices than older people and because 88% of the Dutch diabetes population is >50 years of age. Data about the target group were gathered through literature research and interviews. The literature research covered data about their device use and education preferences. To gain insight into the daily life of diabetes patients and current diabetes education processes, 20 diabetes patients and 10 medical experts were interviewed. The interviews were analyzed using affinity diagrams. Those diagrams, together with the literature data, formed the basis for two personas and corresponding customer journey maps. Literature showed that diabetes prevalence is inversely correlated to educational level. Computer and device use is relatively low within the target group, but is growing. The interviews showed that young seniors like to play board, card, and computer games, with others or alone. Family and loved ones play an important role in their lives. Medical experts are crucial in the diabetes education of young senior diabetes patients. These findings are translated into a list of design aspects that can be used for creating educational solutions.

Protective Effects of Scutellarin on Human Cardiac Microvascular Endothelial Cells against Hypoxia-Reoxygenation Injury and Its Possible Target-Related Proteins

PubMed Central

Shi, Meina; Liu, Yingting; Feng, Lixing; Cui, Yingbo; Chen, Yajuan; Wang, Peng; Wu, Wenjuan; Chen, Chen; Liu, Xuan; Yang, Weimin

2015-01-01

Scutellarin (SCU) is one of the main components of traditional Chinese medicine plant Erigeron breviscapus (Vant.) Hand.-Mazz. In this paper, we studied the protective effects of SCU on human cardiac microvascular endothelial cells (HCMECs) against hypoxia-reoxygenation (HR) injury and its possible target-related proteins. Results of MTT assay showed that pretreatment of SCU at doses of 1, 5, and 10 μM for 2 h could significantly inhibit the decrease in cell viability of HCMECs induced by HR injury. Subcellular fractions of cells treated with vehicle control, 1 μM SCU, HR injury, or 1 μM SCU + HR injury were separated by ultracentrifugation. The protein expression profiles of cytoplasm and membrane/nuclei fractions were checked using protein two-dimensional electrophoresis (2-DE). Proteins differentially expressed between control and SCU-treated group, control and HR group, or HR and SCU + HR group were identified using mass spectrometry (MS/MS). Possible interaction network of these target-related proteins was predicted using bioinformatic analysis. The influence of SCU on the expression levels of these proteins was confirmed using Western blotting assay. The results indicated that proteins such as p27BBP protein (EIF6), heat shock 60 kDa protein 1 (HSPD1), and chaperonin containing TCP1 subunit 6A isoform (CCT6A) might play important roles in the effects of SCU. PMID:26557144

Protective Effects of Scutellarin on Human Cardiac Microvascular Endothelial Cells against Hypoxia-Reoxygenation Injury and Its Possible Target-Related Proteins.

PubMed

Shi, Meina; Liu, Yingting; Feng, Lixing; Cui, Yingbo; Chen, Yajuan; Wang, Peng; Wu, Wenjuan; Chen, Chen; Liu, Xuan; Yang, Weimin

2015-01-01

Scutellarin (SCU) is one of the main components of traditional Chinese medicine plant Erigeron breviscapus (Vant.) Hand.-Mazz. In this paper, we studied the protective effects of SCU on human cardiac microvascular endothelial cells (HCMECs) against hypoxia-reoxygenation (HR) injury and its possible target-related proteins. Results of MTT assay showed that pretreatment of SCU at doses of 1, 5, and 10 μM for 2 h could significantly inhibit the decrease in cell viability of HCMECs induced by HR injury. Subcellular fractions of cells treated with vehicle control, 1 μM SCU, HR injury, or 1 μM SCU + HR injury were separated by ultracentrifugation. The protein expression profiles of cytoplasm and membrane/nuclei fractions were checked using protein two-dimensional electrophoresis (2-DE). Proteins differentially expressed between control and SCU-treated group, control and HR group, or HR and SCU + HR group were identified using mass spectrometry (MS/MS). Possible interaction network of these target-related proteins was predicted using bioinformatic analysis. The influence of SCU on the expression levels of these proteins was confirmed using Western blotting assay. The results indicated that proteins such as p27BBP protein (EIF6), heat shock 60 kDa protein 1 (HSPD1), and chaperonin containing TCP1 subunit 6A isoform (CCT6A) might play important roles in the effects of SCU.

[Pulmonary hypertension: the future has begun].

PubMed

Olschewski, Horst

2006-04-15

In recent years, pulmonary hypertension got into the focus of research due to the development of efficacious medications and the discovery of important pathologic mechanisms of disease. Currently, prostanoids, endothelin receptor antagonists and phosphodiesterase 5 inhibitors are the most important substance groups used for treatment. Substances that are emerging in tumor therapy (tyrosine kinase inhibitors, epidermal growth factor [EGF] und platelet-derived growth factor [PDGF] receptor blockers), vasoactive intestinal peptide (VIP), rho-kinase inhibitors and targeted drugs for endothelial dysfunction will be evaluated as future drugs for pulmonary hypertension. Improving early diagnosis of pulmonary hypertension will be an important task in the future. Both the development of diagnostic methods with increased sensitivity and specificity and a broad awareness program will be necessary to achieve this goal.

Transcranial route of brain targeted delivery of methadone in oil.

PubMed

Pathirana, W; Abhayawardhana, P; Kariyawasam, H; Ratnasooriya, W D

2009-05-01

The unique anatomical arrangement of blood vessels and sinuses in the human skull and the brain, the prevalence of a high density of skin appendages in the scalp, extracranial vessels of the scalp communicating with the brain via emissary veins and most importantly, the way that the scalp is used in Ayurvedic medical system in treating diseases associated with the brain show that a drug could be transcranially delivered and targeted to the brain through the scalp. The present study was to investigate by measuring the antinociceptive effect on rats whether the opioid analgesic methadone could be delivered and targeted to the brain by transcranial delivery route. A non aqueous solution of methadone base in sesame oil was used for the application on the scalp. Animal studies were carried out using six groups of male rats consisting of group 1, the oral control treated with distilled water 1 ml; group 2, the oral positive control treated with methadone hydrochloride solution 316.5 mug/ml; group 3, the negative control treated transcranially with the blank sesame oil 0.2 ml and three test groups 4, 5 and 6 treated with three different dose levels of the transcranial oil formulation of methadone base, 41.6 mug/0.2 ml, 104 mug/0.2 ml and 208 mug/0.2 ml, respectively. The antinociceptive effects were examined by subjecting the rats to the hot plate and tail flick tests. The two higher concentrations of the three transcranial methadone formulations yielded response vs time curves showing nearly equal maximum antinociceptive effects similar to that of the oral positive control. Maximum analgesic effect after transcranial administration was observed between 1st and 2nd h and declined up to 6th hour. The results indicate that the transcranial brain targeted delivery of methadone base in the form of an oil based non aqueous solution results in statistically significant antinociceptive effects under experimental conditions. Therefore, it is possible to deliver central nervous system drugs through the proposed transcranial route when suitably formulated.

Assessing Pharmacy Students’ Self-Perception of Cultural Competence

PubMed Central

Echeverri, Margarita; Brookover, Cecile; Kennedy, Kathleen

2014-01-01

Pharmacists play an increasingly important role in medication therapy management, which requires communicating effectively with patients. Pharmacy students completed the Self-Assessment of Perceived Level of Cultural Competence (SAPLCC) questionnaire, and their results were used to identify patterns in self-assessment of cultural competence. In general, students rated their knowledge as less than their skills and attitudes. Important differences were found by race, comparing each group with its counterparts: African American students rated their perceived competencies regarding patient discrimination and barriers to health care at a significantly higher level; Asian American students rated their attitudes to engaging in self-reflection and their knowledge in multicultural issues at significantly lower level; and White students rated their awareness regarding racial dynamics at a significantly lower level. It is recommended to consider the students’ cultural, racial, and ethnic backgrounds before developing curriculum in cultural competence and, perhaps, to develop targeted educational interventions for specific groups. PMID:23395945

Erratum to ‘Identifying policy target groups with qualitative and quantitative methods: the case of wildfire risk on nonindustrial private forest lands’ [Forest Policy and Economics. 25: 62–71

Treesearch

A. Paige Fischer; Jeffrey D. Kline; Susan Charnley; Christine Olsen

2013-01-01

Designing policies to harness the potential of heterogeneous target groups such as nonindustrial private forest owners to contribute to public policy goals can be challenging. The behaviors of such groups are shaped by their diverse motivations and circumstances. Segmenting heterogeneous target groups into more homogeneous subgroups may improve the chances of...

How Do Tsetse Recognise Their Hosts? The Role of Shape in the Responses of Tsetse (Glossina fuscipes and G. palpalis) to Artificial Hosts

PubMed Central

Tirados, Inaki; Esterhuizen, Johan; Rayaisse, Jean Baptiste; Diarrassouba, Abdoulaye; Kaba, Dramane; Mpiana, Serge; Vale, Glyn A.; Solano, Philippe; Lehane, Michael J.; Torr, Stephen J.

2011-01-01

Palpalis-group tsetse, particularly the subspecies of Glossina palpalis and G. fuscipes, are the most important transmitters of human African trypanomiasis (HAT), transmitting >95% of cases. Traps and insecticide-treated targets are used to control tsetse but more cost-effective baits might be developed through a better understanding of the fly's host-seeking behaviour. Electrocuting grids were used to assess the numbers of G. palpalis palpalis and G. fuscipes quanzensis attracted to and landing on square or oblong targets of black cloth varying in size from 0.01 m2 to 1.0 m2. For both species, increasing the size of a square target from 0.01 m2 (dimensions = 0.1×0.1 m) to 1.0 m2 (1.0×1.0 m) increased the catch ∼4x however the numbers of tsetse killed per unit area of target declined with target size suggesting that the most cost efficient targets are not the largest. For G. f. quanzensis, horizontal oblongs, (1 m wide×0.5 m high) caught ∼1.8x more tsetse than vertical ones (0.5 m wide×1.0 m high) but the opposite applied for G. p. palpalis. Shape preference was consistent over the range of target sizes. For G. p. palpalis square targets caught as many tsetse as the oblong; while the evidence is less strong the same appears to apply to G. f. quanzensis. The results suggest that targets used to control G. p. palpalis and G. f. quanzensis should be square, and that the most cost-effective designs, as judged by the numbers of tsetse caught per area of target, are likely to be in the region of 0.25×0.25 m2. The preference of G. p. palpalis for vertical oblongs is unique amongst tsetse species, and it is suggested that this response might be related to its anthropophagic behaviour and hence importance as a vector of HAT. PMID:21829734

How do tsetse recognise their hosts? The role of shape in the responses of tsetse (Glossina fuscipes and G. palpalis) to artificial hosts.

PubMed

Tirados, Inaki; Esterhuizen, Johan; Rayaisse, Jean Baptiste; Diarrassouba, Abdoulaye; Kaba, Dramane; Mpiana, Serge; Vale, Glyn A; Solano, Philippe; Lehane, Michael J; Torr, Stephen J

2011-08-01

Palpalis-group tsetse, particularly the subspecies of Glossina palpalis and G. fuscipes, are the most important transmitters of human African trypanomiasis (HAT), transmitting >95% of cases. Traps and insecticide-treated targets are used to control tsetse but more cost-effective baits might be developed through a better understanding of the fly's host-seeking behaviour. Electrocuting grids were used to assess the numbers of G. palpalis palpalis and G. fuscipes quanzensis attracted to and landing on square or oblong targets of black cloth varying in size from 0.01 m(2) to 1.0 m(2). For both species, increasing the size of a square target from 0.01 m(2) (dimensions=0.1 × 0.1 m) to 1.0 m(2) (1.0 × 1.0 m) increased the catch ~4x however the numbers of tsetse killed per unit area of target declined with target size suggesting that the most cost efficient targets are not the largest. For G. f. quanzensis, horizontal oblongs, (1 m wide × 0.5 m high) caught ~1.8x more tsetse than vertical ones (0.5 m wide × 1.0 m high) but the opposite applied for G. p. palpalis. Shape preference was consistent over the range of target sizes. For G. p. palpalis square targets caught as many tsetse as the oblong; while the evidence is less strong the same appears to apply to G. f. quanzensis. The results suggest that targets used to control G. p. palpalis and G. f. quanzensis should be square, and that the most cost-effective designs, as judged by the numbers of tsetse caught per area of target, are likely to be in the region of 0.25 × 0.25 m(2). The preference of G. p. palpalis for vertical oblongs is unique amongst tsetse species, and it is suggested that this response might be related to its anthropophagic behaviour and hence importance as a vector of HAT.

Transcriptome Analysis and Screening for Potential Target Genes for RNAi-Mediated Pest Control of the Beet Armyworm, Spodoptera exigua.

PubMed

Li, Hang; Jiang, Weihua; Zhang, Zan; Xing, Yanru; Li, Fei

2013-01-01

The beet armyworm, Spodoptera exigua (Hübner), is a serious pest worldwide that causes significant losses in crops. Unfortunately, genetic resources for the beet armyworm is extremely scarce. To improve these resources we sequenced the transcriptome of S. exigua representing all stages including eggs, 1(st) to 5(th) instar larvae, pupae, male and female adults using the Illumina Solexa platform. We assembled the transcriptome with Trinity that yielded 31,414 contigs. Of these contigs, 18,592 were annotated as protein coding genes by Blast searches against the NCBI nr database. It has been shown that knockdown of important insect genes by dsRNAs or siRNAs is a feasible mechanism to control insect pests. The first key step towards developing an efficient RNAi-mediated pest control technique is to find suitable target genes. To screen for effective target genes in the beet armyworm, we selected nine candidate genes. The sequences of these genes were amplified using the RACE strategy. Then, siRNAs were designed and chemically synthesized. We injected 2 µl siRNA (2 µg/µl) into the 4(th) instar larvae to knock down the respective target genes. The mRNA abundance of target genes decreased to different levels (∼20-94.3%) after injection of siRNAs. Knockdown of eight genes including chitinase7, PGCP, chitinase1, ATPase, tubulin1, arf2, tubulin2 and arf1 caused a significantly high level of mortality compared to the negative control (P<0.05). About 80% of the surviving insects in the siRNA-treated group of five genes (PGCP, chitinase1, tubulin1, tubulin2 and helicase) showed retarded development. In chitinase1-siRNA and chitinase7-siRNA administered groups, 12.5% survivors exhibited "half-ecdysis". In arf1-siRNA and arf2-siRNA groups, the body color of 15% became black 48 h after injections. In summary, the transcriptome could be a valuable genetic resource for identification of genes in S. exigua and this study provided putative targets for RNAi pest control.

Transcriptome Analysis and Screening for Potential Target Genes for RNAi-Mediated Pest Control of the Beet Armyworm, Spodoptera exigua

PubMed Central

Zhang, Zan; Xing, Yanru; Li, Fei

2013-01-01

The beet armyworm, Spodoptera exigua (Hübner), is a serious pest worldwide that causes significant losses in crops. Unfortunately, genetic resources for the beet armyworm is extremely scarce. To improve these resources we sequenced the transcriptome of S. exigua representing all stages including eggs, 1st to 5th instar larvae, pupae, male and female adults using the Illumina Solexa platform. We assembled the transcriptome with Trinity that yielded 31,414 contigs. Of these contigs, 18,592 were annotated as protein coding genes by Blast searches against the NCBI nr database. It has been shown that knockdown of important insect genes by dsRNAs or siRNAs is a feasible mechanism to control insect pests. The first key step towards developing an efficient RNAi-mediated pest control technique is to find suitable target genes. To screen for effective target genes in the beet armyworm, we selected nine candidate genes. The sequences of these genes were amplified using the RACE strategy. Then, siRNAs were designed and chemically synthesized. We injected 2 µl siRNA (2 µg/µl) into the 4th instar larvae to knock down the respective target genes. The mRNA abundance of target genes decreased to different levels (∼20–94.3%) after injection of siRNAs. Knockdown of eight genes including chitinase7, PGCP, chitinase1, ATPase, tubulin1, arf2, tubulin2 and arf1 caused a significantly high level of mortality compared to the negative control (P<0.05). About 80% of the surviving insects in the siRNA-treated group of five genes (PGCP, chitinase1, tubulin1, tubulin2 and helicase) showed retarded development. In chitinase1-siRNA and chitinase7-siRNA administered groups, 12.5% survivors exhibited “half-ecdysis”. In arf1-siRNA and arf2-siRNA groups, the body color of 15% became black 48 h after injections. In summary, the transcriptome could be a valuable genetic resource for identification of genes in S. exigua and this study provided putative targets for RNAi pest control. PMID:23823756

The evolution of Homo sapiens denisova and Homo sapiens neanderthalensis miRNA targeting genes in the prenatal and postnatal brain.

PubMed

Gunbin, Konstantin V; Afonnikov, Dmitry A; Kolchanov, Nikolay A; Derevianko, Anatoly P; Rogaev, Eugeny I

2015-01-01

As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain. A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development. Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.

The evolution of Homo sapiens denisova and Homo sapiens neanderthalensis miRNA targeting genes in the prenatal and postnatal brain

PubMed Central

2015-01-01

Background As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain. Results A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development. Conclusions Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines. PMID:26693966

The projected effectiveness of Clostridium difficile vaccination as part of an integrated infection control strategy.

PubMed

van Kleef, Esther; Deeny, Sarah R; Jit, Mark; Cookson, Barry; Goldenberg, Simon D; Edmunds, W John; Robotham, Julie V

2016-11-04

Early clinical trials of a Clostridium difficile toxoid vaccine show efficacy in preventing C. difficile infection (CDI). The optimal patient group to target for vaccination programmes remains unexplored. This study performed a model-based evaluation of the effectiveness of different CDI vaccination strategies, within the context of existing infection prevention and control strategies such as antimicrobial stewardship. An individual-based transmission model of CDI in a high-risk hospital setting was developed. The model incorporated data on patient movements between the hospital, and catchment populations from the community and long-term care facilities (LTCF), using English national and local level data for model-parameterisation. We evaluated vaccination of: (1) discharged patients who had an CDI-occurrence in the ward; (2) LTCF-residents; (3) Planned elective surgical admissions and (4) All three strategies combined. Without vaccination, 10.9 [Interquartile range: 10.0-11.8] patients per 1000 ward admissions developed CDI, of which 31% were ward-acquired. Immunising all three patient groups resulted in a 43% [42-44], reduction of ward-onset CDI on average. Among the strategies restricting vaccination to one target group, vaccinating elective surgical patients proved most effective (35% [34-36] reduction), but least efficient, requiring 146 [133-162] courses to prevent one ICU-onset case. Immunising LTCF residents was most efficient, requiring just 13 [11-16] courses to prevent one case, but considering this only comprised a small group of our hospital population, it only reduced ICU-onset CDI by 9% [8-11]. Vaccination proved most efficient when ward-based transmission rates and antimicrobial consumption were high. Strategy success depends on the interaction between hospital and catchment populations, and importantly, consideration of importations of CDI from outside the hospital which we found to substantially impact hospital dynamics. Vaccination may be most desirable in settings or patient groups where levels of broad-spectrum antimicrobial use are high and difficult to reduce. Copyright © 2016 Elsevier Ltd. All rights reserved.

'Love and trust, you can be blinded': HIV risk within relationships among Latina women in Miami, Florida.

PubMed

Ibañez, Gladys E; Whitt, Elaine; Avent, Tenesha; Martin, Steve S; Varga, Leah M; Cano, Miguel A; O'Connell, Daniel J

2017-10-01

Latina women are disproportionately affected by HIV in the US, and account for 30% of all HIV infections in Miami-Dade County, Florida. The main risk for Latina women is heterosexual contact. Little is known about the relational and cultural factors that may impact women's HIV risk perception. This study aims to describe Latina women's perception of their HIV risk within a relational, cultural, and linguistic context. Eight focus groups of Latina women (n = 28), four English speaking groups and four Spanish speaking groups, were conducted between December 2013 and May 2014. Women were recruited from a diversion program for criminal justice clients and by word of mouth. Eligibility criteria included the following: self-identify as Hispanic/Latino, 18-49 years of age, and self-identify as heterosexual. A two-level open coding analytic approach was conducted to identify themes across groups. Most participants were foreign-born (61%) and represented the following countries: Cuba (47%), Honduras (17.5%), Mexico (12%), as well as Nicaragua, Puerto Rico, Colombia, and Venezuela (15%). Participant ages ranged between 18 and 49, with a mean age of 32 years. Relationship factors were important in perceiving HIV risk including male infidelity, women's trust in their male partners, relationship type, and getting caught up in the heat of the moment. For women in the English speaking groups, drug use and trading sex for drugs were also reasons cited for putting them at risk for HIV. English speaking women also reported that women should take more responsibility regarding condom use. Findings emphasize the importance of taking relational and cultural context into account when developing HIV prevention programs for Latina women. Interventions targeting English speaking Latina women should focus on women being more proactive in their sexual health; interventions focused on Spanish speaking women might target their prevention messages to either men or couples.

Social identity and support for counteracting tobacco company marketing that targets vulnerable populations.

PubMed

Baig, Sabeeh A; Pepper, Jessica K; Morgan, Jennifer C; Brewer, Noel T

2017-06-01

Tobacco companies use advertising to target vulnerable populations, including youth, racial/ethnic minorities, and sexual minorities. We sought to examine how personal identity affects support for population-specific anti-smoking advertisements that could serve as countermeasures to industry marketing practices. In 2014-2015, we surveyed probability phone samples of adults and adolescents (n = 6,139) and an online convenience sample of adults (n = 4,137) in the United States. We experimentally varied the description of tobacco industry marketing practices (no description, general, or specific to a target group). The four prevention target groups were teens; African Americans; Latinos; and gays, lesbians, and bisexuals (GLBs). Participants were either members or non-members of their prevention target group. Support was highest for anti-smoking advertisements targeting teens, moderate for Latinos and African Americans, and lowest for GLBs. In-group members expressed higher support than out-group members when anti-smoking advertisements targeted African Americans, Latinos, and GLBs (all p < 0.05). However, when teens were the target prevention group, in-group members expressed lower support than out-group members (p < 0.05). The description of industry marketing practices did not have an effect. Results were similar across the phone and online studies. Our findings suggest that the public strongly supports advertisements to prevent smoking among teens, but support for similar efforts among other vulnerable populations is comparatively low. Anti-smoking campaigns for vulnerable populations may benefit from a greater understanding of the role of social identity in shaping public support for such campaigns. Copyright © 2017 Elsevier Ltd. All rights reserved.

Therapeutic effects of Euphorbia Pekinensis and Glycyrrhiza glabra on Hepatocellular Carcinoma Ascites Partially Via Regulating the Frk-Arhgdib-Inpp5d-Avpr2-Aqp4 Signal Axis

PubMed Central

Zhang, Yanqiong; Yan, Chen; Li, Yuting; Mao, Xia; Tao, Weiwei; Tang, Yuping; Lin, Ya; Guo, Qiuyan; Duan, Jingao; Lin, Na

2017-01-01

To clarify unknown rationalities of herbaceous compatibility of Euphorbia Pekinensis (DJ) and Glycyrrhiza glabra (GC) acting on hepatocellular carcinoma (HCC) ascites, peritoneum transcriptomics profiling of 15 subjects, including normal control (Con), HCC ascites mouse model (Mod), DJ-alone, DJ/GC-synergy and DJ/GC-antagonism treatment groups were performed on OneArray platform, followed by differentially expressed genes (DEGs) screening. DEGs between Mod and Con groups were considered as HCC ascites-related genes, and those among different drug treatment and Mod groups were identified as DJ/GC-combination-related genes. Then, an interaction network of HCC ascites-related gene-DJ/GC combination-related gene-known therapeutic target gene for ascites was constructed. Based on nodes’ degree, closeness, betweenness and k-coreness, the Frk-Arhgdib-Inpp5d-Avpr2-Aqp4 axis with highly network topological importance was demonstrated to be a candidate target of DJ/GC combination acting on HCC ascites. Importantly, both qPCR and western blot analyses verified this regulatory effects based on HCC ascites mice in vivo and M-1 collecting duct cells in vitro. Collectively, different combination designs of DJ and GC may lead to synergistic or antagonistic effects on HCC ascites partially via regulating the Frk-Arhgdib-Inpp5d-Avpr2-Aqp4 axis, implying that global gene expression profiling combined with network analysis can offer an effective way to understand pharmacological mechanisms of traditional Chinese medicine prescriptions. PMID:28165501

Diabetes prevention among American Indians: the role of self-efficacy, risk perception, numeracy and cultural identity.

