Nurse opinions and pulse oximeter saturation target limits for preterm infants.

PubMed

Nghiem, Tuyet-Hang; Hagadorn, James I; Terrin, Norma; Syke, Sally; MacKinnon, Brenda; Cole, Cynthia H

2008-05-01

The objectives of this study were to compare pulse oximeter saturation limits targeted by nurses for extremely preterm infants during routine care with nurse opinions regarding appropriate pulse oximeter saturation limits and with policy-specified pulse oximeter saturation limits and to identify factors that influence pulse oximeter saturation limits targeted by nurses. We surveyed nurses in US NICUs with neonatal-perinatal fellowships in 2004. Data collected included pulse oximeter saturation limits targeted by nurses and by NICU policy when present, nurses' opinions about appropriate pulse oximeter saturation limits, and NICU and nurse characteristics. Factors associated with pulse oximeter saturation limits targeted by nurses were identified with hierarchical linear modeling. Among those eligible, 2805 (45%) nurses in 59 (60%) NICUs responded. Forty (68%) of 59 NICUs had a policy that specified a pulse oximeter saturation target range for extremely preterm infants. Among 1957 nurses at NICUs with policies, 540 (28%) accurately identified the upper and lower limits of their NICU's policy and also targeted these values in practice. NICU-specific SDs for individual nurse target limits were less at NICUs with versus without a policy for both upper and lower limits. Hierarchical linear modeling identified presence of pulse oximeter saturation policy, NICU-specific nurse group opinion, and individual nurse opinion as factors significantly associated with individual pulse oximeter saturation target limits. For each percentage point increase in individual opinion upper limit, the individual target upper limit increased by 0.41 percentage point at NICUs with a policy compared with 0.6 percentage point at NICUs with no policy. Presence of policy-specified pulse oximeter saturation limits, nurse group opinion, and individual nurse opinion were independently associated with individual nurse pulse oximeter saturation target limits during routine care of extremely preterm infants. The presence of a policy reduced the influence of individual nurse opinion on targeted pulse oximeter saturation limits and reduced variation among nurse target limits within NICUs.

Attentional Blink Impairment in Social Anxiety Disorder: Depression Comorbidity Matters

PubMed Central

Morrison, Amanda S.; Brozovich, Faith A.; Lakhan-Pal, Shreya; Jazaieri, Hooria; Goldin, Philippe R.; Heimberg, Richard G.; Gross, James J.

2015-01-01

Background and Objectives Difficulties with attentional control have long been thought to play a key role in anxiety and depressive disorders. However, the nature and extent of attentional control difficulties in social anxiety disorder (SAD) are not yet well understood. The current study was designed to assess whether attentional control for non-emotional information is impaired in SAD when taking comorbid depression into account. Methods Individuals with SAD and healthy controls (HCs) were administered an attentional blink (AB) task in which they identified number targets in a rapid serial visual presentation stream of letters. Results Individuals with SAD and current comorbid depression exhibited reduced accuracy to identify a target that fell within the AB window after the presentation of a first target compared to individuals with SAD without current comorbid depression, as well as to HCs. The latter two groups did not differ from each other, and the three groups did not differ in accuracy for the second target when it was presented after the AB window. Limitations Although we included two clinical groups and the sample size for the noncomorbid SAD group was large, the comorbid SAD group was relatively small. Conclusions These results suggest that impaired attentional control among individuals with SAD may be limited to those suffering from current comorbid depression. PMID:26370394

Motivation of restraint system usage among specific target groups of drivers and passengers

DOT National Transportation Integrated Search

1983-07-14

Thirty focus groups were conducted in seven different cities. These focus groups were used to determine potentially effective motivational approaches, develop appropriate themes and general content of messages and, finally, to identify corresponding ...

Strategic planning to reduce conflicts for offshore wind development in Taiwan: A social marketing perspective.

PubMed

Chen, Jyun-Long; Liu, Hsiang-Hsi; Chuang, Ching-Ta

2015-10-15

This study aims to improve the current inefficiency and ineffectiveness of communications among stakeholders when planning and constructing offshore wind farms (OWFs). An analysis using a social marketing approach with segmentation techniques is used to identify the target market based on stakeholders' perceptions. The empirical results identify three stakeholder segments: (1) impact-attend group; (2) comprehensive group; and (3) benefit-attend group. The results suggest that communication should be implemented to alter stakeholders' attitudes toward the construction of OWFs. Furthermore, based on the results of segmentation, target markets are identified to plan the communication strategies for reducing the conflicts among stakeholders of OWF construction. The results also indicated that in the planning phase of construction for OWFs, effective stakeholder participation and policy communication can enhance the perception of benefits to reduce conflict with local communities and ocean users. Copyright © 2015 Elsevier Ltd. All rights reserved.

A systematic review on US-based community health navigator (CHN) interventions for cancer screening promotion--comparing community- versus clinic-based navigator models.

PubMed

Hou, Su-I; Roberson, Kiersten

2015-03-01

This study synthesized lessons learned from US-based community and clinic health navigator (CHN) interventions on cancer screening promotion to identify characteristics of models and approaches for addressing cancer disparities. The combination terms "cancer screening" and "community health workers or navigators" or "patient navigators" were used in searching Medline, CINAHL, and PsycInfo. A total of 27 articles published during January 2005∼April 2014 were included. Two CHN models were identified: community-based (15 studies) and clinic/hospital-based (12 studies). While both models used the term "navigators," most community-based programs referred them as community health workers/navigators/advisors, whereas clinic-based programs often called them patient navigators. Most community-based CHN interventions targeted specific racial/ethnic minority or rural groups, while clinic-based programs mostly targeted urban low income or mixed ethnic groups. Most community-based CHN programs outreached members from community networks, while clinic-based programs commonly worked with pre-identified in-service clients. Overall, regardless model type, CHNs had similar roles and responsibilities, and interventions demonstrated effective outcomes. Our review identified characteristics of CHN interventions with attention to different settings. Lessons learned have implication on the dissemination and implementation of CHN interventions for cancer screening promotion across setting and target groups.

Mechanisms Used for Genomic Proliferation by Thermophilic Group II Introns

PubMed Central

Mohr, Georg; Ghanem, Eman; Lambowitz, Alan M.

2010-01-01

Mobile group II introns, which are found in bacterial and organellar genomes, are site-specific retroelments hypothesized to be evolutionary ancestors of spliceosomal introns and retrotransposons in higher organisms. Most bacteria, however, contain no more than one or a few group II introns, making it unclear how introns could have proliferated to higher copy numbers in eukaryotic genomes. An exception is the thermophilic cyanobacterium Thermosynechococcus elongatus, which contains 28 closely related copies of a group II intron, constituting ∼1.3% of the genome. Here, by using a combination of bioinformatics and mobility assays at different temperatures, we identified mechanisms that contribute to the proliferation of T. elongatus group II introns. These mechanisms include divergence of DNA target specificity to avoid target site saturation; adaptation of some intron-encoded reverse transcriptases to splice and mobilize multiple degenerate introns that do not encode reverse transcriptases, leading to a common splicing apparatus; and preferential insertion within other mobile introns or insertion elements, which provide new unoccupied sites in expanding non-essential DNA regions. Additionally, unlike mesophilic group II introns, the thermophilic T. elongatus introns rely on elevated temperatures to help promote DNA strand separation, enabling access to a larger number of DNA target sites by base pairing of the intron RNA, with minimal constraint from the reverse transcriptase. Our results provide insight into group II intron proliferation mechanisms and show that higher temperatures, which are thought to have prevailed on Earth during the emergence of eukaryotes, favor intron proliferation by increasing the accessibility of DNA target sites. We also identify actively mobile thermophilic introns, which may be useful for structural studies, gene targeting in thermophiles, and as a source of thermostable reverse transcriptases. PMID:20543989

77 FR 46092 - Agency Information Collection Activities; Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-02

... at www.admongo.gov . The proposed evaluation will test a large group of students in these skills and..., one hour of online game playing, one hour of homework assignments, and 20 minutes for the test). With... specific skills: How to identify ads, how to identify the ways advertisers target certain groups of...

Initiatives on early detection and intervention to proactively identify health and social problems in older people: experiences from the Netherlands.

PubMed

Lette, Manon; Baan, Caroline A; van den Berg, Matthijs; de Bruin, Simone R

2015-10-30

Over the last years, several initiatives on early detection and intervention have been put in place to proactively identify health and social problems in (frail) older people. An overview of the initiatives currently available in the Netherlands is lacking, and it is unknown whether they meet the preferences and needs of older people. Therefore, the objectives of this study were threefold: 1. To identify initiatives on early detection and intervention for older people in the Netherlands and compare their characteristics; 2. To explore the experiences of professionals with these initiatives; and 3. To explore to what extent existing initiatives meet the preferences and needs of older people. We performed a qualitative descriptive study in which we conducted semi-structured interviews with seventeen experts in preventive elderly care and three group interviews with volunteer elderly advisors. Data were analysed using the framework analysis method. We identified eight categories of initiatives based on the setting (e.g. general practitioner practice, hospital, municipality) in which they were offered. Initiatives differed in their aims and target groups. The utilization of peers to identify problems and risks, as was done by some initiatives, was seen as a strength. Difficulties were experienced with identifying the target group that would benefit from proactive delivery of care and support most, and with addressing prevalent issues among older people (e.g. psychosocial issues, self-reliance issues). Although there is a broad array of initiatives available, there is a discrepancy between supply and demand. Current initiatives insufficiently address needs of (frail) older people. More insight is needed in "what should be done by whom, for which target group and at what moment", in order to improve current practice in preventive elderly care.

Contrast-Enhanced Computed Tomography Evaluation of Hepatic Metastases in Breast Cancer Patients Before and After Cytotoxic Chemotherapy or Targeted Therapy.

PubMed

He, Hongying; Cai, Chunyan; Charnsangavej, Chusilp; Theriault, Richard L; Green, Marjorie; Quraishi, Mohammad A; Yang, Wei T

2015-11-01

To evaluate change in size vs computed tomography (CT) density of hepatic metastases in breast cancer patients before and after cytotoxic chemotherapy or targeted therapy. A database search in a single institution identified 48 breast cancer patients who had hepatic metastases treated with either cytotoxic chemotherapy alone or targeted therapy alone, and who had contrast-enhanced CT (CECT) scans of the abdomen at baseline and within 4 months of initiation of therapy in the past 10 years. Two radiologists retrospectively evaluated CT scans and identified up to 2 index lesions in each patient. The size (centimeters) of each lesion was measured according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and CT density (Hounsfield units) was measured by drawing a region of interest around the margin of the entire lesion. The percent change in sum of lesion size and mean CT density on pre- and post-treatment scans was computed for each patient; results were compared within each treatment group. Thirty-nine patients with 68 lesions received cytotoxic chemotherapy only; 9 patients with 15 lesions received targeted therapy only. The mean percent changes in sum of lesion size and mean CT density were statistically significant within the cytotoxic chemotherapy group before and after treatment, but not significant in the targeted therapy group. The patients in the targeted therapy group tend to have better 2-year survival. The patients who survived at 2 years tend to have more decrease in tumour size in the cytotoxic chemotherapy group. Cytotoxic chemotherapy produced significant mean percent decrease in tumour size and mean CT density of hepatic metastases from breast cancer before and after treatment, whereas targeted therapy did not. Nonetheless, there is a trend that the patients in the targeted therapy group had better 2-year survival rate. This suggests that RECIST is potentially inadequate in evaluating tumour response in breast cancer liver metastases treated with targeted therapy alone, calling for an alternative marker for response evaluation in this subset of patients. Copyright © 2015 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Target marketing strategies for occupational therapy entrepreneurs.

PubMed

Kautzmann, L N; Kautzmann, F N; Navarro, F H

1989-01-01

Understanding marketing techniques is one of the skills needed by successful entre renews. Target marketing is an effective method for occupational therapy entrepreneurs to use in determining when and where to enter the marketplace. The two components of target marketing, market segmentation and the development of marketing mix strategies for each identified market segment, are described. The Profife of Attitudes Toward Health Care (PATH) method of psychographic market segmentation of health care consumers is presented. Occupational therapy marketing mix strategies for each PATH consumer group are delineated and compatible groupings of market segments are suggested.

Characterizing Blood Metabolomics Profiles Associated with Self-Reported Food Intakes in Female Twins

PubMed Central

Pallister, Tess; Jennings, Amy; Mohney, Robert P.; Yarand, Darioush; Mangino, Massimo; Cassidy, Aedin; MacGregor, Alexander; Spector, Tim D.; Menni, Cristina

2016-01-01

Using dietary biomarkers in nutritional epidemiological studies may better capture exposure and improve the level at which diet-disease associations can be established and explored. Here, we aimed to identify and evaluate reproducibility of novel biomarkers of reported habitual food intake using targeted and non-targeted metabolomic blood profiling in a large twin cohort. Reported intakes of 71 food groups, determined by FFQ, were assessed against 601 fasting blood metabolites in over 3500 adult female twins from the TwinsUK cohort. For each metabolite, linear regression analysis was undertaken in the discovery group (excluding MZ twin pairs discordant [≥1 SD apart] for food group intake) with each food group as a predictor adjusting for age, batch effects, BMI, family relatedness and multiple testing (1.17x10-6 = 0.05/[71 food groups x 601 detected metabolites]). Significant results were then replicated (non-targeted: P<0.05; targeted: same direction) in the MZ discordant twin group and results from both analyses meta-analyzed. We identified and replicated 180 significant associations with 39 food groups (P<1.17x10-6), overall consisting of 106 different metabolites (74 known and 32 unknown), including 73 novel associations. In particular we identified trans-4-hydroxyproline as a potential marker of red meat intake (0.075[0.009]; P = 1.08x10-17), ergothioneine as a marker of mushroom consumption (0.181[0.019]; P = 5.93x10-22), and three potential markers of fruit consumption (top association: apple and pears): including metabolites derived from gut bacterial transformation of phenolic compounds, 3-phenylpropionate (0.024[0.004]; P = 1.24x10-8) and indolepropionate (0.026[0.004]; P = 2.39x10-9), and threitol (0.033[0.003]; P = 1.69x10-21). With the largest nutritional metabolomics dataset to date, we have identified 73 novel candidate biomarkers of food intake for potential use in nutritional epidemiological studies. We compiled our findings into the DietMetab database (http://www.twinsuk.ac.uk/dietmetab-data/), an online tool to investigate our top associations. PMID:27355821

Characterizing Blood Metabolomics Profiles Associated with Self-Reported Food Intakes in Female Twins.

PubMed

Pallister, Tess; Jennings, Amy; Mohney, Robert P; Yarand, Darioush; Mangino, Massimo; Cassidy, Aedin; MacGregor, Alexander; Spector, Tim D; Menni, Cristina

2016-01-01

Using dietary biomarkers in nutritional epidemiological studies may better capture exposure and improve the level at which diet-disease associations can be established and explored. Here, we aimed to identify and evaluate reproducibility of novel biomarkers of reported habitual food intake using targeted and non-targeted metabolomic blood profiling in a large twin cohort. Reported intakes of 71 food groups, determined by FFQ, were assessed against 601 fasting blood metabolites in over 3500 adult female twins from the TwinsUK cohort. For each metabolite, linear regression analysis was undertaken in the discovery group (excluding MZ twin pairs discordant [≥1 SD apart] for food group intake) with each food group as a predictor adjusting for age, batch effects, BMI, family relatedness and multiple testing (1.17x10-6 = 0.05/[71 food groups x 601 detected metabolites]). Significant results were then replicated (non-targeted: P<0.05; targeted: same direction) in the MZ discordant twin group and results from both analyses meta-analyzed. We identified and replicated 180 significant associations with 39 food groups (P<1.17x10-6), overall consisting of 106 different metabolites (74 known and 32 unknown), including 73 novel associations. In particular we identified trans-4-hydroxyproline as a potential marker of red meat intake (0.075[0.009]; P = 1.08x10-17), ergothioneine as a marker of mushroom consumption (0.181[0.019]; P = 5.93x10-22), and three potential markers of fruit consumption (top association: apple and pears): including metabolites derived from gut bacterial transformation of phenolic compounds, 3-phenylpropionate (0.024[0.004]; P = 1.24x10-8) and indolepropionate (0.026[0.004]; P = 2.39x10-9), and threitol (0.033[0.003]; P = 1.69x10-21). With the largest nutritional metabolomics dataset to date, we have identified 73 novel candidate biomarkers of food intake for potential use in nutritional epidemiological studies. We compiled our findings into the DietMetab database (http://www.twinsuk.ac.uk/dietmetab-data/), an online tool to investigate our top associations.

Communicating with nonindustrial private forest-land owners: Getting programs on target

Treesearch

Thomas W. Birch; Nancy A. Pywell; Nancy A. Pywell

1986-01-01

Nonindustrial private forest-land owners can be motivated 1, by programs directed to their needs and objectives. Seven target audiences in Pennsylvania were defined and outlets for information programs identified for each target I audience. The primary objectives of each group and the benefits they expect from owning forest land were considered in the preparation of...

Finding future high-cost cases: comparing prior cost versus diagnosis-based methods.

PubMed Central

Ash, A S; Zhao, Y; Ellis, R P; Schlein Kramer, M

2001-01-01

OBJECTIVE: To examine the value of two kinds of patient-level dat a (cost and diagnoses) for identifying a very small subgroup of a general population with high future costs that may be mitigated with medical management. DATA SOURCES: The study used the MEDSTAT Market Scan (R) Research Database, consisting of inpatient and ambulatory health care encounter records for individuals covered by employee- sponsored benefit plans during 1997 and 1998. STUDY DESIGN: Prior cost and a diagnostic cost group (DCG) risk model were each used with 1997 data to identify 0.5-percent-sized "top groups" of people most likely to be expensive in 1998. We compared the distributions of people, cost, and diseases commonly targeted for disease management for people in the two top groups and, as a bench mark, in the full population. PRINCIPAL FINDINGS: the prior cost- and DCG-identified top groups overlapped by only 38 percent. Each top group consisted of people with high year-two costs and high rates of diabetes, heart failure, major lung disease, and depression. The DCG top group identified people who are both somewhat more expensive ($27,292 vs. $25,981) and more likely ( 49.4 percent vs. 43.8 percent ) th an the prior-cost top group to have at least one of the diseases commonly targeted for disease management. The overlap group average cost was $46,219. CONCLUSIONS: Diagnosis-based risk models are at least as powerful as prior cost for identifying people who will be expensive. Combined cost and diagnostic data are even more powerful and more operation ally useful, especially because the diagnostic information identifies the medical problems that may be managed to achieve better out comes and lower costs. PMID:16148969

Receptor Diversity and Host Interaction of Bacteriophages Infecting Salmonella enterica Serovar Typhimurium

PubMed Central

Kim, Hyeryen; Choi, Younho; Heu, Sunggi; Ryu, Sangryeol

2012-01-01

Background Salmonella enterica subspecies enterica serovar Typhimurium is a Gram-negative pathogen causing salmonellosis. Salmonella Typhimurium-targeting bacteriophages have been proposed as an alternative biocontrol agent to antibiotics. To further understand infection and interaction mechanisms between the host strains and the bacteriophages, the receptor diversity of these phages needs to be elucidated. Methodology/Principal Findings Twenty-five Salmonella phages were isolated and their receptors were identified by screening a Tn5 random mutant library of S. Typhimurium SL1344. Among them, three types of receptors were identified flagella (11 phages), vitamin B12 uptake outer membrane protein, BtuB (7 phages) and lipopolysaccharide-related O-antigen (7 phages). TEM observation revealed that the phages using flagella (group F) or BtuB (group B) as a receptor belong to Siphoviridae family, and the phages using O-antigen of LPS as a receptor (group L) belong to Podoviridae family. Interestingly, while some of group F phages (F-I) target FliC host receptor, others (F-II) target both FliC and FljB receptors, suggesting that two subgroups are present in group F phages. Cross-resistance assay of group B and L revealed that group L phages could not infect group B phage-resistant strains and reversely group B phages could not infect group L SPN9TCW-resistant strain. Conclusions/Significance In this report, three receptor groups of 25 newly isolated S. Typhimurium-targeting phages were determined. Among them, two subgroups of group F phages interact with their host receptors in different manner. In addition, the host receptors of group B or group L SPN9TCW phages hinder other group phage infection, probably due to interaction between receptors of their groups. This study provides novel insights into phage-host receptor interaction for Salmonella phages and will inform development of optimal phage therapy for protection against Salmonella. PMID:22927964

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.

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.

Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells.

PubMed

De Bellis, A; Sinisi, A A; Pane, E; Dello Iacovo, A; Bellastella, G; Di Scala, G; Falorni, A; Giavoli, C; Gasco, V; Giordano, R; Ambrosio, M R; Colao, A; Bizzarro, A; Bellastella, A

2012-10-01

Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. We conducted a cross-sectional cohort study. Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

The whole-genome landscape of medulloblastoma subtypes.

PubMed

Northcott, Paul A; Buchhalter, Ivo; Morrissy, A Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Gröbner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa A; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M; Erkek, Serap; Jones, David T W; Worst, Barbara C; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D; Wolf, Stephan; Robinson, Giles W; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M G; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M; Mora, Jaume; McLendon, Roger E; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A; Mungall, Andrew J; Mungall, Karen L; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J M; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A; Pfister, Stefan M; Taylor, Michael D; Lichter, Peter

2017-07-19

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

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.

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

Proteomic Identification of Non-Gal Antibody Targets After Pig-to-Primate Cardiac Xenotransplantation

PubMed Central

Byrne, Guerard W.; Stalboerger, Paul G.; Davila, Eduardo; Heppelmann, Carrie J.; Gazi, Mozammel H.; McGregor, Hugh C. J.; LaBreche, Peter T.; Davies, William R.; Rao, Vinay P.; Oi, Keiji; Tazelaar, Henry D.; Logan, John S.; McGregor, Christopher G. A.

2008-01-01

Background Experience with non-antigenic galactose α1,3 galactose (αGal) polymers and development of αGal deficient pigs has reduced or eliminated the significance of this antigen in xenograft rejection. Despite these advances, delayed xenograft rejection (DXR) continues to occur most likely due to antibody responses to non-Gal endothelial cell (EC) antigens. Methods To gauge the diversity of the non-Gal antibody response we used antibody derived from CD46 transgenic heterotopic cardiac xenografts performed without T-cell immunosuppression, Group A (n = 4) and Gal knockout (GT-KO) heart transplants under tacrolimus and sirolimus immunosuppression, Group B (n = 8). Non-Gal antibody was measured by flow cytometry and by Western blots using GT-KO EC membrane antigens. A nanoLC/MS/MS analysis of proteins recovered from 2D gels was used to identify target antigens. Results Group A recipients exhibited a mixed cellular and humoral rejection. Group B recipients mainly exhibited classical DXR. Western blot analysis showed a non-Gal antibody response induced by GT+ and GT-KO hearts to an overlapping set of pig aortic EC membrane antigens. Proteomic analysis identified 14 potential target antigens but failed to define several immunodominant targets. Conclusions These experiments indicate that the non-Gal antibody response is directed to a number of stress response and inflammation related pig EC antigens and a few undefined targets. Further analysis of these antibody specificities using alternative methods is required to more fully define the repertoire of non-Gal antibody responses. PMID:18957049

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.

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.

Evaluating remote sensing methods for targeting erosion in riparian corridors

USDA-ARS?s Scientific Manuscript database

State agencies in the United States and other groups developing water quality programs have begun using satellite imagery with hydrologic/water quality modeling to identify possible critical source areas of erosion. To optimize the use of available funds, quantitative targeting of areas with the hig...

Wellness at work. Boost wellness center participation with target marketing strategies.

PubMed

DeMoranville, C W; Schoenbachler, D D; Przytulski, J

1998-01-01

By using target marketing strategies, corporate wellness programs can increase employee participation rates and tailor activities to meet employee needs. The authors examined this issue through a research survey that segmented a university's staff and employee population into three wellness program groups: High Participators, Moderate Participators, and Low Participators. Participators' views on the following issues were analyzed: health management programs, exercise programs, wellness center use inhibitors, wellness center use incentives, wellness center communications, and willingness to pay for the wellness center. The results identified unique lifestyle characteristics for each group that can help make target marketing strategies effective.

Identifying members of the domain Archaea with rRNA-targeted oligonucleotide probes.