PubMed

Simonds, Vanessa W; Omidpanah, Adam; Buchwald, Dedra

2017-10-02

According to the Risk Perception Attitude (RPA) framework, classifying people according to their perceptions of disease risk and their self-efficacy beliefs allows us to predict their likelihood for engaging in preventive behaviors. Health interventions can then be targeted according to RPA group. We applied the framework to type 2 diabetes prevention behaviors among American Indians and expanded it to include culture and numeracy. Using a cross-sectional study design, we surveyed a sample of Northern Plains American Indians in a reservation community setting on self-reported perceptions of diabetes risk, objective diabetes risk, self-efficacy, engagement in healthy behaviors, knowledge of diabetes risk factors, and covariates including demographics, numeracy, and cultural identity. We used the RPA framework to classify participants into four groups based on their perceptions of risk and self-efficacy. Analyses of variance and covariance estimated inter-group differences in behaviors associated with type 2 diabetes prevention. Among 128 participants, our only finding consistent with the RPA framework was that self-efficacy and risk perception predicted knowledge about diabetes risk factors. We found limited evidence for the influence of cultural identity within the RPA framework. Overall, participants had lower numeracy skills which tended to be associated with inaccurate perceptions of higher levels of risk. The theoretical framework may benefit from inclusion of further contextual factors that influence these behaviors. Attention to numeracy skills stands out in our study as an important influence on the RPA framework, highlighting the importance of attending to numeracy when targeting and tailoring risk information to participants segmented by the RPA framework.

Earlier triple therapy with pioglitazone in patients with type 2 diabetes.

PubMed

Charpentier, G; Halimi, S

2009-09-01

This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA(1c)) 6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA(1c) (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-B) were calculated. Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA(1c) and -2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA(1c) level of <8.5% achieved the HbA(1c) target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA(1c) level was >or= 8.5%, 13% achieved the HbA(1c) target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA(1c), FPG and surrogate measures of beta-cell function. Patients were more likely to reach target HbA(1c) levels (< 7.0%) with pioglitazone treatment if their baseline HbA(1c) levels were < 8.5%, highlighting the importance of early triple therapy.

Myositis non-inflammatory mechanisms: An up-dated review.

PubMed

Manole, Emilia; Bastian, Alexandra E; Butoianu, Niculina; Goebel, Hans H

2017-01-01

Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of rare muscular diseases, with no clearly known causes. IIM frequently have an incomplete response to treatment due to the difficulty in distinguishing between IIM forms, and due to neglect their non-inflammatory causes. Important data concerning non-immune mechanisms in IIM pathology have been recently accumulated. There is a correlation between inflammatory and non-inflammatory mechanisms, but their involvement in IIM pathogenesis is still unknown. Here we review some of the most important data regarding the non-immune IIM pathology, highlighting possible future therapeutic targets: endoplasmic reticulum stress, ATP metabolism, ROS generation, autophagy, and microRNAs disturbances.

Visual Search in ASD: Instructed Versus Spontaneous Local and Global Processing.

PubMed

Van der Hallen, Ruth; Evers, Kris; Boets, Bart; Steyaert, Jean; Noens, Ilse; Wagemans, Johan

2016-09-01

Visual search has been used extensively to investigate differences in mid-level visual processing between individuals with ASD and TD individuals. The current study employed two visual search paradigms with Gaborized stimuli to assess the impact of task distractors (Experiment 1) and task instruction (Experiment 2) on local-global visual processing in ASD versus TD children. Experiment 1 revealed both groups to be equally sensitive to the absence or presence of a distractor, regardless of the type of target or type of distractor. Experiment 2 revealed a differential effect of task instruction for ASD compared to TD, regardless of the type of target. Taken together, these results stress the importance of task factors in the study of local-global visual processing in ASD.

Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target.

PubMed

Chiba, Shuntaro; Ikeda, Kazuyoshi; Ishida, Takashi; Gromiha, M Michael; Taguchi, Y-H; Iwadate, Mitsuo; Umeyama, Hideaki; Hsin, Kun-Yi; Kitano, Hiroaki; Yamamoto, Kazuki; Sugaya, Nobuyoshi; Kato, Koya; Okuno, Tatsuya; Chikenji, George; Mochizuki, Masahiro; Yasuo, Nobuaki; Yoshino, Ryunosuke; Yanagisawa, Keisuke; Ban, Tomohiro; Teramoto, Reiji; Ramakrishnan, Chandrasekaran; Thangakani, A Mary; Velmurugan, D; Prathipati, Philip; Ito, Junichi; Tsuchiya, Yuko; Mizuguchi, Kenji; Honma, Teruki; Hirokawa, Takatsugu; Akiyama, Yutaka; Sekijima, Masakazu

2015-11-26

A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective.

Attributions of blame and responsibility in sexual harassment: reexamining a psychological model.

PubMed

Klein, Kristen M; Apple, Kevin J; Kahn, Arnold S

2011-04-01

Kelley's (Nebr Symp Motiv 15:192-238, 1967) attribution theory can inform sexual harassment research by identifying how observers use consensus, consistency, and distinctiveness information in determining whether a target or perpetrator is responsible for a sexual harassment situation. In this study, Kelley's theory is applied to a scenario in which a male perpetrator sexually harasses a female target in a university setting. Results from 314 predominantly female college students indicate that consistency and consensus information significantly affect participants' judgments of blame and responsibility for the situation. The authors discuss the importance of the reference groups used to derive consensus and distinctiveness information, and reintroduce Kelley's attribution theory as a means of understanding observers' perceptions of sexual harassment.

Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target

PubMed Central

Chiba, Shuntaro; Ikeda, Kazuyoshi; Ishida, Takashi; Gromiha, M. Michael; Taguchi, Y-h.; Iwadate, Mitsuo; Umeyama, Hideaki; Hsin, Kun-Yi; Kitano, Hiroaki; Yamamoto, Kazuki; Sugaya, Nobuyoshi; Kato, Koya; Okuno, Tatsuya; Chikenji, George; Mochizuki, Masahiro; Yasuo, Nobuaki; Yoshino, Ryunosuke; Yanagisawa, Keisuke; Ban, Tomohiro; Teramoto, Reiji; Ramakrishnan, Chandrasekaran; Thangakani, A. Mary; Velmurugan, D.; Prathipati, Philip; Ito, Junichi; Tsuchiya, Yuko; Mizuguchi, Kenji; Honma, Teruki; Hirokawa, Takatsugu; Akiyama, Yutaka; Sekijima, Masakazu

2015-01-01

A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective. PMID:26607293

Rho protein GTPases and their interactions with NFκB: crossroads of inflammation and matrix biology

PubMed Central

Tong, Louis; Tergaonkar, Vinay

2014-01-01

The RhoGTPases, with RhoA, Cdc42 and Rac being major members, are a group of key ubiquitous proteins present in all eukaryotic organisms that subserve such important functions as cell migration, adhesion and differentiation. The NFκB (nuclear factor κB) is a family of constitutive and inducible transcription factors that through their diverse target genes, play a major role in processes such as cytokine expression, stress regulation, cell division and transformation. Research over the past decade has uncovered new molecular links between the RhoGTPases and the NFκB pathway, with the RhoGTPases playing a positive or negative regulatory role on NFκB activation depending on the context. The RhoA–NFκB interaction has been shown to be important in cytokine-activated NFκB processes, such as those induced by TNFα (tumour necrosis factor α). On the other hand, Rac is important for activating the NFκB response downstream of integrin activation, such as after phagocytosis. Specific residues of Rac1 are important for triggering NFκB activation, and mutations do obliterate this response. Other upstream triggers of the RhoGTPase–NFκB interactions include the suppressive p120 catenin, with implications for skin inflammation. The networks described here are not only important areas for further research, but are also significant for discovery of targets for translational medicine. PMID:24877606

Detection of the corrosion in reinforced concrete with GPR: the case study of the Park Guell

NASA Astrophysics Data System (ADS)

Sossa, Viviana; Perez-Gracia, Vega; Gonzalez-Drigo, Ramon; Caselles, Oriol; Clapes, Jaume

2017-04-01

Detection of corrosion is important in cultural heritage assessment. Many structures contain metallic targets embedded in masonry or mortar, and corrosion cab cause important damage. However, detection using non-destructive methods is difficult and highly localized, providing in most cases incomplete results. In order to obtain a more extended analysis, GPR was applied and evaluated to detect damage as consequence of corrosion. This technique is a non-destructive method that covers a large area of study while other methods are constrained to a small areas or specific points. Therefore, some controlled laboratory tests were designed to determine possible differences in radargrams obtained in the case of corroded and non-corroded targets. These analysis allowed to observe that the corrosion seems to increase the attenuation of the radar signal, being difficult to detect targets near the damaged bars. The results were applied to study the mosaic roofs in the Park Guell, in Barcelona. This park is one of the most important Modernista (Art Noveau) complex in Barcelona. It is characterized by structures with roofs and banks with tessellation. Some of these structures are most likely supported by metal elements, and seepage cause important damage observed over the tessellation. The objective of the study was to define the possible existence of those metallic targets, determining their location. And, in the case of existence of metallic elements, defining which are the zones more affected by corrosion. The results demonstrates the existence of metallic supports in many parts, as well as some defined areas that could be damaged. Acknowledgement: This work has been partially funded by the Spanish Government and by the European Commission with FEDER funds, through the research projects CGL2011-23621 and CGL2015-65913-P. The study is also a contribution to the EU funded COST Action TU1208, "Civil Engineering Applications of Ground Penetrating Radar", to the working group 2.2.

Origin of discrepancies between crater size-frequency distributions of coeval lunar geologic units via target property contrasts

NASA Astrophysics Data System (ADS)

van der Bogert, C. H.; Hiesinger, H.; Dundas, C. M.; Krüger, T.; McEwen, A. S.; Zanetti, M.; Robinson, M. S.

2017-12-01

Recent work on dating Copernican-aged craters, using Lunar Reconnaissance Orbiter (LRO) Camera data, re-encountered a curious discrepancy in crater size-frequency distribution (CSFD) measurements that was observed, but not understood, during the Apollo era. For example, at Tycho, Copernicus, and Aristarchus craters, CSFDs of impact melt deposits give significantly younger relative and absolute model ages (AMAs) than impact ejecta blankets, although these two units formed during one impact event, and would ideally yield coeval ages at the resolution of the CSFD technique. We investigated the effects of contrasting target properties on CSFDs and their resultant relative and absolute model ages for coeval lunar impact melt and ejecta units. We counted craters with diameters through the transition from strength- to gravity-scaling on two large impact melt deposits at Tycho and King craters, and we used pi-group scaling calculations to model the effects of differing target properties on final crater diameters for five different theoretical lunar targets. The new CSFD for the large King Crater melt pond bridges the gap between the discrepant CSFDs within a single geologic unit. Thus, the observed trends in the impact melt CSFDs support the occurrence of target property effects, rather than self-secondary and/or field secondary contamination. The CSFDs generated from the pi-group scaling calculations show that targets with higher density and effective strength yield smaller crater diameters than weaker targets, such that the relative ages of the former are lower relative to the latter. Consequently, coeval impact melt and ejecta units will have discrepant apparent ages. Target property differences also affect the resulting slope of the CSFD, with stronger targets exhibiting shallower slopes, so that the final crater diameters may differ more greatly at smaller diameters. Besides their application to age dating, the CSFDs may provide additional information about the characteristics of the target. For example, the transition diameter from strength- to gravity-scaling could provide a tool for investigating the relative strengths of different geologic units. The magnitude of the offset between the impact melt and ejecta isochrons may also provide information about the relative target properties and/or exposure/degradation ages of the two units. Robotic or human sampling of coeval units on the Moon could provide a direct test of the importance and magnitude of target property effects on CSFDs.

Origin of discrepancies between crater size-frequency distributions of coeval lunar geologic units via target property contrasts

USGS Publications Warehouse

Van der Bogert, Carolyn H.; Hiesinger, Harald; Dundas, Colin M.; Kruger, T.; McEwen, Alfred S.; Zanetti, Michael; Robinson, Mark S.

2017-01-01

Recent work on dating Copernican-aged craters, using Lunar Reconnaissance Orbiter (LRO) Camera data, re-encountered a curious discrepancy in crater size-frequency distribution (CSFD) measurements that was observed, but not understood, during the Apollo era. For example, at Tycho, Copernicus, and Aristarchus craters, CSFDs of impact melt deposits give significantly younger relative and absolute model ages (AMAs) than impact ejecta blankets, although these two units formed during one impact event, and would ideally yield coeval ages at the resolution of the CSFD technique. We investigated the effects of contrasting target properties on CSFDs and their resultant relative and absolute model ages for coeval lunar impact melt and ejecta units. We counted craters with diameters through the transition from strength- to gravity-scaling on two large impact melt deposits at Tycho and King craters, and we used pi-group scaling calculations to model the effects of differing target properties on final crater diameters for five different theoretical lunar targets. The new CSFD for the large King Crater melt pond bridges the gap between the discrepant CSFDs within a single geologic unit. Thus, the observed trends in the impact melt CSFDs support the occurrence of target property effects, rather than self-secondary and/or field secondary contamination. The CSFDs generated from the pi-group scaling calculations show that targets with higher density and effective strength yield smaller crater diameters than weaker targets, such that the relative ages of the former are lower relative to the latter. Consequently, coeval impact melt and ejecta units will have discrepant apparent ages. Target property differences also affect the resulting slope of the CSFD, with stronger targets exhibiting shallower slopes, so that the final crater diameters may differ more greatly at smaller diameters. Besides their application to age dating, the CSFDs may provide additional information about the characteristics of the target. For example, the transition diameter from strength- to gravity-scaling could provide a tool for investigating the relative strengths of different geologic units. The magnitude of the offset between the impact melt and ejecta isochrons may also provide information about the relative target properties and/or exposure/degradation ages of the two units. Robotic or human sampling of coeval units on the Moon could provide a direct test of the importance and magnitude of target property effects on CSFDs.

Gender differences in leadership amongst first-year medical students in the small-group setting.

PubMed

Wayne, Nancy L; Vermillion, Michelle; Uijtdehaage, Sebastian

2010-08-01

To investigate the extent of gender bias in the volunteerism of small-group leaders amongst first-year medical students, and whether bias could be eliminated with special instructions to the students. The gender of leaders in small-group sessions in a real academic setting was monitored under two conditions: control conditions, in which basic instructions were provided to participants, and intervention conditions, in which the same basic instructions were provided plus a brief "pep talk" on the importance of experiencing a leadership role in a safe environment. During the small-group sessions, an observer noted the gender and names of group leaders for later analysis. After a class debriefing, a subset of leaders and nonleaders from both the control and intervention groups were invited to be interviewed about their perceptions of the small-group experience. Interviews were tape recorded and transcribed for analysis. In 2007-2008 and 2008-2009, disproportionately fewer women than men volunteered to become small-group leaders under control conditions. This gender bias was eliminated under intervention conditions. The interviews illustrated how a subtle change in instructions helped some female students take on a leadership role. Gender bias in leadership in the small-group setting amongst medical students-even when women make up half of the class-may persist without targeted intervention. The authors suggest that frequent and consistent intervention during medical school could be an important factor in encouraging women to identify themselves as leaders, promoting confidence to consider leadership roles in medicine.

Ecological-niche modeling and prioritization of conservation-area networks for Mexican herpetofauna.

PubMed

Urbina-Cardona, J Nicolás; Flores-Villela, Oscar

2010-08-01

One of the most important tools in conservation biology is information on the geographic distribution of species and the variables determining those patterns. We used maximum-entropy niche modeling to run distribution models for 222 amphibian and 371 reptile species (49% endemics and 27% threatened) for which we had 34,619 single geographic records. The planning region is in southeastern Mexico, is 20% of the country's area, includes 80% of the country's herpetofauna, and lacks an adequate protected-area system. We used probabilistic data to build distribution models of herpetofauna for use in prioritizing conservation areas for three target groups (all species and threatened and endemic species). The accuracy of species-distribution models was better for endemic and threatened species than it was for all species. Forty-seven percent of the region has been deforested and additional conservation areas with 13.7% to 88.6% more native vegetation (76% to 96% of the areas are outside the current protected-area system) are needed. There was overlap in 26 of the main selected areas in the conservation-area network prioritized to preserve the target groups, and for all three target groups the proportion of vegetation types needed for their conservation was constant: 30% pine and oak forests, 22% tropical evergreen forest, 17% low deciduous forest, and 8% montane cloud forests. The fact that different groups of species require the same proportion of habitat types suggests that the pine and oak forests support the highest proportion of endemic and threatened species and should therefore be given priority over other types of vegetation for inclusion in the protected areas of southeastern Mexico.

Effective heart disease prevention: lessons from a qualitative study of user perspectives in Bangladeshi, Indian and Pakistani communities.

PubMed

Netto, G; McCloughan, L; Bhatnagar, A

2007-03-01

Coronary heart disease (CHD) has a high mortality, incidence and prevalence among Indian, Pakistani and Bangladeshi communities in the UK, indicating the need for effective heart disease prevention initiatives for these communities. This paper considers how service user perspectives can be used to develop effective, culturally focused CHD prevention interventions for these target groups by addressing identified barriers, including deeply held cultural beliefs. A qualitative research study, using a longitudinal action research approach. This was a community-based study in Edinburgh. Six focus group discussions--two for each community--were organized with participants from these communities at the beginning of the project. A further six focus group discussions for the same communities were organized six months later. Over the period examined, participants reported varying changes in levels of knowledge relating to the nature, causes and symptoms of CHD. Some participants reported taking slight to significant steps to reduce or prevent heart disease, while others did not. The project was viewed as helpful in increasing knowledge about CHD and preventive measures and encouraging healthier lifestyles. However, persistent barriers to change were also identified, requiring changes to the project that involved not only matching intervention materials and messages to observable, superficial characteristics of the target population, but more fundamental changes that address the cultural, social, historical, environmental and psychological forces that influence health behaviour. CHD prevention initiatives need to identify and respond to deep-rooted influences on health-behaviour in 'at-risk' groups, in addition to superficial characteristics of the target populations. It is important for specific prevention initiatives to be linked into wider CHD frameworks to ensure transferability of learning and integration within wider service provision.

Exploiting differential RNA splicing patterns: a potential new group of therapeutic targets in cancer.

PubMed

Jyotsana, Nidhi; Heuser, Michael

2018-02-01

Mutations in genes associated with splicing have been found in hematologic malignancies, but also in solid cancers. Aberrant cancer specific RNA splicing either results from mutations or misexpression of the spliceosome genes directly, or from mutations in splice sites of oncogenes or tumor suppressors. Areas covered: In this review, we present molecular targets of aberrant splicing in various malignancies, information on existing and emerging therapeutics against such targets, and strategies for future drug development. Expert opinion: Alternative splicing is an important mechanism that controls gene expression, and hence pharmacologic and genetic control of aberrant alternative RNA splicing has been proposed as a potential therapy in cancer. To identify and validate aberrant RNA splicing patterns as therapeutic targets we need to (1) characterize the most common genetic aberrations of the spliceosome and of splice sites, (2) understand the dysregulated downstream pathways and (3) exploit in-vivo disease models of aberrant splicing. Antisense oligonucleotides show promising activity, but will benefit from improved delivery tools. Inhibitors of mutated splicing factors require improved specificity, as alternative and aberrant splicing are often intertwined like two sides of the same coin. In summary, targeting aberrant splicing is an early but emerging field in cancer treatment.

Classification of video sequences into chosen generalized use classes of target size and lighting level.

PubMed

Leszczuk, Mikołaj; Dudek, Łukasz; Witkowski, Marcin

The VQiPS (Video Quality in Public Safety) Working Group, supported by the U.S. Department of Homeland Security, has been developing a user guide for public safety video applications. According to VQiPS, five parameters have particular importance influencing the ability to achieve a recognition task. They are: usage time-frame, discrimination level, target size, lighting level, and level of motion. These parameters form what are referred to as Generalized Use Classes (GUCs). The aim of our research was to develop algorithms that would automatically assist classification of input sequences into one of the GUCs. Target size and lighting level parameters were approached. The experiment described reveals the experts' ambiguity and hesitation during the manual target size determination process. However, the automatic methods developed for target size classification make it possible to determine GUC parameters with 70 % compliance to the end-users' opinion. Lighting levels of the entire sequence can be classified with an efficiency reaching 93 %. To make the algorithms available for use, a test application has been developed. It is able to process video files and display classification results, the user interface being very simple and requiring only minimal user interaction.

First characterization of a microsporidial triosephosphate isomerase and the biochemical mechanisms of its inactivation to propose a new druggable target.

PubMed

García-Torres, Itzhel; De la Mora-De la Mora, Ignacio; Hernández-Alcántara, Gloria; Molina-Ortiz, Dora; Caballero-Salazar, Silvia; Olivos-García, Alfonso; Nava, Gabriela; López-Velázquez, Gabriel; Enríquez-Flores, Sergio

2018-06-05

The microsporidia are a large group of intracellular parasites with a broad range of hosts, including humans. Encephalitozoon intestinalis is the second microsporidia species most frequently associated with gastrointestinal disease in humans, especially immunocompromised or immunosuppressed individuals, including children and the elderly. The prevalence reported worldwide in these groups ranges from 0 to 60%. Currently, albendazole is most commonly used to treat microsporidiosis caused by Encephalitozoon species. However, the results of treatment are variable, and relapse can occur. Consequently, efforts are being directed toward identifying more effective drugs for treating microsporidiosis, and the study of new molecular targets appears promising. These parasites lack mitochondria, and oxidative phosphorylation therefore does not occur, which suggests the enzymes involved in glycolysis as potential drug targets. Here, we have for the first time characterized the glycolytic enzyme triosephosphate isomerase of E. intestinalis at the functional and structural levels. Our results demonstrate the mechanisms of inactivation of this enzyme by thiol-reactive compounds. The most striking result of this study is the demonstration that established safe drugs such as omeprazole, rabeprazole and sulbutiamine can effectively inactivate this microsporidial enzyme and might be considered as potential drugs for treating this important disease.

Measuring participant rurality in Web-based interventions.

PubMed

Danaher, Brian G; Hart, L Gary; McKay, H Garth; Severson, Herbert H

2007-08-31

Web-based health behavior change programs can reach large groups of disparate participants and thus they provide promise of becoming important public health tools. Data on participant rurality can complement other demographic measures to deepen our understanding of the success of these programs. Specifically, analysis of participant rurality can inform recruitment and social marketing efforts, and facilitate the targeting and tailoring of program content. Rurality analysis can also help evaluate the effectiveness of interventions across population groupings. We describe how the RUCAs (Rural-Urban Commuting Area Codes) methodology can be used to examine results from two Randomized Controlled Trials of Web-based tobacco cessation programs: the ChewFree.com project for smokeless tobacco cessation and the Smokers' Health Improvement Program (SHIP) project for smoking cessation. Using RUCAs methodology helped to highlight the extent to which both Web-based interventions reached a substantial percentage of rural participants. The ChewFree program was found to have more rural participation which is consistent with the greater prevalence of smokeless tobacco use in rural settings as well as ChewFree's multifaceted recruitment program that specifically targeted rural settings. Researchers of Web-based health behavior change programs targeted to the US should routinely include RUCAs as a part of analyzing participant demographics. Researchers in other countries should examine rurality indices germane to their country.

The role of sensory perception in the development and targeting of tobacco products.