PubMed

Burggraf, S; Mayer, T; Amann, R; Schadhauser, S; Woese, C R; Stetter, K O

1994-09-01

Two 16S rRNA-targeted oligonucleotide probes were designed for the archaeal kingdoms Euryachaeota and Crenarchaeota. Probe specificities were evaluated by nonradioactive dot blot hybridization against selected reference organisms. The successful application of fluorescent-probe derivatives for whole-cell hybridization required organism-specific optimizations of fixation and hybridization conditions to assure probe penetration and morphological integrity of the cells. The probes allowed preliminary grouping of three new hyperthermophilic isolates. Together with other group-specific rRNA-targeted oligonucleotide probes, these probes will facilitate rapid in situ monitoring of the populations present in hydrothermal systems and support cultivation attempts.

Functional Significance of Conflicting Age and Wealth Cross-Categorization: The Dominant Role of Categories That Violate Stereotypical Expectations

PubMed Central

Song, Jingjing; Zuo, Bin

2016-01-01

The purpose of the current study was to identify the functional significance of conflicting stereotypes and to identify the dominant category in such conflicts. In the present research we examined the conflicting crossed categories of age and wealth with regard to warmth and competence perceptions. It was found (Pilot Study and Study 1) that the old-rich targets presented a conflicting stereotype group in the perception of warmth, whereas young-poor targets presented a conflicting stereotype group in the perception of competence. In addition, the old stereotype dominated the warmth evaluation of old-rich targets, whereas the poor stereotype dominated the competence evaluation of young-poor targets. In Study 2, participants provided warmth and competence evaluations after they learned about the targets' behaviors which demonstrated high or low warmth and high or low competence. The results suggest that for the warmth evaluation of the old-rich target the category that did not match the behavior (i.e., contradicted the stereotype expectation) was more salient and drove judgments. However, the effect of stereotype expectation violation was not found in the competence evaluation of the young-poor target. The results are discussed in terms of their implications for understanding factors that activate and inhibit stereotyped perceptions. PMID:27818640

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.

Effects of differential rates of alternative reinforcement on resurgence of human behavior.

PubMed

Smith, Brooke M; Smith, Gregory S; Shahan, Timothy A; Madden, Gregory J; Twohig, Michael P

2017-01-01

Despite the success of exposure-based psychotherapies in anxiety treatment, relapse remains problematic. Resurgence, the return of previously eliminated behavior following the elimination of an alternative source of reinforcement, is a promising model of operant relapse. Nonhuman resurgence research has shown that higher rates of alternative reinforcement result in faster, more comprehensive suppression of target behavior, but also in greater resurgence when alternative reinforcement is eliminated. This study investigated rich and lean rates of alternative reinforcement on response suppression and resurgence in typically developing humans. In Phase 1, three groups (Rich, n = 18; Lean, n = 18; Control, n = 10) acquired the target response. In Phase 2, target responding was extinguished and alternative reinforcement delivered on RI 1 s, RI 3 s, and extinction schedules, respectively. Resurgence was assessed during Phase 3 under extinction conditions for all groups. Target responding was suppressed most thoroughly in Rich and partially in Lean. Target responding resurged in the Rich and Lean groups, but not in the Control group. Between groups, resurgence was more pronounced in the Rich group than the Lean and Control groups. Clinical implications of these findings, including care on the part of clinicians when identifying alternative sources of reinforcement, are discussed. © 2017 Society for the Experimental Analysis of Behavior.

Older smokers could be the strongest supporters for U.S. government regulation of tobacco: a focus group study

PubMed Central

2013-01-01

Background Targeting of marginalized groups with aggressive tobacco marketing has been identified as exacerbating health disparities. However, interpretation of such targeting by groups varies, from surprise and outrage to regarding such marketing as evidence of social legitimacy. We sought to learn how an often-overlooked marginalized group, older adults, would respond to industry documents offering evidence of tobacco company target marketing. Methods We conducted 10 focus groups in California cities with older (≥50 years) smokers and former smokers. A set of previously-undisclosed tobacco industry documents related to target marketing was shown to the group in sequence. Audiotaped discussions were transcribed and data analyzed using qualitative approaches. Results Responses to evidence of tobacco industry targeting varied, with some regarding it as exploitive and others as normal business practice. However, in most groups, discussions turned to government’s failure to protect the public—even though government action /inaction was not prompted nor addressed in the discussion documents. Conclusion Given the Food and Drug Administration’s new authority to regulate tobacco products, these findings suggest that some of the tobacco industry’s “best customers” (older, established smokers and ex-smokers) may be strong supporters of government regulation of tobacco. PMID:23958397

Promoting learning, memory, and transfer in a time-constrained, high hazard environment.

PubMed

Molesworth, Brett R C; Bennett, Lauren; Kehoe, E James

2011-05-01

Two methods of metacognitive reflection for promoting compliance with an aviation safety rule were tested in a transfer design. Two groups of pilots (n = 10) conducted a simulated flight entailing a search for a target on the ground. During this flight, only 35% of the pilots stayed above an altitude of 500 ft, the minimum allowed by relevant regulations. Following the flight, one group completed a self-explanation questionnaire, in which they explained their actions during the initial flight and what they would do in future flights. The other group completed a relapse-prevention questionnaire, in which they identified the circumstances leading to safety lapses and their future avoidance. A third group (n = 10) formed a rest control; they conducted a familiarization flight without a ground target or debriefing. One week later, all pilots conducted a series of test flights with the same or different ground targets as the initial flight. The self-explanation group showed 100% compliance when the ground target remained the same, but less so (<70%) when the ground target was different. The relapse-prevention group and control groups both showed low levels of compliance across all test flights (<30%). The results are discussed from theoretical and applied perspectives. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Typology of Middle School Girls: Audience Segmentation Related to Physical Activity

PubMed Central

Staten, Lisa K.; Birnbaum, Amanda S.; Jobe, Jared B.; Elder, John P.

2008-01-01

The Trial of Activity for Adolescent Girls (TAAG) combines social ecological and social marketing approaches to promote girls’ participation in physical activity programs implemented at 18 middle schools throughout the United States. Key to the TAAG approach is targeting materials to a variety of audience segments. TAAG segments are individuals who share one or more common characteristic that is expected to correlate with physical activity. Thirteen focus groups with seventh and eighth grade girls were conducted to identify and characterize segments. Potential messages and channels of communication were discussed for each segment. Based on participant responses, six primary segments were identified: athletic, preppy, quiet, rebel, smart, and tough. The focus group information was used to develop targeted promotional tools to appeal to a diversity of girls. Using audience segmentation for targeting persuasive communication is potentially useful for intervention programs but may be sensitive; therefore, ethical issues must be critically examined. PMID:16397160

A typology of middle school girls: audience segmentation related to physical activity.

PubMed

Staten, Lisa K; Birnbaum, Amanda S; Jobe, Jared B; Elder, John P

2006-02-01

The Trial of Activity for Adolescent Girls (TAAG) combines social ecological and social marketing approaches to promote girls' participation in physical activity programs implemented at 18 middle schools throughout the United States. Key to the TAAG approach is targeting materials to a variety of audience segments. TAAG segments are individuals who share one or more common characteristic that is expected to correlate with physical activity. Thirteen focus groups with seventh and eighth grade girls were conducted to identify and characterize segments. Potential messages and channels of communication were discussed for each segment. Based on participant responses, six primary segments were identified: athletic, preppy, quiet, rebel, smart, and tough. The focus group information was used to develop targeted promotional tools to appeal to a diversity of girls. Using audience segmentation for targeting persuasive communication is potentially useful for intervention programs but may be sensitive; therefore, ethical issues must be critically examined.

Neural dynamics of grouping and segmentation explain properties of visual crowding.

PubMed

Francis, Gregory; Manassi, Mauro; Herzog, Michael H

2017-07-01

Investigations of visual crowding, where a target is difficult to identify because of flanking elements, has largely used a theoretical perspective based on local interactions where flanking elements pool with or substitute for properties of the target. This successful theoretical approach has motivated a wide variety of empirical investigations to identify mechanisms that cause crowding, and it has suggested practical applications to mitigate crowding effects. However, this theoretical approach has been unable to account for a parallel set of findings that crowding is influenced by long-range perceptual grouping effects. When the target and flankers are perceived as part of separate visual groups, crowding tends to be quite weak. Here, we describe how theoretical mechanisms for grouping and segmentation in cortical neural circuits can account for a wide variety of these long-range grouping effects. Building on previous work, we explain how crowding occurs in the model and explain how grouping in the model involves connected boundary signals that represent a key aspect of visual information. We then introduce new circuits that allow nonspecific top-down selection signals to flow along connected boundaries or within a surface contained by boundaries and thereby induce a segmentation that can separate the visual information corresponding to the flankers from the visual information corresponding to the target. When such segmentation occurs, crowding is shown to be weak. We compare the model's behavior to 5 sets of experimental findings on visual crowding and show that the model does a good job explaining the key empirical findings. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Functionalized Media and Methods of Making and Using Therefor

NASA Technical Reports Server (NTRS)

Huang, Yongsong (Inventor); Dillon, James (Inventor)

2017-01-01

Methods, compositions, devices and kits are provided herein for separating, scavenging, capturing or identifying a metal from a target using a medium or scaffold with a selenium-containing functional group. The medium or the scaffold including the selenium-containing functional group has affinity and specificity to metal ions or compounds having one or more metals, and efficiently separates, recovers, and scavenges of the metals from a target such as a sample, solution, suspension, or mixture.

Strategy Generalization across Orientation Tasks: Testing a Computational Cognitive Model

DTIC Science & Technology

2008-07-01

arranged in groups ( clusters ). The space, itself, was divided into four quadrants, which had 1, 2, 3, and 4 objects, respectively. The arrangement of... clusters , of objects play an important role in the model’s performance, by providing some context for narrowing the search for the target to a portion of the...model uses a hierarchical approach to accomplish this. First, the model identifies a group or cluster of objects that contains the target. The number of

Understanding barriers to implementing the Norwegian national guidelines for healthy school meals: a case study involving three secondary schools.

PubMed

Holthe, Asle; Larsen, Torill; Samdal, Oddrun

2011-07-01

The main goal of the present study was to investigate the barriers to implementing the Norwegian national guidelines for healthy school meals as perceived by principals, project leaders, teachers and students. This study employed a multiple-case design using an explorative approach. Data were collected at three secondary schools in Norway participating in the intervention project Physical activity and healthy school meals. Individual interviews were conducted with school principals and project leaders, and focus group interviews were conducted separately with teachers and students. Four categories of barriers were identified: (1) lack of adaptation of the guidelines to the target group; (2) lack of resources and funding; (3) conflicting values and goals; and (4) access to unhealthy food outside school. The research identified differences in perceived barriers between the staff responsible for implementation and the students as the target group of the measures. All staff groups perceived barriers relating to both resources, and conflicting values and goals. The teachers were more concerned about issues of relevance for adaptation to the target groups than were the principals and project leaders. The students were concerned mostly with issues directly affecting their experience with items offered in the canteen. © 2010 Blackwell Publishing Ltd.

Probing Needs Assessment Data in Depth to Target Programs More Effectively

ERIC Educational Resources Information Center

Skelly, JoAnne; Hill, George; Singletary, Loretta

2014-01-01

Extension professionals often assess community needs to determine programs and target audiences. Data can be collected through surveys, focus group and individual interviews, meta-analysis, systematic observation, and other methods. Knowledge gaps are identified, and programs are designed to resolve the deficiencies. However, do Extension…

Proteomic identification of aldolase A as an autoantibody target in patients with atypical movement disorders.

PubMed

Privitera, Daniela; Corti, Valeria; Alessio, Massimo; Volontè, Maria Antonietta; Volontè, Antonietta; Lampasona, Vito; Comi, Giancarlo; Martino, Gianvito; Franciotta, Diego; Furlan, Roberto; Fazio, Raffaella

2013-03-01

We tried to identify the target/s of autoantibodies to basal ganglia neurons found in a patient with hyperkinetic movement disorders (HMD) characterized by rapid, rhythmic involuntary movements or spasms in both face and neck. Patient and control sera were used in Western blot to probe mouse brain homogenates. Two-dimensional gel electrophoresis (2-DE) SDS-PAGE protein spots recognized by the patient's antibodies were excised and sequenced by mass spectrometry analysis, and the glycolytic enzyme aldolase A was identified as the antigen recognized by the patient's autoantibodies. To assess relevance and specificity of these antibodies to the identified targets as biomarkers of autoimmunity in movement disorders, autoantibody responses to the identified target were then measured by ELISA in various diseases of the central nervous system. Anti-aldolase A autoantibodies were associated mainly with HMD (7/17, 41%) and Parkinson's disease (4/30, 13%) patients, and undetectable in subjects with other inflammatory and non-inflammatory central nervous system diseases. We, thus, identified aldolase A as an autoantigen in a sub-group of patients with HMD, a clinically ill-defined syndrome. Anti-aldolase A antibodies may represent a useful biomarker of autoimmunity in HMD patients.

Human papillomavirus and vaccine-related perceptions among men who have sex with men: a systematic review.

PubMed

Nadarzynski, Tom; Smith, Helen; Richardson, Daniel; Jones, Christina J; Llewellyn, Carrie D

2014-11-01

Targeted human papillomavirus (HPV) vaccine could prevent HPV-related cancers and genital warts among men who have sex with men (MSM). In order to develop effective vaccination programmes for MSM, it is crucial to understand their knowledge, beliefs about HPV and attitudes towards HPV vaccine. A systematic search of 10 databases examined articles investigating HPV knowledge and HPV-related perceptions among MSM. Each paper was assessed to identify potential research directions in the context of targeted HPV vaccination for MSM. We identified 16 studies that included 5185 MSM and conducted mainly in North America. Generally, participants were over 26 years old, had poor-to-moderate knowledge about HPV and were not concerned about HPV-related diseases. Over a half of MSM were willing to accept HPV vaccine, if offered. However, there was large variability in HPV vaccine acceptability, partially due to inconsistencies in methods of ascertainment but also different levels of HPV vaccine awareness. Despite several misconceptions and poor knowledge of HPV infection, MSM might be receptive to HPV vaccination. However, further research is needed to identify which factors contribute to potential vaccine uptake in hypothetical MSM-targeted HPV vaccination. Future studies need to target those MSM with little sexual experience, who would benefit most from HPV vaccination. 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.

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

Timing matters: sonar call groups facilitate target localization in bats.

PubMed

Kothari, Ninad B; Wohlgemuth, Melville J; Hulgard, Katrine; Surlykke, Annemarie; Moss, Cynthia F

2014-01-01

To successfully negotiate a cluttered environment, an echolocating bat must control the timing of motor behaviors in response to dynamic sensory information. Here we detail the big brown bat's adaptive temporal control over sonar call production for tracking prey, moving predictably or unpredictably, under different experimental conditions. We studied the adaptive control of vocal-motor behaviors in free-flying big brown bats, Eptesicus fuscus, as they captured tethered and free-flying insects, in open and cluttered environments. We also studied adaptive sonar behavior in bats trained to track moving targets from a resting position. In each of these experiments, bats adjusted the features of their calls to separate target and clutter. Under many task conditions, flying bats produced prominent sonar sound groups identified as clusters of echolocation pulses with relatively stable intervals, surrounded by longer pulse intervals. In experiments where bats tracked approaching targets from a resting position, bats also produced sonar sound groups, and the prevalence of these sonar sound groups increased when motion of the target was unpredictable. We hypothesize that sonar sound groups produced during flight, and the sonar call doublets produced by a bat tracking a target from a resting position, help the animal resolve dynamic target location and represent the echo scene in greater detail. Collectively, our data reveal adaptive temporal control over sonar call production that allows the bat to negotiate a complex and dynamic environment.

Timing matters: sonar call groups facilitate target localization in bats

PubMed Central

Kothari, Ninad B.; Wohlgemuth, Melville J.; Hulgard, Katrine; Surlykke, Annemarie; Moss, Cynthia F.

2014-01-01

To successfully negotiate a cluttered environment, an echolocating bat must control the timing of motor behaviors in response to dynamic sensory information. Here we detail the big brown bat's adaptive temporal control over sonar call production for tracking prey, moving predictably or unpredictably, under different experimental conditions. We studied the adaptive control of vocal-motor behaviors in free-flying big brown bats, Eptesicus fuscus, as they captured tethered and free-flying insects, in open and cluttered environments. We also studied adaptive sonar behavior in bats trained to track moving targets from a resting position. In each of these experiments, bats adjusted the features of their calls to separate target and clutter. Under many task conditions, flying bats produced prominent sonar sound groups identified as clusters of echolocation pulses with relatively stable intervals, surrounded by longer pulse intervals. In experiments where bats tracked approaching targets from a resting position, bats also produced sonar sound groups, and the prevalence of these sonar sound groups increased when motion of the target was unpredictable. We hypothesize that sonar sound groups produced during flight, and the sonar call doublets produced by a bat tracking a target from a resting position, help the animal resolve dynamic target location and represent the echo scene in greater detail. Collectively, our data reveal adaptive temporal control over sonar call production that allows the bat to negotiate a complex and dynamic environment. PMID:24860509

Coping with Stress: A Group Counseling Approach.

ERIC Educational Resources Information Center

Newman, Betsy

A group approach to dealing with stress is the basis for a series of workshops outlined in this paper. The stress management program materials, especially suitable for those in the helping professions, identifies the nature and causes of stress, and uses group supports to target and work to change counter-productive stress-related behaviors. The…

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

Improving medication adherence with a targeted, technology-driven disease management intervention.

PubMed

Lawrence, David B; Allison, Wanda; Chen, Joyce C; Demand, Michael

2008-06-01

Treatment adherence is critical in managing chronic disease, but achieving it remains an elusive goal across many prevalent conditions. As part of its care management strategy, BlueCross BlueShield of South Carolina (BCBSSC) implemented the Longitudinal Adherence Treatment Evaluation program, a behavioral intervention to improve medication adherence among members with cardiovascular disease and/or diabetes. The objectives of this study were to 1) assess the effectiveness of telephonic intervention in influencing reinitiation of medication therapy, and 2) evaluate the rate and timing of medication reinitiation. BCBSSC applied algorithms against pharmacy claims data to identify patients prescribed targeted medications who were 60 or more days overdue for refills. This information was provided to care managers to address during their next patient contact. Care managers received focused training on techniques for medication behavior change, readiness to change, motivational interviewing, and active listening. Training also addressed common barriers to adherence and available resources, including side effect management, mail order benefits, drug assistance programs, medication organizers, and reminder systems. Overdue refills were tracked for 12 months, with medication reinitiation followed for an additional 3 months. In the intervention group, 94 patients were identified with 123 instances of late medication refills. In the age- and gender-matched comparison group, 61 patients were identified with 76 late refills. The intervention group had a significantly higher rate of medication reinitiation (59.3%) than the control group (42.1%; P < 0.05). Time to reinitiation was significantly shorter in the intervention group, 59.5 (+/- 69.0) days vs. 107.4 (+/- 109) days for the control group (P < 0.05). This initiative demonstrated that a targeted disease management intervention promoting patient behavior change increased the number of patients who reinitiated therapy after a period of nonadherence and decreased the time from nonadherence to adherence.

Improved Targeting Through Collaborative Decision-Making and Brain Computer Interfaces

NASA Technical Reports Server (NTRS)

Stoica, Adrian; Barrero, David F.; McDonald-Maier, Klaus

2013-01-01

This paper reports a first step toward a brain-computer interface (BCI) for collaborative targeting. Specifically, we explore, from a broad perspective, how the collaboration of a group of people can increase the performance on a simple target identification task. To this end, we requested a group of people to identify the location and color of a sequence of targets appearing on the screen and measured the time and accuracy of the response. The individual results are compared to a collective identification result determined by simple majority voting, with random choice in case of drawn. The results are promising, as the identification becomes significantly more reliable even with this simple voting and a small number of people (either odd or even number) involved in the decision. In addition, the paper briefly analyzes the role of brain-computer interfaces in collaborative targeting, extending the targeting task by using a BCI instead of a mechanical response.

Impelling and Inhibitory Forces in Aggression: Sex-of-Target and Relationship Effects

ERIC Educational Resources Information Center

Davidovic, Anna; Bell, Kurtis; Ferguson, Colin; Gorski, Elizabeth; Campbell, Anne

2011-01-01

The finding of symmetry in intimate partner aggression is now generally accepted, but the convergence of male and female rates in these relationships remains unexplained. From qualitative analysis of male and female focus group discussions, we identified factors believed to influence the expression of aggression toward targets differing in sex and…

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

Attentional blink in children with attention deficit hyperactivity disorder.

PubMed

Amador-Campos, Juan A; Aznar-Casanova, J Antonio; Bezerra, Izabela; Torro-Alves, Nelson; Sánchez, Manuel M

2015-01-01

To explore the temporal mechanism of attention in children with attention deficit hyperactivity disorder (ADHD) and controls using a rapid serial visual presentation (RSVP) task in which two letters (T1 and T2) were presented in close temporal proximity among distractors (attentional blink [AB]). Thirty children aged between 9 and 13 years (12 with ADHD combined type and 18 controls) took part in the study. Both groups performed two kinds of RSVP task. In the single task, participants simply had to identify a target letter (T1), whereas in the dual task, they had to identify a target letter (T1) and a probe letter (T2). The ADHD and control groups were equivalent in their single-task performance. However, in the dual-task condition, there were significant between-group differences in the rate of detection of the probe letter (T2) at lag + 1 and lag + 4. The ADHD group exhibited a larger overall AB compared with controls. Our findings provide support for a link between ADHD and attentional blink.

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.

Analysis of histological findings obtained combining US/mp-MRI fusion-guided biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection and false negative.

PubMed

Faiella, Eliodoro; Santucci, Domiziana; Greco, Federico; Frauenfelder, Giulia; Giacobbe, Viola; Muto, Giovanni; Zobel, Bruno Beomonte; Grasso, Rosario Francesco

2018-02-01

To evaluate the diagnostic accuracy of mp-MRI correlating US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in prostate cancer diagnosis. 137 suspected prostatic abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion biopsy and prostatic sampling was completed by US-guided systematic random 12-core biopsies. Histological analysis and Gleason score were established for all the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS score was correlated with the histological results, divided in three groups (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four categories considering the new Grading system of the ISUP 2014, using t test. Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA level and abnormalities axial diameter. When the random core biopsies showed carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value were compared with those of carcinomas identified by mp-MRI (true-positives), using t test. There was statistically significant difference between PI-RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24, respectively) and between PI-RADS score in Gleason < 7 group and Gleason > 7 group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130 (11.25%) mp-MRI false-negative were identified. There was no statistic difference in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true-positives, but a significant lower PSA median value was demonstrated (7.08 vs 7.53 ng/ml). mp-MRI remains the imaging modality of choice to identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion target lesions sampling, 3.49% of false-negative were identified.

Express saccades in distinct populations: east, west, and in-between.

PubMed

Knox, Paul C; Wolohan, Felicity D A; Helmy, Mai S

2017-12-01

Express saccades are low latency (80-130 ms), visually guided saccades. While their occurrence is encouraged by the use of gap tasks (the fixation target is extinguished 200 ms prior to the saccade target appearing) and suppressed by the use of overlap tasks (the fixation target remains present when the saccade target appears), there are some healthy, adult participants, "express saccade makers" (ESMs), who persist in generating high proportions (> 30%) of express saccades in overlap conditions. These participants are encountered much more frequently in Chinese participant groups than amongst the Caucasian participants tested to date. What is not known is whether this high number of ESMs is only a feature of Chinese participant groups. More broadly, there are few comparative studies of saccade behaviour across large participant groups drawn from different populations. We, therefore, tested an independent group of 70 healthy adult Egyptian participants, using the same equipment and procedures as employed in the previous studies. Each participant was exposed to two blocks of 200 gap, and two blocks of 200 overlap trials, with block order counterbalanced. Results from the Schwartz Value Survey were used to confirm that this group of participants was culturally distinct from the Chinese and Caucasian (white British) groups tested previously. Fourteen percent (10/70) of this new group were ESMs, and the pattern of latency distribution in these ESMs was identical to that identified in the other participant groups, with a prominent peak in the express latency range in overlap conditions. Overall, we identified three modes in the distribution of saccade latency in overlap conditions, the timing of which (express peak at 110 ms, subsequent peaks at 160 and 210 ms) were strikingly consistent with our previous observations. That these behavioural patterns of saccade latency are observed consistently in large participant groups, drawn from geographically, ethnically, and culturally distinct populations, suggests that they relate to the underlying architecture of the saccade system.

A Systematic Review of Training Interventions Addressing Sexual Violence against Marginalized At-Risk Groups of Women

ERIC Educational Resources Information Center

Kouta, Christiana; Pithara, Christalla; Zobnina, Anna; Apostolidou, Zoe; Christodoulou, Josie; Papadakaki, Maria; Chliaoutakis, Joannes

2015-01-01

Women from marginalized groups working in occupations such as domestic work are at increased risk for sexual violence. Scarce evidence exists about training interventions targeting such groups. The article aims to identify community and workplace-based training interventions aiming to increase capacity among marginalized at-risk women to deal with…

Community-Based Intervention to Improve Cardiometabolic Targets in Patients With Stroke: A Randomized Controlled Trial.

PubMed

Olaiya, Muideen T; Cadilhac, Dominique A; Kim, Joosup; Nelson, Mark R; Srikanth, Velandai K; Gerraty, Richard P; Bladin, Christopher F; Fitzgerald, Sharyn M; Phan, Thanh; Frayne, Judith; Thrift, Amanda G

2017-09-01

Many guidelines for secondary prevention of stroke focus on controlling cardiometabolic risk factors. We investigated the effectiveness of a management program for attaining cardiometabolic targets in survivors of stroke/transient ischemic attack. Randomized controlled trial of survivors of stroke/transient ischemic attack aged ≥18 years. General practices were randomized to usual care (control) or an intervention comprising specialist review of care plans and nurse education in addition to usual care. The outcome is attainment of pre-defined cardiometabolic targets based on Australian guidelines. Multivariable regression was undertaken to determine efficacy and identify factors associated with attaining targets. Overall, 283 subjects were randomized to the intervention and 280 to controls. Although we found no between-group difference in overall cardiometabolic targets achieved at 12 months, the intervention group more often achieved control of low-density lipoprotein cholesterol (odds ratio, 1.97; 95% confidence interval, 1.18-3.29) than controls. At 24 months, no between-group differences were observed. Medication adherence was ≥80% at follow-up, but uptake of lifestyle/behavioral habits was poor. Older age, being male, being married/living with partner, and having greater functional ability or a history of diabetes mellitus were associated with attaining targets. The intervention in this largely negative trial only had a detectable effect on attaining target for lipids but not for other factors at 12 months or any factor at 24 months. This limited effect may be attributable to inadequate uptake of behavioral/lifestyle interventions, highlighting the need for new or better approaches to achieve meaningful behavioral change. URL: http://www.clinicaltrials.gov. Unique identifier: ACTRN12608000166370. © 2017 American Heart Association, Inc.

Altered expression of four miRNA (miR-1238-3p, miR-202-3p, miR-630 and miR-766-3p) and their potential targets in peripheral blood from vitiligo patients.

PubMed

Shang, Zhiwei; Li, Hongwen

2017-10-01

Vitiligo is an acquired skin disease with pigmentary disorder. Autoimmune destruction of melanocytes is thought to be major factor in the etiology of vitiligo. miRNA-based regulators of gene expression have been reported to play crucial roles in autoimmune disease. Therefore, we attempt to profile the miRNA expressions and predict their potential targets, assessing the biological functions of differentially expressed miRNA. Total RNA was extracted from peripheral blood of vitiligo (experimental group, n = 5) and non-vitiligo (control group, n = 5) age-matched patients. Samples were hybridized to a miRNA array. Box, scatter and principal component analysis plots were performed, followed by unsupervised hierarchical clustering analysis to classify the samples. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was conducted for validation of microarray data. Three different databases, TargetScan, PITA and microRNA.org, were used to predict the potential target genes. Gene ontology (GO) annotation and pathway analysis were performed to assess the potential functions of predicted genes of identified miRNA. A total of 100 (29 upregulated and 71 downregulated) miRNA were filtered by volcano plot analysis. Four miRNA were validated by quantitative RT-PCR as significantly downregulated in the vitiligo group. The functions of predicted target genes associated with differentially expressed miRNA were assessed by GO analysis, showing that the GO term with most significantly enriched target genes was axon guidance, and that the axon guidance pathway was most significantly correlated with these miRNA. In conclusion, we identified four downregulated miRNA in vitiligo and assessed the potential functions of target genes related to these differentially expressed miRNA. © 2017 Japanese Dermatological Association.

Three Generations of Lancashire Women

ERIC Educational Resources Information Center

Biscomb, Kay

2012-01-01

In 1914 opportunities for working-class women's sports participation were limited and peripheral, but the 1980s, policy reforms resulted in the then Sports Council identifying women as a "target group". Subsequently the notion that barriers to women's participation are issues to be identified and resolved has become commonplace in…

Clinical and psychosocial predictors of exceeding target length of stay during inpatient stroke rehabilitation.

PubMed

Lai, Wesley; Buttineau, Mackenzie; Harvey, Jennifer K; Pucci, Rebecca A; Wong, Anna P M; Dell'Erario, Linda; Bosnyak, Stephanie; Reid, Shannon; Salbach, Nancy M

2017-10-01

In Ontario, Canada, patients admitted to inpatient rehabilitation hospitals post-stroke are classified into rehabilitation patient groups based on age and functional level. Clinical practice guidelines, called quality-based procedures, recommend a target length of stay (LOS) for each group. The study objective was to evaluate the extent to which patients post-stroke at an inpatient rehabilitation hospital are meeting LOS targets and to identify patient characteristics that predict exceeding target LOS. A quantitative, longitudinal study from an inpatient rehabilitation hospital was conducted. Participants included adult patients (≥18 years) with stroke, admitted to an inpatient rehabilitation hospital between 2014 and 2015. The percentage of patients exceeding the recommended target LOS was determined. Logistic regression was performed to identify clinical and psychosocial patient characteristics associated with exceeding target LOS after adjusting for stroke severity. Of 165 patients, 38.8% exceeded their target LOS. Presence of ataxia, recurrent stroke, living alone, absence of a caregiver at admission, and acquiring a caregiver during hospital LOS was each associated with significantly higher odds of exceeding target LOS in comparison to patients without these characteristics after adjusting for stroke severity (p < 0.05). Findings suggest that social and stroke-specific factors may be helpful to adjust LOS expectations and promote efficient resource allocation. This exploratory study was limited to findings from one inpatient rehabilitation hospital. Cross-validation of results using data-sets from multiple rehabilitation hospitals across Ontario is recommended.

Multi-Morbidity in Hospitalised Older Patients: Who Are the Complex Elderly?

PubMed Central

Ruiz, Milagros; Bottle, Alex; Long, Susannah; Aylin, Paul

2015-01-01

Background No formal definition for the “complex elderly” exists; moreover, these older patients with high levels of multi-morbidity are not readily identified as such at point of hospitalisation, thus missing a valuable opportunity to manage the older patient appropriately within the hospital setting. Objectives To empirically identify the complex elderly patient based on degree of multi-morbidity. Design Retrospective observational study using administrative data. Setting English hospitals during the financial year 2012–13. Subjects All admitted patients aged 65 years and over. Methods By using exploratory analysis (correspondence analysis) we identify multi-morbidity groups based on 20 target conditions whose hospital prevalence was ≥ 1%. Results We examined a total of 2788900 hospital admissions. Multi-morbidity was highly prevalent, 62.8% had 2 or more of the targeted conditions while 4.7% had six or more. Multi-morbidity increased with age from 56% (65-69yr age-groups) up to 67% (80-84yr age-group). The average multi-morbidity was 3.2±1.2 (SD). Correspondence analysis revealed 3 distinct groups of older patients. Group 1 (multi-morbidity ≤2), associated with cancer and/or metastasis; Group 2 (multi-morbidity of 3, 4 or 5), associated with chronic pulmonary disease, lung disease, rheumatism and osteoporosis; finally Group 3 with the highest level of multi-morbidity (≥6) and associated with heart failure, cerebrovascular accident, diabetes, hypertension and myocardial infarction. Conclusions By using widely available hospital administrative data, we propose patients in Groups 2 and 3 to be identified as the complex elderly. Identification of multi-morbidity patterns can help to predict the needs of the older patient and improve resource provision. PMID:26716440

Moving forward with actionable therapeutic targets and opportunities in endometrial cancer: NCI clinical trials planning meeting report on identifying key genes and molecular pathways for targeted endometrial cancer trials

PubMed Central

MacKay, Helen J.; Levine, Douglas A.; Bae-Jump, Victoria L.; Bell, Daphne W.; McAlpine, Jessica N.; Santin, Alessandro; Fleming, Gini F.; Mutch, David G.; Nephew, Kenneth P.; Wentzensen, Nicolas; Goodfellow, Paul J.; Dorigo, Oliver; Nijman, Hans W.; Broaddus, Russell; Kohn, Elise C.

2017-01-01

The incidence and mortality rates from endometrial cancer are increasing. There have been no new drugs approved for the treatment of endometrial cancer in decades. The National Cancer Institute, Gynecologic Cancer Steering Committee identified the integration of molecular and/or histologic stratification into endometrial cancer management as a top strategic priority. Based on this, they convened a group of experts to review the molecular data in this disease. Here we report on the actionable opportunities and therapeutic directions identified for incorporation into future clinical trials. PMID:29137450

People with diabetic peripheral neuropathy display a decreased stepping accuracy during walking: potential implications for risk of tripping.

PubMed

Handsaker, J C; Brown, S J; Bowling, F L; Marple-Horvat, D E; Boulton, A J M; Reeves, N D

2016-05-01

To examine the stepping accuracy of people with diabetes and diabetic peripheral neuropathy. Fourteen patients with diabetic peripheral neuropathy (DPN), 12 patients with diabetes but no neuropathy (D) and 10 healthy non-diabetic control participants (C). Accuracy of stepping was measured whilst the participants walked along a walkway consisting of 18 stepping targets. Preliminary data on visual gaze characteristics were also captured in a subset of participants (diabetic peripheral neuropathy group: n = 4; diabetes-alone group: n = 4; and control group: n = 4) during the same task. Patients in the diabetic peripheral neuropathy group, and patients in the diabetes-alone group were significantly less accurate at stepping on targets than were control subjects (P < 0.05). Preliminary visual gaze analysis identified that patients diabetic peripheral neuropathy were slower to look between targets, resulting in less time being spent looking at a target before foot-target contact. Impaired motor control is theorized to be a major factor underlying the changes in stepping accuracy, and potentially altered visual gaze behaviour may also play a role. Reduced stepping accuracy may indicate a decreased ability to control the placement of the lower limbs, leading to patients with neuropathy potentially being less able to avoid observed obstacles during walking. © 2015 Diabetes UK.

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.

Grouping principles in direct competition.

PubMed

Schmidt, Filipp; Schmidt, Thomas

2013-08-09

We (1) introduce a primed flanker task as an objective method to measure perceptual grouping, and (2) use it to directly compare the efficiency of different grouping cues in rapid visuomotor processing. In two experiments, centrally presented primes were succeeded by flanking targets with varying stimulus-onset asynchronies (SOAs). Primes and targets were grouped by the same or by different grouping cues (Exp. 1: brightness/shape, Exp. 2: brightness/size) and were consistent or inconsistent with respect to the required response. Subjective grouping strength was varied to identify its influence on overall response times, error rates, and priming effects, that served as a measure of visual feedforward processing. Our results show that stronger grouping in the targets enhanced overall response times while stronger grouping in the primes enhanced priming effects in motor responses. Also, we obtained differences between rapid visuomotor processing and the subjective impression with cues of brightness and shape but not with cues of brightness and size. Our findings establish the primed flanker task as an objective method to study the speeded visuomotor processing of grouping cues, making it a useful method for the comparative study of feedforward-transmitted base groupings (Roelfsema & Houtkamp, 2011). Copyright © 2013 Elsevier Ltd. All rights reserved.

Academic [Activities]: Looking for Symbols in the Built Landscape; What Is Service?

ERIC Educational Resources Information Center

Charney, Len; Sims, Cheryl

1999-01-01

Describes two experiential, academic activities for middle and high school students. Includes target group, group size, time and space requirements, activity level, props/preparation, and instructions. The activities enable students to identify the symbolic value of community places and architecture or raise student awareness about the…

Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models. | Office of Cancer Genomics

Cancer.gov

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs).

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

DOE PAGES

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric; ...

2015-03-30

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

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

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less

Neural mechanisms tracking popularity in real-world social networks.

PubMed

Zerubavel, Noam; Bearman, Peter S; Weber, Jochen; Ochsner, Kevin N

2015-12-08

Differences in popularity are a key aspect of status in virtually all human groups and shape social interactions within them. Little is known, however, about how we track and neurally represent others' popularity. We addressed this question in two real-world social networks using sociometric methods to quantify popularity. Each group member (perceiver) viewed faces of every other group member (target) while whole-brain functional MRI data were collected. Independent functional localizer tasks were used to identify brain systems supporting affective valuation (ventromedial prefrontal cortex, ventral striatum, amygdala) and social cognition (dorsomedial prefrontal cortex, precuneus, temporoparietal junction), respectively. During the face-viewing task, activity in both types of neural systems tracked targets' sociometric popularity, even when controlling for potential confounds. The target popularity-social cognition system relationship was mediated by valuation system activity, suggesting that observing popular individuals elicits value signals that facilitate understanding their mental states. The target popularity-valuation system relationship was strongest for popular perceivers, suggesting enhanced sensitivity to differences among other group members' popularity. Popular group members also demonstrated greater interpersonal sensitivity by more accurately predicting how their own personalities were perceived by other individuals in the social network. These data offer insights into the mechanisms by which status guides social behavior.

Cognitive Inflexibility and Frontal-Cortical Activation in Pediatric Obsessive-Compulsive Disorder

PubMed Central

Britton, Jennifer C.; Rauch, Scott L.; Rosso, Isabelle M.; Killgore, William D.S.; Price, Lauren M.; Ragan, Jennifer; Chosak, Anne; Hezel, Dianne M.; Pine, Daniel S.; Leibenluft, Ellen; Pauls, David L.; Jenike, Michael A.; Stewart, S. Evelyn

2014-01-01

Objective Deficits in cognitive flexibility and response inhibition have been linked to perturbations in cortico-striatal-thalamic circuitry in adult obsessive-compulsive disorder (OCD). Although similar cognitive deficits have been identified in pediatric OCD, few neuroimaging studies have been conducted to examine its neural correlates in the developing brain. In this study, we tested hypotheses regarding group differences in the behavioral and neural correlates of cognitive flexibility in a pediatric OCD and a healthy comparison (HC) sample. Method In this functional magnetic resonance imaging (fMRI) study, a pediatric sample of 10- to 17-year-old subjects, 15 with OCD and 20 HC, completed a set-shifting task. The task, requiring an extradimensional shift to identify a target, examines cognitive flexibility. Within each block, the dimension (color or shape) that identified the target either alternated (i.e., mixed) or remained unchanged (i.e., repeated). Results Compared with the HC group, the OCD group tended to be slower to respond to trials within mixed blocks. Compared with the HC group, the OCD group exhibited less left inferior frontal gyrus/BA47 activation in the set-shifting contrast (i.e., HC > OCD, mixed versus repeated); only the HC group exhibited significant activation in this region. The correlation between set shifting-induced right caudate activation and shift cost (i.e., reaction time differential in response to mixed versus repeated trials) was significantly different between HC and OCD groups, in that we found a positive correlation in HC and a negative correlation in OCD. Conclusions In pediatric OCD, less fronto-striatal activation may explain previously identified deficits in shifting cognitive sets. PMID:20732630

Patients with schizophrenia do not preserve automatic grouping when mentally re-grouping figures: shedding light on an ignored difficulty.

PubMed

Giersch, Anne; van Assche, Mitsouko; Capa, Rémi L; Marrer, Corinne; Gounot, Daniel

2012-01-01

Looking at a pair of objects is easy when automatic grouping mechanisms bind these objects together, but visual exploration can also be more flexible. It is possible to mentally "re-group" two objects that are not only separate but belong to different pairs of objects. "Re-grouping" is in conflict with automatic grouping, since it entails a separation of each item from the set it belongs to. This ability appears to be impaired in patients with schizophrenia. Here we check if this impairment is selective, which would suggest a dissociation between grouping and "re-grouping," or if it impacts on usual, automatic grouping, which would call for a better understanding of the interactions between automatic grouping and "re-grouping." Sixteen outpatients with schizophrenia and healthy controls had to identify two identical and contiguous target figures 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. Identical figures were grouped by a connector (grouped automatically) or not (to be re-grouped). Attention modulation of automatic grouping was tested by manipulating the proportion of connected and unconnected targets, thus prompting subjects to focalize on either connected or unconnected pairs. Both groups were sensitive to automatic grouping in most conditions, but patients were unusually slowed down for connected targets while focalizing on unconnected pairs. In addition, this unusual effect occurred only when targets were presented within the same hemifield. Patients and controls differed on this asymmetry between within- and across-hemifield presentation, suggesting that patients with schizophrenia do not re-group figures in the same way as controls do. We discuss possible implications on how "re-grouping" ties in with ongoing, automatic perception in healthy volunteers.

Immunological Targeting of Tumor Initiating Prostate Cancer Cells

DTIC Science & Technology

2014-10-01

clinically using well-accepted immuno-competent animal models. 2) Keywords: Prostate Cancer, Lymphocyte, Vaccine, Antibody 3) Overall Project Summary...castrate animals . Task 1: Identify and verify antigenic targets from CAstrate Resistant Luminal Epithelial Cells (CRLEC) (months 1-16... animals per group will be processed to derive sufficient RNA for microarray analysis; the experiment will be repeated x 3. Microarray analysis will

One size does not fit all: how the tobacco industry has altered cigarette design to target consumer groups with specific psychological and psychosocial needs.

PubMed

Cook, Benjamin Lê; Wayne, Geoffrey Ferris; Keithly, Lois; Connolly, Gregory

2003-11-01

To identify whether the tobacco industry has targeted cigarette product design towards individuals with varying psychological/psychosocial needs. Internal industry documents were identified through searches of an online archival document research tool database using relevancy criteria of consumer segmentation and needs assessment. The industry segmented consumer markets based on psychological needs (stress relief, behavioral arousal, performance enhancement, obesity reduction) and psychosocial needs (social acceptance, personal image). Associations between these segments and smoking behaviors, brand and design preferences were used to create cigarette brands targeting individuals with these needs. Cigarette brands created to address the psychological/psychosocial needs of smokers may increase the likelihood of smoking initiation and addiction. Awareness of targeted product development will improve smoking cessation and prevention efforts.

Comparing Demographic, Health Status and Psychosocial Strategies of Audience Segmentation to Promote Physical Activity

ERIC Educational Resources Information Center

Boslaugh, Sarah E.; Kreuter, Matthew W.; Nicholson, Robert A.; Naleid, Kimberly

2005-01-01

The goal of audience segmentation is to identify population subgroups that are homogeneous with respect to certain variables associated with a given outcome or behavior. When such groups are identified and understood, targeted intervention strategies can be developed to address their unique characteristics and needs. This study compares the…

Network pharmacology-based identification of protective mechanism of Panax Notoginseng Saponins on aspirin induced gastrointestinal injury.

PubMed

Zhu, Baochen; Zhang, Wantong; Lu, Yang; Hu, Shaonan; Gao, Rui; Sun, Zongxi; Chen, Xiaonan; Ma, Junming; Guo, Shuang; Du, Shouying; Li, Pengyue

2018-05-29

Aspirin is the first line therapy for cardiovascular and cerebrovascular diseases and is widely used. However aspirin-induced gastrointestinal injury is one of its most common side effect which limits long-term use. Panax Notoginseng Saponins(PNS) which is also used to prevent thrombus may alleviate this side effect according to previous clinical evidences. Owing to the complexity of drug combination, the protective mechanism of PNS on aspirin-induced gastrointestinal injury remains unclear. Therefore, a network pharmacology-based strategy was proposed in this study to address this problem. A network pharmacology approach comprising multiple components, candidate targets of each component, known therapeutic targets, network analysis has been used in this study. Also, we establish aspirin-induced gastrointestinal injury model by the oral administration of aspirin (0.5 g/kg body weight) to verify the predicted targets from network pharmacology. All rats was randomly allocated to control groups (n = 6),aspirin groups (n = 6)and aspirin + PNS groups (n = 6) and conducted H&E staining and ELISA for VEGFA. The comprehensive systematic approach was successfully to identify 5 compounds and 154 candidate targets in PNS and 479 candidate targets in aspirin. After network establishment and analysis, 27 potential targets hit by PNS, aspirin and 6 kind of gastrointestinal diseases were found. The experiments results indicated that aspirin group has visible inflammation and lesions while aspirin + PNS group have not. The higher expression of VEGFA in aspirin + PNS group verified the predicted potential protective targets of PNS. PNS may have protective function for aspirin-induced gastrointestinal injury through increasing VEGFA expression. Network pharmacology strategy may provide a forceful tool for exploring the mechanism of herb medicine and discovering novel bioactive ingredients. Copyright © 2018. Published by Elsevier Masson SAS.

Long Term Follow up of the Delayed Effects of Acute Radiation Exposure in Primates

DTIC Science & Technology

2017-10-01

66 of 94 We will then use shRNAs and/or CRISPR constructs targeting the gene of interest to knock down its expression in stem cells prior to...DLBCLs Mutational profiling identifies 150 driver genes Gene expression identifies sub- groups including cell of origin Unbiased CRISPR screen...Exome sequencing in 1,001 DLBCL patients comprehensively identifies 150 driver genes d Unbiased CRISPR screen in DLBCL cell lines identifies essential

A simple rapid approach using coupled multivariate statistical methods, GIS and trajectory models to delineate areas of common oil spill risk

NASA Astrophysics Data System (ADS)

Guillen, George; Rainey, Gail; Morin, Michelle

2004-04-01

Currently, the Minerals Management Service uses the Oil Spill Risk Analysis model (OSRAM) to predict the movement of potential oil spills greater than 1000 bbl originating from offshore oil and gas facilities. OSRAM generates oil spill trajectories using meteorological and hydrological data input from either actual physical measurements or estimates generated from other hydrological models. OSRAM and many other models produce output matrices of average, maximum and minimum contact probabilities to specific landfall or target segments (columns) from oil spills at specific points (rows). Analysts and managers are often interested in identifying geographic areas or groups of facilities that pose similar risks to specific targets or groups of targets if a spill occurred. Unfortunately, due to the potentially large matrix generated by many spill models, this question is difficult to answer without the use of data reduction and visualization methods. In our study we utilized a multivariate statistical method called cluster analysis to group areas of similar risk based on potential distribution of landfall target trajectory probabilities. We also utilized ArcView™ GIS to display spill launch point groupings. The combination of GIS and multivariate statistical techniques in the post-processing of trajectory model output is a powerful tool for identifying and delineating areas of similar risk from multiple spill sources. We strongly encourage modelers, statistical and GIS software programmers to closely collaborate to produce a more seamless integration of these technologies and approaches to analyzing data. They are complimentary methods that strengthen the overall assessment of spill risks.

Culture and Language Learning: Middle Eastern Students.

ERIC Educational Resources Information Center

Magrath, Douglas

Middle Eastern students face cultural conflicts in adapting to the western value system. While feeling obligated to maintain their native culture they also need to feel comfortable with the culture of their target language. In attempting to identify with a new group, ESL students may sense a loss of membership in their native group. Culture stress…

microRNA regulatory mechanism by which PLLA aligned nanofibers influence PC12 cell differentiation

NASA Astrophysics Data System (ADS)

Yu, Yadong; Lü, Xiaoying; Ding, Fei

2015-08-01

Objective. Aligned nanofibers (AFs) are regarded as promising biomaterials in nerve tissue engineering. However, a full understanding of the biocompatibility of AFs at the molecular level is still challenging. Therefore, the present study focused on identifying the microRNA (miRNA)-mediated regulatory mechanism by which poly-L-lactic acid (PLLA) AFs influence PC12 cell differentiation. Approach. Firstly, the effects of PLLA random nanofibers (RFs)/AFs and PLLA films (control) on the biological responses of PC12 cells that are associated with neuronal differentiation were examined. Then, SOLiD sequencing and cDNA microarray were employed to profile the expressions of miRNAs and mRNAs. The target genes of the misregulated miRNAs were predicted and compared with the mRNA profile data. Functions of the matched target genes (the intersection between the predicted target genes and the experimentally-determined, misregulated genes) were analyzed. Main results. The results revealed that neurites spread in various directions in control and RF groups. In the AF group, most neurites extended in parallel with each other. The glucose consumption and lactic acid production in the RF and AF groups were higher than those in the control group. Compared with the control group, 42 and 94 miRNAs were significantly dysregulated in the RF and AF groups, respectively. By comparing the predicted target genes with the mRNA profile data, five and 87 matched target genes were found in the RF and AF groups, respectively. Three of the matched target genes in the AF group were found to be associated with neuronal differentiation, whereas none had this association in the RF group. The PLLA AFs induced the dysregulation of miRNAs that regulate many biological functions, including axonal guidance, lipid metabolism and long-term potentiation. In particular, two miRNA-matched target gene-biological function modules associated with neuronal differentiation were identified as follows: (1) miR-23b, miR-18a, miR-107 and miR-103 regulate the Rras2 and Nf1 gene and thereby, affect cytoskeleton regulation and MAPK pathway; (2) miR-92a, miR-339-5p, miR-25, miR-125a-5p, miR-351 and miR-19b co-regulate the Pafah1b1 gene, affecting PC12 cell migration and differentiation. Significance. This work demonstrates a bioinformatic approach to accomplish miRNA-mRNA profile integrative analysis and provides more insights for understanding the regulatory mechanism of miRNA in AFs affecting neuronal differentiation. These findings will be greatly beneficial for the application and design of AFs in nerve tissue engineering.