PubMed

Carpenter, Carrie M; Wayne, Geoffrey Ferris; Connolly, Gregory N

2007-01-01

To examine tobacco industry research on smoking-related sensory effects, including differences in sensory perception across smoker groups, and to determine whether this research informed targeted product development and impacted the development of commercial tobacco products. We searched previously secret internal tobacco industry documents available online through document databases housed at Tobacco Documents Online, the British American Tobacco Document Archive and the Legacy Tobacco Documents Library. We identified relevant documents using a snowball sampling method to first search the databases using an initial set of key words and to then establish further search terms. Sensory research is a priority within the tobacco industry directly impacting commercial markets both in the United States and internationally. Sensory factors contribute to smoker satisfaction and product acceptance, and play an important role in controlling puffing behavior. Cigarette manufacturers have capitalized on distinct sensory preferences across gender, age and ethnic groups by tailoring products for specific populations. Regulation of tobacco products is needed to address product changes that are used to reinforce or contribute to tobacco dependence; for instance, the incorporation of additives that target attributes such as smoothness, harshness and aftertaste. Greater understanding of the role of sensory effects on smoking behavior may also help to inform the development of tobacco treatment options that support long-term tobacco abstinence.

Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

PubMed Central

Otto, Christoph; Kaemmerer, Ulrike; Illert, Bertram; Muehling, Bettina; Pfetzer, Nadja; Wittig, Rainer; Voelker, Hans Ullrich; Thiede, Arnulf; Coy, Johannes F

2008-01-01

Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further studies are needed to address the impact of this diet on other tumour-relevant functions such as invasive growth and metastasis. PMID:18447912

Quality of care, quality of life, and attitudes toward disabilities: perspectives from a qualitative focus group study in Porto Alegre, Brazil.

PubMed

Mattevi, Betina S; Bredemeier, Juliana; Fam, Cláudia; Fleck, Marcelo P

2012-03-01

To explore the concepts of quality of life (QOL), quality of care (QOC), and attitudes toward disabilities in Porto Alegre, Brazil, from the perspective of people living with disabilities, including their relatives and caregivers. This was a qualitative study that interviewed a total of 23 participants in five focus groups, during May-August 2006. After an open discussion about QOL, the WHOQOL-Bref, a generic questionnaire for the assessment of QOL, was presented to participants. The study was performed simultaneously in 15 international centers. Analysis was based on Bardin's content analysis. Regarding QOL, important themes that emerged were: work, education, leisure, universal accessibility, integration in the society, and social inclusion. Concerning QOC, professional qualifications, disabilities-related training for health and education professionals, and access to health services were considered important. Regarding attitudes toward disabilities, the participants perceived the attitudes of others, especially of caregivers, to significantly impact the QOL of people with disabilities. People living with disabilities value many of the same themes considered important by the general public; however, several additional themes specific to disabilities and specific to these groups of participants emerged. This information highlights the importance of taking into account the unique perceptions and cultural traits of the target population when measuring QOL, QOC, and attitudes toward disabilities.

Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas.

PubMed

Zhao, Lingzhou; Zhu, Jingyi; Cheng, Yongjun; Xiong, Zhijuan; Tang, Yueqin; Guo, Lilei; Shi, Xiangyang; Zhao, Jinhua

2015-09-09

Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide 131I were synthesized and utilized for targeted single photon emission computed tomography (SPECT) imaging and radiotherapy of cancer. In this study, generation five amine-terminated poly(amidoamine) dendrimers were used as a platform to be sequentially conjugated with polyethylene glycol (PEG), targeting agent chlorotoxin (CTX), and 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO). This was followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with 131I to form the targeted theranostic dendrimeric nanoplatform. We show that the dendrimer platform possessing approximately 7.7 CTX and 21.1 HPAO moieties on each dendrimer displays excellent cytocompatibility in a given concentration range (0-20 μM) and can specifically target cancer cells overexpressing matrix metallopeptidase 2 (MMP2) due to the attached CTX. With the attached HPAO moiety having the phenol group, the dendrimer platform can be effectively labeled with radioactive 131I with good stability and high radiochemical purity. Importantly, the 131I labeling renders the dendrimer platform with an ability to be used for targeted SPECT imaging and radiotherapy of an MMP2-overexpressing glioma model in vivo. The developed radiolabeled multifunctional dendrimeric nanoplatform may hold great promise to be used for targeted theranostics of human gliomas.

Drug-target interaction prediction from PSSM based evolutionary information.

PubMed

Mousavian, Zaynab; Khakabimamaghani, Sahand; Kavousi, Kaveh; Masoudi-Nejad, Ali

2016-01-01

The labor-intensive and expensive experimental process of drug-target interaction prediction has motivated many researchers to focus on in silico prediction, which leads to the helpful information in supporting the experimental interaction data. Therefore, they have proposed several computational approaches for discovering new drug-target interactions. Several learning-based methods have been increasingly developed which can be categorized into two main groups: similarity-based and feature-based. In this paper, we firstly use the bi-gram features extracted from the Position Specific Scoring Matrix (PSSM) of proteins in predicting drug-target interactions. Our results demonstrate the high-confidence prediction ability of the Bigram-PSSM model in terms of several performance indicators specifically for enzymes and ion channels. Moreover, we investigate the impact of negative selection strategy on the performance of the prediction, which is not widely taken into account in the other relevant studies. This is important, as the number of non-interacting drug-target pairs are usually extremely large in comparison with the number of interacting ones in existing drug-target interaction data. An interesting observation is that different levels of performance reduction have been attained for four datasets when we change the sampling method from the random sampling to the balanced sampling. Copyright © 2015 Elsevier Inc. All rights reserved.

PHD Finger Recognition of Unmodified Histone H3R2 Links UHRF1 to Regulation of Euchromatic Gene Expression

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

E Rajakumara; Z Wang; H Ma

2011-12-31

Histone methylation occurs on both lysine and arginine residues, and its dynamic regulation plays a critical role in chromatin biology. Here we identify the UHRF1 PHD finger (PHD{sub UHRF1}), an important regulator of DNA CpG methylation, as a histone H3 unmodified arginine 2 (H3R2) recognition modality. This conclusion is based on binding studies and cocrystal structures of PHD{sub UHRF1} bound to histone H3 peptides, where the guanidinium group of unmodified R2 forms an extensive intermolecular hydrogen bond network, with methylation of H3R2, but not H3K4 or H3K9, disrupting complex formation. We have identified direct target genes of UHRF1 from microarraymore » and ChIP studies. Importantly, we show that UHRF1's ability to repress its direct target gene expression is dependent on PHD{sub UHRF1} binding to unmodified H3R2, thereby demonstrating the functional importance of this recognition event and supporting the potential for crosstalk between histone arginine methylation and UHRF1 function.« less

PHD Finger Recognition of Unmodified Histone H3R2 Links UHRF1 to Regulation of Euchromatic Gene Expression

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

Rajakumara, Eerappa; Wang, Zhentian; Ma, Honghui

2011-08-29

Histone methylation occurs on both lysine and arginine residues, and its dynamic regulation plays a critical role in chromatin biology. Here we identify the UHRF1 PHD finger (PHD{sub UHRF1}), an important regulator of DNA CpG methylation, as a histone H3 unmodified arginine 2 (H3R2) recognition modality. This conclusion is based on binding studies and cocrystal structures of PHD{sub UHRF1} bound to histone H3 peptides, where the guanidinium group of unmodified R2 forms an extensive intermolecular hydrogen bond network, with methylation of H3R2, but not H3K4 or H3K9, disrupting complex formation. We have identified direct target genes of UHRF1 from microarraymore » and ChIP studies. Importantly, we show that UHRF1's ability to repress its direct target gene expression is dependent on PHD{sub UHRF1} binding to unmodified H3R2, thereby demonstrating the functional importance of this recognition event and supporting the potential for crosstalk between histone arginine methylation and UHRF1 function.« less

Interoceptive Accuracy in Youth with Tic Disorders: Exploring Links with Premonitory Urge, Anxiety and Quality of Life.

PubMed

Pile, Victoria; Lau, Jennifer Y F; Topor, Marta; Hedderly, Tammy; Robinson, Sally

2018-05-18

Aberrant interoceptive accuracy could contribute to the co-occurrence of anxiety and premonitory urge in chronic tic disorders (CTD). If it can be manipulated through intervention, it would offer a transdiagnostic treatment target for tics and anxiety. Interoceptive accuracy was first assessed consistent with previous protocols and then re-assessed following an instruction attempting to experimentally enhance awareness. The CTD group demonstrated lower interoceptive accuracy than controls but, importantly, this group difference was no longer significant following instruction. In the CTD group, better interoceptive accuracy was associated with higher anxiety and lower quality of life, but not with premonitory urge. Aberrant interoceptive accuracy may represent an underlying trait in CTD that can be manipulated, and relates to anxiety and quality of life.

Spreading to localized targets in complex networks

NASA Astrophysics Data System (ADS)

Sun, Ye; Ma, Long; Zeng, An; Wang, Wen-Xu

2016-12-01

As an important type of dynamics on complex networks, spreading is widely used to model many real processes such as the epidemic contagion and information propagation. One of the most significant research questions in spreading is to rank the spreading ability of nodes in the network. To this end, substantial effort has been made and a variety of effective methods have been proposed. These methods usually define the spreading ability of a node as the number of finally infected nodes given that the spreading is initialized from the node. However, in many real cases such as advertising and news propagation, the spreading only aims to cover a specific group of nodes. Therefore, it is necessary to study the spreading ability of nodes towards localized targets in complex networks. In this paper, we propose a reversed local path algorithm for this problem. Simulation results show that our method outperforms the existing methods in identifying the influential nodes with respect to these localized targets. Moreover, the influential spreaders identified by our method can effectively avoid infecting the non-target nodes in the spreading process.

Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection

PubMed Central

Mukherjee, Uma A.; Ong, Sang-Bing; Ong, Sang-Ging; Hausenloy, Derek J.

2015-01-01

Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotection. In dopaminergic neurons of the substantia nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death—through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis. These rare familial forms of PD may therefore provide important insights into the pathophysiology underlying mitochondrial dysfunction and the development of PD. Interestingly, these PD proteins are also present in the heart, but their role in myocardial health and disease is not clear. In this article, we review the role of these PD proteins in the heart and explore their potential as novel mitochondrial targets for cardioprotection. PMID:26481155

Zamilon, a novel virophage with Mimiviridae host specificity.

PubMed

Gaia, Morgan; Benamar, Samia; Boughalmi, Mondher; Pagnier, Isabelle; Croce, Olivier; Colson, Philippe; Raoult, Didier; La Scola, Bernard

2014-01-01

Virophages, which are potentially important ecological regulators, have been discovered in association with members of the order Megavirales. Sputnik virophages target the Mimiviridae, Mavirus was identified with the Cafeteria roenbergensis virus, and virophage genomes reconstructed by metagenomic analyses may be associated with the Phycodnaviridae. Despite the fact that the Sputnik virophages were isolated with viruses belonging to group A of the Mimiviridae, they can grow in amoebae infected by Mimiviridae from groups A, B or C. In this study we describe Zamilon, the first virophage isolated with a member of group C of the Mimiviridae family. By co-culturing amoebae with purified Zamilon, we found that the virophage is able to multiply with members of groups B and C of the Mimiviridae family but not with viruses from group A. Zamilon has a 17,276 bp DNA genome that potentially encodes 20 genes. Most of these genes are closely related to genes from the Sputnik virophage, yet two are more related to Megavirus chiliensis genes, a group B Mimiviridae, and one to Moumouvirus monve transpoviron.

Affective expressions in groups and inferences about members' relational well-being: The effects of socially engaging and disengaging emotions.

PubMed

Rothman, Naomi B; Magee, Joe C

2016-01-01

Our findings draw attention to the interpersonal communication function of a relatively unexplored dimension of emotions-the level of social engagement versus disengagement. In four experiments, regardless of valence and target group gender, observers infer greater relational well-being (more cohesiveness and less conflict) between group members from socially engaging (sadness and appreciation) versus disengaging (anger and pride) emotion expressions. Supporting our argument that social (dis)engagement is a critical dimension communicated by these emotions, we demonstrate (1) that inferences about group members' self-interest mediate the effect of socially engaging emotions on cohesiveness and (2) that the influence of socially disengaging emotion expressions on inferences of conflict is attenuated when groups have collectivistic norms (i.e., members value a high level of social engagement). Furthermore, we show an important downstream consequence of these inferences of relational well-being: Groups that seem less cohesive because of their members' proud (versus appreciative) expressions are also expected to have worse task performance.

Assessing the role of syringe dispensing machines and mobile van outlets in reaching hard-to-reach and high-risk groups of injecting drug users (IDUs): a review

PubMed Central

Islam, Md Mofizul; Conigrave, Katherine M

2007-01-01

Reaching hard-to-reach and high-risk injecting drug users (IDUs) is one of the most important challenges for contemporary needle syringe programs (NSPs). The aim of this review is to examine, based upon the available international experience, the effectiveness of syringe vending machines and mobile van/bus based NSPs in making services more accessible to these hard-to-reach and high-risk groups of IDUs. A literature search revealed 40 papers/reports, of which 18 were on dispensing machines (including vending and exchange machines) and 22 on mobile vans. The findings demonstrate that syringe dispensing machines and mobile vans are promising modalities of NSPs, which can make services more accessible to the target group and in particular to the harder-to-reach and higher-risk groups of IDUs. Their anonymous and confidential approaches make services attractive, accessible and acceptable to these groups. These two outlets were found to be complementary to each other and to other modes of NSPs. Services through dispensing machines and mobile vans in strategically important sites are crucial elements in continuing efforts in reducing the spread of HIV and other blood borne viruses among IDUs. PMID:17958894

Bridging the Cultural Communication Gap Between America and Its Army

DTIC Science & Technology

2008-03-19

interest in serving in the military, versus 15% of boys.”12 This target market, also known as Generation Y , has different norms, beliefs and...Generation Y in order to know what values and beliefs are important to potential recruits. According to a Business Week cover story Feb. 15, 1999...marketing to the members of Generation Y is an entirely new game. This group, born between 1979 and 1994 are 60 million strong and view life

Heterobivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2011-04-01

specific membrane antigen (PSMA), showed promise in the clinic for identifying candidates for salvage radiotherapy. (4, 5) Because of the important...removed benzyl group to afford the Lys- Urea-Glu 14 in 85% yield. Compound 14 was conjugated with the suberic acid bis-(N- hydroxysuccinimide ( DSS ) in...directed against human and mouse prostate-specific membrane antigen. Prostate 2004; 61: 1-11. 4. Chang SS, Heston WD. The clinical role of prostate

Evaluation of the Pilot Program for Home School and ChalleNGe Program Recruits

DTIC Science & Technology

2004-07-01

religious values . Home schoolers have strong aca- demic achievement. 4 The ChalleNGe Program targets 16- to 18-year-old high school drop- outs and...percent of home school association leaders listed an exhibit table at association events, such as conferences, book fairs , and support group meetings...affiliation. Because the average values of attributes of the home school popula- tion may vary among its different segments, it is important that the

Task demands determine the specificity of the search template.

PubMed

Bravo, Mary J; Farid, Hany

2012-01-01

When searching for an object, an observer holds a representation of the target in mind while scanning the scene. If the observer repeats the search, performance may become more efficient as the observer hones this target representation, or "search template," to match the specific demands of the search task. An effective search template must have two characteristics: It must reliably discriminate the target from the distractors, and it must tolerate variability in the appearance of the target. The present experiment examined how the tolerance of the search template is affected by the search task. Two groups of 18 observers trained on the same set of stimuli blocked either by target image (block-by-image group) or by target category (block-by-category group). One or two days after training, both groups were tested on a related search task. The pattern of test results revealed that the two groups of observers had developed different search templates, and that the templates of the block-by-category observers better captured the general characteristics of the category. These results demonstrate that observers match their search templates to the demands of the search task.

Improving the Management of Psoriatic Arthritis and Axial Spondyloarthritis: Roundtable Discussions with Healthcare Professionals and Patients.

PubMed

Garrido-Cumbrera, Marco; Hillmann, Ottfrid; Mahapatra, Raj; Trigos, David; Zajc, Petra; Weiss, Luisa; Bostynets, Galya; Gossec, Laure; Coates, Laura C

2017-12-01

Psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) are both chronic, inflammatory conditions that result in a substantial burden of disease and reduced quality of life for patients. Patient involvement in developing optimal disease management strategies, including defining appropriate goals, therapies, and treatment options, as well as in setting policy priorities and agendas, is key. A working group of patient organization representatives and rheumatologists explored what patients consider to be unmet needs, important treatment gaps, and future priorities in PsA and AxSpA management. Reducing pain and fatigue, and improving physical and social functioning and work productivity were identified as important treatment goals for patients. Although the major treatment target for both PsA and AxSpA is remission, with low/minimal disease activity an alternative target for patients with established or long-standing disease, the meaning of remission from the patient's perspective needs to be explored further as it may differ considerably from the physician's perspective. Key recommendations from the working group to tackle unmet needs included reducing time to diagnosis, increasing patient and physician disease awareness, focusing on patients' priorities for treatment goals, and improving patient-physician communication. By addressing these key action points moving forward, the hope is that outcomes will continue to improve for patients with PsA and AxSpA.

Vaccination decision-making of immigrant parents in the Netherlands; a focus group study.

PubMed

Harmsen, Irene A; Bos, Helien; Ruiter, Robert A C; Paulussen, Theo G W; Kok, Gerjo; de Melker, Hester E; Mollema, Liesbeth

2015-12-10

Although the vaccination coverage in most high income countries is high, variations in coverage rates on the national level among different ethnic backgrounds are reported. A qualitative study was performed to explore factors that influence decision-making among parents with different ethnic backgrounds in the Netherlands. Six focus groups were conducted with 33 mothers of Moroccan, Turkish and other ethnic backgrounds with at least one child aged 0-4 years. Data were analysed using thematic analysis. Parents had a positive attitude towards childhood vaccination and a high confidence in the advices of Child Vaccine Providers (CVPs). Vaccinating their children was perceived as self-evident and important. Parents do perceive a language barrier in understanding the provided NIP-information, and they had a need for more NIP- information, particularly about the targeted diseases. Another barrier parents perceived was the distance to the Child Welfare Center (CWC), especially when the weather was bad and when they had no access to a car. More information about targeted diseases and complete information regarding benefits and drawbacks of the NIP should be provided to the parents. To fulfill parents' information needs, NIP information meetings can be organized at CWCs in different languages. Providing NIP information material in Turkish, Arabic and Berber language with easy access is also recommended. Providing information tailored to these parents' needs is important to sustain high vaccination participation, and to ensure acceptance of future vaccinations.

Age-dependent parathormone levels and different CKD-MBD treatment practices of dialysis patients in Hungary - results from a nationwide clinical audit

PubMed Central

2013-01-01

Background Achieving target levels of laboratory parameters of bone and mineral metabolism in chronic kidney disease (CKD) patients is important but also difficult in those living with end-stage kidney disease. This study aimed to determine if there are age-related differences in chronic kidney disease-mineral and bone disorder (CKD-MBD) characteristics, including treatment practice in Hungarian dialysis patients. Methods Data were collected retrospectively from a large cohort of dialysis patients in Hungary. Patients on hemodialysis and peritoneal dialysis were also included. The enrolled patients were allocated into two groups based on their age (<65 years and ≥65 years). Characteristics of the age groups and differences in disease-related (epidemiology, laboratory, and treatment practice) parameters between the groups were analyzed. Results A total of 5008 patients were included in the analysis and the mean age was 63.4±14.2 years. A total of 47.2% of patients were women, 32.8% had diabetes, and 11.4% were on peritoneal dialysis. Diabetes (37.9% vs 27.3%), bone disease (42.9% vs 34.1%), and soft tissue calcification (56.3% vs 44.7%) were more prevalent in the older group than the younger group (p<0.001 for all). We found an inverse relationship between age and parathyroid hormone (PTH) levels (p<0.001). Serum PTH levels were lower in patients with diabetes compared with those without diabetes below 80 years (p<0.001). Diabetes and age were independently associated with serum PTH levels (interaction: diabetes × age groups, p=0.138). Older patients were more likely than younger patients to achieve laboratory target ranges for each parameter (Ca: 66.9% vs 62.1%, p<0.001; PO4: 52.6% vs 49.2%, p<0.05; and PTH: 50.6% vs 46.6%, p<0.01), and for combined parameters (19.8% vs 15.8%, p<0.001). Older patients were less likely to receive related medication than younger patients (66.9% vs 79.7%, p<0.001). Conclusions The achievement of laboratory target ranges for bone and mineral metabolism and clinical practice in CKD depends on the age of the patients. A greater proportion of older patients met target criteria and received less medication compared with younger patients. PMID:23865464

The Generic Short Patient Experiences Questionnaire (GS-PEQ): identification of core items from a survey in Norway

PubMed Central

2011-01-01

Background Questionnaires are commonly used to collect patient, or user, experiences with health care encounters; however, their adaption to specific target groups limits comparison between groups. We present the construction of a generic questionnaire (maximum of ten questions) for user evaluation across a range of health care services. Methods Based on previous testing of six group-specific questionnaires, we first constructed a generic questionnaire with 23 items related to user experiences. All questions included a "not applicable" response option, as well as a follow-up question about the item's importance. Nine user groups from one health trust were surveyed. Seven groups received questionnaires by mail and two by personal distribution. Selection of core questions was based on three criteria: applicability (proportion "not applicable"), importance (mean scores on follow-up questions), and comprehensiveness (content coverage, maximum two items per dimension). Results 1324 questionnaires were returned providing subsample sizes ranging from 52 to 323. Ten questions were excluded because the proportion of "not applicable" responses exceeded 20% in at least one user group. The number of remaining items was reduced to ten by applying the two other criteria. The final short questionnaire included items on outcome (2), clinician services (2), user involvement (2), incorrect treatment (1), information (1), organisation (1), and accessibility (1). Conclusion The Generic Short Patient Experiences Questionnaire (GS-PEQ) is a short, generic set of questions on user experiences with specialist health care that covers important topics for a range of groups. It can be used alone or with other instruments in quality assessment or in research. The psychometric properties and the relevance of the GS-PEQ in other health care settings and countries need further evaluation. PMID:21510871

Genome-Wide Identification, Evolution and Expression Analysis of mTERF Gene Family in Maize

PubMed Central

Zhao, Yanxin; Cai, Manjun; Zhang, Xiaobo; Li, Yurong; Zhang, Jianhua; Zhao, Hailiang; Kong, Fei; Zheng, Yonglian; Qiu, Fazhan

2014-01-01

Plant mitochondrial transcription termination factor (mTERF) genes comprise a large family with important roles in regulating organelle gene expression. In this study, a comprehensive database search yielded 31 potential mTERF genes in maize (Zea mays L.) and most of them were targeted to mitochondria or chloroplasts. Maize mTERF were divided into nine main groups based on phylogenetic analysis, and group IX represented the mitochondria and species-specific clade that diverged from other groups. Tandem and segmental duplication both contributed to the expansion of the mTERF gene family in the maize genome. Comprehensive expression analysis of these genes, using microarray data and RNA-seq data, revealed that these genes exhibit a variety of expression patterns. Environmental stimulus experiments revealed differential up or down-regulation expression of maize mTERF genes in seedlings exposed to light/dark, salts and plant hormones, respectively, suggesting various important roles of maize mTERF genes in light acclimation and stress-related responses. These results will be useful for elucidating the roles of mTERF genes in the growth, development and stress response of maize. PMID:24718683

[Social marketing applied to condom promotion: a proposal for intervention in groups at risk for sexually transmitted diseases].

PubMed

García España, F; March Cerdá, J C; Gómez Villegas, I

1994-01-01

Sexually transmitted diseases (STDs) are an important worldwide health problem. Their association with AIDS an other insidious viral processes have brought them to the foreground of sanitary authorities and general population concern. Often, health services have to struggle with reinfections, which concentrate in pockets of risk that consume large amount of care and constitute an important link in the transmission of these diseases. General publicity have little impact among high risk groups. Thus, it becomes necessary to be more precise and divide into segments the target population we want to reach. Prevention of reinfection in these communities requires the implementation of healthy behaviours through the promotion of a tangible product (condom). Regarding these considerations, social marketing emerges as the right instrument to be used. Through individual focused interviews with prostitutes, homosexual and young promiscuous heterosexual patients from a STDs Prevention, Diagnosis and Treatment Centre, determining factors of the use condoms and related behaviour guidelines have been identified. Also, a social marketing strategy is suggested to prevent these diseases among groups at risk by means of condom promotion.

SUMO proteases as potential targets for cancer therapy.

PubMed

Bialik, Piotr; Woźniak, Katarzyna

2017-12-08

Sumoylation is one of the post-translational modifications of proteins, responsible for the regulation of many cellular processes, such as DNA replication and repair, transcription, signal transduction and nuclear transport. During sumoylation, SUMO proteins are covalently attached to the ε-amino group of lysine in target proteins via an enzymatic cascade that requires the sequential action of E1, E2 and E3 enzymes. An important aspect of sumoylation is its reversibility, which involves SUMO-specific proteases called SENPs. SENPs (sentrin/SUMO-specific proteases) catalyze the deconjugation of SUMO proteins using their isopeptidase activity. These enzymes participate through hydrolase activity in the reaction of SUMO protein maturation, which involves the removal of a short fragment on the C-terminus of SUMO inactive form and exposure two glycine residues. SENPs are important for maintaining the balance between sumoylated and desumoylated proteins required for normal cellular physiology. Six SENP isoforms (SENP1, SENP2, SENP3, SENP5, SENP6 and SENP7) have been identified in mammals. These SENPs can be divided into three subfamilies based on their sequence homology, substrate specificity and subcellular localization. Results of studies indicate the role of SUMO proteases in the development of human diseases including cancer, suggesting that these proteins may be attractive targets for new drugs.

Human, vector and parasite Hsp90 proteins: A comparative bioinformatics analysis.

PubMed

Faya, Ngonidzashe; Penkler, David L; Tastan Bishop, Özlem

2015-01-01

The treatment of protozoan parasitic diseases is challenging, and thus identification and analysis of new drug targets is important. Parasites survive within host organisms, and some need intermediate hosts to complete their life cycle. Changing host environment puts stress on parasites, and often adaptation is accompanied by the expression of large amounts of heat shock proteins (Hsps). Among Hsps, Hsp90 proteins play an important role in stress environments. Yet, there has been little computational research on Hsp90 proteins to analyze them comparatively as potential parasitic drug targets. Here, an attempt was made to gain detailed insights into the differences between host, vector and parasitic Hsp90 proteins by large-scale bioinformatics analysis. A total of 104 Hsp90 sequences were divided into three groups based on their cellular localizations; namely cytosolic, mitochondrial and endoplasmic reticulum (ER). Further, the parasitic proteins were divided according to the type of parasite (protozoa, helminth and ectoparasite). Primary sequence analysis, phylogenetic tree calculations, motif analysis and physicochemical properties of Hsp90 proteins suggested that despite the overall structural conservation of these proteins, parasitic Hsp90 proteins have unique features which differentiate them from human ones, thus encouraging the idea that protozoan Hsp90 proteins should be further analyzed as potential drug targets.

Experiences with Recruitment of Marginalized Groups in a Danish Health Promotion Program: A Document Evaluation Study.

PubMed

Rasmussen, Marianne; Poulsen, Eva Kanstrup; Rytter, Anne Stoffersen; Kristiansen, Tine Mechlenborg; Bak, Carsten Kronborg

2016-01-01

Studies have found that marginalized groups living in deprived neighborhoods are less likely to participate in health programs compared to the majority of society. This study evaluates recruitment approaches conducted during a national government-funded project in 12 deprived neighborhoods across Denmark between 2010 and 2014. The aim of this study was to understand how recruitment approaches could promote participation in health programs within deprived neighborhoods to reach marginalized groups. Documents from all 12 of the included municipalities were collected to conduct a document evaluation. The collected documents consisted of 1,500 pages of written material with 12 project descriptions, three midterm and 10 final evaluations. The collected data were analyzed through a qualitative content analysis. The results are based on the fact that only 10 municipalities have developed evaluations related to recruitment, and only three evaluations provided a description of which marginalized groups were recruited. Challenges related to recruitment consist of difficulties involving the target group, including general distrust, language barriers and a lack of ability to cope with new situations and strangers. Additional geographical challenges emerged, especially in rural areas. Positive experiences with recruitment approaches were mainly related to relationship building and trust building, especially through face-to-face contact and the project employees' presence in the neighborhood. Additionally, adjusting some of the interventions and the recruitment strategy increased participation. This study found that relation and trust between the residents and the project employees is an important factor in the recruitment of marginalized groups in deprived neighborhoods as well as adjusting the health interventions or recruitment strategy to the target groups. In future research, it is necessary to examine which recruitment approaches are effective under which circumstances to increase participation among marginalized groups.

The Role of 3T Magnetic Resonance Imaging for Targeting the Human Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease.

PubMed

Longhi, Michele; Ricciardi, Giuseppe; Tommasi, Giorgio; Nicolato, Antonio; Foroni, Roberto; Bertolasi, Laura; Beltramello, Alberto; Moretto, Giuseppe; Tinazzi, Michele; Gerosa, Massimo

2015-05-01

Chronic stimulation of the human subthalamic nucleus (STN) is gradually becoming accepted as a long-term therapeutic option for patients with advanced Parkinson disease (PD). 3Tesla (T) magnetic resonance imaging (MRI) improves contrast resolution in basal ganglia nuclei containing high levels of iron, because of magnetic susceptibility effects that increase significantly as the magnetic field gets higher. This phenomenon can be used for better visualization of the STN and may reduce the time necessary for detailed microrecording (MER) mapping, increasing surgery efficacy and lowering morbidity. The objective of this retrospective study is to analyze a population of 20 deep brain stimulation (DBS) electrode implanted patients with PD divided into two groups in which different targeting methods were used. Mean age was 56 years (range 37 to 69 years). Mean disease duration was 11.6 years. Mean follow-up was 12 months (range 6 to 36 months). Patients were divided into two groups: Group A contained 6 patients who underwent STN targeting using 1T stereotactic (T1w + T2w) MRI plus STN indirect atlas derived targeting. Group B consisted of 14 patients who underwent STN targeting using 3T nonstereotactic (T2w) MRI fused with 1T T1w stereotactic MRI and STN direct targeting. For statistical analysis, we compared (five different parameters in both (matched) groups: Unified Parkinson's disease rating scale (UPDRS) score reduction (medication off before surgery against stimulation on/medication off after surgery), postoperative drug reduction, duration of surgery, the "central preoperative track" chosen as final implantation track during surgery, and correspondence between the targeted STN and the intraoperative neurophysiologic data. Mean UPDRS III score reduction (medication off/stimulation on versus preoperative medication off) was 69% in Group A and 74% in Group B (p = 0.015, log-rank test) respectively. Postoperatively, antiparkinsonian treatment was reduced by 66% in Group A and 75% in Group B (p = 0.006, log-rank test). The preoperative "central" track (which corresponds to ideal STN targeting) proved to be the most clinically effective in 2/12 leads for Group A versus 21/28 for Group B (p < 0.001).Neurophysiologic data confirmed these results; the hypothetical target was confirmed by MER data in 76% of tracks in Group A, and in 75% of tracks in Group B (p < 0.001, univariate and multivariate analysis). 3T MRI appears to be a useful tool in STN-DBS preoperative targeting. Neurophysiologic testing remains fundamental to determine lead deepness (and prevent clinical side effects. Georg Thieme Verlag KG Stuttgart · New York.

The communication of social stereotypes: the effects of group discussion and information distribution on stereotypic appraisals.

PubMed

Brauer, M; Judd, C M; Jacquelin, V

2001-09-01

Stereotypes are fundamentally social constructs, formulated and modified through discussion and interaction with others. The present studies examined the impact of group discussion on stereotypes. In both studies, groups of participants discussed their impressions about a hypothetical target group after having read behaviors performed by target group members. These behaviors included both stereotypic and counterstereotypic examples, and the distribution of these behaviors varied across discussion group members. In some groups only 1 member knew of the counterstereotypic behaviors; in other groups this information was distributed across all group members. In general, discussion led to a polarization of the target group stereotypes, but this effect was lessened when the counterstereotypic behaviors were concentrated in 1 group member. In this case, these counterstereotypic behaviors were discussed more and retained better.

Targeted cardiopulmonary resuscitation training focused on the family members of high-risk patients at a regional medical center: A comparison between family members of high-risk and no-risk patients.

PubMed

Han, Kap Su; Lee, Ji Sung; Kim, Su Jin; Lee, Sung Woo

2018-05-01

We developed a hospital-based cardiopulmonary resuscitation (CPR) training model focused on the target population (family members of patients with potential risks for cardiac arrest) and compared the outcome of CPR training between target and non-target populations for validity. Family members of patients in training were divided into three groups on the basis of patients' diseases, as follows: 1) the cardio-specific (CS) risk group, including family members of patients with cardiac disease at risk of cardiac arrest; 2) the cardiovascular (CV) risk group, including family members of patients with risk factors for cardiovascular disease; and 3) the no-risk group. Pre- and posttraining surveys and skill tests as well as a post-training 3-month telephone survey were conducted. Educational outcomes were analyzed. A total of 203 family members were enrolled into 21 CPR training classes. The CS group (n=88) included elderly persons and housewives with a lower level of education compared with the CV (n=79) and no-risk groups (n=36). The CS group was motivated by healthcare professionals and participated in the training course. The CS, CV, and no-risk groups showed improvements in knowledge, willingness to perform CPR, and skills. Despite the older age and lower level of education in the CS group, the effects of education were similar to those in the other groups. A high rate of response and secondary propagation of CPR training were observed in the CS group. Family members of patients with heart disease could be an appropriate target population for CPR training, particularly in terms of recruitment and secondary propagation. Targeted intervention may be an effective training strategy to improve bystander CPR rates.

A cluster randomized controlled trial to assess the impact of SAFE on spousal violence against women and girls in slums of Dhaka, Bangladesh.

PubMed

Naved, Ruchira Tabassum; Mamun, Mahfuz Al; Mourin, Sanjida Akhter; Parvin, Kausar

2018-01-01

Bangladesh reports one of the highest rates of intimate partner violence (IPV) in the world. Despite wide recognition of IPV as an important public health and human rights issue, evidence for IPV prevention is still inadequate. Lack of guidance on effective IPV prevention in Bangladesh resulted in targeting only women in most of the programmes. This paper assesses impact of SAFE, a 20-month intervention (March 2012 to October 2013) in slums of Dhaka on IPV and tests effectiveness of female only groups vs. no groups; and female + male groups vs. female only groups on IPV in the community using a three-arm cluster randomized controlled trial. SAFE's core activities included interactive group sessions, community mobilisation, and services. The last two activities were common across arms. Regression analyses (female survey: baseline n = 2,666; endline n = 2,670) showed no effect of SAFE on IPV against women aged 15-29. However, sub-group analyses demonstrated 21% risk reduction of physical IPV against adolescent girls aged 15-19 in the female + male group intervention arm. A consistent reduction in sexual violence was observed in both female and female + male arms for both groups of women, but the results were not statistically significant. The findings emphasise the importance of combining male and female interventions for reducing physical IPV against adolescent girls. Implications for future research have been discussed.

Leadership, consensus decision making and collective behaviour in humans

PubMed Central

Dyer, John R.G.; Johansson, Anders; Helbing, Dirk; Couzin, Iain D.; Krause, Jens

2008-01-01

This paper reviews the literature on leadership in vertebrate groups, including recent work on human groups, before presenting the results of three new experiments looking at leadership and decision making in small and large human groups. In experiment 1, we find that both group size and the presence of uninformed individuals can affect the speed with which small human groups (eight people) decide between two opposing directional preferences and the likelihood of the group splitting. In experiment 2, we show that the spatial positioning of informed individuals within small human groups (10 people) can affect the speed and accuracy of group motion. We find that having a mixture of leaders positioned in the centre and on the edge of a group increases the speed and accuracy with which the group reaches their target. In experiment 3, we use large human crowds (100 and 200 people) to demonstrate that the trends observed from earlier work using small human groups can be applied to larger crowds. We find that only a small minority of informed individuals is needed to guide a large uninformed group. These studies build upon important theoretical and empirical work on leadership and decision making in animal groups. PMID:19073481

Does flexibility in perceptual organization compete with automatic grouping?

PubMed

van Assche, Mitsouko; Gos, Pierre; Giersch, Anne

2012-02-06

Segregated objects can be sought simultaneously, i.e., mentally "re-grouped." Although the mechanisms underlying such "re-grouping" clearly differ from automatic grouping, it is unclear whether or not the end products of "re-grouping" and automatic grouping are the same. If they are, they would have similar impact on visual organization but would be in conflict. We compared the consequences of grouping and re-grouping on the performance cost induced by stimuli presented across hemifields. Two identical and contiguous target figures had to be identified within a display of circles and squares alternating around a fixation point. Eye tracking was used to check central fixation. The target pair could be located in the same or separate hemifields. A large cost of presenting targets across hemifields was observed. Grouping by connectedness yielded two types of target pair, connected and unconnected. Subjects prioritized unconnected pairs efficiently when prompted to do so, suggesting "re-grouping." However, unlike automatic grouping, this did not affect the cost of across-hemifield presentation. The suggestion is that re-grouping yields different outputs to automatic grouping, such that a fresh representation resulting from re-grouping complements the one resulting from automatic grouping but does not replace it. This is one step toward understanding how our mental exploration of the world ties in and coexists with ongoing perception.

Novel phage group infecting Lactobacillus delbrueckii subsp. lactis, as revealed by genomic and proteomic analysis of bacteriophage Ldl1.

PubMed

Casey, Eoghan; Mahony, Jennifer; Neve, Horst; Noben, Jean-Paul; Dal Bello, Fabio; van Sinderen, Douwe

2015-02-01

Ldl1 is a virulent phage infecting the dairy starter Lactobacillus delbrueckii subsp. lactis LdlS. Electron microscopy analysis revealed that this phage exhibits a large head and a long tail and bears little resemblance to other characterized phages infecting Lactobacillus delbrueckii. In vitro propagation of this phage revealed a latent period of 30 to 40 min and a burst size of 59.9 +/- 1.9 phage particles. Comparative genomic and proteomic analyses showed remarkable similarity between the genome of Ldl1 and that of Lactobacillus plantarum phage ATCC 8014-B2. The genomic and proteomic characteristics of Ldl1 demonstrate that this phage does not belong to any of the four previously recognized L. delbrueckii phage groups, necessitating the creation of a new group, called group e, thus adding to the knowledge on the diversity of phages targeting strains of this industrially important lactic acid bacterial species.

Backlash: The Politics and Real-World Consequences of Minority Group Dehumanization.

PubMed

Kteily, Nour; Bruneau, Emile

2017-01-01

Research suggests that members of advantaged groups who feel dehumanized by other groups respond aggressively. But little is known about how meta-dehumanization affects disadvantaged minority group members, historically the primary targets of dehumanization. We examine this important question in the context of the 2016 U.S. Republican Primaries, which have witnessed the widespread derogation and dehumanization of Mexican immigrants and Muslims. Two initial studies document that Americans blatantly dehumanize Mexican immigrants and Muslims; this dehumanization uniquely predicts support for aggressive policies proposed by Republican nominees, and dehumanization is highly associated with supporting Republican candidates (especially Donald Trump). Two further studies show that, in this climate, Latinos and Muslims in the United States feel heavily dehumanized, which predicts hostile responses including support for violent versus non-violent collective action and unwillingness to assist counterterrorism efforts. Our results extend theorizing on dehumanization, and suggest that it may have cyclical and self-fulfilling consequences.

Motion reconstruction of animal groups: From schooling fish to swarming mosquitoes

NASA Astrophysics Data System (ADS)

Butail, Sachit

The long-term goal of this research is to provide kinematic data for the design and validation of spatial models of collective behavior in animal groups. The specific research objective of this dissertation is to apply methods from nonlinear estimation and computer vision to construct multi-target tracking systems that process multi-view calibrated video to reconstruct the three-dimensional movement of animals in a group. We adapt the tracking systems for the study of two animal species: Danio aequipinnatus, a common species of schooling fish, and Anopheles gambiae, the most important vector of malaria in sub-Saharan Africa. Together these tracking systems span variability in target size on image, density, and movement. For tracking fish, we automatically initialize, predict, and reconstruct shape trajectories of multiple fish through occlusions. For mosquitoes, which appear as faded streaks on in-field footage, we provide methods to extract velocity information from the streaks, adaptively seek missing measurements, and resolve occlusions within a multi-hypothesis framework. In each case the research has yielded an unprecedented volume of trajectory data for subsequent analysis. We present kinematic data of fast-start response in fish schools and first-ever trajectories of wild mosquito swarming and mating events. The broader impact of this work is to advance the understanding of animal groups for the design of bio-inspired robotic systems, where, similar to the animal groups we study, the collective is able to perform tasks far beyond the capabilities of a single inexpensive robot.

Study on relationship between expression level and molecular conformations of gene drugs targeting to hepatoma cells in vitro

PubMed Central

Yang, Dong-Ye; Lu, Fang-Gen; Tang, Xi-Xiang; Zhao, Shui-Ping; Ouyang, Chun-Hui; Wu, Xiao-Ping; Liu, Xiao-Wei; Wu, Xiao-Ying

2003-01-01

AIM: To increase exogenous gene expression level by modulating molecular conformations of targeting gene drugs. METHODS: The full length cDNAs of both P40 and P35 subunits of human interleukin 12 were amplified through polymerase chain reaction (PCR) and cloned into eukaryotic expressing vectors pcDNA3.1 (±) to construct plasmids of P (+)/IL-12, P (+)/P40 and P (-)/P35. These plasmids were combined with ASOR-PLL to form two targeting gene drugs [ASOR-PLL-P (+)/IL-12 and ASOR-PLL-P (+)/P40 + ASOR-PLL-P (-)/P35] in optimal ratios. The conformations of these two drugs at various concentrations adjuvant were examined under electron microscope (EM) and the drugs were transfected into HepG2 (ASGr+) cells. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed with total RNA extracted from the transfected cells to determine the hIL12 mRNA transcript level. The hIL12 protein in the cultured supernatant was measured with enzyme-linked immunosorbent assay (ELISA) 48 hours after transfection. RESULTS: Targeting gene drugs, whose structures were granular and circle-like and diameters ranged from 25 nm to 150 nm, had the highest hIL-12 expression level. The hIL-12 expression level in the group co-transfected with ASOR-PLL-P (+)/P40 and ASOR-PLL-P (-)/P35 was higher than that of ASOR-PLL-P (+)/IL-12 transfected group. CONCLUSION: The molecular conformations of targeting gene drugs play an important role in exogenous gene expression level, the best structures are granular and circle-like and their diameters range from 25 nm to 150 nm. The sizes and linking styles of exogenous genes also have some effects on their expression level. PMID:12970883

Octa-ammonium POSS-conjugated single-walled carbon nanotubes as vehicles for targeted delivery of paclitaxel

PubMed Central

Naderi, Naghmeh; Madani, Seyed Y.; Mosahebi, Afshin; Seifalian, Alexander M.

2015-01-01

Background Carbon nanotubes (CNTs) have unique physical and chemical properties. Furthermore, novel properties can be developed by attachment or encapsulation of functional groups. These unique properties facilitate the use of CNTs in drug delivery. We developed a new nanomedicine consisting of a nanocarrier, cell-targeting molecule, and chemotherapeutic drug and assessed its efficacy in vitro. Methods The efficacy of a single-walled carbon nanotubes (SWCNTs)-based nanoconjugate system is assessed in the targeted delivery of paclitaxel (PTX) to cancer cells. SWCNTs were oxidized and reacted with octa-ammonium polyhedral oligomeric silsesquioxanes (octa-ammonium POSS) to render them biocompatible and water dispersable. The functionalized SWCNTs were loaded with PTX, a chemotherapeutic agent toxic to cancer cells, and Tn218 antibodies for cancer cell targeting. The nanohybrid composites were characterized with transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and ultraviolet–visible–near-infrared (UV–Vis–NIR). Additionally, their cytotoxic effects on Colon cancer cell (HT-29) and Breast cancer cell (MCF-7) lines were assessed in vitro. Results TEM, FTIR, and UV–Vis–NIR studies confirmed side-wall functionalization of SWCNT with COOH-groups, PTX, POSS, and antibodies. Increased cell death was observed with PTX–POSS–SWCNT, PTX–POSS–Ab–SWCNT, and free PTX compared to functionalized-SWCNT (f-SWCNT), POSS–SWCNT, and cell-only controls at 48 and 72 h time intervals in both cell lines. At all time intervals, there was no significant cell death in the POSS–SWCNT samples compared to cell-only controls. Conclusion The PTX-based nanocomposites were shown to be as cytotoxic as free PTX. This important finding indicates successful release of PTX from the nanocomposites and further reiterates the potential of SWCNTs to deliver drugs directly to targeted cells and tissues. PMID:26356347

Myositis-specific autoantibodies: an important tool to support diagnosis of myositis.

PubMed

Betteridge, Z; McHugh, N

2016-07-01

The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in myositis pathogenesis, and myositis-specific autoantibodies, targeting important intracellular proteins, are regarded as key biomarkers aiding in the diagnosis of patients. In recent years, a number of novel myositis autoantibodies including anti-TIF1, anti-NXP2, anti-MDA5, anti-SAE, anti-HMGCR and anti-cN1A have been identified in both adult and juvenile patients. These autoantibodies correlate with distinct clinical manifestations and importantly are found in inclusion body, statin-induced, clinically amyopathic and juvenile groups of myositis patients, previously believed to be mainly autoantibody negative. In this review, we will describe the main myositis-specific and myositis-associated autoantibodies and their frequencies and clinical associations across different ages and ethnic groups. We will also discuss preliminary studies investigating correlations between specific myositis autoantibody titres and clinical markers of disease course, collectively demonstrating the utility of myositis autoantibodies as both diagnostic and prognostic markers of disease. © 2015 The Association for the Publication of the Journal of Internal Medicine.

Concise Synthesis and Biological Evaluation of 2-Aroyl-5-Amino Benzo[b]thiophene Derivatives As a Novel Class of Potent Antimitotic Agents

PubMed Central

Romagnoli, Romeo; Baraldi, Pier Giovanni; Lopez-Cara, Carlota; Preti, Delia; Tabrizi, Mojgan Aghazadeh; Balzarini, Jan; Bassetto, Marcella; Brancale, Andrea; Fu, Xian-Hua; Gao, Yang; Li, Jun; Zhang, Su-Zhan; Hamel, Ernest; Bortolozzi, Roberta; Basso, Giuseppe; Viola, Giampietro

2014-01-01

The biological importance of microtubules make them an interesting target for the synthesis of antitumor agents. The 2-(3′,4′,5′-trimethoxybenzoyl)-5-aminobenzo[b]thiophene moiety was identified as a novel scaffold for the preparation of potent inhibitors of microtubule polymerization acting through the colchicine site of tubulin. The position of the methoxy group on the benzo[b]thiophene was important for maximal antiproliferative activity. Structure–activity relationship analysis established that the best activities were obtained with amino and methoxy groups placed at the C-5 and C-7 positions, respectively. Compounds 3c–e showed more potent inhibition of tubulin polymerization than combretastatin A-4 and strong binding to the colchicine site. These compounds also demonstrated substantial antiproliferative activity, with IC50 values ranging from 2.6 to 18 nM in a variety of cancer cell lines. Importantly, compound 3c (50 mg/kg), significantly inhibited the growth of the human osteosarcoma MNNG/HOS xenograft in nude mice. PMID:24164557

Patients with type 2 diabetes demonstrate proprioceptive deficit in the knee

PubMed Central

Ettinger, Lucas Richard; Boucher, Ami; Simonovich, Elisabeth

2018-01-01

AIM To investigate proprioceptive discrepancies in the lower extremity in persons with type 2 diabetes mellitus (T2DM). METHODS In this cross-sectional study, a total of 46 older persons were divided into a T2DM group (n = 23) and a control group who did not have T2DM (n = 23). Participants were given a brief warm up with stretching exercises. Diabetic neuropathy scores were collected prior to proprioceptive testing. For proprioceptive testing, participants performed leg extensions to randomized target positions of 15°, 30°, 45, 60° degrees of elevation in the sagittal plane, each target was repeated a total of four times. Subjects were guided to target positions in the absence of visual feedback via auditory cues from a custom JPS application. When the participant entered the target position, they memorized the location of their limb in space and subsequently attempted to re-locate this position in space. Proprioceptive errors were measured from the target positioned, target remembered, target repositioned protocol. RESULTS Proprioceptive accuracy was lower in the diabetic group at all levels of target angle than the control group (P < 0.05). The diabetic group had 46% greater inaccuracy than the control group at all levels of target position. Diabetics also reported greater neuropathy scores than controls in the past 12 mo P < 0.01. CONCLUSION Deficits in lower limb localization and greater diabetic neuropathy scores were identified in this study. Our findings may be associated with deafferentation as peripheral neuropathy is a common complication with the disease. These findings may help to explain the declining balance function in the older persons with T2DM which is also commonly reported. PMID:29607003

Changes in Renal Function of Patients with Metastatic Renal Cell Carcinoma During Treatment with Molecular-Targeted Agents.