Improving the identification accuracy of senior witnesses: do prelineup questions and sequential testing help?

PubMed

Memon, Amina; Gabbert, Fiona

2003-04-01

Eyewitness research has identified sequential lineup testing as a way of reducing false lineup choices while maintaining accurate identifications. The authors examined the usefulness of this procedure for reducing false choices in older adults. Young and senior witnesses viewed a crime video and were later presented with target present orabsent lineups in a simultaneous or sequential format. In addition, some participants received prelineup questions about their memory for a perpetrator's face and about their confidence in their ability to identify the culprit or to correctly reject the lineup. The sequential lineup reduced false choosing rates among young and older adults in target-absent conditions. In target-present conditions, sequential testing significantly reduced the correct identification rate in both age groups.

Patients with Schizophrenia Do Not Preserve Automatic Grouping When Mentally Re-Grouping Figures: Shedding Light on an Ignored Difficulty

PubMed Central

Giersch, Anne; van Assche, Mitsouko; Capa, Rémi L.; Marrer, Corinne; Gounot, Daniel

2012-01-01

Looking at a pair of objects is easy when automatic grouping mechanisms bind these objects together, but visual exploration can also be more flexible. It is possible to mentally “re-group” two objects that are not only separate but belong to different pairs of objects. “Re-grouping” is in conflict with automatic grouping, since it entails a separation of each item from the set it belongs to. This ability appears to be impaired in patients with schizophrenia. Here we check if this impairment is selective, which would suggest a dissociation between grouping and “re-grouping,” or if it impacts on usual, automatic grouping, which would call for a better understanding of the interactions between automatic grouping and “re-grouping.” Sixteen outpatients with schizophrenia and healthy controls had to identify two identical and contiguous target figures 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. Identical figures were grouped by a connector (grouped automatically) or not (to be re-grouped). Attention modulation of automatic grouping was tested by manipulating the proportion of connected and unconnected targets, thus prompting subjects to focalize on either connected or unconnected pairs. Both groups were sensitive to automatic grouping in most conditions, but patients were unusually slowed down for connected targets while focalizing on unconnected pairs. In addition, this unusual effect occurred only when targets were presented within the same hemifield. Patients and controls differed on this asymmetry between within- and across-hemifield presentation, suggesting that patients with schizophrenia do not re-group figures in the same way as controls do. We discuss possible implications on how “re-grouping” ties in with ongoing, automatic perception in healthy volunteers. PMID:22912621

Using formative research to lay the foundation for community level HIV prevention efforts: an example from the AIDS Community Demonstration Projects.

PubMed Central

Higgins, D L; O'Reilly, K; Tashima, N; Crain, C; Beeker, C; Goldbaum, G; Elifson, C S; Galavotti, C; Guenther-Grey, C

1996-01-01

The AIDS Community Demonstration Projects provided community-level HIV prevention interventions to historically hard-to-reach groups at high risk for HIV infection. The projects operated under a common research protocol which encompassed formative research, intervention delivery, process evaluation, and outcome evaluation. A formative research process specifically focusing on intervention development was devised to assist project staff in identifying, prioritizing, accessing, and understanding the intervention target groups. This process was central to the creation of interventions that were acceptable and unique to the target populations. Intended to be rapid, the process took 6 months to complete. Drawn from the disciplines of anthropology, community psychology, sociology, and public health, the formative research process followed distinct steps which included (a) defining the populations at high-risk for HIV; (b) gathering information about these populations through interviews with persons who were outside of, but who had contact with, the target groups (such as staff from the health department and alcohol and drug treatment facilities, as well as persons who interacted in an informal manner with the target groups, such as clerks in neighborhood grocery stores and bartenders); (c) interviewing people with access to the target populations (gatekeepers), and conducting observations in areas where these high-risk groups were reported to gather (from previous interviews); (d) interviewing members of these groups at high risk for HIV infection or transmission; and (e) systematically integrating information throughout the process. Semistructured interview schedules were used for all data collection in this process. This standardized systematic method yielded valuable information about the focal groups in each demonstration project site. The method, if adopted by others, would assist community intervention specialists in developing interventions that are culturally appropriate and meaningful to their respective target populations. PMID:8862154

Cost-effectiveness of targeted versus tailored interventions to promote mammography screening among women military veterans in the United States.

PubMed

Lairson, David R; Chan, Wen; Chang, Yu-Chia; del Junco, Deborah J; Vernon, Sally W

2011-05-01

We conducted an economic evaluation of mammography promotion interventions in a population-based, nationally representative sample of 5500 women veterans. Women 52 years and older were randomly selected from the National Registry of Women Veterans and randomly assigned to a survey-only control group and two intervention groups that varied in the extent of personalization (tailored vs. targeted). Effectiveness measures were the prevalence of at least one self-reported post-intervention mammogram and two post-intervention mammograms 6-15 months apart. Incremental cost-effectiveness ratios (ICERs) were the incremental cost per additional person screened. Uncertainty was examined with sensitivity analysis and bootstrap simulation. The targeted intervention cost $25 per person compared to $52 per person for the tailored intervention. About 27% of the cost was incurred in identifying and recruiting the eligible population. The percent of women reporting at least one mammogram were .447 in the control group, .469 in the targeted group, and .460 in the tailored group. The ICER was $1116 comparing the targeted group to the control group (95% confidence interval (CI)=$493 to dominated). The tailored intervention was dominated (more costly and less effective) by the targeted intervention. Decision-makers should consider effectiveness evidence and the full recruitment and patient time costs associated with the implementation of screening interventions when making investments in mammography screening promotion programs. Identification and recruitment of eligible participants add substantial costs to outreach screening promotion interventions. Tailoring adds substantial cost to the targeted mammography promotion strategy without a commensurate increase in effectiveness. Although cost-effectiveness has been reported to be higher for some in-reach screening promotion interventions, a recent meta-analysis revealed significant heterogeneity in the effect sizes of published health-plan based intervention studies for repeat mammography (i.e., some studies reported null effects compared with control groups). Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

Contexts, Mechanisms, and Outcomes That Matter in Dutch Community-Based Physical Activity Programs Targeting Socially Vulnerable Groups.

PubMed

Herens, Marion; Wagemakers, Annemarie; Vaandrager, Lenneke; van Ophem, Johan; Koelen, Maria

2017-09-01

This article presents a practitioner-based approach to identify key combinations of contextual factors (C) and mechanisms (M) that trigger outcomes (O) in Dutch community-based health-enhancing physical activity (CBHEPA) programs targeting socially vulnerable groups. Data were collected in six programs using semi-structured interviews and focus groups using a timeline technique. Sessions were recorded, anonymized, and transcribed. A realist synthesis protocol was used for data-driven and thematic analysis of CMO configurations. CMO configurations related to community outreach, program sustainability, intersectoral collaboration, and enhancing participants' active lifestyles. We have refined the CBHEPA program theory by showing that actors' passion for, and past experiences with, physical activity programs trigger outcomes, alongside their commitment to socially vulnerable target groups. Project discontinuity, limited access to resources, and a trainer's stand-alone position were negative configurations. The authors conclude that local governance structures appear often to lack adaptive capacity to accommodate multilevel processes to sustain programs.

Adverse drug reaction prediction using scores produced by large-scale drug-protein target docking on high-performance computing machines.

PubMed

LaBute, Montiago X; Zhang, Xiaohua; Lenderman, Jason; Bennion, Brian J; Wong, Sergio E; Lightstone, Felice C

2014-01-01

Late-stage or post-market identification of adverse drug reactions (ADRs) is a significant public health issue and a source of major economic liability for drug development. Thus, reliable in silico screening of drug candidates for possible ADRs would be advantageous. In this work, we introduce a computational approach that predicts ADRs by combining the results of molecular docking and leverages known ADR information from DrugBank and SIDER. We employed a recently parallelized version of AutoDock Vina (VinaLC) to dock 906 small molecule drugs to a virtual panel of 409 DrugBank protein targets. L1-regularized logistic regression models were trained on the resulting docking scores of a 560 compound subset from the initial 906 compounds to predict 85 side effects, grouped into 10 ADR phenotype groups. Only 21% (87 out of 409) of the drug-protein binding features involve known targets of the drug subset, providing a significant probe of off-target effects. As a control, associations of this drug subset with the 555 annotated targets of these compounds, as reported in DrugBank, were used as features to train a separate group of models. The Vina off-target models and the DrugBank on-target models yielded comparable median area-under-the-receiver-operating-characteristic-curves (AUCs) during 10-fold cross-validation (0.60-0.69 and 0.61-0.74, respectively). Evidence was found in the PubMed literature to support several putative ADR-protein associations identified by our analysis. Among them, several associations between neoplasm-related ADRs and known tumor suppressor and tumor invasiveness marker proteins were found. A dual role for interstitial collagenase in both neoplasms and aneurysm formation was also identified. These associations all involve off-target proteins and could not have been found using available drug/on-target interaction data. This study illustrates a path forward to comprehensive ADR virtual screening that can potentially scale with increasing number of CPUs to tens of thousands of protein targets and millions of potential drug candidates.

Using risk-adjustment models to identify high-cost risks.

PubMed

Meenan, Richard T; Goodman, Michael J; Fishman, Paul A; Hornbrook, Mark C; O'Keeffe-Rosetti, Maureen C; Bachman, Donald J

2003-11-01

We examine the ability of various publicly available risk models to identify high-cost individuals and enrollee groups using multi-HMO administrative data. Five risk-adjustment models (the Global Risk-Adjustment Model [GRAM], Diagnostic Cost Groups [DCGs], Adjusted Clinical Groups [ACGs], RxRisk, and Prior-expense) were estimated on a multi-HMO administrative data set of 1.5 million individual-level observations for 1995-1996. Models produced distributions of individual-level annual expense forecasts for comparison to actual values. Prespecified "high-cost" thresholds were set within each distribution. The area under the receiver operating characteristic curve (AUC) for "high-cost" prevalences of 1% and 0.5% was calculated, as was the proportion of "high-cost" dollars correctly identified. Results are based on a separate 106,000-observation validation dataset. For "high-cost" prevalence targets of 1% and 0.5%, ACGs, DCGs, GRAM, and Prior-expense are very comparable in overall discrimination (AUCs, 0.83-0.86). Given a 0.5% prevalence target and a 0.5% prediction threshold, DCGs, GRAM, and Prior-expense captured $963,000 (approximately 3%) more "high-cost" sample dollars than other models. DCGs captured the most "high-cost" dollars among enrollees with asthma, diabetes, and depression; predictive performance among demographic groups (Medicaid members, members over 64, and children under 13) varied across models. Risk models can efficiently identify enrollees who are likely to generate future high costs and who could benefit from case management. The dollar value of improved prediction performance of the most accurate risk models should be meaningful to decision-makers and encourage their broader use for identifying high costs.

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

Genetic Manipulation of Lactococcus lactis by Using Targeted Group II Introns: Generation of Stable Insertions without Selection

PubMed Central

Frazier, Courtney L.; San Filippo, Joseph; Lambowitz, Alan M.; Mills, David A.

2003-01-01

Despite their commercial importance, there are relatively few facile methods for genomic manipulation of the lactic acid bacteria. Here, the lactococcal group II intron, Ll.ltrB, was targeted to insert efficiently into genes encoding malate decarboxylase (mleS) and tetracycline resistance (tetM) within the Lactococcus lactis genome. Integrants were readily identified and maintained in the absence of a selectable marker. Since splicing of the Ll.ltrB intron depends on the intron-encoded protein, targeted invasion with an intron lacking the intron open reading frame disrupted TetM and MleS function, and MleS activity could be partially restored by expressing the intron-encoded protein in trans. Restoration of splicing from intron variants lacking the intron-encoded protein illustrates how targeted group II introns could be used for conditional expression of any gene. Furthermore, the modified Ll.ltrB intron was used to separately deliver a phage resistance gene (abiD) and a tetracycline resistance marker (tetM) into mleS, without the need for selection to drive the integration or to maintain the integrant. Our findings demonstrate the utility of targeted group II introns as a potential food-grade mechanism for delivery of industrially important traits into the genomes of lactococci. PMID:12571038

A New Strategy to Reduce Influenza Escape: Detecting Therapeutic Targets Constituted of Invariance Groups

PubMed Central

Lao, Julie; Vanet, Anne

2017-01-01

The pathogenicity of the different flu species is a real public health problem worldwide. To combat this scourge, we established a method to detect drug targets, reducing the possibility of escape. Besides being able to attach a drug candidate, these targets should have the main characteristic of being part of an essential viral function. The invariance groups that are sets of residues bearing an essential function can be detected genetically. They consist of invariant and synthetic lethal residues (interdependent residues not varying or slightly varying when together). We analyzed an alignment of more than 10,000 hemagglutinin sequences of influenza to detect six invariance groups, close in space, and on the protein surface. In parallel we identified five potential pockets on the surface of hemagglutinin. By combining these results, three potential binding sites were determined that are composed of invariance groups located respectively in the vestigial esterase domain, in the bottom of the stem and in the fusion area. The latter target is constituted of residues involved in the spring-loaded mechanism, an essential step in the fusion process. We propose a model describing how this potential target could block the reorganization of the hemagglutinin HA2 secondary structure and prevent viral entry into the host cell. PMID:28257108

Sensitizing Black Adult and Youth Consumers to Targeted Food Marketing Tactics in Their Environments

PubMed Central

Isselmann DiSantis, Katherine; Kumanyika, Shiriki; Rohm Young, Deborah; Grier, Sonya A.; Lassiter, Vikki

2017-01-01

Food marketing environments of Black American consumers are heavily affected by ethnically-targeted marketing of sugar sweetened beverages, fast foods, and other products that may contribute to caloric overconsumption. This qualitative study assessed Black consumers’ responses to targeted marketing. Black adults (2 mixed gender groups; total n = 30) and youth (2 gender specific groups; total n = 35) from two U.S. communities participated before and after a sensitization procedure—a critical practice used to understand social justice concerns. Pre-sensitization focus groups elicited responses to scenarios about various targeted marketing tactics. Participants were then given an informational booklet about targeted marketing to Black Americans, and all returned for the second (post-sensitization) focus group one week later. Conventional qualitative content analysis of transcripts identified several salient themes: seeing the marketer’s perspective (“it’s about demand”; “consumers choose”), respect for community (“marketers are setting us up for failure”; “making wrong assumptions”), and food environments as a social justice issue (“no one is watching the door”; “I didn’t realize”). Effects of sensitization were reflected in participants’ stated reactions to the information in the booklet, and also in the relative occurrence of marketer-oriented themes and social justice-oriented themes, respectively, less and more after sensitization. PMID:29109377

Sensitizing Black Adult and Youth Consumers to Targeted Food Marketing Tactics in Their Environments.

PubMed

Isselmann DiSantis, Katherine; Kumanyika, Shiriki; Carter-Edwards, Lori; Rohm Young, Deborah; Grier, Sonya A; Lassiter, Vikki

2017-10-29

Food marketing environments of Black American consumers are heavily affected by ethnically-targeted marketing of sugar sweetened beverages, fast foods, and other products that may contribute to caloric overconsumption. This qualitative study assessed Black consumers' responses to targeted marketing. Black adults (2 mixed gender groups; total n = 30) and youth (2 gender specific groups; total n = 35) from two U.S. communities participated before and after a sensitization procedure-a critical practice used to understand social justice concerns. Pre-sensitization focus groups elicited responses to scenarios about various targeted marketing tactics. Participants were then given an informational booklet about targeted marketing to Black Americans, and all returned for the second (post-sensitization) focus group one week later. Conventional qualitative content analysis of transcripts identified several salient themes: seeing the marketer's perspective ("it's about demand"; "consumers choose"), respect for community ("marketers are setting us up for failure"; "making wrong assumptions"), and food environments as a social justice issue ("no one is watching the door"; "I didn't realize"). Effects of sensitization were reflected in participants' stated reactions to the information in the booklet, and also in the relative occurrence of marketer-oriented themes and social justice-oriented themes, respectively, less and more after sensitization.

Opposites Detract: Middle School Peer Group Antipathies

PubMed Central

Laursen, Brett; Bukowski, William M.; Nurmi, Jari-Eri; Marion, Donna; Salmela-Aro, Katariina; Kiuru, Noona

2010-01-01

This study examines variability in patterns of peer group antipathy. Same-grade adolescent peer groups were identified from sociometric nominations of preferred affiliates in a community sample of 600 Finnish 9th grade middle school students (M = 15.0 years-old). Hierarchical linear modeling determined characteristics of youth in actor groups (nominators) that predicted antipathy for youth in target groups (nominatees) on the basis of target group characteristics. Most antipathies were based on dissimilarity between groups representing the mainstream culture and groups opposed to it. The higher a peer group's school burnout, the more its members disliked students in peer groups with higher school grades and students in peer groups with higher sports participation. Conversely, the higher a peer group's school grades, the more its members disliked students in peer groups with higher school burnout. Students in peer groups with less problem behavior disliked students in peer groups with more problem behavior. There was some evidence of rivalry within the mainstream culture: The higher a group's school grades, the more its members disliked those in groups whose members participated in sports. PMID:20378125

Identifying depressive symptom trajectory groups among Korean adults and psychosocial factors as group determinants.

PubMed

Kwon, Tae Yeon

2015-06-01

Longitudinal research is needed to examine the depressive symptom trajectories of different groups during adulthood and their antecedents and consequences, because depressive symptoms may be changeable and heterogeneous over time. This study examined the number of trajectory groups describing the depressive symptoms of Korean adults, as well as the shape of the trajectories and the association between trajectory group membership and psychosocial factors identified based on the ecosystem model. This study used Nagin's semi-parametric group-based modeling to analyze Year 1 to Year 7 data from Korea Welfare Panel Survey (N = 13,735), a nationally representative sample of community-dwelling adults. Three distinct trajectory groups were identified: a low stable depressive symptoms group, a moderate depressive symptoms group and a high depressive symptoms group. Result from multinominal logit analysis showed that all psychosocial factors except family relationships affected the likelihood of membership in the three depressive symptoms groups. Especially, self-esteem was the psychosocial factor with the largest impact on depressive symptom trajectory group membership. When screening for depressive symptoms, individuals with a low socioeconomic status should be a primary concern and intervention should be made available to them. Prevention or intervention with members of the identified trajectory groups would likely require integrative approaches targeting psychosocial factors across multiple contexts. © The Author(s) 2015.

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

Age-Related Changes in Temporal Allocation of Visual Attention: Evidence from the Rapid Serial Visual Presentation (RSVP) Paradigm

ERIC Educational Resources Information Center

Berger, Carole; Valdois, Sylviane; Lallier, Marie; Donnadieu, Sophie

2015-01-01

The present study explored the temporal allocation of attention in groups of 8-year-old children, 10-year-old children, and adults performing a rapid serial visual presentation task. In a dual-condition task, participants had to detect a briefly presented target (T2) after identifying an initial target (T1) embedded in a random series of…

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.

The Contrast Between Title I and Non-Title I Schools.

ERIC Educational Resources Information Center

Fortune, Jim C.; Hutchinson, Thomas E.

The problem addressed in this paper is to compare the schools identified as participating in Title I, 1965 Elementary Secondary Education Act programs, with those identified as not participating in Title I, with regard to percentage of pupils on welfare, number of target group pupils, percentage of pupils reading below grade level, percentage of…

Identification of tissue-specific targeting peptide

NASA Astrophysics Data System (ADS)

Jung, Eunkyoung; Lee, Nam Kyung; Kang, Sang-Kee; Choi, Seung-Hoon; Kim, Daejin; Park, Kisoo; Choi, Kihang; Choi, Yun-Jaie; Jung, Dong Hyun

2012-11-01

Using phage display technique, we identified tissue-targeting peptide sets that recognize specific tissues (bone-marrow dendritic cell, kidney, liver, lung, spleen and visceral adipose tissue). In order to rapidly evaluate tissue-specific targeting peptides, we performed machine learning studies for predicting the tissue-specific targeting activity of peptides on the basis of peptide sequence information using four machine learning models and isolated the groups of peptides capable of mediating selective targeting to specific tissues. As a representative liver-specific targeting sequence, the peptide "DKNLQLH" was selected by the sequence similarity analysis. This peptide has a high degree of homology with protein ligands which can interact with corresponding membrane counterparts. We anticipate that our models will be applicable to the prediction of tissue-specific targeting peptides which can recognize the endothelial markers of target tissues.

Targeted physical activity messages for parents of children with disabilities: A qualitative investigation of parents' informational needs and preferences.

PubMed

Bassett-Gunter, R L; Ruscitti, R J; Latimer-Cheung, A E; Fraser-Thomas, J L

2017-05-01

Physical activity (PA) has myriad benefits for children with disabilities (CWD). Information and messaging campaigns can promote PA among CWD. The overall purpose of the study was to gain an understanding of the development of PA information and messages targeting parents of CWD. The specific objectives were to identify parents' preferences regarding PA information and messaging content and preferred methods and sources of communication. Focus groups were conducted with parents of CWD (N=28). Qualitative data were collected and transcribed. Inductive content analyses were employed to identify key themes. Three key thematic areas were identified: 1) Preferred content (e.g., targeted information, self-regulatory strategies, inclusive images), 2) Challenges (e.g., lack of information and language clarity), 3) Preferred sources (e.g., other parents, reliable organizations, central information hub). Parents' needs and preferences regarding PA information could be incorporated into campaigns to enhance parent PA support and PA among CWD. Stakeholders (e.g., PA organizations, programs and practitioners) can employ these strategies in campaigns and resources targeting parents of CWD. Research is necessary to empirically develop and evaluate PA information and messaging campaigns targeting parents of CWD. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Whole CMV Proteome Pattern Recognition Analysis after HSCT Identifies Unique Epitope Targets Associated with the CMV Status

PubMed Central

Pérez-Bercoff, Lena; Valentini, Davide; Gaseitsiwe, Simani; Mahdavifar, Shahnaz; Schutkowski, Mike; Poiret, Thomas; Pérez-Bercoff, Åsa; Ljungman, Per; Maeurer, Markus J.

2014-01-01

Cytomegalovirus (CMV) infection represents a vital complication after Hematopoietic Stem Cell Transplantation (HSCT). We screened the entire CMV proteome to visualize the humoral target epitope-focus profile in serum after HSCT. IgG profiling from four patient groups (donor and/or recipient +/− for CMV) was performed at 6, 12 and 24 months after HSCT using microarray slides containing 17174 of 15mer-peptides overlapping by 4 aa covering 214 proteins from CMV. Data were analyzed using maSigPro, PAM and the ‘exclusive recognition analysis (ERA)’ to identify unique CMV epitope responses for each patient group. The ‘exclusive recognition analysis’ of serum epitope patterns segregated best 12 months after HSCT for the D+/R+ group (versus D−/R−). Epitopes were derived from UL123 (IE1), UL99 (pp28), UL32 (pp150), this changed at 24 months to 2 strongly recognized peptides provided from UL123 and UL100. Strongly (IgG) recognized CMV targets elicited also robust cytokine production in T-cells from patients after HSCT defined by intracellular cytokine staining (IL-2, TNF, IFN and IL-17). High-content peptide microarrays allow epitope profiling of entire viral proteomes; this approach can be useful to map relevant targets for diagnostics and therapy in patients with well defined clinical endpoints. Peptide microarray analysis visualizes the breadth of B-cell immune reconstitution after HSCT and provides a useful tool to gauge immune reconstitution. PMID:24740411

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.

Making the case for change: What researchers need to consider when designing behavior change interventions aimed at improving medication dispensing.