PubMed

Miyake, Hideaki; Muramaki, Mototsugu; Imai, Satoshi; Harada, Ken-Ichi; Fujisawa, Masato

2016-06-01

Impairment of renal function is a serious issue that should be considered in patients undergoing treatment with molecular-targeted agents for metastatic renal cell carcinoma (mRCC). The objective of this study was to assess the impact of molecular-targeted therapy on changes in renal function among patients with mRCC. The study included 408 mRCC patients treated with sunitinib, sorafenib, axitinib, everolimus and/or temsirolimus. Among these, 185, 128 and 95 received molecular-targeted agents as first-line (group 1), second-line (group 2) and third-line (group 3) therapy, respectively. No significant differences between the estimated glomerular filtration rate (eGFR) at baseline and that at the end of molecular-targeted therapy were noted among the three groups of patients. In addition, there were no significant differences between eGFR prior to the introduction of molecular-targeted therapy and that at the end of therapy across agents and lines of targeted therapy, with the exception of patients treated with axitinib and everolimus in second-line and third-line therapy, respectively. In group 1, a reduction in eGFR of >10 % from baseline was independently associated with performance status, hypertension and treatment duration, while in groups 2 and 3, only treatment duration was independently related to a reduction in eGFR of >10 %. It appears that renal function in patients with mRCC is not markedly impaired by molecular-targeted therapies, irrespective of the specific agents introduced; however, it may be necessary to pay special attention to deterioration in renal function when molecular-targeted therapy is continued for longer periods.

Ironic and Reinvestment Effects in Baseball Pitching: How Information About an Opponent Can Influence Performance Under Pressure.

PubMed

Gray, Rob; Orn, Anders; Woodman, Tim

2017-02-01

Are pressure-induced performance errors in experts associated with novice-like skill execution (as predicted by reinvestment/conscious processing theories) or expert execution toward a result that the performer typically intends to avoid (as predicted by ironic processes theory)? The present study directly compared these predictions using a baseball pitching task with two groups of experienced pitchers. One group was shown only their target, while the other group was shown the target and an ironic (avoid) zone. Both groups demonstrated significantly fewer target hits under pressure. For the target-only group, this was accompanied by significant changes in expertise-related kinematic variables. In the ironic group, the number of pitches thrown in the ironic zone was significantly higher under pressure, and there were no significant changes in kinematics. These results suggest that information about an opponent can influence the mechanisms underlying pressure-induced performance errors.

Overcorrection for Social-Categorization Information Moderates Impact Bias in Affective Forecasting.

PubMed

Lau, Tatiana; Morewedge, Carey K; Cikara, Mina

2016-10-01

Plural societies require individuals to forecast how others-both in-group and out-group members-will respond to gains and setbacks. Typically, correcting affective forecasts to include more relevant information improves their accuracy by reducing their extremity. In contrast, we found that providing affective forecasters with social-category information about their targets made their forecasts more extreme and therefore less accurate. In both political and sports contexts, forecasters across five experiments exhibited greater impact bias for both in-group and out-group members (e.g., a Democrat or Republican) than for unspecified targets when predicting experiencers' responses to positive and negative events. Inducing time pressure reduced the extremity of forecasts for group-labeled but not unspecified targets, which suggests that the increased impact bias was due to overcorrection for social-category information, not different intuitive predictions for identified targets. Finally, overcorrection was better accounted for by stereotypes than by spontaneous retrieval of extreme group exemplars.

Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer

PubMed Central

Remenyi, Judit; Banerji, Christopher R.S.; Lai, Chun-Fui; Periyasamy, Manikandan; Lombardo, Ylenia; Busonero, Claudia; Ottaviani, Silvia; Passey, Alun; Quinlan, Philip R.; Purdie, Colin A.; Jordan, Lee B.; Thompson, Alastair M.; Finn, Richard S.; Rueda, Oscar M.; Caldas, Carlos; Gil, Jesus; Coombes, R. Charles; Fuller-Pace, Frances V.; Teschendorff, Andrew E.; Buluwela, Laki; Ali, Simak

2015-01-01

The Nuclear Receptor (NR) superfamily of transcription factors comprises 48 members, several of which have been implicated in breast cancer. Most important is estrogen receptor-α (ERα), which is a key therapeutic target. ERα action is facilitated by co-operativity with other NR and there is evidence that ERα function may be recapitulated by other NRs in ERα-negative breast cancer. In order to examine the inter-relationships between nuclear receptors, and to obtain evidence for previously unsuspected roles for any NRs, we undertook quantitative RT-PCR and bioinformatics analysis to examine their expression in breast cancer. While most NRs were expressed, bioinformatic analyses differentiated tumours into distinct prognostic groups that were validated by analyzing public microarray data sets. Although ERα and progesterone receptor were dominant in distinguishing prognostic groups, other NR strengthened these groups. Clustering analysis identified several family members with potential importance in breast cancer. Specifically, RORγ is identified as being co-expressed with ERα, whilst several NRs are preferentially expressed in ERα-negative disease, with TLX expression being prognostic in this subtype. Functional studies demonstrated the importance of TLX in regulating growth and invasion in ERα-negative breast cancer cells. PMID:26280373

Postmortem volumetric analysis of the nucleus accumbens in male heroin addicts: implications for deep brain stimulation.

PubMed

Müller, Ulf J; Truebner, Kurt; Schiltz, Kolja; Kuhn, Jens; Mawrin, Christian; Dobrowolny, Henrik; Bernstein, Hans-Gert; Bogerts, Bernhard; Steiner, Johann

2015-12-01

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is increasingly investigated in neuropsychiatric disorders. DBS requires computer-assisted 3D planning to implant the stimulation electrode precisely. Recently, there has been a debate about the true dimensions of NAc in healthy as well as in mentally ill individuals. Knowing its true dimensions in different neuropsychiatric disorders may improve even more precise targeting of NAc for therapeutic DBS. Volumes of NAc of heroin addicts (n = 14) and healthy controls (n = 12) were calculated by using morphometry of serial whole-brain sections. Total brain volume was larger in the heroin group (mean 1478.85 ± 62.34 vs. mean 1352.38 ± 103.24 cm(3)), as the heroin group was more than 10 years younger (p = 0.001). However, the mean volume of the NAc in heroin addicts was smaller than in controls (0.528 ± 0.166 vs. 0.623 ± 0.196 cm(3); p = 0.019). This group effect did not significantly differ between the hemispheres. When assessed separately, left-hemispheric NAc volume was 15 % lower (p = 0.020), while right-hemispheric NAc volume was 16 % lower (p = 0.047) in the heroin-addicted group compared to controls. Based on these diagnosis-related differences, we believe it is important to further analyze NAc volumes in different psychiatric disorders to further improve precise targeting and electrode placement.

How Do Low-Literacy Populations Perceive "Dirty Bombs"? Implications for Preparedness Messages.

PubMed

Bass, Sarah Bauerle; Gordon, Thomas F; Maurer, Laurie; Greener, Judith; Mora, Gabriella; Ruggieri, Dominique; Wolak, Caitlin; Parvanta, Claudia

2016-01-01

Potential terror events such as "dirty bombs" could have significant public health effects, but little is known about how low-literacy populations perceive dirty bombs, their trust in public health or government officials to provide credible information, and their willingness to comply with recommended actions. We surveyed 50 low-literacy adults from a large urban center; they were mostly members of ethnic minority groups. We used unique social marketing methods-perceptual mapping and vector message modeling-to create 3-dimensional models that reflected respondents' knowledge of what a dirty bomb is, their intended behaviors should one occur, and their concerns about complying with "shelter in place" recommendations. To further understand individual variations in this at-risk group, a k-means cluster analysis was used to identify 3 distinct segments, differing on trust of local authorities and their emergency response, willingness to comply with emergency directives, and trust of information sources. Message strategies targeting each segment were developed to focus on concepts important to moving the groups toward a "shelter in place" behavior, revealing key differences in how best to communicate with risk communication. We discuss how these methods helped elucidate specific differences in each segment's understanding of and likely response during the event of a "dirty bomb" and how these techniques can be used to create more effective message strategies targeted to these groups.

How Do Low-Literacy Populations Perceive “Dirty Bombs”? Implications for Preparedness Messages

PubMed Central

Gordon, Thomas F.; Maurer, Laurie; Greener, Judith; Mora, Gabriella; Ruggieri, Dominique; Wolak, Caitlin; Parvanta, Claudia

2016-01-01

Potential terror events such as “dirty bombs” could have significant public health effects, but little is known about how low-literacy populations perceive dirty bombs, their trust in public health or government officials to provide credible information, and their willingness to comply with recommended actions. We surveyed 50 low-literacy adults from a large urban center; they were mostly members of ethnic minority groups. We used unique social marketing methods—perceptual mapping and vector message modeling—to create 3-dimensional models that reflected respondents' knowledge of what a dirty bomb is, their intended behaviors should one occur, and their concerns about complying with “shelter in place” recommendations. To further understand individual variations in this at-risk group, a k-means cluster analysis was used to identify 3 distinct segments, differing on trust of local authorities and their emergency response, willingness to comply with emergency directives, and trust of information sources. Message strategies targeting each segment were developed to focus on concepts important to moving the groups toward a “shelter in place” behavior, revealing key differences in how best to communicate with risk communication. We discuss how these methods helped elucidate specific differences in each segment's understanding of and likely response during the event of a “dirty bomb” and how these techniques can be used to create more effective message strategies targeted to these groups. PMID:27584855

Using adolescents' drawings to reveal stereotypes about ethnic groups in Guatemala.

PubMed

Ashdown, Brien K; Gibbons, Judith L; de Baessa, Yetilú; Brown, Carrie M

2017-01-01

It is important to identify stereotypes about indigenous people because those stereotypes influence prejudice and discrimination, both obstacles to social justice and universal human rights. The purpose of the current study was to document the stereotypes, as held by Guatemalan adolescents, of indigenous Maya people (e.g., Maya) and nonindigenous Ladinos in Guatemala (the 2 main ethnic groups in Guatemala). Guatemalan adolescents (N = 465; 38.3% female; Mage = 14.51 years; SDage = 1.81 years) provided drawings and written characteristics about indigenous Maya and nonindigenous Ladino people, which were then coded for patterns in the data. These patterns included negative stereotypes, such as the Maya being lazy and Ladina women being weak; and positive stereotypes, such as the Maya being caring and warm and Ladino men being successful. There were also interactions between the participants' own gender and ethnicity and how they depicted the target they were assigned. For example, male participants were unlikely to depict male targets of either ethnicity engaging in homemaking activities. Finally, there was evidence of in-group bias based both on gender and ethnicity. These findings suggest that perhaps because indigenous groups around the world share some common negative stereotypes, an understanding of these stereotypes will aid in decreasing prejudice and discrimination against indigenous people, could reduce intergroup conflict, and increase access to basic human rights. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Do motifs reflect evolved function?--No convergent evolution of genetic regulatory network subgraph topologies.

PubMed

Knabe, Johannes F; Nehaniv, Chrystopher L; Schilstra, Maria J

2008-01-01

Methods that analyse the topological structure of networks have recently become quite popular. Whether motifs (subgraph patterns that occur more often than in randomized networks) have specific functions as elementary computational circuits has been cause for debate. As the question is difficult to resolve with currently available biological data, we approach the issue using networks that abstractly model natural genetic regulatory networks (GRNs) which are evolved to show dynamical behaviors. Specifically one group of networks was evolved to be capable of exhibiting two different behaviors ("differentiation") in contrast to a group with a single target behavior. In both groups we find motif distribution differences within the groups to be larger than differences between them, indicating that evolutionary niches (target functions) do not necessarily mold network structure uniquely. These results show that variability operators can have a stronger influence on network topologies than selection pressures, especially when many topologies can create similar dynamics. Moreover, analysis of motif functional relevance by lesioning did not suggest that motifs were of greater importance to the functioning of the network than arbitrary subgraph patterns. Only when drastically restricting network size, so that one motif corresponds to a whole functionally evolved network, was preference for particular connection patterns found. This suggests that in non-restricted, bigger networks, entanglement with the rest of the network hinders topological subgraph analysis.

Identification of the interaction between bta-miR-370 and OLR1 gene in bovine adipocyte.

PubMed

Li, H F; Wang, S H; Guo, Y; Zhao, H B; Li, X Y; Wang, X

2017-08-01

It has been shown that the oxidized low density lipoprotein receptor 1 (OLR1) gene plays an important role in the degradation of oxidized low density lipoprotein. Previous studies found a SNP in the 3'-untranslated region (3'-UTR) of the OLR1 gene associated with milk production traits in different dairy cattle populations and with loin eye area and marbling depth in beef cattle. MicroRNAs can regulate gene expression by binding the 3'-UTR of target genes to degrade or to repress the translation of target genes. Bioinformatics have shown that there is a binding site of bta-miR-370 in the 3'-UTR of the OLR1 gene, and a previous luciferase reporter assay system showed that the A/C mutation occurring in the 3'-UTR of this gene caused the binding sites of bta-miR-370 to disappear in HEK293 cells. To further validate whether OLR1 was the target gene of bta-miR-370, the over-expression and interference expression of bta-miR-370 were determined by transfecting bta-miR-370 mimics and inhibitor supplementations into bovine adipocyte. The qRT-PCR result showed that the relative expression of OLR1 gene significantly decreased in the mimics group compared to the control, whereas the expression level in inhibitor group was higher than its control group. The above results were further verified by a Western blot at the protein level. In addition, lipid formation analysis of bovine adipocytes was performed via oil red O staining, and we found that cytoplasm lipid droplets in the inhibitor group showed a tendency to increase compared to the control group, whereas in the mimics group, we observed an obvious decrease of cytoplasm lipid droplets compared to the control and inhibitor groups. Taken together, our data here suggest that bta-miR-370 has a negative regulation role for OLR1 both at the gene expression and protein levels and bovine adipocytes cytoplasm lipid droplets formation, which provides a reference for illustrating how the OLR1 gene affects milk production and beef quality traits in cattle. © 2017 Stichting International Foundation for Animal Genetics.

Efficacy of a Pelvic Lateral Positioner With a Mechanical Cup Navigator Based on the Anatomical Pelvic Plane in Total Hip Arthroplasty.

PubMed

Iwakiri, Kentaro; Kobayashi, Akio; Ohta, Yoichi; Minoda, Yukihide; Takaoka, Kunio; Nakamura, Hiroaki

2017-12-01

The acetabular component orientation in total hip arthroplasty (THA) is of critical importance to the good clinical results. However, traditional widely used cup alignment guides for cup placement are reported to be relatively unreliable. The present study aims at comparing a novel cup alignment guide, which can be attached to our anatomical pelvic plane (APP) pelvic lateral positioner for reducing discrepancies in sagittal pelvic tilt and indicate a targeted cup angle based on the APP, with a conventional cup alignment guide. The subjects were 136 hips of 136 patients who underwent unilateral THA using the APP positioner. The procedure was performed with the conventional cup alignment guide (conventional group; 60 hips) and with the novel cup navigator (mechanical navigator group; 76 hips). Postoperative cup angles and discrepancies of postoperative cup angles (inclination and anteversion angles) from the targeted angles were compared between the 2 groups to evaluate the usefulness of these navigators. The mean cup angles in the conventional group were 39.0° ± 5.3° for the inclination angle and 21.7° ± 6.4° for the anteversion angle, whereas those in the mechanical navigator group were 40.6° ± 3.2° and 18.3° ± 4.6°, respectively (P = .018, P < .0001). The discrepancies from the targeted angles were 3.5° ± 3.1° for the inclination angle and 4.6° ± 3.4° for the anteversion angle in the conventional group and 2.3° ± 2.3° and 3.2° ± 2.7°, respectively, in the mechanical navigator group (P = .020, P = .012). The mechanical cup navigator easily attachable to the APP positioner is a tool that can improve the accuracy of cup placement in a simple, economical, and noninvasive manner in THA via the lateral position. Copyright © 2017 Elsevier Inc. All rights reserved.

Effective reduction of the interleukin-1β transcript in osteoarthritis-prone guinea pig chondrocytes via short hairpin RNA mediated RNA interference influences gene expression of mediators implicated in disease pathogenesis.

PubMed

Santangelo, K S; Bertone, A L

2011-12-01

To ascertain a viral vector-based short hairpin RNA (shRNA) capable of reducing the interleukin-1β (IL-1β) transcript in osteoarthritis (OA)-prone chondrocytes and detect corresponding changes in the expression patterns of several critical disease mediators. Cultured chondrocytes from 2-month-old Hartley guinea pigs were screened for reduction of the IL-1β transcript following plasmid-based delivery of U6-driven shRNA sequences. A successful plasmid/shRNA knockdown combination was identified and used to construct an adeno-associated virus serotype 5 (AAV5) vector for further evaluation. Relative real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify in vitro transcript changes of IL-1β and an additional nine genes following transduction with this targeting knockdown vector. To validate in vitro findings, this AAV5 vector was injected into one knee, while either an equivalent volume of saline vehicle (three animals) or non-targeting control vector (three animals) were injected into opposite knees. Fold differences and subsequent percent gene expression levels relative to control groups were calculated using the comparative CT (2(-ΔΔCT)) method. Statistically significant decreases in IL-1β expression were achieved by the targeting knockdown vector relative to both the mock-transduced control and non-targeting vector control groups in vitro. Transcript levels of anabolic transforming growth factor-β (TGF-β) were significantly increased by use of this targeting knockdown vector. Transduction with this targeting AAV5 vector also significantly decreased the transcript levels of key inflammatory cytokines [tumor necrosis factor-α (TNF-α), IL-2, IL-8, and IL-12] and catabolic agents [matrix metalloproteinase (MMP)13, MMP2, interferon-γ (IFN-γ), and inducible nitrous oxide synthase (iNOS)] relative to both mock-transduced and non-targeting vector control groups. In vivo application of this targeting knockdown vector resulted in a >50% reduction (P=0.0045) or >90% (P=0.0001) of the IL-1β transcript relative to vehicle-only or non-targeting vector control exposed cartilage, respectively. Successful reduction of the IL-1β transcript was achieved via RNA interference (RNAi) techniques. Importantly, this alteration significantly influenced the transcript levels of several major players involved in OA pathogenesis in the direction of disease modification. Investigations to characterize additional gene expression changes influenced by targeting knockdown AAV5 vector-based diminution of the IL-1β transcript in vivo are warranted. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Expert opinions on good practice in evaluation of health promotion and primary prevention measures related to children and adolescents in Germany.

PubMed

Korber, Katharina; Becker, Christian

2017-10-02

Determining what constitutes "good practice" in the measurement of the costs and effects of health promotion and disease prevention measures is of particular importance. The aim of this paper was to gather expert knowledge on (economic) evaluations of health promotion and prevention measures for children and adolescents, especially on the practical importance, the determinants of project success, meaningful parameters for evaluations, and supporting factors, but also on problems in their implementation. This information is targeted at people responsible for the development of primary prevention or health promotion programs. Partially structured open interviews were conducted by two interviewers and transcribed, paraphrased, and summarized for further use. Eight experts took part in the interviews. The interviewed experts saw evaluation as a useful tool to establish the effects of prevention programs, to inform program improvement and further development, and to provide arguments to decision making. The respondents' thought that determinants of a program's success were effectiveness with evidence of causality, cost benefit relation, target-group reach and sustainability. It was considered important that hard and soft factors were included in an evaluation; costs were mentioned only by one expert. According to the experts, obstacles to evaluation were lacking resources, additional labor requirements, and the evaluators' unfamiliarity with a program's contents. It was recommended to consider evaluation design before a program is launched, to co-operate with people involved in a program and to make use of existing structures. While in in this study only a partial view of expert knowledge is represented, it could show important points to consider when developing evaluations of prevention programs. By considering these points, researchers could further advance towards a more comprehensive approach of evaluation targeting measures in children and adolescents.

Impaired Retention of Motor Learning of Writing Skills in Patients with Parkinson’s Disease with Freezing of Gait

PubMed Central

Heremans, Elke; Nackaerts, Evelien; Vervoort, Griet; Broeder, Sanne; Swinnen, Stephan P.; Nieuwboer, Alice

2016-01-01

Background Patients with Parkinson’s disease (PD) and freezing of gait (FOG) suffer from more impaired motor and cognitive functioning than their non-freezing counterparts. This underlies an even higher need for targeted rehabilitation programs in this group. However, so far it is unclear whether FOG affects the ability for consolidation and generalization of motor learning and thus the efficacy of rehabilitation. Objective To investigate the hallmarks of motor learning in people with FOG compared to those without by comparing the effects of an intensive motor learning program to improve handwriting. Methods Thirty five patients with PD, including 19 without and 16 with FOG received six weeks of handwriting training consisting of exercises provided on paper and on a touch-sensitive writing tablet. Writing training was based on single- and dual-task writing and was supported by means of visual target zones. To investigate automatization, generalization and retention of learning, writing performance was assessed before and after training in the presence and absence of cues and dual tasking and after a six-week retention period. Writing amplitude was measured as primary outcome measure and variability of writing and dual-task accuracy as secondary outcomes. Results Significant learning effects were present on all outcome measures in both groups, both for writing under single- and dual-task conditions. However, the gains in writing amplitude were not retained after a retention period of six weeks without training in the patient group without FOG. Furthermore, patients with FOG were highly dependent on the visual target zones, reflecting reduced generalization of learning in this group. Conclusions Although short-term learning effects were present in both groups, generalization and retention of motor learning were specifically impaired in patients with PD and FOG. The results of this study underscore the importance of individualized rehabilitation protocols. PMID:26862915

Twenty-four-hour ambulatory blood pressure monitoring for clinical evaluation of hypertensive patients in primary care: which groups would most benefit?

PubMed

Grezzana, Guilherme B; Stein, Airton T; Pellanda, Lucia C

2017-04-01

Arterial hypertension is an important risk factor for cardiovascular outcomes. Blood pressure (BP) control levels remain largely out of target among primary healthcare (PHC) patients. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) may contribute toward the identification of cardiovascular risk groups. To assess concordance between conventional office BP measurements and 24-h ABPM of hypertension control in cardiovascular risk groups of PHC hypertensive patients. A cross-sectional study with 569 hypertensive patients was carried out. The evaluation of BP was performed by a PHC doctor, and the 24-h ABPM was performed by a different and blinded provider. The therapeutic targets for BP followed the guidance of The Eighth Joint National Committee, the Brazilian guideline, and the 2013 European Society of Hypertension. Considering the hypertension control therapeutic targets, the guidelines were not similar and were used to evaluate differences in BP value concordances compared with BP standard measurements. After a multivariate logistic regression analysis, a conventional BP was used in comparison with ABPM in different cardiovascular risk groups of hypertensive patients. According to the ABPM by European Society of Hypertension guideline, the subgroup of inactive patients (P=0.006), with altered glycemia (P=0.015) and over 30 mg/dl albuminuria (P=0.001), presented discordance among methods. When a conventional BP measurement in comparison with the ABPM results according to the Brazilian ABPM guideline was used, the discordance occurred significantly in inactive (P=0.001) and microalbuminuria more than 30 mg/dl (P=0.022) subgroups. However, in this comparison, a concordance between high-density lipoprotein more than 60 mg/dl (P=0.015) and obesity (P=0.035) subgroups occurred. Uncontrolled glucose levels, a sedentary lifestyle, and the presence of microalbuminuria correspond to some cardiovascular risk groups that would particularly benefit from 24-h ABPM as a tool for the control of BP with the PHC hypertensive patients of this study.