PubMed

Cadogan, Cathal A; Ryan, Cristín; Hughes, Carmel

2016-01-01

There is a growing emphasis on behavior change in intervention development programmes aimed at improving public health and healthcare professionals' practice. A number of frameworks and methodological tools have been established to assist researchers in developing interventions seeking to change healthcare professionals' behaviors. The key features of behavior change intervention design involve specifying the target group (i.e. healthcare professional or patient cohort), the target behavior and identifying mediators (i.e. barriers and facilitators) of behavior change. Once the target behavior is clearly specified and understood, specific behavior change techniques can then be used as the basis of the intervention to target identified mediators of behavior change. This commentary outlines the challenges for pharmacy practice-based researchers in targeting dispensing as a behavior when developing behavior change interventions aimed at pharmacists and proposes a definition of dispensing to consider in future research. Copyright © 2016 Elsevier Inc. All rights reserved.

The whole-genome landscape of medulloblastoma subtypes

PubMed Central

Northcott, Paul A.; Buchhalter, Ivo; Morrissy, A. Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Groebner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H.; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M.; Erkek, Serap; Jones, David T.W.; Worst, Barbara C.; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D.; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D.; Wolf, Stephan; Robinson, Giles W.; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M.G.; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L.; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M.; Mora, Jaume; McLendon, Roger E.; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J.M.; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O.; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A.; Pfister, Stefan M.; Taylor, Michael D.; Lichter, Peter

2018-01-01

Summary Current therapies for medulloblastoma (MB), a highly malignant childhood brain tumor, impose debilitating effects on the developing child, warranting deployment of molecularly targeted treatments with reduced toxicities. Prior studies failed to disclose the full spectrum of driver genes and molecular processes operative in MB subgroups. Herein, we detail the somatic landscape across 491 sequenced MBs and molecular heterogeneity amongst 1,256 epigenetically analyzed cases, identifying subgroup-specific driver alterations including previously unappreciated actionable targets. Driver mutations explained the majority of Group 3 and Group 4 patients, remarkably enhancing previous knowledge. Novel molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions targeting KBTBD4 and ‘enhancer hijacking’ driving PRDM6 activation. Thus, application of integrative genomics to an unprecedented cohort of clinical samples derived from a single childhood cancer entity disclosed a series of new cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for treating MB patients. PMID:28726821

An ecological model of the Northern and Central Adriatic Sea: Analysis of ecosystem structure and fishing impacts

NASA Astrophysics Data System (ADS)

Coll, Marta; Santojanni, Alberto; Palomera, Isabel; Tudela, Sergi; Arneri, Enrico

2007-08-01

A trophic mass-balance model was developed to characterise the food web structure and functioning of the Northern and Central Adriatic Sea and to quantify the ecosystem impacts of fishing during the 1990s. Forty functional groups were described, including target and non-target fish and invertebrate groups, and three detritus groups (natural detritus, discards and by-catch of cetaceans and marine turtles). Results highlighted that there was an important coupling between pelagic-benthic production of plankton, benthic invertebrates and detritus. Organisms located at low and medium trophic levels, (i.e. benthic invertebrates, zooplankton and anchovy), as well as dolphins, were identified as keystone groups of the ecosystem. Jellyfish were an important element in terms of consumption and production of trophic flows within the ecosystem. The analysis of trophic flows of zooplankton and detritus groups indirectly underlined the importance of the microbial food web in the Adriatic Sea. Fishing activities inflicted notable impacts on the ecosystem during the 1990s, with a high gross efficiency of the fishery, a high consumption of fishable production, high exploitation rates for various target and non target species, a low trophic level of the catch and medium values of primary production required to sustain the fishery. Moreover, the analysis of Odum's ecological indicators highlighted that the ecosystem was in a low-medium developmental stage. Bottom trawling ( Strascico), mid-water trawling ( Volante) and beam trawling ( Rapido) fleets had the highest impacts on both target and non target ecological groups. On the contrary, purse seining ( Lampara) showed medium to low impacts on the ecosystem; cetaceans, marine turtles and sea birds were not significantly involved in competition with fishing activity.

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.

Depression screening with patient-targeted feedback in cardiology: DEPSCREEN-INFO randomised clinical trial.

PubMed

Löwe, Bernd; Blankenberg, Stefan; Wegscheider, Karl; König, Hans-Helmut; Walter, Dirk; Murray, Alexandra M; Gierk, Benjamin; Kohlmann, Sebastian

2017-02-01

International guidelines advocate depression screening in patients with coronary heart disease (CHD) and other chronic illnesses, but evidence is lacking. To test the differential efficacy of written patient-targeted feedback v. no written patient feedback after depression screening. Patients with CHD or hypertension from three cardiology settings were randomised and screened for depression (ClinicalTrials.gov Identifier: NCT01879111). Compared with the control group, where only cardiologists received written feedback, in the intervention group both cardiologists and patients received written feedback regarding depression status. Depression severity was measured 1 month (primary outcome) and 6 months after screening. The control group (n = 220) and the patient-feedback group (n = 155) did not differ in depression severity 1 month after screening. Six months after screening, the patient-feedback group showed significantly greater improvements in depression severity and was twice as likely to seek information about depression compared with the control group. Patient-targeted feedback in addition to screening has a significant but small effect on depression severity after 6 months and may encourage patients to take an active role in the self-management of depression. © The Royal College of Psychiatrists 2017.

Targeting nursing homes under the Quality Improvement Organization program's 9th statement of work.

PubMed

Stevenson, David G; Mor, Vincent

2009-09-01

In the Quality Improvement Organization (QIO) program's latest Statement of Work, the Centers for Medicare and Medicaid Services (CMS) is targeting its nursing home activities toward facilities that perform poorly on two quality measures-pressure ulcers and restraint use. The designation of target facilities is a shift in strategy for CMS and a direct response to criticism that QIO program resources were not being targeted effectively to facilities or clinical areas that most needed improvement. Using administrative data, this article analyzes implications of using narrowly defined criteria to identify facilities that need improvement, particularly in light of considerable evidence showing that nursing home quality is multidimensional and may change over time. The analyses show that one in four facilities is targeted for improvement nationally but that approximately half of some states' facilities are targeted while other states have almost none targeted. The analyses also convey deeper limitations to using threshold values on individual measures to identify poorly performing homes. Target facilities can be among the top performers on a range of other quality measures, and their performance on targeted measures themselves may change over time. The implication of these features is that a very different group of facilities would have been chosen had the QIO program targeted other measures or examined performance at a different point in time. Ultimately, CMS has chosen a blunt instrument to identify poorly performing nursing homes, and supplemental strategies-such as soliciting input from state survey agencies and more closely aligning quality improvement and quality assurance efforts-should be considered to address potential limitations.

Switching on after nine: Black gay-identified men’s perceptions of sexual identities and partnerships in South African towns

PubMed Central

Mantell, Joanne; Tocco, Jack; Osmand, Thomas; Sandfort, Theo; Lane, Tim

2016-01-01

There is considerable diversity, fluidity and complexity in the expressions of sexuality and gender among men who have sex with men (MSM). Some non-gay identified MSM are known colloquially by gay-identified men in Mpumalanga, South Africa, as “After-Nines” because they do not identify as gay and present as straight during the day but also have sex with other men at night. Based on targeted ethnography, including structured observations, key informant interviews and focus group discussions in two districts in Mpumalanga, we explored Black gay-identified men’s perceptions of and relationships with After-Nine men, focusing on sexual and gender identities and their social consequences. Gay-identified men expressed ambivalence about their After-Nine partners, desiring them for their masculinity, yet often feeling dissatisfied and exploited in their relationships with them. The exchange of sex for commodities, especially alcohol, was common. Gay men’s characterisation of After-Nines as men who ignore them during the day but have sex them at night highlights the diversity of how same-sex practicing men perceive themselves and their sexual partners. Sexual health promotion programmes targeting ‘MSM’ must understand this diversity to effectively support the community in developing strategies for reaching and engaging different groups of gay and non-gay identified men. PMID:26878380

Oxygen Saturation Targets in Preterm Infants and Outcomes at 18–24 Months: A Systematic Review

PubMed Central

Manja, Veena; Saugstad, Ola D.

2017-01-01

CONTEXT: The optimal oxygen saturation target for extremely preterm infants remains unclear. OBJECTIVE: To systematically review evidence evaluating the effect of lower (85%–89%) versus higher (91%–95%) pulse oxygen saturation (Spo2) target on mortality and neurodevelopmental impairment (NDI) at 18 to 24 months. DATA SOURCES: Electronic databases and all published randomized trials evaluating lower versus higher Spo2 target in preterm infants. STUDY SELECTION: A total of 2896 relevant citations were identified; 5 trials were included in the final analysis. DATA EXTRACTION: Data from 5 trials were analyzed for quality of evidence and risk of bias. LIMITATIONS: Limitations include heterogeneity in age at enrollment and comorbidities between trials and change in oximeter algorithm midway through 3 trials. RESULTS: There was no difference in the incidence of primary outcome (death/NDI at 18–24 months) in the 2 groups; risk ratio,1.05, 95% confidence interval 0.98–1.12, P = .18. Mortality before 18 to 24 months was higher in the lower-target group (risk ratio,1.16, 95% confidence interval 1.03–1.31, P = .02). Rates of NDI and severe visual loss did not differ between the 2 groups. Proportion of time infants spent outside the target range while on supplemental oxygen ranged from 8.2% to 27.4% <85% and 8.1% to 22.4% >95% with significant overlap between the 2 groups. CONCLUSIONS: There was no difference in primary outcome between the 2 Spo2 target groups. The collective data suggest that risks associated with restricting the upper Spo2 target limit to 89% outweigh the benefits. The quality of evidence was moderate. We speculate that a wider target range (lower alarm limit, 89% and upper, 96%) may increase time spent within range, but the safety profile of this approach remains to be determined. PMID:27940510

Educational services in health sciences libraries: an analysis of the periodical literature, 1975-1986.

PubMed Central

Zachert, M J

1987-01-01

The periodical literature on group instructional services in health sciences libraries was analyzed to determine the nature of these services, their target audiences, and their institutional settings. Three kinds of reports were identified: descriptions of services (70%), reviews of the literature (10.5%), and future-oriented articles that advocate various group instructional services (19.5%). Five target audiences were identified: library users, staff, librarian peers, library science students, and patients. Instructional services were offered primarily in medical school/center libraries, hospital libraries, and the National Library of Medicine and its Regional Medical Libraries (RMLs). To a lesser extent, health sciences educational services are offered through other professional school libraries, library associations and consortia, and schools of library science. There are gaps in the literature in the areas of library experience with marketing, evaluation, administration of the offered educational services, and continuing education for health sciences librarians. PMID:3676534

Educational services in health sciences libraries: an analysis of the periodical literature, 1975-1986.

PubMed

Zachert, M J

1987-07-01

The periodical literature on group instructional services in health sciences libraries was analyzed to determine the nature of these services, their target audiences, and their institutional settings. Three kinds of reports were identified: descriptions of services (70%), reviews of the literature (10.5%), and future-oriented articles that advocate various group instructional services (19.5%). Five target audiences were identified: library users, staff, librarian peers, library science students, and patients. Instructional services were offered primarily in medical school/center libraries, hospital libraries, and the National Library of Medicine and its Regional Medical Libraries (RMLs). To a lesser extent, health sciences educational services are offered through other professional school libraries, library associations and consortia, and schools of library science. There are gaps in the literature in the areas of library experience with marketing, evaluation, administration of the offered educational services, and continuing education for health sciences librarians.

Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs.

PubMed

Zhang, Chengjuan; Wei, Bing; Li, Peng; Yang, Ke; Wang, Zhizhong; Ma, Jie; Guo, Yongjun

2017-01-01

Epidermal growth factor receptor (EGFR) specific mutations have been known to improve survival of patients with non-small-cell lung carcinoma (NSCLC). However, whether there are any changes of EGFR mutations after targeted therapy and its clinical significance is unclear. This study was to identify the status of EGFR mutations after targeted therapy and predict the prognostic significance for NSCLC patients. A total of forty-five (45) NSCLC patients who received EGFR-TKI therapy were enrolled. We identified the changes of EGFR mutations in plasma ctDNA by Amplification Refractory Mutation System (ARMS) PCR technology. In the 45 cases of NSCLC with EGFR mutations, the EGFR mutation status changed in 26 cases, in which, 12 cases (26.7%) from positive to negative, and 14 cases (31.1%) from T790M mutation negative to positive after TKI targeted therapy. The T790M occurance group had a shorter Progression -Free-Survival (PFS) than the groups of EGFR mutation undetected and EGFR mutation turned out to have no change after EGFR-TKI therapy (p < 0.05). According to this study, it's necessary to closely monitor EGFR mutations during follow-up to predict the prognosis of NSCLC patients who are to receive the TKI targeted therapy.

Targeted Metabolomics Demonstrates Distinct and Overlapping Maternal Metabolites Associated With BMI, Glucose, and Insulin Sensitivity During Pregnancy Across Four Ancestry Groups.

PubMed

Jacob, Saya; Nodzenski, Michael; Reisetter, Anna C; Bain, James R; Muehlbauer, Michael J; Stevens, Robert D; Ilkayeva, Olga R; Lowe, Lynn P; Metzger, Boyd E; Newgard, Christopher B; Scholtens, Denise M; Lowe, William L

2017-07-01

We used targeted metabolomics in pregnant mothers to compare maternal metabolite associations with maternal BMI, glycemia, and insulin sensitivity. Targeted metabolomic assays of clinical metabolites, amino acids, and acylcarnitines were performed on fasting and 1-h postglucose serum samples from European ancestry, Afro-Caribbean, Thai, and Mexican American mothers (400 from each ancestry group) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and underwent an oral glucose tolerance test at ∼28 weeks gestation. K-means clustering, which identified patterns of metabolite levels across ancestry groups, demonstrated that, at both fasting and 1-h, levels of the majority of metabolites were similar across ancestry groups. Meta-analyses demonstrated association of a broad array of fasting and 1-h metabolites, including lipids and amino acids and their metabolites, with maternal BMI, glucose levels, and insulin sensitivity before and after adjustment for the different phenotypes. At fasting and 1 h, a mix of metabolites was identified that were common across phenotypes or associated with only one or two phenotypes. Partial correlation estimates, which allowed comparison of the strength of association of different metabolites with maternal phenotypes, demonstrated that metabolites most strongly associated with different phenotypes included some that were common across as well as unique to each phenotype. Maternal BMI and glycemia have metabolic signatures that are both shared and unique to each phenotype. These signatures largely remain consistent across different ancestry groups and may contribute to the common and independent effects of these two phenotypes on adverse pregnancy outcomes. © 2017 by the American Diabetes Association.

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.

Modeling health gains and cost savings for ten dietary salt reduction targets.

PubMed

Wilson, Nick; Nghiem, Nhung; Eyles, Helen; Mhurchu, Cliona Ni; Shields, Emma; Cobiac, Linda J; Cleghorn, Christine L; Blakely, Tony

2016-04-26

Dietary salt reduction is included in the top five priority actions for non-communicable disease control internationally. We therefore aimed to identify health gain and cost impacts of achieving a national target for sodium reduction, along with component targets in different food groups. We used an established dietary sodium intervention model to study 10 interventions to achieve sodium reduction targets. The 2011 New Zealand (NZ) adult population (2.3 million aged 35+ years) was simulated over the remainder of their lifetime in a Markov model with a 3 % discount rate. Achieving an overall 35 % reduction in dietary salt intake via implementation of mandatory maximum levels of sodium in packaged foods along with reduced sodium from fast foods/restaurant food and discretionary intake (the "full target"), was estimated to gain 235,000 QALYs over the lifetime of the cohort (95 % uncertainty interval [UI]: 176,000 to 298,000). For specific target components the range was from 122,000 QALYs gained (for the packaged foods target) down to the snack foods target (6100 QALYs; and representing a 34-48 % sodium reduction in such products). All ten target interventions studied were cost-saving, with the greatest costs saved for the mandatory "full target" at NZ$1260 million (US$820 million). There were relatively greater health gains per adult for men and for Māori (indigenous population). This work provides modeling-level evidence that achieving dietary sodium reduction targets (including specific food category targets) could generate large health gains and cost savings for a national health sector. Demographic groups with the highest cardiovascular disease rates stand to gain most, assisting in reducing health inequalities between sex and ethnic groups.

Presence and Image of Women in the Information Media Aimed at Adolescents Aged 10 to 16.

ERIC Educational Resources Information Center

Dansereau, Stephanie; Maranda, Jeanne

An exploratory study identified the areas of information most commonly featured in the printed and electronic media designed specifically for adolescents aged 10-16 and also identified the presence and role of women in the information targeted to this age group. A content analysis was made of both French- and English-language television programs…

The Identification of Reasons, Solutions, and Techniques Informing a Theory-Based Intervention Targeting Recreational Sports Participation

ERIC Educational Resources Information Center

St Quinton, Tom; Brunton, Julie A.

2018-01-01

Purpose: This study is the 3rd piece of formative research utilizing the theory of planned behavior to inform the development of a behavior change intervention. Focus groups were used to identify reasons for and solutions to previously identified key beliefs in addition to potentially effective behavior change techniques. Method: A purposive…

New Wnt/β-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals.

PubMed

Qi, Jingjing; Yu, Yong; Akilli Öztürk, Özlem; Holland, Jane D; Besser, Daniel; Fritzmann, Johannes; Wulf-Goldenberg, Annika; Eckert, Klaus; Fichtner, Iduna; Birchmeier, Walter

2016-10-01

We have previously identified a 115-gene signature that characterises the metastatic potential of human primary colon cancers. The signature included the canonical Wnt target gene BAMBI, which promoted experimental metastasis in mice. Here, we identified three new direct Wnt target genes from the signature, and studied their functions in epithelial-mesenchymal transition (EMT), cell migration and experimental metastasis. We examined experimental liver metastases following injection of selected tumour cells into spleens of NOD/SCID mice. Molecular and cellular techniques were used to identify direct transcription target genes of Wnt/β-catenin signals. Microarray analyses and experiments that interfered with cell migration through inhibitors were performed to characterise downstream signalling systems. Three new genes from the colorectal cancer (CRC) metastasis signature, BOP1, CKS2 and NFIL3, were identified as direct transcription targets of β-catenin/TCF4. Overexpression and knocking down of these genes in CRC cells promoted and inhibited, respectively, experimental metastasis in mice, EMT and cell motility in culture. Cell migration was repressed by interfering with distinct signalling systems through inhibitors of PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. Gene expression profiling identified a series of migration-promoting genes, which were induced by BOP1, CKS2 and NFIL3, and could be repressed by inhibitors that are specific to these pathways. We identified new direct Wnt/β-catenin target genes, BOP1, CKS2 and NFIL3, which induced EMT, cell migration and experimental metastasis of CRC cells. These genes crosstalk with different downstream signalling systems, and activate migration-promoting genes. These pathways and downstream genes may serve as therapeutic targets in the treatment of CRC metastasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Planning for sedentary behaviour interventions: office workers' survey and focus group responses.

PubMed

McGuckin, Teneale; Sealey, Rebecca; Barnett, Fiona

2017-11-01

As sedentary behaviour is becoming more prominent in office-based work environments, this study aimed to explore office workers' perceptions of sedentary behaviour, explore potential behavioural strategies to reduce sedentary behaviour in the workplace and identify barriers which may hamper behaviour change. A total of 140 office workers were recruited and surveyed from the same workplace. The survey included questions regarding perceptions of the relationship between sitting time and health. Following the survey, 12 employees also participated in focus groups to identify potential sedentary behaviour intervention strategies and barriers. The responses from the survey and focus groups were thematically analysed. In total, 88% of all participants surveyed agreed that there was a relationship between sitting time and their health. The most prominent theme identified was musculoskeletal complaints followed by general health and weight gain or obesity. The focus groups identified that interventions targeting reducing sitting time should include education, supportive and knowledgeable managers, and a variety of behaviour change strategies to address individual preferences and barriers. Multiple behavioural strategies were identified, which appear to be appropriate for sedentary behaviour change.

Today's Recruitment Trends.

ERIC Educational Resources Information Center

Sugarman, Joe

1996-01-01

Five trends in the creation of college student recruitment publications are identified: (1) using market research and marketing principles; (2) targeting specific groups; (3) honesty about campus personality and reputation; (4) cost-effectiveness; and (5) creativity in using effective copy and design. (MSE)

Specialized transit and elderly, disabled, and families in poverty populations

DOT National Transportation Integrated Search

2001-03-01

This report presents results of three separate listening sessions to identify the transportation accessibility issues for a target group of users: the elderly, the disabled, and families in poverty. The sessions revealed that the need for coordinated...

Carbonylated plasma proteins as potential biomarkers of obesity induced type 2 diabetes mellitus.

PubMed

Bollineni, Ravi Chand; Fedorova, Maria; Blüher, Matthias; Hoffmann, Ralf

2014-11-07

Protein carbonylation is a common nonenzymatic oxidative post-translational modification, which is often considered as biomarker of oxidative stress. Recent evidence links protein carbonylation also to obesity and type 2 diabetes mellitus (T2DM), though the protein targets of carbonylation in human plasma have not been identified. In this study, we profiled carbonylated proteins in plasma samples obtained from lean individuals and obese patients with or without T2DM. The plasma samples were digested with trypsin, carbonyl groups were derivatized with O-(biotinylcarbazoylmethyl)hydroxylamine, enriched by avidin affinity chromatography, and analyzed by RPC-MS/MS. Signals of potentially modified peptides were targeted in a second LC-MS/MS analysis to retrieve the peptide sequence and the modified residues. A total of 158 unique carbonylated proteins were identified, of which 52 were detected in plasma samples of all three groups. Interestingly, 36 carbonylated proteins were detected only in obese patients with T2DM, whereas 18 were detected in both nondiabetic groups. The carbonylated proteins originated mostly from liver, plasma, platelet, and endothelium. Functionally, they were mainly involved in cell adhesion, signaling, angiogenesis, and cytoskeletal remodeling. Among the identified carbonylated proteins were several candidates, such as VEGFR-2, MMP-1, argin, MKK4, and compliment C5, already connected before to diabetes, obesity and metabolic diseases.

Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing.

PubMed

Valdés-Alemán, Javier; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Godoy-Lozano, Elizabeth; Velázquez-Ramírez, Daniel; Valdovinos-Torres, Humberto; Gómez-Barreto, Rosa E; Martinez-Barnetche, Jesús

2014-01-01

High-throughput sequencing of the antibody repertoire is enabling a thorough analysis of B cell diversity and clonal selection, which may improve the novel antibody discovery process. Theoretically, an adequate bioinformatic analysis could allow identification of candidate antigen-specific antibodies, requiring their recombinant production for experimental validation of their specificity. Gene synthesis is commonly used for the generation of recombinant antibodies identified in silico. Novel strategies that bypass gene synthesis could offer more accessible antibody identification and validation alternatives. We developed a hybridization-based recovery strategy that targets the complementarity-determining region 3 (CDRH3) for the enrichment of cDNA of candidate antigen-specific antibody sequences. Ten clonal groups of interest were identified through bioinformatic analysis of the heavy chain antibody repertoire of mice immunized with hen egg white lysozyme (HEL). cDNA from eight of the targeted clonal groups was recovered efficiently, leading to the generation of recombinant antibodies. One representative heavy chain sequence from each clonal group recovered was paired with previously reported anti-HEL light chains to generate full antibodies, later tested for HEL-binding capacity. The recovery process proposed represents a simple and scalable molecular strategy that could enhance antibody identification and specificity assessment, enabling a more cost-efficient generation of recombinant antibodies.

Identification of Protein Targets of 12/15-Lipoxygenase-Derived Lipid Electrophiles in Mouse Peritoneal Macrophages Using Omega-Alkynyl Fatty Acid.

PubMed

Isobe, Yosuke; Kawashima, Yusuke; Ishihara, Tomoaki; Watanabe, Kenji; Ohara, Osamu; Arita, Makoto

2018-04-20

The 12/15-lipoxygenase (12/15-LOX) enzyme introduces peroxyl groups, in a position-specific manner, into polyunsaturated fatty acids to form various kinds of bioactive lipid metabolites, including lipid-derived electrophiles (LDE). The resident peritoneal macrophage is the site of highest 12/15-LOX expression in the mouse. However, the role of the enzyme in the regulation of resident macrophages is not fully understood. Here, we describe a chemoproteomic method to identify the targets of enzymatically generated LDE. By treating mouse peritoneal macrophages with omega-alkynyl arachidonic acid (aAA), we identified a series of proteins adducted by LDE generated through a 12/15-LOX catalyzed reaction. Pathway analysis revealed a dramatic enrichment of proteins involved in energy metabolism and found that glycolytic flux and mitochondrial respiration were significantly affected by the expression of 12/15-LOX. Our findings thus highlight the utility of chemoproteomics using aAA for identifying intracellular targets of enzymatically generated LDE.

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

Targeted Embolization of Aneurysms Associated With Brain Arteriovenous Malformations at High Risk for Surgical Resection: A Case-Control Study.

PubMed

Alexander, Matthew D; Hippe, Daniel S; Cooke, Daniel L; Hallam, Danial K; Hetts, Steven W; Kim, Helen; Lawton, Michael T; Sekhar, Laligam N; Kim, Louis J; Ghodke, Basavaraj V

2018-03-01

High-risk components of brain arteriovenous malformations (BAVMs) can be targeted to reduce the risk of lesion rupture. To evaluate targeted embolization of aneurysms against other means of treatment with a case-control analysis; we previously investigated this approach associated with BAVMs. Retrospective analysis of patients with BAVMs was performed, identifying patients treated with intention to occlude only an aneurysm associated with a BAVM. For each targeted aneurysm embolization (TAE) patient identified, 4 control patients were randomly selected, controlling for rupture status, age, and Spetzler-Martin plus Lawton-Young supplemental score. Analysis was performed to compare rates of adverse events (hemorrhage, new seizure, and death) between the 2 groups. Thirty-two patients met inclusion criteria, and 128 control patients were identified, out of 1103 patients treated during the study period. Thirty-four adverse events occurred (15 ruptures, 15 new seizures, and 11 deaths) during the follow-up period (mean 1157 d for the TAE cohort and 1036 d for the non-TAE cohort). Statistically lower associations were noted for the TAE group for any adverse event (hazard ratio 0.28, P = .037) and the composite outcome of hemorrhage or new seizure (hazard ratio 0.20, P = .029). For BAVMs at high risk for surgical resection, TAE can be performed safely and effectively. Patients treated with TAE had better outcomes than matched patients undergoing other combinations of treatment. TAE can be considered for BAVMs with high operative risk prior to radiosurgery or when no other treatment options are available. Copyright © 2017 by the Congress of Neurological Surgeons

Comparison of the nutritional content of products, with and without nutrient claims, targeted at children in Brazil.

PubMed

Rodrigues, Vanessa Mello; Rayner, Mike; Fernandes, Ana Carolina; de Oliveira, Renata Carvalho; Proença, Rossana Pacheco da Costa; Fiates, Giovanna Medeiros Rataichesck

2016-06-01

Many children's food products highlight positive attributes on their front-of-package labels in the form of nutrient claims. This cross-sectional study investigated all retailed packaged foods (n 5620) in a major Brazilian supermarket, in order to identify the availability of products targeted at children, and to compare the nutritional content of products with and without nutrient claims on labels. Data on energy, carbohydrate, protein, fibre, Na and total and SFA content, along with the presence and type of nutrient claims, were obtained in-store from labels of all products. Products targeted at children were identified, divided into eight food groups and compared for their nutritional content per 100 g/ml and the presence of nutrient claims using the Mann-Whitney U test (P<0·05). Of the 535 food products targeted at children (9·5 % of all products), 270 (50·5 %) displayed nutrient claims on their labels. Children's products with nutrient claims had either a similar or worse nutritional content than their counterparts without nutrient claims. The major differences among groups were found in Group 8 (e.g. sauces and ready meals), in which children's products bearing nutrient claims had higher energy, carbohydrate, Na and total and SFA content per 100 g/ml than products without nutrient claims (P<0·05). This suggests that, to prevent misleading parents who are seeking healthier products for their children, the regulation on the use of nutrient claims should be revised, so that only products with appropriate nutrient profiles are allowed to display them.

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.

Resistance to AHAS inhibitor herbicides: current understanding.

PubMed

Yu, Qin; Powles, Stephen B

2014-09-01

Acetohydroxyacid synthase (AHAS) inhibitor herbicides currently comprise the largest site-of-action group (with 54 active ingredients across five chemical groups) and have been widely used in world agriculture since they were first introduced in 1982. Resistance evolution in weeds to AHAS inhibitors has been rapid and identified in populations of many weed species. Often, evolved resistance is associated with point mutations in the target AHAS gene; however non-target-site enhanced herbicide metabolism occurs as well. Many AHAS gene resistance mutations can occur and be rapidly enriched owing to a high initial resistance gene frequency, simple and dominant genetic inheritance and lack of major fitness cost of the resistance alleles. Major advances in the elucidation of the crystal structure of the AHAS (Arabidopsis thaliana) catalytic subunit in complex with various AHAS inhibitor herbicides have greatly improved current understanding of the detailed molecular interactions between AHAS, cofactors and herbicides. Compared with target-site resistance, non-target-site resistance to AHAS inhibitor herbicides is less studied and hence less understood. In a few well-studied cases, non-target-site resistance is due to enhanced rates of herbicide metabolism (metabolic resistance), mimicking that occurring in tolerant crop species and often involving cytochrome P450 monooxygenases. However, the specific herbicide-metabolising, resistance-endowing genes are yet to be identified in resistant weed species. The current state of mechanistic understanding of AHAS inhibitor herbicide resistance is reviewed, and outstanding research issues are outlined. © 2013 Society of Chemical Industry.

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

Weight change in control group participants in behavioural weight loss interventions: a systematic review and meta-regression study

PubMed Central

2012-01-01

Background Unanticipated control group improvements have been observed in intervention trials targeting various health behaviours. This phenomenon has not been studied in the context of behavioural weight loss intervention trials. The purpose of this study is to conduct a systematic review and meta-regression of behavioural weight loss interventions to quantify control group weight change, and relate the size of this effect to specific trial and sample characteristics. Methods Database searches identified reports of intervention trials meeting the inclusion criteria. Data on control group weight change and possible explanatory factors were abstracted and analysed descriptively and quantitatively. Results 85 trials were reviewed and 72 were included in the meta-regression. While there was no change in control group weight, control groups receiving usual care lost 1 kg more than control groups that received no intervention, beyond measurement. Conclusions There are several possible explanations why control group changes occur in intervention trials targeting other behaviours, but not for weight loss. Control group participation may prevent weight gain, although more research is needed to confirm this hypothesis. PMID:22873682

Weight change in control group participants in behavioural weight loss interventions: a systematic review and meta-regression study.

PubMed

Waters, Lauren; George, Alexis S; Chey, Tien; Bauman, Adrian

2012-08-08

Unanticipated control group improvements have been observed in intervention trials targeting various health behaviours. This phenomenon has not been studied in the context of behavioural weight loss intervention trials. The purpose of this study is to conduct a systematic review and meta-regression of behavioural weight loss interventions to quantify control group weight change, and relate the size of this effect to specific trial and sample characteristics. Database searches identified reports of intervention trials meeting the inclusion criteria. Data on control group weight change and possible explanatory factors were abstracted and analysed descriptively and quantitatively. 85 trials were reviewed and 72 were included in the meta-regression. While there was no change in control group weight, control groups receiving usual care lost 1 kg more than control groups that received no intervention, beyond measurement. There are several possible explanations why control group changes occur in intervention trials targeting other behaviours, but not for weight loss. Control group participation may prevent weight gain, although more research is needed to confirm this hypothesis.

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.

[HPV-associated head and neck cancer. The basics of molecular and translational research].

PubMed

Wittekindt, C; Wagner, S; Klussmann, J P

2011-09-01

Translational research refers to the interfaces between preclinical research and targeted short- and medium-term developments through to clinical standards. There are two distinct groups of oropharyngeal malignancies: those caused by tobacco and alcohol abuse and those caused by HPV infection. Although the prognosis of patients in the latter group is significantly better, this is not taken into consideration in the choice of treatment. However, less intensive use of radiotherapy, chemotherapy, or surgery, as well as targeted multimodal therapeutic approaches, is under research. This article summarizes the main events in the HPV life cycle, with emphasis on carcinogenic mechanisms and potential new molecular targets. Identifying distinct tumor entities of the oropharynx enables the design and development of new preventive and therapeutic strategies to reduce the incidence and mortality of HPV-associated oropharyngeal cancers in the near future.

Transcription factor FOXA2-centered transcriptional regulation network in non-small cell lung cancer

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

Jang, Sang-Min; An, Joo-Hee; Kim, Chul-Hong

2015-08-07

Lung cancer is the leading cause of cancer-mediated death. Although various therapeutic approaches are used for lung cancer treatment, these mainly target the tumor suppressor p53 transcription factor, which is involved in apoptosis and cell cycle arrest. However, p53-targeted therapies have limited application in lung cancer, since p53 is found to be mutated in more than half of lung cancers. In this study, we propose tumor suppressor FOXA2 as an alternative target protein for therapies against lung cancer and reveal a possible FOXA2-centered transcriptional regulation network by identifying new target genes and binding partners of FOXA2 by using various screeningmore » techniques. The genes encoding Glu/Asp-rich carboxy-terminal domain 2 (CITED2), nuclear receptor subfamily 0, group B, member 2 (NR0B2), cell adhesion molecule 1 (CADM1) and BCL2-associated X protein (BAX) were identified as putative target genes of FOXA2. Additionally, the proteins including highly similar to heat shock protein HSP 90-beta (HSP90A), heat shock 70 kDa protein 1A variant (HSPA1A), histone deacetylase 1 (HDAC1) and HDAC3 were identified as novel interacting partners of FOXA2. Moreover, we showed that FOXA2-dependent promoter activation of BAX and p21 genes is significantly reduced via physical interactions between the identified binding partners and FOXA2. These results provide opportunities to understand the FOXA2-centered transcriptional regulation network and novel therapeutic targets to modulate this network in p53-deficient lung cancer. - Highlights: • Identification of new target genes of FOXA2. • Identifications of novel interaction proteins of FOXA2. • Construction of FOXA2-centered transcriptional regulatory network in non-small cell lung cancer.« less

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

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.

Who helps the leaders? Difficulties experienced by cancer support group leaders.

PubMed

Kirsten, Laura; Butow, Phyllis; Price, Melanie; Hobbs, Kim; Sunquist, Kendra

2006-07-01

Cancer support groups are an important source of support for cancer patients, yet little is known about the challenges and training needs of both professionally trained and untrained leaders. The aim of this study was to discover the difficulties experienced and training desired by cancer support group leaders. Twenty-seven leaders of 34 cancer support groups participated in focus groups or individual interviews. Groups were purposively selected as representative of 173 support groups identified in New South Wales which were for adults with cancer and/or their adult carers and were not therapeutic or education-only groups. Difficulties identified included dealing with people's different communication styles and needs; dealing with recurrence, metastases and death; practical issues, including resources, setting the programme and funding security; maintaining personal balance and preventing burn out; establishing group credibility; dealing with group cycles; and leading groups in rural areas. Leaders also identified benefits and rewards from group leadership such as contributing to others' well-being, self-development and insight into others' lives. Non-professionally trained leaders experienced more difficulties, particularly in dealing with group process and practical issues. Difficulties identified were related both to working with a cancer population specifically and to working with groups in general. While some issues were common to both health professionals and non-health professionals, non-health professionals reported greater supportive needs. Clear guidelines, targeted training and development of better methods of support to reduce the stress and burn out experienced by group leaders are needed.

Effectiveness of Simultaneous Prompting in Small Group: The Opportunity of Acquiring Non-Target Skills through Observational Learning and Instructive Feedback

ERIC Educational Resources Information Center

Gursel, Oguz; Tekin-Iftar, Elif; Bozkurt, Funda

2006-01-01

A multiple probe study across behaviors, replicated across students, assessed the effectiveness of simultaneous prompting (SP) in a small group teaching arrangement on teaching (a) to show the provinces, rivers, and border countries of Turkey on a map and (b) to expressively identify the names of the symbols which are usually used in math.…

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

Food safety practices among Norwegian consumers.

PubMed

Røssvoll, Elin Halbach; Lavik, Randi; Ueland, Øydis; Jacobsen, Eivind; Hagtvedt, Therese; Langsrud, Solveig

2013-11-01

An informed consumer can compensate for several potential food safety violations or contaminations that may occur earlier in the food production chain. However, a consumer can also destroy the work of others in the chain by poor food handling practices, e.g., by storing chilled ready-to-eat foods at abusive temperatures. To target risk-reducing strategies, consumer groups with high-risk behavior should be identified. The aim of this study was to identify demographic characteristics associated with high-risk food handling practices among Norwegian consumers. More than 2,000 randomly selected Norwegian consumers were surveyed, and the results were analyzed with a risk-based grading system, awarding demerit points for self-reported food safety violations. The violations were categorized into groups, and an ordinary multiple linear regression analysis was run on the summarized demerit score for each group and for the entire survey group as a whole. Young and elderly men were identified as the least informed consumer groups with the most unsafe practices regarding food safety. Single persons reported poorer practices than those in a relationship. People with higher education reported poorer practices than those with lower or no education, and those living in the capital of Norway (Oslo) reported following more unsafe food practices than people living elsewhere in Norway. Men reported poorer food safety practices than women in all categories with two exceptions: parboiling raw vegetables before consumption and knowledge of refrigerator temperature. These findings suggest that risk-reducing measures should target men, and a strategy is needed to change their behavior and attitudes.

Advances in segmentation modeling for health communication and social marketing campaigns.

PubMed

Albrecht, T L; Bryant, C

1996-01-01

Large-scale communication campaigns for health promotion and disease prevention involve analysis of audience demographic and psychographic factors for effective message targeting. A variety of segmentation modeling techniques, including tree-based methods such as Chi-squared Automatic Interaction Detection and logistic regression, are used to identify meaningful target groups within a large sample or population (N = 750-1,000+). Such groups are based on statistically significant combinations of factors (e.g., gender, marital status, and personality predispositions). The identification of groups or clusters facilitates message design in order to address the particular needs, attention patterns, and concerns of audience members within each group. We review current segmentation techniques, their contributions to conceptual development, and cost-effective decision making. Examples from a major study in which these strategies were used are provided from the Texas Women, Infants and Children Program's Comprehensive Social Marketing Program.

Offline Social Relationships and Online Cancer Communication: Effects of Social and Family Support on Online Social Network Building.

PubMed

Namkoong, Kang; Shah, Dhavan V; Gustafson, David H

2017-11-01

This study investigates how social support and family relationship perceptions influence breast cancer patients' online communication networks in a computer-mediated social support (CMSS) group. To examine social interactions in the CMSS group, we identified two types of online social networks: open and targeted communication networks. The open communication network reflects group communication behaviors (i.e., one-to-many or "broadcast" communication) in which the intended audience is not specified; in contrast, the targeted communication network reflects interpersonal discourses (i.e., one-to-one or directed communication) in which the audience for the message is specified. The communication networks were constructed by tracking CMSS group usage data of 237 breast cancer patients who participated in one of two National Cancer Institute-funded randomized clinical trials. Eligible subjects were within 2 months of a diagnosis of primary breast cancer or recurrence at the time of recruitment. Findings reveal that breast cancer patients who perceived less availability of offline social support had a larger social network size in the open communication network. In contrast, those who perceived less family cohesion had a larger targeted communication network in the CMSS group, meaning they were inclined to use the CMSS group for developing interpersonal relationships.

Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates.

PubMed

Pearson, Mark S; Becker, Luke; Driguez, Patrick; Young, Neil D; Gaze, Soraya; Mendes, Tiago; Li, Xiao-Hong; Doolan, Denise L; Midzi, Nicholas; Mduluza, Takafira; McManus, Donald P; Wilson, R Alan; Bethony, Jeffrey M; Nausch, Norman; Mutapi, Francisca; Felgner, Philip L; Loukas, Alex

2015-01-01

Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to S. japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognized by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

Event-related potential correlates of mindfulness meditation competence

PubMed Central

Atchley, Rachel; Klee, Dan; Memmott, Tabatha; Goodrich, Elena; Wahbeh, Helané; Oken, Barry

2016-01-01

Objective This cross-sectional study evaluated event-related potentials (ERPs) across three groups: naïve, novice, and experienced meditators as potential physiological markers of mindfulness meditation competence. Methods Electroencephalographic (EEG) data was collected during a target tone detection task and a Breath Counting task. The Breath Counting task served as the mindfulness meditation condition for the novice and experienced meditator groups. Participants were instructed to respond to target tones with a button press in the first task (Tones), and then ignore the primed tones while breath counting. The primary outcomes were ERP responses to target tones, namely the N2 and P3, as markers of stimulus discrimination and attention, respectively. Results As expected, P3 amplitudes elicited by target tones were attenuated within groups during the Breath Counting task in comparison to the Tones task (p < .001). There was a task by group interaction for P3 (p = .039). Both meditator groups displayed greater change in peak-to-trough P3 amplitudes, with higher amplitudes during the Tones condition and more pronounced reductions in P3 amplitudes during the Breath Counting meditation task in comparison to the naïve group. Conclusions Meditators had stronger P3 amplitude responses to target tones when instructed to attend to the tones, and a greater attenuation of P3 amplitudes when instructed to ignore the same tones during the Breath Counting task. This study introduces the idea of identifying ERP markers as a means of measuring mindfulness meditation competence, and results suggest this may be a valid approach. This information has the potential to improve mindfulness meditation interventions by allowing objective assessment of mindfulness meditation quality. PMID:26850995

Event-related potential correlates of mindfulness meditation competence.

PubMed

Atchley, R; Klee, D; Memmott, T; Goodrich, E; Wahbeh, H; Oken, B

2016-04-21

This cross-sectional study evaluated event-related potentials (ERPs) across three groups: naïve, novice, and experienced meditators as potential physiological markers of mindfulness meditation competence. Electroencephalographic (EEG) data were collected during a target tone detection task and a Breath Counting task. The Breath Counting task served as the mindfulness meditation condition for the novice and experienced meditator groups. Participants were instructed to respond to target tones with a button press in the first task (Tones), and then ignore the primed tones while Breath Counting. The primary outcomes were ERP responses to target tones, namely the N2 and P3, as markers of stimulus discrimination and attention, respectively. As expected, P3 amplitudes elicited by target tones were attenuated within groups during the Breath Counting task in comparison to the Tones task (p<.001). There was a task by group interaction for P3 (p=.039). Both meditator groups displayed greater change in peak-to-trough P3 amplitudes, with higher amplitudes during the Tones condition and more pronounced reductions in P3 amplitudes during the Breath Counting meditation task in comparison to the naïve group. Meditators had stronger P3 amplitude responses to target tones when instructed to attend to the tones, and a greater attenuation of P3 amplitudes when instructed to ignore the same tones during the Breath Counting task. This study introduces the idea of identifying ERP markers as a means of measuring mindfulness meditation competence, and results suggest this may be a valid approach. This information has the potential to improve mindfulness meditation interventions by allowing objective assessment of mindfulness meditation quality. Published by Elsevier Ltd.

Manual method of visually identifying candidate signals for a targeted peptide.

PubMed

Filimonov, Aleksey; Kopylov, Arthur; Lisitsa, Andrey; Archakov, Alexander

2018-04-15

The purpose of this study is to improve peptide signal identification in groups of extracted ion chromatograms (XICs) obtained with the liquid chromatography-selected reaction monitoring (LC-SRM) technique and a triple quadrupole mass spectrometer (QqQ) operating in one of the supported multiple reaction monitoring (MRM) modes. The imperfection of quadrupole mass analyzers causes ion interference, which impedes the identification of peptide signals as chromatographic peak groups in relevant retention time intervals. To investigate this problem in depth, the QqQ conversion of the eluate into XIC groups was considered as the consecutive transformations of the particles' abundances as the corresponding functions of retention time. In this study, the hypothesis that, during this conversion, the same chromatographic profile should be preserved as an implicit sign in each chromatographic peak of the signal was confirmed for peptides. To examine chromatographic profiles, continuous transformations of XIC groups were derived and implemented in srm2prot Express software (s2pe, http://msr.ibmc.msk.ru/s2pe). Because of ion interference, several peptide-like signals may appear in one XIC group. Therefore, these signals must be considered candidates for a targeted peptide's signal and should be resolved after identification. The theoretical investigation of intensity functions as XICs that are not distorted by noise produced three rules for Identifying Candidate Signals for a targeted Peptide (ICSP, http://msr.ibmc.msk.ru/ICSP) that constitute the proposed manual visual method. We theoretically and experimentally compared this method with the conventional semiempirical intuitive technique and found that the former significantly streamlines peptide signal identification and avoids typical errors. Copyright © 2018 Elsevier B.V. All rights reserved.

Hygiene and sanitation promotion strategies among ethnic minority communities in northern Vietnam: a stakeholder analysis.

PubMed

Rheinländer, Thilde; Xuan, Le Thi Thanh; Hoat, Luu Ngoc; Dalsgaard, Anders; Konradsen, Flemming

2012-10-01

Effective rural hygiene and sanitation promotion (RHSP) is a major challenge for many low-income countries. This paper investigates strategies and stakeholders' roles and responsibilities in RHSP implementation in a multi-ethnic area of northern Vietnam, in order to identify lessons learned for future RHSP. A stakeholder analysis was performed, based on 49 semi-structured individual interviews and one group interview with stakeholders in RHSP in a northern province of Vietnam. Participants came from three sectors (agriculture, health and education), unions supported by the Vietnamese government and from four administrative levels (village, commune, district and province). The study villages represented four ethnic minority groups including lowland and highland communities. Stakeholders' roles, responsibilities and promotion methods were outlined, and implementation constraints and opportunities were identified and analysed using thematic content analysis. Effective RHSP in Vietnam is severely constrained despite supporting policies and a multi-sectorial and multi-level framework. Four main barriers for effective implementation of RHSP were identified: (1) weak inter-sectorial collaborations; (2) constraints faced by frontline promoters; (3) almost exclusive information-based and passive promotion methods applied; and (4) context unadjusted promotion strategies across ethnic groups, including a limited focus on socio-economic differences, language barriers and gender roles in the target groups. Highland communities were identified as least targeted and clearly in need of more intensive and effective RHSP. It is recommended that the Vietnamese government gives priority to increasing capacities of and collaboration among stakeholders implementing RHSP activities. This should focus on frontline promoters to perform effective behaviour change communication. It is also recommended to support more participatory and community-based initiatives, which can address the complex socio-economic and cultural determinants of health in multi-ethnic population groups. These lessons learned can improve future RHSP in Vietnam and are also of relevance for health promotion in other minority population groups in the region and globally.

Temporal allocation of attention toward threat in individuals with posttraumatic stress symptoms.

PubMed

Amir, Nader; Taylor, Charles T; Bomyea, Jessica A; Badour, Christal L

2009-12-01

Research suggests that individuals with posttraumatic stress disorder (PTSD) selectively attend to threat-relevant information. However, little is known about how initial detection of threat influences the processing of subsequently encountered stimuli. To address this issue, we used a rapid serial visual presentation paradigm (RSVP; Raymond, J. E., Shapiro, K. L., & Arnell, K. M. (1992). Temporary suppression of visual processing in an RSVP task: An attentional blink? Journal of Experimental Psychology: Human Perception and Performance, 18, 849-860) to examine temporal allocation of attention to threat-related and neutral stimuli in individuals with PTSD symptoms (PTS), traumatized individuals without PTSD symptoms (TC), and non-anxious controls (NAC). Participants were asked to identify one or two targets in an RSVP stream. Typically processing of the first target decreases accuracy of identifying the second target as a function of the temporal lag between targets. Results revealed that the PTS group was significantly more accurate in detecting a neutral target when it was presented 300 or 500ms after threat-related stimuli compared to when the target followed neutral stimuli. These results suggest that individuals with PTSD may process trauma-relevant information more rapidly and efficiently than benign information.

Optimization of brain metabolism using metabolic-targeted therapeutic hypothermia can reduce mortality from traumatic brain injury.

PubMed

Feng, Jin-Zhou; Wang, Wen-Yuan; Zeng, Jun; Zhou, Zhi-Yuan; Peng, Jin; Yang, Hao; Deng, Peng-Chi; Li, Shi-Jun; Lu, Charles D; Jiang, Hua

2017-08-01

Therapeutic hypothermia is widely used to treat traumatic brain injuries (TBIs). However, determining the best hypothermia therapy strategy remains a challenge. We hypothesized that reducing the metabolic rate, rather than reaching a fixed body temperature, would be an appropriate target because optimizing metabolic conditions especially the brain metabolic environment may enhance neurologic protection. A pilot single-blind randomized controlled trial was designed to test this hypothesis, and a nested metabolomics study was conducted to explore the mechanics thereof. Severe TBI patients (Glasgow Coma Scale score, 3-8) were randomly divided into the metabolic-targeted hypothermia treatment (MTHT) group, 50% to 60% rest metabolic ratio as the hypothermia therapy target, and the body temperature-targeted hypothermia treatment (BTHT) control group, hypothermia therapy target of 32°C to 35°C body temperature. Brain and circulatory metabolic pool blood samples were collected at baseline and on days 1, 3, and 7 during the hypothermia treatment, which were selected randomly from a subgroup of MTHT and BTHT groups. The primary outcome was mortality. Using H nuclear magnetic resonance technology, we tracked and located the disturbances of metabolic networks. Eighty-eight severe TBI patients were recruited and analyzed from December 2013 to December 2014, 44 each were assigned in the MTHT and BTHT groups (median age, 42 years; 69.32% men; mean Glasgow Coma Scale score, 6.17 ± 1.02). The mortality was significantly lower in the MTHT than the BTHT group (15.91% vs. 34.09%; p = 0.049). From these, eight cases of MTHT and six cases from BTHT group were enrolled for metabolomics analysis, which showed a significant difference between the brain and circulatory metabolic patterns in MTHT group on day 7 based on the model parameters and scores plots. Finally, metabolites representing potential neuroprotective monitoring parameters for hypothermia treatment were identified through H nuclear magnetic resonance metabolomics. MTHT can significantly reduce the mortality of severe TBI patients. Metabolomics research showed that this strategy could effectively improve brain metabolism, suggesting that reducing the metabolic rate to 50% to 60% should be set as the hypothermia therapy target. Therapeutic study, Level I.

MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes

PubMed Central

He, Jie; Wu, Jiangbin; Xu, Naihan; Xie, Weidong; Li, Mengnan; Li, Jianna; Jiang, Yuyang; Yang, Burton B.; Zhang, Yaou

2013-01-01

MiR-210 is up-regulated in multiple cancer types but its function is disputable and further investigation is necessary. Using a bioinformatics approach, we identified the putative target genes of miR-210 in hypoxia-induced CNE cells from genome-wide scale. Two functional gene groups related to cell cycle and RNA processing were recognized as the major targets of miR-210. Here, we investigated the molecular mechanism and biological consequence of miR-210 in cell cycle regulation, particularly mitosis. Hypoxia-induced up-regulation of miR-210 was highly correlated with the down-regulation of a group of mitosis-related genes, including Plk1, Cdc25B, Cyclin F, Bub1B and Fam83D. MiR-210 suppressed the expression of these genes by directly targeting their 3′-UTRs. Over-expression of exogenous miR-210 disturbed mitotic progression and caused aberrant mitosis. Furthermore, miR-210 mimic with pharmacological doses reduced tumor formation in a mouse metastatic tumor model. Taken together, these results implicate that miR-210 disturbs mitosis through targeting multi-genes involved in mitotic progression, which may contribute to its inhibitory role on tumor formation. PMID:23125370

MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes.

PubMed

He, Jie; Wu, Jiangbin; Xu, Naihan; Xie, Weidong; Li, Mengnan; Li, Jianna; Jiang, Yuyang; Yang, Burton B; Zhang, Yaou

2013-01-07

MiR-210 is up-regulated in multiple cancer types but its function is disputable and further investigation is necessary. Using a bioinformatics approach, we identified the putative target genes of miR-210 in hypoxia-induced CNE cells from genome-wide scale. Two functional gene groups related to cell cycle and RNA processing were recognized as the major targets of miR-210. Here, we investigated the molecular mechanism and biological consequence of miR-210 in cell cycle regulation, particularly mitosis. Hypoxia-induced up-regulation of miR-210 was highly correlated with the down-regulation of a group of mitosis-related genes, including Plk1, Cdc25B, Cyclin F, Bub1B and Fam83D. MiR-210 suppressed the expression of these genes by directly targeting their 3'-UTRs. Over-expression of exogenous miR-210 disturbed mitotic progression and caused aberrant mitosis. Furthermore, miR-210 mimic with pharmacological doses reduced tumor formation in a mouse metastatic tumor model. Taken together, these results implicate that miR-210 disturbs mitosis through targeting multi-genes involved in mitotic progression, which may contribute to its inhibitory role on tumor formation.

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.

A practical framework for evaluating a culturally tailored adolescent substance abuse treatment programme in Molokai, Hawaii.

PubMed

Withy, Kelley M; Lee, Wayde; Renger, Ralph F

2007-11-01

Successful substance abuse treatment requires many changes in behavior, attitude and skills. Culturally tailored approaches to substance abuse treatment have shown initial success, but are not yet accepted as best practice models. In order to document programme effectiveness of a new culturally tailored substance abuse treatment programme on the rural island of Molokai, Hawaii, the authors worked to develop a multi-level evaluation plan to measure behavior changes occurring after participation in activities targeting identified causes of substance abuse in the population of interest. The authors compiled interview results to develop a map of identified causes of substance abuse in the community studied. Strategic planning then identified the specific activities aimed at impacting identified root causes. A literature review was performed to document the effectiveness of such activities. An evaluation plan was developed to measure programme impact on antecedent conditions contributing to substance use in this community. Prioritized causes of substance abuse in the target group included low self esteem, lack of self identity and life plan, and limited communication and conflict resolution skills. Activities targeting these conditions included cultural activities, group counseling, and individual counseling. Literature to support the benefit of addressing these factors was uncovered, and evaluation methodology was developed to measure changes in behaviors, attitudes, and practices, as a measure of programme success. While programme evaluation data is still being collected, the authors have demonstrated a sound foundation for programme activities, and designed methodology for collecting meaningful data to measure programme effectiveness at changing important root causes of substance abuse in a rural Native Hawaiian community.

Cluster analysis of dynamic contrast enhanced MRI reveals tumor subregions related to locoregional relapse for cervical cancer patients.

PubMed

Torheim, Turid; Groendahl, Aurora R; Andersen, Erlend K F; Lyng, Heidi; Malinen, Eirik; Kvaal, Knut; Futsaether, Cecilia M

2016-11-01

Solid tumors are known to be spatially heterogeneous. Detection of treatment-resistant tumor regions can improve clinical outcome, by enabling implementation of strategies targeting such regions. In this study, K-means clustering was used to group voxels in dynamic contrast enhanced magnetic resonance images (DCE-MRI) of cervical cancers. The aim was to identify clusters reflecting treatment resistance that could be used for targeted radiotherapy with a dose-painting approach. Eighty-one patients with locally advanced cervical cancer underwent DCE-MRI prior to chemoradiotherapy. The resulting image time series were fitted to two pharmacokinetic models, the Tofts model (yielding parameters K trans and ν e ) and the Brix model (A Brix , k ep and k el ). K-means clustering was used to group similar voxels based on either the pharmacokinetic parameter maps or the relative signal increase (RSI) time series. The associations between voxel clusters and treatment outcome (measured as locoregional control) were evaluated using the volume fraction or the spatial distribution of each cluster. One voxel cluster based on the RSI time series was significantly related to locoregional control (adjusted p-value 0.048). This cluster consisted of low-enhancing voxels. We found that tumors with poor prognosis had this RSI-based cluster gathered into few patches, making this cluster a potential candidate for targeted radiotherapy. None of the voxels clusters based on Tofts or Brix parameter maps were significantly related to treatment outcome. We identified one group of tumor voxels significantly associated with locoregional relapse that could potentially be used for dose painting. This tumor voxel cluster was identified using the raw MRI time series rather than the pharmacokinetic maps.

Osmium-Isotope and Platinum-Group-Element Systematics of Impact-Melt Rocks, Chesapeake Bay Impact Structure, Virginia, USA

NASA Technical Reports Server (NTRS)

Lee, Seung Ryeol; Wright Horton, J., Jr.; Walker, Richard J.

2005-01-01

Osmium (Os) isotopes and platinum-group elements (PGEs) are useful for geochemically identifying a meteoritic component within impact structures, because meteorites are typically characterized by low (187)Os/(188)Os ratios and high PGE concentrations. In contrast, most types of crustal target rocks have high radiogenic Os and very low PGE concentrations. We have examined Os isotope and PGE systematics of impact-melt rocks and pre-impact target rocks from a 2004 test hole in the late Eocene Chesapeake Bay impact structure and from nearby coreholes. Our goal is to determine the proportion of the projectile component in the melt rock Additional information is included in the original extended abstract.

Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography.

PubMed

Harman, David J; Ryder, Stephen D; James, Martin W; Jelpke, Matthew; Ottey, Dominic S; Wilkes, Emilie A; Card, Timothy R; Aithal, Guruprasad P; Guha, Indra Neil

2015-05-03

To assess the feasibility of a novel diagnostic algorithm targeting patients with risk factors for chronic liver disease in a community setting. Prospective cross-sectional study. Two primary care practices (adult patient population 10,479) in Nottingham, UK. Adult patients (aged 18 years or over) fulfilling one or more selected risk factors for developing chronic liver disease: (1) hazardous alcohol use, (2) type 2 diabetes or (3) persistently elevated alanine aminotransferase (ALT) liver function enzyme with negative serology. A serial biomarker algorithm, using a simple blood-based marker (aspartate aminotransferase:ALT ratio for hazardous alcohol users, BARD score for other risk groups) and subsequently liver stiffness measurement using transient elastography (TE). Diagnosis of clinically significant liver disease (defined as liver stiffness ≥8 kPa); definitive diagnosis of liver cirrhosis. We identified 920 patients with the defined risk factors of whom 504 patients agreed to undergo investigation. A normal blood biomarker was found in 62 patients (12.3%) who required no further investigation. Subsequently, 378 patients agreed to undergo TE, of whom 98 (26.8% of valid scans) had elevated liver stiffness. Importantly, 71/98 (72.4%) patients with elevated liver stiffness had normal liver enzymes and would be missed by traditional investigation algorithms. We identified 11 new patients with definite cirrhosis, representing a 140% increase in the number of diagnosed cases in this population. A non-invasive liver investigation algorithm based in a community setting is feasible to implement. Targeting risk factors using a non-invasive biomarker approach identified a substantial number of patients with previously undetected cirrhosis. The diagnostic algorithm utilised for this study can be found on clinicaltrials.gov (NCT02037867), and is part of a continuing longitudinal cohort study. 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.

Moving Research into Practice: Can We Make Dissemination Stick?

ERIC Educational Resources Information Center

Cook, Bryan G.; Cook, Lysandra; Landrum, Timothy J.

2013-01-01

Although researchers in special education have made significant advances in defining and identifying evidence-based practices, scholars often constitute an insular group that disseminates research findings primarily through outlets and venues targeting like-minded researchers using traditional approaches. Thus, despite tangible results in…

Assessment of Equine Fecal Contamination: The Search for Alternative Bacterial Source-tracking Targets

EPA Science Inventory

16S rDNA clone libraries were evaluated for detection of fecal source-identifying bacteria from a collapsed equine manure pile. Libraries were constructed using universal eubacterial primers and Bacteroides-Prevotella group-specific primers. Eubacterial sequences indicat...

Self-assembling multimeric nucleic acid constructs

DOEpatents

Cantor, Charles R.; Niemeyer, Christof M.; Smith, Cassandra L.; Sano, Takeshi; Hnatowich, Donald J.; Rusckowski, Mary

1999-10-12

The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products.

Self-assembling multimeric nucleic acid constructs

DOEpatents

Cantor, Charles R.; Niemeyer, Christof M.; Smith, Cassandra L.; Sano, Takeshi; Hnatowich, Donald J.; Rusckowski, Mary

1996-01-01

The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products.

Self-assembling multimeric nucleic acid constructs

DOEpatents

Cantor, C.R.; Niemeyer, C.M.; Smith, C.L.; Sano, Takeshi; Hnatowich, D.J.; Rusckowski, M.

1996-10-01

The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products. 5 figs.

Can a print-based intervention increase screening for first degree relatives of people with colorectal cancer? A randomised controlled trial.

PubMed

Carey, Mariko; Sanson-Fisher, Robert; Macrae, Finlay; Cameron, Emilie; Hill, David; D'Este, Catherine; Simmons, Jody; Doran, Christopher

2016-12-01

To test the effectiveness of a targeted print-based intervention to improve screening adherence in first degree relatives of people with colorectal cancer (CRC). People with CRC and their adult first degree relatives were identified through a population-based cancer registry and randomly allocated as a family unit to the intervention or control condition. The control group received general information about CRC screening. The intervention group received printed advice regarding screening that was targeted to their risk level. Screening adherence was assessed at baseline and at 12 months via self report. 752 (25%) index cases and 574 (34%) eligible first degree relatives consented to take part in the trial and completed baseline interviews. At 12 months, 58% of first degree relatives in the control group and 61% in the intervention group were adherent to screening guidelines (mixed effects logistic regression group by time interaction effect =2.7; 95%CI=1.2-5.9; P=0.013). Subgroup analysis indicated that the intervention was only effective for those with the lowest risk. Provision of personalised risk information may have a modest effect on adherence to CRC screening recommendations among first degree relatives of people diagnosed with CRC. Improved strategies for identifying and engaging first degree relatives are needed to maximise the population impact of the intervention. © 2016 The Authors.

Methodological Challenges in Protein Microarray and Immunohistochemistry for the Discovery of Novel Autoantibodies in Paediatric Acute Disseminated Encephalomyelitis

PubMed Central

Peschl, Patrick; Ramberger, Melanie; Höftberger, Romana; Jöhrer, Karin; Baumann, Matthias; Rostásy, Kevin; Reindl, Markus

2017-01-01

Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients. Therefore, we aimed to identify novel autoantibody targets in ADEM patients. Sixteen ADEM patients (11 seronegative, 5 seropositive for MOG antibodies) were analysed for potential new biomarkers, using a protein microarray and immunohistochemistry on rat brain tissue to identify antibodies against intracellular and surface neuronal and glial antigens. Nine candidate antigens were identified in the protein microarray analysis in at least two patients per group. Immunohistochemistry on rat brain tissue did not reveal new target antigens. Although no new autoantibody targets could be found here, future studies should aim to identify new biomarkers for therapeutic and prognostic purposes. The microarray analysis and immunohistochemistry methods used here have several limitations, which should be considered in future searches for biomarkers. PMID:28327523

Systemic bioinformatics analysis of skeletal muscle gene expression profiles of sepsis

PubMed Central

Yang, Fang; Wang, Yumei

2018-01-01

Sepsis is a type of systemic inflammatory response syndrome with high morbidity and mortality. Skeletal muscle dysfunction is one of the major complications of sepsis that may also influence the outcome of sepsis. The aim of the present study was to explore and identify potential mechanisms and therapeutic targets of sepsis. Systemic bioinformatics analysis of skeletal muscle gene expression profiles from the Gene Expression Omnibus was performed. Differentially expressed genes (DEGs) in samples from patients with sepsis and control samples were screened out using the limma package. Differential co-expression and coregulation (DCE and DCR, respectively) analysis was performed based on the Differential Co-expression Analysis package to identify differences in gene co-expression and coregulation patterns between the control and sepsis groups. Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways of DEGs were identified using the Database for Annotation, Visualization and Integrated Discovery, and inflammatory, cancer and skeletal muscle development-associated biological processes and pathways were identified. DCE and DCR analysis revealed several potential therapeutic targets for sepsis, including genes and transcription factors. The results of the present study may provide a basis for the development of novel therapeutic targets and treatment methods for sepsis. PMID:29805480

Proteomics analysis of tissue samples from patients with squamous cell carcinoma of the penis and positive to human papillomavirus.

PubMed

Koifman, Leandro; Ornellas, Paulo; Ornellas, Antonio Augusto; Pereira, Denise de Abreu; Zingali, Benedeta Russolina; Cavalcanti, Silvia Maria Baeta; Afonso, Larissa Alves; Sandim, Vanessa; Alves, Gilda

2015-01-01

The aim of this study was to identify possible protein biomarkers and/or candidates for therapeutic targets in tissues of patients with SCCP, infected by HPV, applying one dimensional electrophoresis (1DE), followed by direct mass spectrometry (MS) analysis. Tissues from 10 HPV positive patients with SCCP and from 10 patients with HPV negative non-tumorous penile foreskins were analyzed applying 1D electrophoresis, followed by analysis with direct mass spectrometry (MS). Sixty-three different proteins were identified in the first group and 50 in the second group. Recognition was possible for 28 proteins exclusively detected in Group 1 and 21 proteins presented only in Group 2. Some proteins in the first group are directly involved in the development of other types of cancer, and therefore, suitable for analysis. Complement C3 protein is a strong candidate for evaluating SCCP patients.

Use of patient ethnography to support quality improvement in benign prostatic hyperplasia.

PubMed

Kaplan, A L; Klein, M P; Tan, H J; Setlur, N P; Agarwal, N; Steinberg, K; Saigal, C S

2014-12-01

Patient-centeredness is a primary aim of quality improvement (QI) but optimal strategies to achieve that goal remain elusive. Benign prostatic hyperplasia (BPH) is one of the commonest urologic diagnoses and significantly affects quality of life. Patient ethnography is an emerging qualitative method of observation and dynamic interviews to understand the context through which the patient experiences care. We implemented patient ethnography to support our QI infrastructure and improve patient-centeredness in BPH. Little is known about how to measure whether processes of care are patient-centered. We did not know whether the care processes our patients experienced provided value from their perspective. We sought to discover previously unrecognized components of care that patients perceived to be of low value. Our primary goal was to develop QI initiatives that targeted low-value themes identified in the ethnography. Our secondary goal was a rapid rollout of three targeted initiatives. We used a 4-step patient ethnography: (1) created detailed process maps to define phases of care, (2) interviewed patients, (3) synthesized transcript data in focus groups using the Crawford Slip method, and (4) targeted undesirable components of care for QI. Semi-structured interviews with seven representative patients identified low-value themes. Focus groups, comprised of primary care physicians, case coordinators, nurses, and urologists, evaluated the interview transcripts and generated improvement opportunities prioritized based on feasibility, patient value, scalability, and innovation. We used affinity mapping and priority matrix techniques to prioritize QI opportunities. We identified five low-value themes from the patient interviews and developed corresponding QI opportunities. These included issues surrounding the referral and consultation process as well as postoperative care, especially home urinary catheter maintenance. Six months after completing the ethnography three of five targeted improvement opportunities had been implemented. Copyright © 2014 Elsevier Inc. All rights reserved.

High-Throughput Sequencing Reveals Diverse Sets of Conserved, Nonconserved, and Species-Specific miRNAs in Jute

PubMed Central

Islam, Md. Tariqul; Ferdous, Ahlan Sabah; Najnin, Rifat Ara; Sarker, Suprovath Kumar; Khan, Haseena

2015-01-01

MicroRNAs play a pivotal role in regulating a broad range of biological processes, acting by cleaving mRNAs or by translational repression. A group of plant microRNAs are evolutionarily conserved; however, others are expressed in a species-specific manner. Jute is an agroeconomically important fibre crop; nonetheless, no practical information is available for microRNAs in jute to date. In this study, Illumina sequencing revealed a total of 227 known microRNAs and 17 potential novel microRNA candidates in jute, of which 164 belong to 23 conserved families and the remaining 63 belong to 58 nonconserved families. Among a total of 81 identified microRNA families, 116 potential target genes were predicted for 39 families and 11 targets were predicted for 4 among the 17 identified novel microRNAs. For understanding better the functions of microRNAs, target genes were analyzed by Gene Ontology and their pathways illustrated by KEGG pathway analyses. The presence of microRNAs identified in jute was validated by stem-loop RT-PCR followed by end point PCR and qPCR for randomly selected 20 known and novel microRNAs. This study exhaustively identifies microRNAs and their target genes in jute which will ultimately pave the way for understanding their role in this crop and other crops. PMID:25861616

Mining, identification and function analysis of microRNAs and target genes in peanut (Arachis hypogaea L.).

PubMed

Zhang, Tingting; Hu, Shuhao; Yan, Caixia; Li, Chunjuan; Zhao, Xiaobo; Wan, Shubo; Shan, Shihua

2017-02-01

In the present investigation, a total of 60 conserved peanut (Arachis hypogaea L.) microRNA (miRNA) sequences, belonging to 16 families, were identified using bioinformatics methods. There were 392 target gene sequences, identified from 58 miRNAs with Target-align software and BLASTx analyses. Gene Ontology (GO) functional analysis suggested that these target genes were involved in mediating peanut growth and development, signal transduction and stress resistance. There were 55 miRNA sequences, verified employing a poly (A) tailing test, with a success rate of up to 91.67%. Twenty peanut target gene sequences were randomly selected, and the 5' rapid amplification of the cDNA ends (5'-RACE) method were used to validate the cleavage sites of these target genes. Of these, 14 (70%) peanut miRNA targets were verified by means of gel electrophoresis, cloning and sequencing. Furthermore, functional analysis and homologous sequence retrieval were conducted for target gene sequences, and 26 target genes were chosen as the objects for stress resistance experimental study. Real-time fluorescence quantitative PCR (qRT-PCR) technology was applied to measure the expression level of resistance-associated miRNAs and their target genes in peanut exposed to Aspergillus flavus (A. flavus) infection and drought stress, respectively. In consequence, 5 groups of miRNAs & targets were found accorded with the mode of miRNA negatively controlling the expression of target genes. This study, preliminarily determined the biological functions of some resistance-associated miRNAs and their target genes in peanut. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Altered molecular profile in thyroid cancers from patients affected by the Three Mile Island nuclear accident.

PubMed

Goldenberg, David; Russo, Mariano; Houser, Kenneth; Crist, Henry; Derr, Jonathan B; Walter, Vonn; Warrick, Joshua I; Sheldon, Kathryn E; Broach, James; Bann, Darrin V

2017-07-01

In 1979, Three Mile Island (TMI) nuclear power plant experienced a partial meltdown with release of radioactive material. The effects of the accident on thyroid cancer (TC) in the surrounding population remain unclear. Radiation-induced TCs have a lower incidence of single nucleotide oncogenic driver mutations and higher incidence of gene fusions. We used next generation sequencing (NGS) to identify molecular signatures of radiation-induced TC in a cohort of TC patients residing near TMI during the time of the accident. Case series. We identified 44 patients who developed papillary thyroid carcinoma between 1974 and 2014. Patients who developed TC between 1984 and 1996 were at risk for radiation-induced TC, patients who developed TC before 1984 or after 1996 were the control group. We used targeted NGS of paired tumor and normal tissue from each patient to identify single nucleotide oncogenic driver mutations. Oncogenic gene fusions were identified using quantitative reverse transcription polymerase chain reaction. We identified 15 patients in the at-risk group and 29 patients in the control group. BRAF V600E mutations were identified in 53% patients in the at-risk group and 83% patients in the control group. The proportion of patients with BRAF mutations in the at-risk group was significantly lower than predicted by the The Cancer Genome Atlas cohort. Gene fusion or somatic copy number alteration drivers were identified in 33% tumors in the at-risk group and 14% of tumors in the control group. Findings were consistent with observations from other radiation-exposed populations. These data raise the possibility that radiation released from TMI may have altered the molecular profile of TC in the population surrounding TMI. 4 Laryngoscope, 127:S1-S9, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Legislative, educational, policy and other interventions targeting physicians' interaction with pharmaceutical companies: a systematic review.

PubMed

Alkhaled, Lina; Kahale, Lara; Nass, Hala; Brax, Hneine; Fadlallah, Racha; Badr, Kamal; Akl, Elie A

2014-07-01

Pharmaceutical company representatives likely influence the prescribing habits and professional behaviour of physicians. The objective of this study was to systematically review the effects of interventions targeting practising physicians' interactions with pharmaceutical companies. We included observational studies, non-randomised controlled trials (non-RCTs) and RCTs evaluating legislative, educational, policy or other interventions targeting the interactions between physicians and pharmaceutical companies. The search strategy included an electronic search of MEDLINE and EMBASE. Two reviewers performed duplicate and independent study selection, data abstraction and assessment of risk of bias. We assessed the risk of bias in each included study. We summarised the findings narratively because the nature of the data did not allow a meta-analysis to be conducted. We assessed the quality of evidence by outcome using the GRADE methodology. Of 11 189 identified citations, one RCT and three observational studies met the eligibility criteria. All four studies specifically targeted one type of interaction with pharmaceutical companies, that is, interactions with drug representatives. The RCT provided moderate quality evidence of no effect of a 'collaborative approach' between the pharmaceutical industry and a health authority. The three observational studies provided low quality evidence suggesting a positive effect of policies aiming to reduce interaction between physicians and pharmaceutical companies (by restricting free samples, promotional material, and meetings with pharmaceutical company representatives) on prescription behaviour. We identified too few studies to allow strong conclusions. Available evidence suggests a potential impact of policies aiming to reduce interaction between physicians and drug representatives on physicians' prescription behaviour. We found no evidence concerning interventions affecting other types of interaction with pharmaceutical companies. 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.

Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.

PubMed

Jackson, Belinda M; Abete-Luzi, Patricia; Krause, Michael W; Eisenmann, David M

2014-04-16

The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin-dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.

Decision Tree Identified Risk Groups with High Suicidal Ideation in South Korea: A Population-Based Study.