Merging of the Recruitment Branch and the Political Information Branch of the German Armed Forces and Application of this Recruitment Network to Saudi Arabia

DTIC Science & Technology

2013-03-01

18 a. Reduce Expenditures ................................................. 18 b. Increase Target Group Contacts...84 x THIS PAGE INTENTIONALLY LEFT BLANK xi LIST OF TABLES Table 1. Target Group and Population Forecast for...forces. Both branches are kept separate from each other, but focus on the same target group (young people between 16 and 24 years of age). While

Effectiveness of a quality improvement intervention targeting cardiovascular risk factors: are patients responsive to information and encouragement by mail or post?

PubMed

Senesael, Ellie; Borgermans, Liesbeth; Van De Vijver, Erwin; Devroey, Dirk

2013-01-01

There is important evidence on the beneficial effects of treatment of cardiovascular risk factors in terms of morbidity and mortality, but important challenges remain in motivating patients to adhere to their treatment regimen. This study aimed to describe the effectiveness of a quality improvement intervention that included information and regular encouragement by email or letter on cardiovascular risk factors for patients at high risk for cardiovascular disease. This randomized single-blind study included patients of both sexes aged between 45 and 80 years old who had increased cardiovascular risk. Patients were randomly allocated to either a usual care group (UCG) or advanced care group (ACG). Patients in the UCG received regular care while patients in the ACG received usual care plus regular information and encouragement on cardiovascular risk factors by email or letter. Visits for both groups were planned at 0, 3, and 6 months. The outcome measures were blood pressure, weight, body mass index (BMI), waist circumference (WC), and smoking status. Out of 178 eligible patients from one single primary care practice, 55 participated in the study, three of whom dropped out. After 6 months, there was a significant decrease in mean systolic and diastolic blood pressure in the UCG and ACG (P < 0.05). The decreases were already significant after 3 months, except for systolic blood pressure in the UCG. There was also a significant increase in the proportion of patients who met the target values for blood pressure in the UCG and ACG. There was a nonsignificant decrease of the average weight in the ACG, but significantly more patients lost weight in the UCG (P = 0.02). BMI, WC, and smoking status did not change in either group. This study found that there was a significant decrease of systolic and diastolic blood pressure in both study groups. Weight, BMI, WC, and smoking did not improve in either group. Information on cardiovascular risk factors and encouragement by means of letters or email did not provide additional benefits. Thus, effective patient empowerment probably requires more behaviorally sophisticated support to increase self-management, self-efficacy, and self-esteem in patients.

Pilot study of a targeted dance class for physical rehabilitation in children with cerebral palsy.

PubMed

López-Ortiz, Citlali; Egan, Tara; Gaebler-Spira, Deborah J

2016-01-01

This pilot study evaluates the effects of a targeted dance class utilizing classical ballet principles for rehabilitation of children with cerebral palsy on balance and upper extremity control. Twelve children with cerebral palsy (ages 7-15 years) with Gross Motor Function Classification scores II-IV participated in this study and were assigned to either a control group or targeted dance class group. Targeted dance class group participated in 1-h classes three times per week in a 4-week period. The Pediatric Balance Scale and the Quality of Upper Extremity Skills Test were administered before, after, and 1 month after the targeted dance class. Improvements in the Pediatric Balance Scale were present in the targeted dance class group in before versus after and before versus 1 month follow-up comparisons (p-value = 0.0088 and p-value = 0.019, respectively). The Pediatric Balance Scale changes were not significant in the control group. The Quality of Upper Extremity Skills Test did not reach statistical differences in either group. Classical ballet as an art form involves physical training, musical accompaniment, social interactions, and emotional expression that could serve as adjunct to traditional physical therapy. This pilot study demonstrated improvements in balance control. A larger study with a more homogeneous sample is warranted.

NMR investigations of the dual targeting peptide of Thr-tRNA synthetase and its interaction with the mitochondrial Tom20 receptor in Arabidopsis thaliana.

PubMed

Ye, Weihua; Spånning, Erika; Unnerståle, Sofia; Gotthold, David; Glaser, Elzbieta; Mäler, Lena

2012-10-01

Most mitochondrial proteins are synthesized in the cytosol as precursor proteins containing an N-terminal targeting peptide and are imported into mitochondria through the import machineries, the translocase of the outer mitochondrial membrane (TOM) and the translocase of the inner mitochondrial membrane (TIM). The N-terminal targeting peptide of precursor proteins destined for the mitochondrial matrix is recognized by the Tom20 receptor and plays an important role in the import process. Protein import is usually organelle specific, but several plant proteins are dually targeted into mitochondria and chloroplasts using an ambiguous dual targeting peptide. We present NMR studies of the dual targeting peptide of Thr-tRNA synthetase and its interaction with Tom20 in Arabidopsis thaliana. Our findings show that the targeting peptide is mostly unstructured in buffer, with a propensity to form α-helical structure in one region, S6-F27, and a very weak β-strand propensity for Q34-Q38. The α-helical structured region has an amphiphilic character and a φχχφφ motif, both of which have previously been shown to be important for mitochondrial import. Using NMR we have mapped out two regions in the peptide that are important for Tom20 recognition: one of them, F9-V28, overlaps with the amphiphilic region, and the other comprises residues L30-Q39. Our results show that the targeting peptide may interact with Tom20 in several ways. Furthermore, our results indicate a weak, dynamic interaction. The results provide for the first time molecular details on the interaction of the Tom20 receptor with a dual targeting peptide. © 2012 The Authors Journal compilation © 2012 FEBS.

Vestibular and Non-vestibular Contributions to Eye Movements that Compensate for Head Rotations during Viewing of Near Targets

NASA Technical Reports Server (NTRS)

Han, Yanning H.

2006-01-01

We studied horizontal eye movements induced by en-bloc yaw rotation, over a frequency range 0.2 - 2.8 Hz, in 10 normal human subjects as they monocularly viewed a target located at their near point of focus. We measured gain and phase relationships between eye-in-head velocity and head velocity when the near target was either earth-fixed or head-fixed. During viewing of the earth-fixed near target, median gain was 1.49 (range 1.24 - 1.87) at 0.2 Hz for the group of subjects, but declined at higher frequencies, so that at 2.8 Hz median gain was 1.08 (range 0.68 - 1.67). During viewing of the head-fixed near target , median gain was 0.03 (range 0.01 - 0.10) at 0.2 Hz for the group of subjects, but increased at higher frequencies, so that at 2.8 Hz median gain was 0.71 (range 0.28 - 0.94). We estimated the vestibular contribution to these responses vestibulo-ocular reflex gain (Gvor) by applying transient head perturbations (peak acceleration> 1,000 deg/s(exp 2)) during sinusoidal rotation under the two viewing conditions. Median Gvor, estimated < 70ms after the onset of head perturbation, was 0.98 (range 0.39 - 1.42) while viewing the earth-fixed near target, and 0.97 (range 0.37 - 1.33) while viewing the head-fixed near target. For the group of subjects, 9 out of 10 subjects showed no significant difference of Gvor between the two viewing conditions ( p > 0.053 ) at all test frequencies. Since Gvor accounted for only -73% of the overall response gain during viewing of the earth-fixed target, we investigated the relative contributions of non-vestibular factors. When subjects viewed the earth-fixed target under strobe illumination, to eliminate retinal image slip information, the gain of compensatory eye movements declined compared with viewing in ambient room light. During sum-of-sine head rotations, while viewing the earth-fixed target, to Han et al./VOR during near-viewing minimize contributions from predictive mechanisms, gain also declined Nonetheless, simple superposition of smooth-pursuit tracking of sinusoidal target motion could not fully account for the overall response at higher frequencies, suggesting other nonvestibular contributions. During binocular viewing conditions when vergence angle was significantly greater than monocular viewing (p < 0.00l), the gain of compensatory eye movements did not show proportional change; indeed, gain could not be correlated with vergence angle during monocular or binocular viewing. We conclude that several separate factors contribute to generate eye rotations during sinusoidal yaw head rotations while viewing a near target; these include the VOR, visual-tracking eye movements that utilize retinal image motion, predictive eye movements and, possibly, other unidentified non-vestibular factors. For these experiments, vergence was not an important determinant of response gam.

Vestibular and Non-vestibular Contributions to Eye Movements that Compensate for Head Rotations during Viewing of Near Targets

NASA Technical Reports Server (NTRS)

Han, Yanning H.; Kumar, Arun N.; Reschke, Millard F.; Somers, Jeffrey T.; Dell'Osso, Louis F.; Leigh, R. John

2004-01-01

We studied horizontal eye movements induced by en-bloc yaw rotation, over a frequency range 0.2 - 2.8 Hz, in 10 normal human subjects as th ey monocularly viewed a target located at their near point of focus. We measured gain and phase relationships between eye-in-head velocity and head velocity when the near target was either earth-fixed or head-fixed. During viewing of the earth-fixed near target,median gain was 1.49 (range 1.24 - 1.87) at 0.2 Hz for the group of subjects, but decl ined at higher frequencies, so that at 2.8 Hz median gain was 1.08 (r ange 0.68 - 1.67). During viewing of the head-fixed near target, median gain was 0.03 (range 0.01 - 0.10) at 0.2 Hz for the group of subjec ts, but increased at higher frequencies, so that at 2.8 Hz median gai n was 0.71 (range 0.28 - 0.94). We estimated the vestibular contribution to these responses (vestibulo-ocular reflex gain, Gvor) by applyin g transient head perturbations (peak acceleration> 1,000 deg's(exp 2) ) during sinusoidal rotation under the two viewing conditions. Median Gvor, estimated < 70m after the onset of head perturbation, was 0.98 (range 0.39 - 1.42) while viewing the earth-fixed near target, and 0. 97 (range 0.37 - 1.33) while viewing the head-fixed near target. For the group of subjects, 9 out of 10 subjects showed no sigificant diff erence of Gvor between the two viewing conditions ( p > 0.053 ) at all test frequencies. Since Gvor accounted for only approximately 73% of the overall response gain during viewing of the earth-fixed target, we investigated the relative contributions of non-vestibular factors. When subjects viewed the earth-fixed target under strobe illumination , to eliminate retinal image slip information, the gain of compensato ry eye movements declined compared with viewing in ambient room light . During sum-of-sine head rotations, while viewing the earth-fixed target, to minimize contributions from predictive mechanisms, gain also declined Nonetheless, simple superposition of smooth-pursuit tracking of sinusoidal target motion could not fully account for the overall r esponse at higher frequencies, suggesting other non-vestibular contributions. During binocular viewing conditions when vergence angle was s ignificantly greater than monocular viewing (p < 0.001), this gain of compensatory eye movements did not show proportional change; indeed, gain could not be correlated with vergence angle during monocular or binocular viewing. We conclude that several separate factors contribute to generate eye rotations during sinusoidal yaw head rotations whi le viewing a near target; these include the VOR, visual-tracking eye movements that utilize retinal image motion, predictive eye movements and, possibly, other unidentified nonvestibular factors. For these experiments, vergence was not an important determinant of response gain .

Differences in the molecular biology of adenocarcinoma of the esophagus, gastric cardia, and upper gastric third.

PubMed

Lehmann, Kuno; Schneider, Paul M

2010-01-01

Adenocarcinoma of the distal esophagus, gastric cardia, and upper gastric third are grouped in type I-III by the Siewert classification. This classification is based on the endoscopic localisation of the tumor center, and is the most important diagnostic tool to group these tumors. On a molecular level, there is currently no marker that would allow to differentiate the three different types. Furthermore, the Siewert classification was not uniformly used in the recent literature, making interpretation and generalization of these results difficult. However, several potential targets have been identified that may help to separate these tumors by molecular markers, and are summarized in this chapter.

Heterogeneity in TV fast food advertisement exposure in South Korea.

PubMed

Kim, Tae Hyun; Han, Euna; Jang, Sunmee

2014-03-01

To assess TV fast food ad exposure in South Korea. We assessed time trends of targeted ratings (licensed from Nielsen Media Research Korea) by household income and education during 2004-2010. Lower income groups saw more fast food TV ads during the study period. Exposure decreased in all income groups with a bigger income gap in 2010 than in 2004. The relative exposure to local fried chicken franchise TV ads surged from one fifth in 2004 to half of all TV fast food ads seen in 2010 in all socioeconomic status (SES). Future studies should assess the link between TV fast ood ad exposure, an important contextual factor for individual food choices, and actual consumption.

Typology of alcohol consumers in five Australian nighttime entertainment districts.

PubMed

Peacock, Amy; Norman, Thomas; Bruno, Raimondo; Pennay, Amy; Droste, Nicolas; Jenkinson, Rebecca; Quinn, Brendan; Lubman, Dan I; Miller, Peter

2016-09-01

Understanding how types of alcohol consumers differ is important for public policy targeted at reducing adverse events. The aims of the present study were to identify typologies of alcohol consumers in Australian nighttime entertainment districts based on risk factors for harm and to examine variation between the identified groups in drinking setting and harms. Street-intercept surveys were conducted with 5556 alcohol consumers in and around licensed venues in five Australian cities between November 2011 and June 2012. Latent class analysis identified groups based on age and sex, and blood alcohol concentration, pre-drinking, energy drink use and illicit drug use during that night. Four classes were identified: general patron group (33%), young pre-drinker group (27%), intoxicated male pre-drinker group (31%) and intoxicated illicit drug male group (9%). The proportion of the general patron group interviewed decreased over the night, while the other groups increased (particularly in regional cities). As compared with the general patron group, the remaining three groups reported increased odds of being involved in aggression and any alcohol-related injuries in the past 3 months, with highest rates of harm amongst the intoxicated illicit drug male group. Alcohol consumers in nighttime entertainment districts are not a homogeneous group. One-third have a low likelihood of risky consumption practices; however, representation of this consumer class diminishes throughout the night. Elevated harms amongst groups characterised by certain risk factors (e.g. pre-drinking and illicit drug use) emphasise the importance of addressing these behaviours in public policy. [Peacock A, Norman T, Bruno B, Pennay, Droste N, Jenkinson R, Quinn B, Lubman DI, Miller P. Typology of alcohol consumers in five Australian nighttime entertainment districts. Drug Alcohol Rev 2016;35:539-548]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Effects of variability of practice in music: a pilot study on fast goal-directed movements in pianists

PubMed Central

Bangert, Marc; Wiedemann, Anna; Jabusch, Hans-Christian

2014-01-01

Variability of Practice (VOP) refers to the acquisition of a particular target movement by practicing a range of varying targets rather than by focusing on fixed repetitions of the target only. VOP has been demonstrated to have beneficial effects on transfer to a novel task and on skill consolidation. This study extends the line of research to musical practice. In a task resembling a barrier-knockdown paradigm, 36 music students trained to perform a wide left-hand interval leap on the piano. Performance at the target distance was tested before and after a 30-min standardized training session. The high-variability group (VAR) practiced four different intervals including the target. Another group (FIX) practiced the target interval only. A third group (SPA) performed spaced practice on the target only, interweaving with periods of not playing. Transfer was tested by introducing an interval novel to either group. After a 24-h period with no further exposure to the instrument, performance was retested. All groups performed at comparable error levels before training, after training, and after the retention (RET) interval. At transfer, however, the FIX group, unlike the other groups, committed significantly more errors than in the target task. After the RET period, the effect was washed out for the FIX group but then was present for VAR. Thus, the results provide only partial support for the VOP hypothesis for the given setting. Additional exploratory observations suggest tentative benefits of VOP regarding execution speed, loudness, and performance confidence. We derive specific hypotheses and specific recommendations regarding sample selection and intervention duration for future investigations. Furthermore, the proposed leap task measurement is shown to be (a) robust enough to serve as a standard framework for studies in the music domain, yet (b) versatile enough to allow for a wide range of designs not previously investigated for music on a standardized basis. PMID:25157223

Experimental study on ablation of leiomyoma by combination high-intensity focused ultrasound and iodized oil in vitro.

PubMed

Liang, Zhi-Gang; Gao, Yi; Ren, Xiao-Yan; Sun, Cui; Gu, Heng-Fang; Mou, Meng; Xiao, Yan-Bing

2017-10-01

The aim of the current study was to investigate whether iodized oil (IO) enhances high-intensity focused ultrasound (HIFU) ablation of uterine leiomyoma and to determine the features of hyperechoic changes in the target region. Forty samples of uterine leiomyoma were randomly divided into an experimental group and a control group. In the experimental group, the leiomyoma was ablated by HIFU 30 min after 1 mL of iodized oil had been injected into the center of the myoma. The hyperechoic values and areas in the target region were observed by B-modal ultrasound after HIFU ablation. The samples were cut successively into slices and stained by triphenyltetrazolium chloride (TTC) solution within 1 h after HIFU ablation. The diameters of TTC-non-stained areas were measured and tissues in the borderline of the TTC-stained and -non-stained areas were observed pathologically. All procedures in the control group were the same as those in the experimental group except IO was replaced by physiological saline. The hyperechoic value in the target region in the experimental group was higher than that in the control group 4 min after HIFU ablation (P < 0.05). Hyperechoic areas in the target region as well as TTC-non-stained volumes in the experimental group were greater than those in the control group (P < 0.05). Routine pathologic observation showed that coagulation necrosis of leiomyoma occurred in the target region in both groups. IO causes coagulation necrosis, enlarges tissue damage, and postpones the attenuation of hyperechoic changes in the target region when HIFU ablation is carried out for leiomyoma in vitro. © 2017 Japan Society of Obstetrics and Gynecology.

Strategies for Sharing Scientific Research on Sea Level Rise: Suggestions from Stakeholder Focus Groups

NASA Astrophysics Data System (ADS)

DeLorme, D.; Hagen, S. C.; Stephens, S. H.

2013-12-01

This presentation reports results of focus groups with coastal resource managers on suggestions for effectively sharing sea level rise (SLR) scientific research with the public and other target audiences. The focus groups were conducted during three annual stakeholder workshops as an important and innovative component of an ongoing five-year multi-disciplinary NOAA-funded project, Ecological Effects of Sea Level Rise in the Northern Gulf of Mexico (EESLR-NGOM). The EESLR-NGOM project is assessing SLR risks to the natural and built environment along the Mississippi, Alabama, and Florida Panhandle coasts. The purpose was to engage stakeholders (e.g., coastal resource managers) in helping target, translate, and tailor the EESLR-NGOM project's scientific findings and emerging products so they are readily accessible, understandable, and useful. The focus groups provided insight into stakeholders' SLR informational and operational needs, solicited input on the project's products, and gathered suggestions for public communication and outreach. A total of three ninety-minute focus groups of between eight and thirteen participants each were conducted at annual workshops in Alabama, Florida, and Mississippi. The moderator asked a series of open-ended questions about SLR-related topics using an interview guide and encouraged participant interaction. All focus group audio-recordings were transcribed, and analyzed by carefully reading the 102 total pages of transcript data and identifying patterns and themes. Participants thought outreach about SLR impact and the EESLR-NGOM project scientific research/products was vital and acknowledged various communication challenges and opportunities. They identified three target audiences (local officials, general public, coastal resource managers themselves) that likely require different educational efforts and tools. Participants felt confident the EESLR-NGOM project products will benefit their resource planning and decision making and believed the project will have positive implications for diverse vested entities. Gaining public and local leader support was considered crucial in fostering funding and favorable policies with respect to project goals. However, it was expected that certain target audiences will need to be better educated on ecological aspects of the project and convinced of its significance for this to be achieved. Suggested formats for the EESLR-NGOM research results included maps with precision and flexibility for adjustments over time, across geographic domains, and for different levels of user sophistication, as well as simplified presentations that can be readily shared. There was emphasis on visuals and demonstrations for accessibility and engagement by multiple audiences. While participants thought handouts, brochures, and graphical illustrations would be effective, they also advocated using new digital media. Further, participants advised that time frames and language be adjusted to resonate with target audiences, especially in communicating risk. Branding a unique identity for the EESLR-NGOM project/products was encouraged. Message consistency was considered key for optimal outcomes. The ongoing feedback has resulted in year-by-year refinements of the research process and scientific product development, which has been central to gaining confidence of the target audiences.

Design and Evaluation of Perceptual-based Object Group Selection Techniques

NASA Astrophysics Data System (ADS)

Dehmeshki, Hoda

Selecting groups of objects is a frequent task in graphical user interfaces. It is required prior to many standard operations such as deletion, movement, or modification. Conventional selection techniques are lasso, rectangle selection, and the selection and de-selection of items through the use of modifier keys. These techniques may become time-consuming and error-prone when target objects are densely distributed or when the distances between target objects are large. Perceptual-based selection techniques can considerably improve selection tasks when targets have a perceptual structure, for example when arranged along a line. Current methods to detect such groups use ad hoc grouping algorithms that are not based on results from perception science. Moreover, these techniques do not allow selecting groups with arbitrary arrangements or permit modifying a selection. This dissertation presents two domain-independent perceptual-based systems that address these issues. Based on established group detection models from perception research, the proposed systems detect perceptual groups formed by the Gestalt principles of good continuation and proximity. The new systems provide gesture-based or click-based interaction techniques for selecting groups with curvilinear or arbitrary structures as well as clusters. Moreover, the gesture-based system is adapted for the graph domain to facilitate path selection. This dissertation includes several user studies that show the proposed systems outperform conventional selection techniques when targets form salient perceptual groups and are still competitive when targets are semi-structured.

[Clinical use of statins and cholesterol goals in patients with several cardiovascular risk factors].

PubMed

Gómez-Belda, Ana; Rodilla, Enrique; Albert, Amparo; García, Luis; González, Carmen; Pascual, José M

2003-10-25

Our goal was to determine the number of patients who achieve low-density lipoprotein cholesterol (LDL-c) targets according to new guidelines. Descriptive and transversal study of patients from a cardiovascular clinic. LDL-c was calculated and targets were established according the NCEP-ATP III. 1,811 patients (46% males, 54% females) were studied. 35% of these were high-risk patients (group 1: coronary risk > 20% at 10 years), 19% were intermediate-risk patients (group 2: coronary risk 10-20% at 10 years) and 46% were low-risk patients (group 3: coronary risk < 10% at 10 years). Overall, 58% of patients achieved target LDL-c levels, yet success rates were 26% among group 1 patients, 51% among group 2 patients, and 86% among group 3 patients (p = 0.001, for differences between groups). Statin treatment was significantly related to achieving target LDL-c levels in group 1 patients (OR = 1.7; 95% CI, 1.2-2.4; p = 0.007). In group 1.41% of patients had LDL-c levels > 130 mg/dl without receiving lipid-lowering drugs. Although an overall 58% patients achieve target LDL-C levels, only one of four high-risk patients have LDL-c levels < 100 mg/dl, and statin treatment is a determining factor to achieve this goal. These findings indicate that a more aggressive treatment with statins is needed in secondary prevention.

Realism and Effectiveness of Robotic Moving Targets

DTIC Science & Technology

2017-04-01

scenario or be manually controlled . The targets can communicate with other nearby targets, which means they can move independently, as a group , or...present a realistic three- dimensional human-sized target that can freely move with semi-autonomous control . The U.S. Army Research Institute for...Procedure: Performance and survey data were collected during multiple training exercises from Soldiers who engaged the RHTTs. Different groups

Enhancing and sustaining empathy in medical students.

PubMed

Hojat, Mohammadreza; Axelrod, David; Spandorfer, John; Mangione, Salvatore

2013-12-01

Empathy is an important component of physician competence that needs to be enhanced. To test the hypotheses that medical students' empathy can be enhanced and sustained by targeted activities. This was a two-phase study in which 248 medical students participated. In Phase 1, students in the experimental group watched and discussed video clips of patient encounters meant to enhance empathic understanding; those in the control group watched a documentary film. Ten weeks later in Phase 2 of the study, students who were in the experimental group were divided into two groups. One group attended a lecture on empathy in patient care, and the other plus the control group watched a movie about racism. The Jefferson Scale of Empathy (JSE) was administered pre-post in Phase 1 and posttest in Phase 2. In Phase 1, the JSE mean score for the experimental group improved significantly (p < 0.01); no change in the JSE scores was observed in the control group. In Phase 2, the JSE mean score improvement was sustained in the group that attended the lecture, but not in the other group. No change in empathy was noticed in the control group. Research hypotheses were confirmed.

Disparities in Cancer Genetic Risk Assessment and Testing.

PubMed

Underhill, Meghan L; Jones, Tarsha; Habin, Karleen

2016-07-01

Scientific and technologic advances in genomics have revolutionized genetic counseling and testing, targeted therapy, and cancer screening and prevention. Among younger women, African American and Hispanic women have a higher rate of cancers that are associated with hereditary cancer risk, such as triple-negative breast cancer, which is linked to poorer outcomes. Therefore, genetic testing is particularly important in diverse populations. Unfortunately, all races and ethnic groups are not well represented in current genetic testing practices, leading to disparities in cancer prevention and early detection.

Regio- and enantioselective synthesis of N-substituted pyrazoles by rhodium-catalyzed asymmetric addition to allenes.

PubMed

Haydl, Alexander M; Xu, Kun; Breit, Bernhard

2015-06-08

The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with terminal allenes gives access to enantioenriched secondary and tertiary allylic pyrazoles, which can be employed for the synthesis of medicinally important targets. The reaction tolerates a large variety of functional groups and labelling experiments gave insights into the reaction mechanism. This new methodology was further applied in a highly efficient synthesis of JAK 1/2 inhibitor (R)-ruxolitinib. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma.

PubMed

Faria, Claudia C; Agnihotri, Sameer; Mack, Stephen C; Golbourn, Brian J; Diaz, Roberto J; Olsen, Samantha; Bryant, Melissa; Bebenek, Matthew; Wang, Xin; Bertrand, Kelsey C; Kushida, Michelle; Head, Renee; Clark, Ian; Dirks, Peter; Smith, Christian A; Taylor, Michael D; Rutka, James T

2015-08-28

Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor prognosis despite aggressive therapy. We investigated several potential small molecule inhibitors to target Group 3 medulloblastomas based on gene expression data using an in silico drug screen. The Connectivity Map (C-MAP) analysis identified piperlongumine as the top candidate drug for non-WNT medulloblastomas and the cyclin-dependent kinase (CDK) inhibitor alsterpaullone as the compound predicted to have specific antitumor activity against Group 3 medulloblastomas. To validate our findings we used these inhibitors against established Group 3 medulloblastoma cell lines. The C-MAP predicted drugs reduced cell proliferation in vitro and increased survival in Group 3 medulloblastoma xenografts. Alsterpaullone had the highest efficacy in Group 3 medulloblastoma cells. Genomic profiling of Group 3 medulloblastoma cells treated with alsterpaullone confirmed inhibition of cell cycle-related genes, and down-regulation of MYC. Our results demonstrate the preclinical efficacy of using a targeted therapy approach for Group 3 medulloblastomas. Specifically, we provide rationale for advancing alsterpaullone as a targeted therapy in Group 3 medulloblastoma.

Ground-based photometric support for the CoRoT mission by the CoRoT-Hungarian Asteroseismology Group

NASA Astrophysics Data System (ADS)

Bognár, Zs.; Paparó, M.

2012-12-01

The CoRoT-Hungarian Asteroseismology Group was established in 2005 and joined the preparatory work of the CoRoT Mission via an ESA PECS project. After the successful launch of the telescope, we have continued our work of ground-based multi-colour photometric observations and contributed to the analyses of CoRoT data. Our observations were focused on δ Scuti, γ Doradus, and RR Lyrae stars. The follow-up of some selected targets' pulsations in different wavelengths has provided valuable information for mode identification. We provided additional support by the confirmation of relatively faint variables' spectral types. We proved that our ground-based observations can help in the interpretation of a target with a contaminated CoRoT light curve. In this paper, we summarize our most important results of the photometric support for the CoRoT Mission. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

The influence of lifestyle on health behavior and preference for functional foods.

PubMed

Szakály, Zoltán; Szente, Viktória; Kövér, György; Polereczki, Zsolt; Szigeti, Orsolya

2012-02-01

The main objective of this survey is to reveal the relationship between lifestyle, health behavior, and the consumption of functional foods on the basis of Grunert's food-related lifestyle model. In order to achieve this objective, a nationwide representative questionnaire-based survey was launched with 1000 participants in Hungary. The results indicate that a Hungarian consumer makes rational decisions, he or she seeks bargains, and he wants to know whether or not he gets good value for his money. Further on, various lifestyle segments are defined by the authors: the rational, uninvolved, conservative, careless, and adventurous consumer segments. Among these, consumers with a rational approach provide the primary target group for the functional food market, where health consciousness and moderate price sensitivity can be observed together. Adventurous food consumers stand out because they search for novelty; this makes them an equally important target group. Conservative consumers are another, one characterized by positive health behavior. According to the findings of the research, there is a significant relationship between lifestyle, health behavior, and the preference for functional food products. Copyright © 2011 Elsevier Ltd. All rights reserved.

Recommendations for Promoting Physical Activity for Children and Adolescents in Germany. A Consensus Statement

PubMed Central

Graf, Christine; Beneke, Ralph; Bloch, Wilhelm; Bucksch, Jens; Dordel, Sigrid; Eiser, Stefanie; Ferrari, Nina; Koch, Benjamin; Krug, Susanne; Lawrenz, Wolfgang; Manz, Kristin; Naul, Roland; Oberhoffer, Renate; Quilling, Eike; Schulz, Henry; Stemper, Theo; Stibbe, Günter; Tokarski, Walter; Völker, Klaus; Woll, Alexander

2014-01-01

Increasing physical activity and reduction of sedentary behaviour play important roles in health promotion and prevention of lifestyle-related diseases in children and adolescents. However, the question of how much physical activity is useful for which target group is still a matter of debate. International guidelines (World Health Organization; European Association for the Study of Obesity), which are mainly based on expert opinions, recommend 60 min of physical activity every day. Age- and sex-specific features and regional differences are not taken into account. Therefore, expert consensus recommendations for promoting physical activity of children and adolescents in Germany were developed with special respect to national data, but also with respect to aspects of specific target groups, e.g., children with a lower socio-economic status (SES) or with migration background. They propose 90 min/day of physical activity, or at least 12,000 steps daily. Additionally, lifestyle factors, especially restriction of media consumption, were integrated. The recommendations provide orientation for parents and caregivers, for institutions such as schools and kindergartens as well as for communities and stakeholders. PMID:24821136

Type I interferon-mediated autoimmune diseases: pathogenesis, diagnosis and targeted therapy.

PubMed

Psarras, Antonios; Emery, Paul; Vital, Edward M

2017-10-01

Type I interferons (IFN-Is) are a group of molecules with pleiotropic effects on the immune system forming a crucial link between innate and adaptive immune responses. Apart from their important role in antiviral immunity, IFN-Is are increasingly recognized as key players in autoimmune CTDs such as SLE. Novel therapies that target IFN-I appear effective in SLE in early trials, but effectiveness is related to the presence of IFN-I biomarkers. IFN-I biomarkers may also act as positive or negative predictors of response to other biologics. Despite the high failure rate of clinical trials in SLE, subgroups of patients often respond better. Fully optimizing the potential of these agents is therefore likely to require stratification of patients using IFN-I and other biomarkers. This suggests the unified concept of type I IFN-mediated autoimmune diseases as a grouping including patients with a variety of different traditional diagnoses. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Exploring parental behavior and child interactive engagement: A study on children with a significant cognitive and motor developmental delay.

PubMed

Van Keer, Ines; Colla, Stephy; Van Leeuwen, Karla; Vlaskamp, Carla; Ceulemans, Eva; Hoppenbrouwers, Karel; Desoete, Annemie; Maes, Bea

2017-05-01

Parenting factors are one of the most striking gaps in the current scientific literature on the development of young children with significant cognitive and motor disabilities. We aim to explore the characteristics of, and the association between, parental behavior and children's interactive engagement within this target group. Twenty-five parent-child dyads (with children aged 6-59 months) were video-taped during a 15-min unstructured play situation. Parents were also asked to complete the Parental Behavior Scale for toddlers. The video-taped observations were scored using the Child and Maternal Behavior Rating Scales. Low levels of parental discipline and child initiation were found. Parental responsivity was positively related to child attention and initiation. Compared to children with no or other levels of disabilities, this target group exhibits large differences in frequency levels and, to a lesser extent, the concrete operationalization of parenting domains. Further, this study confirms the importance of sensitive responsivity as the primary variable in parenting research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Targeting G protein-coupled receptor kinases (GRKs) in Heart Failure

PubMed Central

Brinks, Henriette; Koch, Walter J

2010-01-01

In the human body, over 1000 different G protein-coupled receptors (GPCRs) mediate a broad spectrum of extracellular signals at the plasma membrane, transmitting vital physiological features such as pain, sight, smell, inflammation, heart rate and contractility of muscle cells. Signaling through these receptors is primarily controlled and regulated by a group of kinases, the GPCR kinases (GRKs), of which only seven are known and thus, interference with these common downstream GPCR regulators suggests a powerful therapeutic strategy. Molecular modulation of the kinases that are ubiquitously expressed in the heart has proven GRK2, and also GRK5, to be promising targets for prevention and reversal of one of the most severe pathologies in man, chronic heart failure (HF). In this article we will focus on the structural aspects of these GRKs important for their physiological and pathological regulation as well as well known and novel therapeutic approaches that target these GRKs in order to overcome the development of cardiac injury and progression of HF. PMID:21218155

ROS-activated anticancer prodrugs: a new strategy for tumor-specific damage

PubMed Central

Peng, Xiaohua; Gandhi, Varsha

2013-01-01

Targeting tumor cells is an important strategy to improve the selectivity of cancer therapies. With the advanced studies in cancer biology, we know that cancer cells are usually under increased oxidative stress. The high level of reactive oxygen species in cancer cells has been exploited for developing novel therapeutic strategies to preferentially kill cancer cells. Our group, amongst others, have used boronic acids/esters as triggers for developing ROS-activated anticancer prodrugs that target cancer cells. The selectivity was achieved by combining a specific reaction between boronates and H2O2 with the efficient masking of drug toxicity in the prodrug via boronates. Prodrugs activated via ferrocene-mediated oxidation have also been developed to improve the selectivity of anticancer drugs. We describe how the strategies of ROS-activation can be used for further development of new ROS-targeting prodrugs, eventually leading to novel approaches and/or combined technology for more efficient and selective treatment of cancers. PMID:22900465

A Qualitative Comparison of Susceptibility and Behavior in Recreational and Occupational Risk Environments: Implications for Promoting Health and Safety.

PubMed

Haas, Emily Joy; Mattson, Marifran

2016-06-01

Although internal factors that influence risk are frequently studied to understand human behavior, external factors, including social, cultural, and institutional factors, should be better utilized to inform ways to efficiently target, tailor, and promote safety messaging to at-risk populations. Semi-structured interviews obtained data from 37 motorcyclists and 18 mineworkers about their risk perceptions and behaviors within their respective dynamic environments. A comparative thematic analysis revealed information about external factors that influence risk perceptions and behaviors. Results support the importance of qualitative approaches for assessing and targeting individuals' risk perceptions and behaviors. In addition, segmenting at-risk subgroups within target populations and tailoring messages for these at-risk groups is critical for safety behavior modification. Practitioners should utilize strategic, culture-centric risk communication that takes into account external factors when determining when, who, and what to communicate via health promotion activities to more accurately disseminate valid, empathetic, and engaging communication with a higher level of fidelity.

Meeting the need for regenerative therapies I: target-based incidence and its relationship to U.S. spending, productivity, and innovation.

PubMed

Parenteau, Nancy; Hardin-Young, Janet; Shannon, William; Cantini, Patrick; Russell, Alan

2012-04-01

Regenerative therapies possess high theoretical potential for medical advance yet their success as commercial therapeutics is still open to debate. Appropriate data on target opportunities that provide perspective and enable strategic decision making is necessary for both efficient and effective translation. Up until now, this data have been out of reach to research scientists and many start-up companies-the very groups currently looked to for the critical advance of these therapies. The target-based estimate of opportunity presented in this report demonstrates its importance in evaluating medical need and technology feasibility. In addition, analysis of U.S. research spending, productivity, and innovation reveals that U.S. basic research in this field would benefit from greater interdisciplinarity. Overcoming the barriers that currently prevent translation into high value therapies that are quickly clinically adopted requires simultaneous integration of engineering, science, business, and clinical practice. Achieving this integration is nontrivial.

Enhancing Motor Network Activity Using Real-Time Functional MRI Neurofeedback of Left Premotor Cortex

PubMed Central

Marins, Theo F.; Rodrigues, Erika C.; Engel, Annerose; Hoefle, Sebastian; Basílio, Rodrigo; Lent, Roberto; Moll, Jorge; Tovar-Moll, Fernanda

2015-01-01

Neurofeedback by functional magnetic resonance imaging (fMRI) is a technique of potential therapeutic relevance that allows individuals to be aware of their own neurophysiological responses and to voluntarily modulate the activity of specific brain regions, such as the premotor cortex (PMC), important for motor recovery after brain injury. We investigated (i) whether healthy human volunteers are able to up-regulate the activity of the left PMC during a right hand finger tapping motor imagery (MI) task while receiving continuous fMRI-neurofeedback, and (ii) whether successful modulation of brain activity influenced non-targeted motor control regions. During the MI task, participants of the neurofeedback group (NFB) received ongoing visual feedback representing the level of fMRI responses within their left PMC. Control (CTL) group participants were shown similar visual stimuli, but these were non-contingent on brain activity. Both groups showed equivalent levels of behavioral ratings on arousal and MI, before and during the fMRI protocol. In the NFB, but not in CLT group, brain activation during the last run compared to the first run revealed increased activation in the left PMC. In addition, the NFB group showed increased activation in motor control regions extending beyond the left PMC target area, including the supplementary motor area, basal ganglia and cerebellum. Moreover, in the last run, the NFB group showed stronger activation in the left PMC/inferior frontal gyrus when compared to the CTL group. Our results indicate that modulation of PMC and associated motor control areas can be achieved during a single neurofeedback-fMRI session. These results contribute to a better understanding of the underlying mechanisms of MI-based neurofeedback training, with direct implications for rehabilitation strategies in severe brain disorders, such as stroke. PMID:26733832

mcrA-Targeted Real-Time Quantitative PCR Method To Examine Methanogen Communities▿

PubMed Central

Steinberg, Lisa M.; Regan, John M.

2009-01-01

Methanogens are of great importance in carbon cycling and alternative energy production, but quantitation with culture-based methods is time-consuming and biased against methanogen groups that are difficult to cultivate in a laboratory. For these reasons, methanogens are typically studied through culture-independent molecular techniques. We developed a SYBR green I quantitative PCR (qPCR) assay to quantify total numbers of methyl coenzyme M reductase α-subunit (mcrA) genes. TaqMan probes were also designed to target nine different phylogenetic groups of methanogens in qPCR assays. Total mcrA and mcrA levels of different methanogen phylogenetic groups were determined from six samples: four samples from anaerobic digesters used to treat either primarily cow or pig manure and two aliquots from an acidic peat sample stored at 4°C or 20°C. Only members of the Methanosaetaceae, Methanosarcina, Methanobacteriaceae, and Methanocorpusculaceae and Fen cluster were detected in the environmental samples. The three samples obtained from cow manure digesters were dominated by members of the genus Methanosarcina, whereas the sample from the pig manure digester contained detectable levels of only members of the Methanobacteriaceae. The acidic peat samples were dominated by both Methanosarcina spp. and members of the Fen cluster. In two of the manure digester samples only one methanogen group was detected, but in both of the acidic peat samples and two of the manure digester samples, multiple methanogen groups were detected. The TaqMan qPCR assays were successfully able to determine the environmental abundance of different phylogenetic groups of methanogens, including several groups with few or no cultivated members. PMID:19447957

MicroRNA expression, target genes, and signaling pathways in infants with a ventricular septal defect.

PubMed

Chai, Hui; Yan, Zhaoyuan; Huang, Ke; Jiang, Yuanqing; Zhang, Lin

2018-02-01

This study aimed to systematically investigate the relationship between miRNA expression and the occurrence of ventricular septal defect (VSD), and characterize the miRNA target genes and pathways that can lead to VSD. The miRNAs that were differentially expressed in blood samples from VSD and normal infants were screened and validated by implementing miRNA microarrays and qRT-PCR. The target genes regulated by differentially expressed miRNAs were predicted using three target gene databases. The functions and signaling pathways of the target genes were enriched using the GO database and KEGG database, respectively. The transcription and protein expression of specific target genes in critical pathways were compared in the VSD and normal control groups using qRT-PCR and western blotting, respectively. Compared with the normal control group, the VSD group had 22 differentially expressed miRNAs; 19 were downregulated and three were upregulated. The 10,677 predicted target genes participated in many biological functions related to cardiac development and morphogenesis. Four target genes (mGLUR, Gq, PLC, and PKC) were involved in the PKC pathway and four (ECM, FAK, PI3 K, and PDK1) were involved in the PI3 K-Akt pathway. The transcription and protein expression of these eight target genes were significantly upregulated in the VSD group. The 22 miRNAs that were dysregulated in the VSD group were mainly downregulated, which may result in the dysregulation of several key genes and biological functions related to cardiac development. These effects could also be exerted via the upregulation of eight specific target genes, the subsequent over-activation of the PKC and PI3 K-Akt pathways, and the eventual abnormal cardiac development and VSD.

Brief Report: Developmental Trajectories of Adaptive Behavior in Children and Adolescents with ASD.

PubMed

Meyer, Allison T; Powell, Patrick S; Butera, Nicole; Klinger, Mark R; Klinger, Laura G

2018-03-17

Research suggests that individuals with autism spectrum disorder (ASD) have significant difficulties with adaptive behavior skills including daily living and functional communication skills. Few studies have examined the developmental trajectory of adaptive behavior across childhood and adolescence. The present study examined longitudinal trajectories of adaptive behavior in a community-based clinic sample of 186 individuals with ASD. The overall pattern indicated an initial increase in adaptive behavior during early childhood followed by a plateau in skills during adolescence for individuals of all IQ groups. Given the importance of adaptive behavior for employment and quality of life, this study emphasizes the importance of targeting adaptive behavior during adolescence to insure continued gains.

Deregulation of F-box proteins and its consequence on cancer development, progression and metastasis

PubMed Central

Heo, Jinho; Eki, Rebeka; Abbas, Tarek

2015-01-01

F-box proteins are substrate receptors of the SCF (SKP1-Cullin 1-F-box protein) E3 ubiquitin ligase that play important roles in a number of physiological processes and activities. Through their ability to assemble distinct E3 ubiquitin ligases and target key regulators of cellular activities for ubiquitylation and degradation, this versatile group of proteins is able to regulate the abundance of cellular proteins whose deregulated expression or activity contributes to disease. In this review, we describe the important roles of select F-box proteins in regulating cellular activities, the perturbation of which contributes to the initiation and progression of a number of human malignancies. PMID:26432751

Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration.

PubMed

Jeong, Jae Young; Hong, Eun-Hye; Lee, Song Yi; Lee, Jae-Young; Song, Jae-Hyoung; Ko, Seung-Hak; Shim, Jae-Seong; Choe, Sunghwa; Kim, Dae-Duk; Ko, Hyun-Jeong; Cho, Hyun-Jong

2017-04-15

(3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface of HACE-AMPB/MB NPs (in the aqueous milieu) may react with the sialic acid over-expressed in cancer cells and intramolecular B‒O bond can be formed. This phenylboronic acid-sialic acid interaction may provide additional tumor targeting and penetration potentials together with an enhanced permeability and retention (EPR) effect (passive tumor targeting) and HA-CD44 receptor interaction (active tumor targeting). Developed HACE-AMPB NP may be one of promising nanocarriers for the imaging and therapy of CD44 receptor-expressed cancers. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Noninvasive Antenatal Determination of Fetal Blood Group Using Next-Generation Sequencing

PubMed Central

Rieneck, Klaus; Clausen, Frederik Banch; Dziegiel, Morten Hanefeld

2016-01-01

Hemolytic disease of the fetus and newborn (HDFN) is a condition characterized by a decreased lifespan of fetal red blood cells caused by maternally produced allospecific antibodies transferred to the fetus during pregnancy. The antibodies bind to the corresponding blood group antigens on fetal red blood cells and induce hemolysis. Cell-free DNA derived from the conceptus circulates in maternal blood. Using next-generation sequencing (NGS), it can be determined if this cell-free fetal DNA encodes the corresponding blood group antigen that is the target of the maternal allospecific antibodies. This determination carries no risk to the fetus. It is important to determine if the fetus is at risk of hemolysis to enable timely intervention. Many tests for blood groups are based solely on the presence or absence of a single nucleotide polymorphism (SNP). Antenatal determination of fetal blood group by NGS analysis holds advantages over polymerase chain reaction (PCR) determination based on allele specific amplification. PMID:26511760

Set Shifting Training with Categorization Tasks

PubMed Central

Soveri, Anna; Waris, Otto; Laine, Matti

2013-01-01

The very few cognitive training studies targeting an important executive function, set shifting, have reported performance improvements that also generalized to untrained tasks. The present randomized controlled trial extends set shifting training research by comparing previously used cued training with uncued training. A computerized adaptation of the Wisconsin Card Sorting Test was utilized as the training task in a pretest-posttest experimental design involving three groups of university students. One group received uncued training (n = 14), another received cued training (n = 14) and the control group (n = 14) only participated in pre- and posttests. The uncued training group showed posttraining performance increases on their training task, but neither training group showed statistically significant transfer effects. Nevertheless, comparison of effect sizes for transfer effects indicated that our results did not differ significantly from the previous studies. Our results suggest that the cognitive effects of computerized set shifting training are mostly task-specific, and would preclude any robust generalization effects with this training. PMID:24324717

Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines.

PubMed

Zhang, Lei; Zeng, Zhanzhuang; Hu, Chaohua; Bellis, Susan L; Yang, Wendi; Su, Yintao; Zhang, Xinyan; Wu, Yunkun

2016-01-01

Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly(D,L-lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group B Streptococcus (GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia, an animal with a relatively simple immune system. The vaccine succeeded in protecting against Streptococcus agalactiae, a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock.

PubMed

Lamontagne, François; Day, Andrew G; Meade, Maureen O; Cook, Deborah J; Guyatt, Gordon H; Hylands, Mathieu; Radermacher, Peter; Chrétien, Jean-Marie; Beaudoin, Nicolas; Hébert, Paul; D'Aragon, Frédérick; Meziani, Ferhat; Asfar, Pierre

2018-01-01

Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets. We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration's instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality. Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87-1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33-6.74). Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.

48 CFR 952.226-73 - Energy Policy Act target group certification.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Energy Policy Act target... ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.226-73 Energy Policy Act target group certification. As prescribed in 926.7007(d), insert the...

48 CFR 952.226-73 - Energy Policy Act target group certification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Energy Policy Act target... ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.226-73 Energy Policy Act target group certification. As prescribed in 926.7007(d), insert the...

48 CFR 952.226-73 - Energy Policy Act target group certification.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Energy Policy Act target... ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.226-73 Energy Policy Act target group certification. As prescribed in 926.7007(d), insert the...

48 CFR 952.226-73 - Energy Policy Act target group certification.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Energy Policy Act target... ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.226-73 Energy Policy Act target group certification. As prescribed in 926.7007(d), insert the...

Impact of target area selection in 125 Iodine seed brachytherapy on locoregional recurrence in patients with non-small cell lung cancer.

PubMed

Yan, Wei-Liang; Lv, Jin-Shuang; Guan, Zhi-Yu; Wang, Li-Yang; Yang, Jing-Kui; Liang, Ji-Xiang

2017-05-01

Computed tomography (CT)-guided percutaneous implantation of 125 Iodine radioactive seeds requires the precise arrangement of seeds by tumor shape. We tested whether selecting target areas, including subclinical areas around tumors, can influence locoregional recurrence in patients with non-small cell lung cancer (NSCLC). We divided 82 patients with NSCLC into two groups. Target areas in group 1 (n = 40) were defined along tumor margins based on lung-window CT. Target areas in group 2 (n = 42) were extended by 0.5 cm in all dimensions outside tumor margins. Preoperative plans for both groups were based on a treatment plan system, which guided 125 I seed implantation. Six months later, patients underwent chest CT to evaluate treatment efficacy (per Response Evaluation Criteria in Solid Tumors version 1). We compared locoregional recurrences between the groups after a year of follow-up. We then used the treatment plan system to extend target areas for group 1 patients by 0.5 cm (defined as group 3 data) and compared these hypothetical group 3 planned seeds with the actual seed numbers used in group 1 patients. All patients successfully underwent implantation; none died during the follow-up period. Recurrence was significantly lower in group 2 than in group 1 ( P  < 0.05). Group 1 patients and group 3 data significantly differed in seed numbers ( P  < 0.01). Our results imply that extending the implantation area for 125 I seeds can decrease recurrence risk by eradicating cancerous lymph-duct blockades within the extended areas. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

MRI target delineation may reduce long-term toxicity after prostate radiotherapy.

PubMed

Sander, Lotte; Langkilde, Niels Christian; Holmberg, Mats; Carl, Jesper

2014-06-01

Aiming for minimal toxicity after radical prostate cancer (PC) radiotherapy (RT), magnetic resonance imaging (MRI) target delineation could be a possible benefit knowing that clinical target volumes (CTV) are up to 30% smaller, when CTV delineation on MRI is compared to standard computed tomography (CT). This study compares long-term toxicity using CT or MRI delineation before PC RT. Urinary and rectal toxicity assessments 36 months after image-guided RT (78 Gy) using CTC-AE scores in two groups of PC patients. Peak symptom score values were registered. One group of patients (n=72) had standard CT target delineation and gold markers as fiducials. Another group of patients (n=73) had MRI target delineation and a nickel-titanium stent as fiducial. At 36 months no difference in overall survival (92% in both groups, p=0.29) or in PSA-relapse free survival was found between the groups (MRI=89% and CT=94%, p=0.67). A significantly smaller CTV was found in the MRI group (p=0.02). Urinary retention and frequency were significantly reduced in the MRI group (p=0.03 in the matter of both). The overall urinary and rectal toxicity did not differ between the two groups. MRI delineation leads to a significantly reduced CTV. Significantly lower urinary frequency and urinary retention toxicity scores were observed following MRI delineation. The study did not find significant differences in overall urinary or rectal toxicity between the two groups. PSA-relapse survival did not differ between the two groups at 36 months.

Scientific teaching targeting faculty from diverse institutions.

PubMed

Gregg, Christopher S; Ales, Jo Dale; Pomarico, Steven M; Wischusen, E William; Siebenaller, Joseph F

2013-01-01

We offered four annual professional development workshops called STAR (for Scientific Teaching, Assessment, and Resources) modeled after the National Academies Summer Institute (SI) on Undergraduate Education in Biology. In contrast to the SI focus on training faculty from research universities, STAR's target was faculty from community colleges, 2-yr campuses, and public and private research universities. Because of the importance of community colleges and 2-yr institutions as entries to higher education, we wanted to determine whether the SI model can be successfully extended to this broader range of institutions. We surveyed the four cohorts; 47 STAR alumni responded to the online survey. The responses were separated into two groups based on the Carnegie undergraduate instructional program categories, faculty from seven associate's and associate's-dominant institutions (23) and faculty from nine institutions with primarily 4-yr degree programs (24). Both groups expressed the opinion that STAR had a positive impact on teaching, student learning, and engagement. The two groups reported using techniques of formative assessment and active learning with similar frequency. The mix of faculty from diverse institutions was viewed as enhancing the workshop experience. The present analysis indicates that the SI model for training faculty in scientific teaching can successfully be extended to a broad range of higher education institutions.

Scientific Teaching Targeting Faculty from Diverse Institutions

PubMed Central

Gregg, Christopher S.; Ales, Jo Dale; Pomarico, Steven M.; Wischusen, E. William; Siebenaller, Joseph F.

2013-01-01

We offered four annual professional development workshops called STAR (for Scientific Teaching, Assessment, and Resources) modeled after the National Academies Summer Institute (SI) on Undergraduate Education in Biology. In contrast to the SI focus on training faculty from research universities, STAR's target was faculty from community colleges, 2-yr campuses, and public and private research universities. Because of the importance of community colleges and 2-yr institutions as entries to higher education, we wanted to determine whether the SI model can be successfully extended to this broader range of institutions. We surveyed the four cohorts; 47 STAR alumni responded to the online survey. The responses were separated into two groups based on the Carnegie undergraduate instructional program categories, faculty from seven associate's and associate's-dominant institutions (23) and faculty from nine institutions with primarily 4-yr degree programs (24). Both groups expressed the opinion that STAR had a positive impact on teaching, student learning, and engagement. The two groups reported using techniques of formative assessment and active learning with similar frequency. The mix of faculty from diverse institutions was viewed as enhancing the workshop experience. The present analysis indicates that the SI model for training faculty in scientific teaching can successfully be extended to a broad range of higher education institutions. PMID:24006387

Using a situational judgement test for selection into dental core training: a preliminary analysis.

PubMed

Rowett, E; Patterson, F; Cousans, F; Elley, K

2017-05-12

Objective and setting This paper describes the evaluation of a pilot situational judgement test (SJT) for selection into UK Dental Core Training (DCT). The SJT's psychometric properties, group differences based on gender and ethnicity, and candidate reactions were assessed.Methods The SJT targets four non-academic attributes important for success in DCT. Data were collected alongside live selection processes from five Health Education England local teams in the UK (N = 386). Candidates completed the pilot SJT and an evaluation questionnaire to examine their reactions to the test.Results SJT scores were relatively normally distributed and showed acceptable levels of internal reliability (α = 0.68). Difficulty level and partial correlations between scenarios and SJT total score were in the expected ranges (64.61% to 90.03% and r = 0.06 to 0.41, respectively). No group differences were found for gender, and group differences between White and BME candidates were minimal. Most candidates perceived the SJT as relevant to the target role, appropriate and fair.Conclusions This study demonstrated the potential suitability of an SJT for use in DCT selection. Future research should replicate these preliminary findings in other cohorts, and assess the predictive validity of the SJT for predicting key training and practice-based outcomes.

Secreted Phospholipases A2 from Animal Venoms in Pain and Analgesia

PubMed Central

Zambelli, Vanessa O.; Picolo, Gisele; Fernandes, Carlos A. H.

2017-01-01

Animal venoms comprise a complex mixture of components that affect several biological systems. Based on the high selectivity for their molecular targets, these components are also a rich source of potential therapeutic agents. Among the main components of animal venoms are the secreted phospholipases A2 (sPLA2s). These PLA2 belong to distinct PLA2s groups. For example, snake venom sPLA2s from Elapidae and Viperidae families, the most important families when considering envenomation, belong, respectively, to the IA and IIA/IIB groups, whereas bee venom PLA2 belongs to group III of sPLA2s. It is well known that PLA2, due to its hydrolytic activity on phospholipids, takes part in many pathophysiological processes, including inflammation and pain. Therefore, secreted PLA2s obtained from animal venoms have been widely used as tools to (a) modulate inflammation and pain, uncovering molecular targets that are implicated in the control of inflammatory (including painful) and neurodegenerative diseases; (b) shed light on the pathophysiology of inflammation and pain observed in human envenomation by poisonous animals; and, (c) characterize molecular mechanisms involved in inflammatory diseases. The present review summarizes the knowledge on the nociceptive and antinociceptive actions of sPLA2s from animal venoms, particularly snake venoms. PMID:29311537

The Trajectory and the Related Physical and Social Determinants of Body Mass Index in Elementary School Children: Results from the Child and Adolescent Behaviors in Long-Term Evolution Study

PubMed Central

Chang, Hsing-Yi; Luh, Dih-Ling; Hurng, Baai-Shyun; Yen, Lee-Lan

2014-01-01

This study explored developmental trajectory patterns of BMI and associated factors. Participants included 1,609 students who were followed from age 7 to 12 years. Data collection involved annual self-administered questionnaires and records of height and weight. An ecological model was used to identify the factors associated with BMI trajectories. Group-based trajectory models and multinomial logit models were used in the statistical analysis. There were gender differences in BMI trajectories. Among boys, four BMI trajectories were normal or slightly underweight, persistently normal weight, overweight becoming obese, and persistently obese. Among girls, four BMI trajectories were persistently slightly underweight, persistently normal weight, persistently overweight, and persistently obese. The mean BMI in each trajectory group demonstrated an upward trend over time. In boys, BMI trajectories were significantly associated with after-school exercise, academic performance, family interactions, overweight parents, and father's education level. In girls, BMI trajectories were significantly associated with television viewing or computer use, family interactions, peer interactions, and overweight parents. Children under age 7 years who are already overweight or obese are an important target for interventions. The different factors associated with BMI trajectories can be used for targeting high risk groups. PMID:25114800

MicroRNA signature of the human developing pancreas.

PubMed

Rosero, Samuel; Bravo-Egana, Valia; Jiang, Zhijie; Khuri, Sawsan; Tsinoremas, Nicholas; Klein, Dagmar; Sabates, Eduardo; Correa-Medina, Mayrin; Ricordi, Camillo; Domínguez-Bendala, Juan; Diez, Juan; Pastori, Ricardo L

2010-09-22

MicroRNAs are non-coding RNAs that regulate gene expression including differentiation and development by either inhibiting translation or inducing target degradation. The aim of this study is to determine the microRNA expression signature during human pancreatic development and to identify potential microRNA gene targets calculating correlations between the signature microRNAs and their corresponding mRNA targets, predicted by bioinformatics, in genome-wide RNA microarray study. The microRNA signature of human fetal pancreatic samples 10-22 weeks of gestational age (wga), was obtained by PCR-based high throughput screening with Taqman Low Density Arrays. This method led to identification of 212 microRNAs. The microRNAs were classified in 3 groups: Group number I contains 4 microRNAs with the increasing profile; II, 35 microRNAs with decreasing profile and III with 173 microRNAs, which remain unchanged. We calculated Pearson correlations between the expression profile of microRNAs and target mRNAs, predicted by TargetScan 5.1 and miRBase algorithms, using genome-wide mRNA expression data. Group I correlated with the decreasing expression of 142 target mRNAs and Group II with the increasing expression of 876 target mRNAs. Most microRNAs correlate with multiple targets, just as mRNAs are targeted by multiple microRNAs. Among the identified targets are the genes and transcription factors known to play an essential role in pancreatic development. We have determined specific groups of microRNAs in human fetal pancreas that change the degree of their expression throughout the development. A negative correlative analysis suggests an intertwined network of microRNAs and mRNAs collaborating with each other. This study provides information leading to potential two-way level of combinatorial control regulating gene expression through microRNAs targeting multiple mRNAs and, conversely, target mRNAs regulated in parallel by other microRNAs as well. This study may further the understanding of gene expression regulation in the human developing pancreas.

MicroRNA signature of the human developing pancreas

PubMed Central

2010-01-01

Background MicroRNAs are non-coding RNAs that regulate gene expression including differentiation and development by either inhibiting translation or inducing target degradation. The aim of this study is to determine the microRNA expression signature during human pancreatic development and to identify potential microRNA gene targets calculating correlations between the signature microRNAs and their corresponding mRNA targets, predicted by bioinformatics, in genome-wide RNA microarray study. Results The microRNA signature of human fetal pancreatic samples 10-22 weeks of gestational age (wga), was obtained by PCR-based high throughput screening with Taqman Low Density Arrays. This method led to identification of 212 microRNAs. The microRNAs were classified in 3 groups: Group number I contains 4 microRNAs with the increasing profile; II, 35 microRNAs with decreasing profile and III with 173 microRNAs, which remain unchanged. We calculated Pearson correlations between the expression profile of microRNAs and target mRNAs, predicted by TargetScan 5.1 and miRBase altgorithms, using genome-wide mRNA expression data. Group I correlated with the decreasing expression of 142 target mRNAs and Group II with the increasing expression of 876 target mRNAs. Most microRNAs correlate with multiple targets, just as mRNAs are targeted by multiple microRNAs. Among the identified targets are the genes and transcription factors known to play an essential role in pancreatic development. Conclusions We have determined specific groups of microRNAs in human fetal pancreas that change the degree of their expression throughout the development. A negative correlative analysis suggests an intertwined network of microRNAs and mRNAs collaborating with each other. This study provides information leading to potential two-way level of combinatorial control regulating gene expression through microRNAs targeting multiple mRNAs and, conversely, target mRNAs regulated in parallel by other microRNAs as well. This study may further the understanding of gene expression regulation in the human developing pancreas. PMID:20860821

Who Should We Target? The Impact of Individual and Family Characteristics on the Expressed Need for Community-Based Treatment Support in HIV Patients in South Africa.

PubMed

Wouters, Edwin; Booysen, Frederik le Roux; Masquillier, Caroline

2016-01-01

Reviews of impact evaluations of community-based health workers and peer support groups highlight the considerable variability in the effectiveness of such support in improving antiretroviral treatment (ART) outcomes. Evidence indicates that community-based support interventions targeting patients known to be at risk will probably display better results than generic interventions aimed at the entire population of people living with HIV. It is however difficult to identify these at-risk populations, rendering knowledge on the characteristics of patients groups who are in need of community-based support a clear research priority. The current study aims to address the knowledge gap by exploring the predictors of the willingness to (1) receive the support from a community-based health worker or (2) to participate in a support group in public sector ART programme of the Free State Province of South Africa. Based on the Individual-Family-Community framework for HIV research, the study employs a comprehensive approach by not only testing classical individual-level but also family-level predictors of the willingness to receive community-based support. In addition to individual-level predictors-such as age, health status and coping styles-our analysis demonstrated the importance of family characteristics. The results indicated that discrepancies in the family's changeability level were an important predictor of the demand for community-based support services. Conversely, the findings indicated that patients living in a family more flexible than deemed ideal are more likely to require the support of a community health worker. The current study expands theory by indicating the need to acknowledge all social ecological levels in the study of chronic HIV care. The detection of both individual level and family level determinants of the expressed need for community-based support can inform health policy to devise strategies to target scarce resources to those vulnerable patients who report the greatest need for this support. In this way, the study results are a first step in an attempt to move away from generic, broad based community-based interventions towards community support that is tailored to the patient needs at both the individual and family level.

The needs and preferences of pregnant smokers regarding tailored Internet-based smoking cessation interventions: a qualitative interview study.

PubMed

Herbec, Aleksandra; Beard, Emma; Brown, Jamie; Gardner, Benjamin; Tombor, Ildiko; West, Robert

2014-10-14

Internet-based Smoking Cessation Interventions (ISCIs) may help pregnant smokers who are unable, or unwilling, to access face-to-face stop smoking support. Targeting ISCIs to specific groups of smokers could increase their uptake and effectiveness. The current study explored the needs and preferences of pregnant women seeking online stop smoking support with an aim to identify features and components of ISCIs that might be most attractive to this population. We conducted qualitative interviews with thirteen pregnant women who completed the intervention arm of a pilot randomized controlled trial of a novel ISCI for pregnant smokers ('MumsQuit'). The interviews explored women's views towards MumsQuit and online support with quitting smoking in general, as well as their suggestions for how ISCIs could be best targeted to pregnancy. Interview transcripts were analyzed using Framework Analysis. Participants expressed preferences for an accessible, highly engaging and targeted to pregnancy smoking cessation website, tailored to individuals' circumstances as well as use of cessation medication, offering comprehensive and novel information on smoking and quitting smoking in pregnancy, ongoing support with cravings management, as well as additional support following relapse to smoking. Participants also viewed as important targeting of the feedback and progress reports to baby's health and development, offering personal support from experts, and providing a discussion forum allowing for communication with other pregnant women wanting to quit . The present study has identified a number of potential building blocks for ISCIs targeted to quitting smoking in pregnancy. Pregnant smokers willing to try using ISCI may particularly value an engaging intervention offering a high degree of targeting of comprehensive information to them as a group and tailoring support and advice to their individual needs, as well as one providing post-relapse support, peer-to-peer communication and personal support from experts.

Effects of benchmarking on the quality of type 2 diabetes care: results of the OPTIMISE (Optimal Type 2 Diabetes Management Including Benchmarking and Standard Treatment) study in Greece

PubMed Central

Tsimihodimos, Vasilis; Kostapanos, Michael S.; Moulis, Alexandros; Nikas, Nikos; Elisaf, Moses S.

2015-01-01

Objectives: To investigate the effect of benchmarking on the quality of type 2 diabetes (T2DM) care in Greece. Methods: The OPTIMISE (Optimal Type 2 Diabetes Management Including Benchmarking and Standard Treatment) study [ClinicalTrials.gov identifier: NCT00681850] was an international multicenter, prospective cohort study. It included physicians randomized 3:1 to either receive benchmarking for glycated hemoglobin (HbA1c), systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) treatment targets (benchmarking group) or not (control group). The proportions of patients achieving the targets of the above-mentioned parameters were compared between groups after 12 months of treatment. Also, the proportions of patients achieving those targets at 12 months were compared with baseline in the benchmarking group. Results: In the Greek region, the OPTIMISE study included 797 adults with T2DM (570 in the benchmarking group). At month 12 the proportion of patients within the predefined targets for SBP and LDL-C was greater in the benchmarking compared with the control group (50.6 versus 35.8%, and 45.3 versus 36.1%, respectively). However, these differences were not statistically significant. No difference between groups was noted in the percentage of patients achieving the predefined target for HbA1c. At month 12 the increase in the percentage of patients achieving all three targets was greater in the benchmarking (5.9–15.0%) than in the control group (2.7–8.1%). In the benchmarking group more patients were on target regarding SBP (50.6% versus 29.8%), LDL-C (45.3% versus 31.3%) and HbA1c (63.8% versus 51.2%) at 12 months compared with baseline (p < 0.001 for all comparisons). Conclusion: Benchmarking may comprise a promising tool for improving the quality of T2DM care. Nevertheless, target achievement rates of each, and of all three, quality indicators were suboptimal, indicating there are still unmet needs in the management of T2DM. PMID:26445642

Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides.

PubMed

Nakajima, Minami; Oda, Yukiko; Wada, Takamasa; Minamikawa, Ryo; Shirokane, Kenji; Sato, Takaaki; Chida, Noritaka

2014-12-22

As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide carbonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor electrophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nucleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2 ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Algorithm for covert convoy of a moving target using a group of autonomous robots

NASA Astrophysics Data System (ADS)

Polyakov, Igor; Shvets, Evgeny

2018-04-01

An important application of autonomous robot systems is to substitute human personnel in dangerous environments to reduce their involvement and subsequent risk on human lives. In this paper we solve the problem of covertly convoying a civilian in a dangerous area with a group of unmanned ground vehicles (UGVs) using social potential fields. The novelty of our work lies in the usage of UGVs as compared to the unmanned aerial vehicles typically employed for this task in the approaches described in literature. Additionally, in our paper we assume that the group of UGVs should simultaneously solve the problem of patrolling to detect intruders on the area. We develop a simulation system to test our algorithms, provide numerical results and give recommendations on how to tune the potentials governing robots' behaviour to prioritize between patrolling and convoying tasks.

The cross-category effect: mere social categorization is sufficient to elicit an own-group bias in face recognition.

PubMed

Bernstein, Michael J; Young, Steven G; Hugenberg, Kurt

2007-08-01

Although the cross-race effect (CRE) is a well-established phenomenon, both perceptual-expertise and social-categorization models have been proposed to explain the effect. The two studies reported here investigated the extent to which categorizing other people as in-group versus out-group members is sufficient to elicit a pattern of face recognition analogous to that of the CRE, even when perceptual expertise with the stimuli is held constant. In Study 1, targets were categorized as members of real-life in-groups and out-groups (based on university affiliation), whereas in Study 2, targets were categorized into experimentally created minimal groups. In both studies, recognition performance was better for targets categorized as in-group members, despite the fact that perceptual expertise was equivalent for in-group and out-group faces. These results suggest that social-cognitive mechanisms of in-group and out-group categorization are sufficient to elicit performance differences for in-group and out-group face recognition.

Comparing the impact of personal and parental risk factors, and parental lifespan on all-cause mortality and cardiovascular disease: findings from the Midspan Family cohort study.

PubMed

Hart, Carole; McCartney, Gerry; Gruer, Laurence; Watt, Graham

2015-10-01

We aimed to identify which personal and parental factors best explained all-cause mortality and cardiovascular disease (CVD). In 1996, data were collected on 2338 adult offspring of the participants in the 1972-1976 Renfrew and Paisley prospective cohort study. Recorded risk factors were assigned to 5 groups: mid-life biological and behavioural (BB), mid-life socioeconomic, parental BB, early-life socioeconomic and parental lifespan. Participants were followed up for mortality and hospital admissions to the end of 2011. Cox proportional hazards models were used to analyse how well each group explained all-cause mortality or CVD. Akaike's Information Criterion (AIC), a measure of goodness-of-fit, identified the most important groups. For all-cause mortality (1997 participants with complete data, 111 deaths), decreases in AIC from the null model (adjusting for age and sex) to models including mid-life BB, mid-life socioeconomic, parental BB, early-life socioeconomic and parental lifespan were 55.8, 21.6, 10.3, 7.3 and 5.9, respectively. For the CVD models (1736 participants, 276 with CVD), decreases were 37.8, 3.7, 6.7, 17.3 and 0.4. Mid-life BB factors were the most important for both all-cause mortality and CVD; mid-life socioeconomic factors were important for all-cause mortality, and early-life socioeconomic factors were important for CVD. Parental lifespan was the weakest factor. As mid-life BB risk factors best explained all-cause mortality and CVD, continued action to reduce these is warranted. Targeting adverse socioeconomic factors in mid-life and early life may contribute to reducing all-cause mortality and CVD risk, respectively. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Radiolabeled Cyclic RGD Peptides as Radiotracers for Imaging Tumors and Thrombosis by SPECT

PubMed Central

Zhou, Yang; Chakraborty, Sudipta; Liu, Shuang

2011-01-01

The integrin family is a group of transmembrane glycoprotein comprised of 19 α- and 8 β-subunits that are expressed in 25 different α/β heterodimeric combinations on the cell surface. Integrins play critical roles in many physiological processes, including cell attachment, proliferation, bone remodeling, and wound healing. Integrins also contribute to pathological events such as thrombosis, atherosclerosis, tumor invasion, angiogenesis and metastasis, infection by pathogenic microorganisms, and immune dysfunction. Among 25 members of the integrin family, the αvβ3 is studied most extensively for its role of tumor growth, progression and angiogenesis. In contrast, the αIIbβ3 is expressed exclusively on platelets, facilitates the intercellular bidirectional signaling (“inside-out” and “outside-in”) and allows the aggregation of platelets during vascular injury. The αIIbβ3 plays an important role in thrombosis by its activation and binding to fibrinogen especially in arterial thrombosis due to the high blood flow rate. In the resting state, the αIIbβ3 on platelets does not bind to fibrinogen; on activation, the conformation of platelet is altered and the binding sites of αIIbβ3 are exposed for fibrinogen to crosslink platelets. Over the last two decades, integrins have been proposed as the molecular targets for diagnosis and therapy of cancer, thrombosis and other diseases. Several excellent review articles have appeared recently to cover a broad range of topics related to the integrin-targeted radiotracers and their nuclear medicine applications in tumor imaging by single photon emission computed tomography (SPECT) or a positron-emitting radionuclide for positron emission tomography (PET). This review will focus on recent developments of αvβ3-targeted radiotracers for imaging tumors and the use of αIIbβ3-targeted radiotracers for thrombosis imaging, and discuss different approaches to maximize the targeting capability of cyclic RGD peptides and improve the radiotracer excretion kinetics from non-cancerous organs. Improvement of target uptake and target-to-background ratios is critically important for target-specific radiotracers. PMID:21547153