PubMed

Kim, Hyun Kyung; Kim, Ji Young; Kim, Jong Hyen; Hyoung, Hee Kyoung

2016-01-01

The aim of this study was to identify risk groups with high suicidal ideation among South Korean adults. A descriptive cross-sectional design was adopted using secondary data from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES). A total of 5,963 adults aged 19 years and older who participated in the 2011 KNHANES served as participants. The prevalence of suicidal ideation and its related factors, including physical, psychological, health behavioral, and sociodemographic characteristics, were examined. Descriptive statistics and a decision tree were used for data analysis. Nine groups with high suicidal ideation were identified. The coexistence of depression and high levels of stress increased the prevalence of suicidal ideation. The highest risk group was widowed or divorced adults with depression and high levels of stress, and 82.5% of these participants had suicidal ideation (the prevalence rate of this group was 5.7 times higher than the mean suicidal ideation prevalence rate in this study). Public health nurses and community mental health professionals should recognize risk groups with high suicidal ideation, and target these groups when implementing preventive interventions. © 2015 Wiley Periodicals, Inc.

Interventions to improve immigrant health. A scoping review

PubMed Central

Ortiz-Barreda, Gaby; Ben-Shlomo, Yoav; Holdsworth, Michelle; Salami, Bukola; Rammohan, Anu; Chung, Roger Yat-Nork; Padmadas, Sabu S.; Krafft, Thomas

2017-01-01

Abstract Background: Disparities in health between immigrants and their host populations have been described across countries and continents. Hence, interventions for improving health targeting general populations are not necessarily effective for immigrants. Aims: To conduct a systematic search of the literature evaluating health interventions for immigrants; to map the characteristics of identified studies including range of interventions, immigrant populations and their host countries, clinical areas targeted and reported evaluations, challenges and limitations of the interventions identified. Following the results, to develop recommendations for research in the field. Methods: A scoping review approach was chosen to provide an overview of the type, extent and quantity of research available. Studies were included if they empirically evaluated health interventions targeting immigrants and/or their descendants, included a control group, and were published in English (PubMed and Embase from 1990 to 2015). Results: Most of the 83 studies included were conducted in the USA, encompassed few immigrant groups and used a randomized controlled trial (RCT) or cluster RCT design. Most interventions addressed chronic and non-communicable diseases and attendance at cancer screening services, used individual targeted approaches, targeted adult women and recruited participants from health centres. Outcome measures were often subjective, with the exception of interventions for cardiovascular risk and diabetes. Generally, authors claimed that interventions were beneficial, despite a number of reported limitations. Conclusions: Recommendations for enhancing interventions to improve immigrant health are provided to help researchers, funders and health care commissioners when deciding upon the scope, nature and design of future research in this area. PMID:28339883

Working women identify influences and obstacles to breast health practices.

PubMed

Stamler, L L; Thomas, B; Lafreniere, K

2000-06-01

To identify factors contributing to participation in breast screening in working women to drive health education planning and implementation. Survey. Automotive plants in southern Canada. Union and nonunion women working in the plants. Survey using "Health Care Practices: A Worksite Survey," modified for Canadian population. Age, education, breast health practices, influences on decision to participate in breast screening, and physician gender. Differences were noted among three age groups (under 30 years, 30-49 years, 50 years or older) in terms of influences and perceived barriers to the different modalities of breast screening. For clinical breast exams, women preferred an expert in breast health, regardless of whether the professional was a physician or a nurse. In all groups, the physician was noted as being very influential; however, perceptions of encouragement from the physician varied across the age groups. Perceptions of barriers to breast screening differed among the age groups and between women with male physicians and those with female physicians. Coworkers were identified as being a strong influence in the older group, whereas friends and family were identified as being more influential in the younger groups. Health promotion and education strategies may need to be stratified for different age groups. Breast health education may need to be seen as an ongoing educational process, with the target groups being both the women and the primary healthcare professionals. The worksite has strong potential as a setting for health promotion activities.

Use of market segmentation to identify untapped consumer needs in vision correction surgery for future growth.

PubMed

Loarie, Thomas M; Applegate, David; Kuenne, Christopher B; Choi, Lawrence J; Horowitz, Diane P

2003-01-01

Market segmentation analysis identifies discrete segments of the population whose beliefs are consistent with exhibited behaviors such as purchase choice. This study applies market segmentation analysis to low myopes (-1 to -3 D with less than 1 D cylinder) in their consideration and choice of a refractive surgery procedure to discover opportunities within the market. A quantitative survey based on focus group research was sent to a demographically balanced sample of myopes using contact lenses and/or glasses. A variable reduction process followed by a clustering analysis was used to discover discrete belief-based segments. The resulting segments were validated both analytically and through in-market testing. Discontented individuals who wear contact lenses are the primary target for vision correction surgery. However, 81% of the target group is apprehensive about laser in situ keratomileusis (LASIK). They are nervous about the procedure and strongly desire reversibility and exchangeability. There exists a large untapped opportunity for vision correction surgery within the low myope population. Market segmentation analysis helped determine how to best meet this opportunity through repositioning existing procedures or developing new vision correction technology, and could also be applied to identify opportunities in other vision correction populations.

Neural mechanisms tracking popularity in real-world social networks

PubMed Central

Zerubavel, Noam; Bearman, Peter S.; Weber, Jochen; Ochsner, Kevin N.

2015-01-01

Differences in popularity are a key aspect of status in virtually all human groups and shape social interactions within them. Little is known, however, about how we track and neurally represent others’ popularity. We addressed this question in two real-world social networks using sociometric methods to quantify popularity. Each group member (perceiver) viewed faces of every other group member (target) while whole-brain functional MRI data were collected. Independent functional localizer tasks were used to identify brain systems supporting affective valuation (ventromedial prefrontal cortex, ventral striatum, amygdala) and social cognition (dorsomedial prefrontal cortex, precuneus, temporoparietal junction), respectively. During the face-viewing task, activity in both types of neural systems tracked targets’ sociometric popularity, even when controlling for potential confounds. The target popularity–social cognition system relationship was mediated by valuation system activity, suggesting that observing popular individuals elicits value signals that facilitate understanding their mental states. The target popularity–valuation system relationship was strongest for popular perceivers, suggesting enhanced sensitivity to differences among other group members’ popularity. Popular group members also demonstrated greater interpersonal sensitivity by more accurately predicting how their own personalities were perceived by other individuals in the social network. These data offer insights into the mechanisms by which status guides social behavior. PMID:26598684

Smoking Cessation for Smokers Not Ready to Quit: Meta-analysis and Cost-effectiveness Analysis.

PubMed

Ali, Ayesha; Kaplan, Cameron M; Derefinko, Karen J; Klesges, Robert C

2018-06-11

To provide a systematic review and cost-effectiveness analysis on smoking interventions targeting smokers not ready to quit, a population that makes up approximately 32% of current smokers. Twenty-two studies on pharmacological, behavioral, and combination smoking-cessation interventions targeting smokers not ready to quit (defined as those who reported they were not ready to quit at the time of the study) published between 2000 and 2017 were analyzed. The effectiveness (measured by the number needed to treat) and cost effectiveness (measured by costs per quit) of interventions were calculated. All data collection and analyses were performed in 2017. Smoking interventions targeting smokers not ready to quit can be as effective as similar interventions for smokers ready to quit; however, costs of intervening on this group may be higher for some intervention types. The most cost-effective interventions identified for this group were those using varenicline and those using behavioral interventions. Updating clinical recommendations to provide cessation interventions for this group is recommended. Further research on development of cost-effective treatments and effective strategies for recruitment and outreach for this group are needed. Additional studies may allow for more nuanced comparisons of treatment types among this group. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

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.

An evidence map of psychosocial interventions for the earliest stages of bipolar disorder

PubMed Central

Vallarino, Martine; Henry, Chantal; Etain, Bruno; Gehue, Lillian J; Macneil, Craig; Scott, Elizabeth M; Barbato, Angelo; Conus, Philippe; Hlastala, Stefanie A; Fristad, Mary; Miklowitz, David J; Scott, Jan

2015-01-01

Depression, schizophrenia, and bipolar disorder are three of the four most burdensome problems in people aged under 25 years. In psychosis and depression, psychological interventions are effective, low-risk, and high-benefit approaches for patients at high risk of first-episode or early-onset disorders. We review the use of psychological interventions for early-stage bipolar disorder in patients aged 15–25 years. Because previous systematic reviews had struggled to identify information about this emerging sphere of research, we used evidence mapping to help us identify the extent, distribution, and methodological quality of evidence because the gold standard approaches were only slightly informative or appropriate. This strategy identified 29 studies in three target groups: ten studies in populations at high risk for bipolar disorder, five studies in patients with a first episode, and 14 studies in patients with early-onset bipolar disorder. Of the 20 completed studies, eight studies were randomised trials, but only two had sample sizes of more than 100 individuals. The main interventions used were family, cognitive behavioural, and interpersonal therapies. Only behavioural family therapies were tested across all of our three target groups. Although the available interventions were well adapted to the level of maturity and social environment of young people, few interventions target specific developmental psychological or physiological processes (eg, ruminative response style or delayed sleep phase), or offer detailed strategies for the management of substance use or physical health. PMID:26360451

An evidence map of psychosocial interventions for the earliest stages of bipolar disorder.

PubMed

Vallarino, Martine; Henry, Chantal; Etain, Bruno; Gehue, Lillian J; Macneil, Craig; Scott, Elizabeth M; Barbato, Angelo; Conus, Philippe; Hlastala, Stefanie A; Fristad, Mary; Miklowitz, David J; Scott, Jan

2015-06-01

Depression, schizophrenia, and bipolar disorder are three of the four most burdensome problems in people aged under 25 years. In psychosis and depression, psychological interventions are effective, low-risk, and high-benefit approaches for patients at high risk of first-episode or early-onset disorders. We review the use of psychological interventions for early-stage bipolar disorder in patients aged 15-25 years. Because previous systematic reviews had struggled to identify information about this emerging sphere of research, we used evidence mapping to help us identify the extent, distribution, and methodological quality of evidence because the gold standard approaches were only slightly informative or appropriate. This strategy identified 29 studies in three target groups: ten studies in populations at high risk for bipolar disorder, five studies in patients with a first episode, and 14 studies in patients with early-onset bipolar disorder. Of the 20 completed studies, eight studies were randomised trials, but only two had sample sizes of more than 100 individuals. The main interventions used were family, cognitive behavioural, and interpersonal therapies. Only behavioural family therapies were tested across all of our three target groups. Although the available interventions were well adapted to the level of maturity and social environment of young people, few interventions target specific developmental psychological or physiological processes (eg, ruminative response style or delayed sleep phase), or offer detailed strategies for the management of substance use or physical health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hitchhiking and epistasis give rise to cohort dynamics in adapting populations

PubMed Central

Buskirk, Sean W.; Peace, Ryan Emily; Lang, Gregory I.

2017-01-01

Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection; yet these targets are inherently enriched for genes of large target size and mutations of large effect. A comprehensive study of individual mutations is necessary to create a realistic picture of the evolutionarily significant spectrum of beneficial mutations. Here we use a bulk-segregant approach to identify the beneficial mutations across 11 lineages of experimentally evolved yeast populations. We report that nearly 80% of detected mutations have no discernible effects on fitness and less than 1% are deleterious. We determine the distribution of driver and hitchhiker mutations in 31 mutational cohorts, groups of mutations that arise synchronously from low frequency and track tightly with one another. Surprisingly, we find that one-third of cohorts lack identifiable driver mutations. In addition, we identify intracohort synergistic epistasis between alleles of hsl7 and kel1, which arose together in a low-frequency lineage. PMID:28720700

Characteristics and effectiveness of diabetes self-management educational programs targeted to racial/ethnic minority groups: a systematic review, meta-analysis and meta-regression.

PubMed

Ricci-Cabello, Ignacio; Ruiz-Pérez, Isabel; Rojas-García, Antonio; Pastor, Guadalupe; Rodríguez-Barranco, Miguel; Gonçalves, Daniela C

2014-07-19

It is not clear to what extent educational programs aimed at promoting diabetes self-management in ethnic minority groups are effective. The aim of this work was to systematically review the effectiveness of educational programs to promote the self-management of racial/ethnic minority groups with type 2 diabetes, and to identify programs' characteristics associated with greater success. We undertook a systematic literature review. Specific searches were designed and implemented for Medline, EMBASE, CINAHL, ISI Web of Knowledge, Scirus, Current Contents and nine additional sources (from inception to October 2012). We included experimental and quasi-experimental studies assessing the impact of educational programs targeted to racial/ethnic minority groups with type 2 diabetes. We only included interventions conducted in countries members of the OECD. Two reviewers independently screened citations. Structured forms were used to extract information on intervention characteristics, effectiveness, and cost-effectiveness. When possible, we conducted random-effects meta-analyses using standardized mean differences to obtain aggregate estimates of effect size with 95% confidence intervals. Two reviewers independently extracted all the information and critically appraised the studies. We identified thirty-seven studies reporting on thirty-nine educational programs. Most of them were conducted in the US, with African American or Latino participants. Most programs obtained some benefits over standard care in improving diabetes knowledge, self-management behaviors and clinical outcomes. A meta-analysis of 20 randomized controlled trials (3,094 patients) indicated that the programs produced a reduction in glycated hemoglobin of -0.31% (95% CI -0.48% to -0.14%). Diabetes knowledge and self-management measures were too heterogeneous to pool. Meta-regressions showed larger reduction in glycated hemoglobin in individual and face to face delivered interventions, as well as in those involving peer educators, including cognitive reframing techniques, and a lower number of teaching methods. The long-term effects remain unknown and cost-effectiveness was rarely estimated. Diabetes self-management educational programs targeted to racial/ethnic minority groups can produce a positive effect on diabetes knowledge and on self-management behavior, ultimately improving glycemic control. Future programs should take into account the key characteristics identified in this review.

Advising Adult Learners. NACADA Task Force Report.

ERIC Educational Resources Information Center

Polson, Cheryl; And Others

A study examined the scope of existing services for adult learners attending universities and colleges. Survey instruments designed to gather data on institutional support for adult learner services, special target groups identified by individual institutions, and institutional barriers confronted by adult learners on campus were mailed to a…

Staff Training Best Practices: Targeting Attitude.

ERIC Educational Resources Information Center

Grayson, Randall

2001-01-01

Enhancing the attitude of camp staff involves hiring staff that already have good attitudes, training staff in small groups that then train the rest, using the power of story, removing structural barriers, helping people understand how their actions influence organizational outcomes, identifying "termites," and placing a weak counselor…

MALDI-TOF mass spectrometry for differentiation between Streptococcus pneumoniae and Streptococcus pseudopneumoniae.

PubMed

van Prehn, Joffrey; van Veen, Suzanne Q; Schelfaut, Jacqueline J G; Wessels, Els

2016-05-01

We compared the Vitek MS and Microflex MALDI-TOF mass spectrometry platform for species differentiation within the Streptococcus mitis group with PCR assays targeted at lytA, Spn9802, and recA as reference standard. The Vitek MS correctly identified 10/11 Streptococcus pneumoniae, 13/13 Streptococcus pseudopneumoniae, and 12/13 S. mitis/oralis. The Microflex correctly identified 9/11 S. pneumoniae, 0/13 S. pseudopneumoniae, and 13/13 S. mitis/oralis. MALDI-TOF is a powerful tool for species determination within the mitis group. Diagnostic accuracy varies depending on platform and database used. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Using Contact Patterns to Inform HIV Interventions in Persons Who Inject Drugs in Northern Vietnam.

PubMed

Smith, M Kumi; Graham, Matthew; Latkin, Carl A; Go, Vivian L

2018-05-01

Population mixing patterns can greatly inform allocation of HIV prevention interventions such as treatment as prevention or preexposure prophylaxis. Characterizing contact patterns among subgroups can help identify the specific combinations of contact expected to result in the greatest number of new infections. Baseline data from an intervention to reduce HIV-related risk behaviors in male persons who inject drugs (PWID) in the Northern Vietnamese province of Thai Nguyen were used for the analysis. Egocentric network data were provided by PWID who reported any drug-injection equipment sharing in the previous 3 months. Age-dependent mixing was assessed to explore its epidemiological implications on risk of HIV transmission risk (among those HIV-infected) and HIV acquisition risk (among those not infected) in PWID. A total of 1139 PWID collectively reported 2070 equipment-sharing partnerships in the previous 3 months. Mixing by age identified the 30-34 and 35-39 years age groups as the groups from whom the largest number of new infections was transmitted, making them primary targets for treatment as prevention. Among the uninfected, 25-29, 30-35, and 35-39 years age groups had the highest HIV acquisition rate, making them the primary targets for preexposure prophylaxis. Collection and analysis of contact patterns in PWID is feasible and can greatly inform infectious disease dynamics and targeting of appropriate interventions. Results presented also provide much needed empirical data on mixing to improve mathematical models of disease transmission in this population.

Translating research into practice through user-centered design: An application for osteoarthritis healthcare planning.

PubMed

Carr, Eloise Cj; Babione, Julie N; Marshall, Deborah

2017-08-01

To identify the needs and requirements of the end users, to inform the development of a user-interface to translate an existing evidence-based decision support tool into a practical and usable interface for health service planning for osteoarthritis (OA) care. We used a user-centered design (UCD) approach that emphasized the role of the end-users and is well-suited to knowledge translation (KT). The first phase used a needs assessment focus group (n=8) and interviews (n=5) with target users (health care planners) within a provincial health care organization. The second phase used a participatory design approach, with two small group sessions (n=6) to explore workflow, thought processes, and needs of intended users. The needs assessment identified five design recommendations: ensuring the user-interface supports the target user group, allowing for user-directed data explorations, input parameter flexibility, clear presentation, and provision of relevant definitions. The second phase identified workflow insights from a proposed scenario. Graphs, the need for a visual overview of the data, and interactivity were key considerations to aid in meaningful use of the model and knowledge translation. A UCD approach is well suited to identify health care planners' requirements when using a decision support tool to improve health service planning and management of OA. We believe this is one of the first applications to be used in planning for health service delivery. We identified specific design recommendations that will increase user acceptability and uptake of the user-interface and underlying decision support tool in practice. Our approach demonstrated how UCD can be used to enable knowledge translation. Copyright © 2017 Elsevier B.V. All rights reserved.

Pure mechanistic analysis of additive neuroprotective effects between baicalin and jasminoidin in ischemic stroke mice.

PubMed

Wang, Peng-Qian; Liu, Qiong; Xu, Wen-Juan; Yu, Ya-Nan; Zhang, Ying-Ying; Li, Bing; Liu, Jun; Wang, Zhong

2018-06-01

Both baicalin (BA) and jasminoidin (JA) are active ingredients in Chinese herb medicine Scutellaria baicalensis and Fructus gardeniae, respectively. They have been shown to exert additive neuroprotective action in ischemic stroke models. In this study we used transcriptome analysis to explore the pure therapeutic mechanisms of BA, JA and their combination (BJ) contributing to phenotype variation and reversal of pathological processes. Mice with middle cerebral artery obstruction were treated with BA, JA, their combination (BJ), or concha margaritifera (CM). Cerebral infarct volume was examined to determine the effect of these compounds on phenotype. Using the hippocampus microarray and ingenuity pathway analysis (IPA) software, we exacted the differentially expressed genes, networks, pathways, and functions in positive-phenotype groups (BA, JA and BJ) by comparing with the negative-phenotype group (CM). In the BA, JA, and BJ groups, a total of 7, 4, and 11 specific target molecules, 1, 1, and 4 networks, 51, 59, and 18 canonical pathways and 70, 53, and 64 biological functions, respectively, were identified. Pure therapeutic mechanisms of BA and JA were mainly overlapped in specific target molecules, functions and pathways, which were related to the nervous system, inflammation and immune response. The specific mechanisms of BA and JA were associated with apoptosis and cancer-related signaling and endocrine and hormone regulation, respectively. In the BJ group, novel target profiles distinct from mono-therapies were revealed, including 11 specific target molecules, 10 functions, and 10 pathways, the majority of which were related to a virus-mediated immune response. The pure additive effects between BA and JA were based on enhanced action in virus-mediated immune response. This pure mechanistic analysis may provide a clearer outline of the target profiles of multi-target compounds and combination therapies.

Targeted case finding for chronic obstructive pulmonary disease versus routine practice in primary care (TargetCOPD): a cluster-randomised controlled trial.

PubMed

Jordan, Rachel E; Adab, Peymané; Sitch, Alice; Enocson, Alexandra; Blissett, Deirdre; Jowett, Sue; Marsh, Jen; Riley, Richard D; Miller, Martin R; Cooper, Brendan G; Turner, Alice M; Jolly, Kate; Ayres, Jon G; Haroon, Shamil; Stockley, Robert; Greenfield, Sheila; Siebert, Stanley; Daley, Amanda J; Cheng, K K; Fitzmaurice, David

2016-09-01

Many individuals with chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. Health-care organisations are implementing case-finding programmes without good evidence of which are the most effective and cost-effective approaches. We assessed the effectiveness and cost-effectiveness of two alternative approaches to targeted case finding for COPD compared with routine practice. In this cluster-randomised controlled trial, participating general practices in the West Midlands, UK, were randomly assigned (1:1), via a computer-generated block randomisation sequence, to either a targeted case-finding group or a routine care group. Eligible patients were ever-smokers aged 40-79 years without a previously recorded diagnosis of COPD. Patients in the targeted case-finding group were further randomly assigned (1:1) via their household to receive either a screening questionnaire at the general practitioner (GP) consultation (opportunistic) or a screening questionnaire at the GP consultation plus a mailed questionnaire (active). Respondents reporting relevant respiratory symptoms were invited for post-bronchodilator spirometry. Patients, clinicians, and investigators were not masked to allocation, but group allocation was concealed from the researchers who performed the spirometry assessments. Primary outcomes were the percentage of the eligible population diagnosed with COPD within 1 year (defined as post-bronchodilator forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] ratio <0·7 in patients with symptoms or a new diagnosis on their GP record) and cost per new COPD diagnosis. Multiple logistic and Poisson regression were used to estimate effect sizes. Costs were obtained from the trial. This trial is registered with ISRCTN, number ISRCTN14930255. From Aug 10, 2012, to June 22, 2014, 74 818 eligible patients from 54 diverse general practices were randomly assigned and completed the trial. At 1 year, 1278 (4%) cases of COPD were newly detected in 32 789 eligible patients in the targeted case-finding group compared with 337 (1%) cases in 42 029 patients in the routine care group (adjusted odds ratio [OR] 7·45 [95% CI 4·80-11·55], p<0·0001). The percentage of newly detected COPD cases was higher in the active case-finding group (822 [5%] of 15 378) than in the opportunistic case-finding group (370 [2%] of 15 387; adjusted OR 2·34 [2·06-2·66], p<0·0001; adjusted risk difference 2·9 per 100 patients [95% CI 2·3-3·6], p<0·0001). Active case finding was more cost-effective than opportunistic case finding (£333 vs £376 per case detected, respectively). In this well established primary care system, routine practice identified few new cases of COPD. An active targeted approach to case finding including mailed screening questionnaires before spirometry is a cost-effective way to identify undiagnosed patients and has the potential to improve their health. National Institute for Health Research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Barriers to pandemic influenza vaccination and uptake of seasonal influenza vaccine in the post-pandemic season in Germany.

PubMed

Böhmer, Merle M; Walter, Dietmar; Falkenhorst, Gerhard; Müters, Stephan; Krause, Gérard; Wichmann, Ole

2012-10-31

In Germany, annual vaccination against seasonal influenza is recommended for certain target groups (e.g. persons aged ≥60 years, chronically ill persons, healthcare workers (HCW)). In season 2009/10, vaccination against pandemic influenza A(H1N1)pdm09, which was controversially discussed in the public, was recommended for the whole population. The objectives of this study were to assess vaccination coverage for seasonal (seasons 2008/09-2010/11) and pandemic influenza (season 2009/10), to identify predictors of and barriers to pandemic vaccine uptake and whether the controversial discussions on pandemic vaccination has had a negative impact on seasonal influenza vaccine uptake in Germany. We analysed data from the 'German Health Update' (GEDA10) telephone survey (n=22,050) and a smaller GEDA10-follow-up survey (n=2,493), which were both representative of the general population aged ≥18 years living in Germany. Overall only 8.8% of the adult population in Germany received a vaccination against pandemic influenza. High socioeconomic status, having received a seasonal influenza shot in the previous season, and belonging to a target group for seasonal influenza vaccination were independently associated with the uptake of pandemic vaccines. The main reasons for not receiving a pandemic vaccination were 'fear of side effects' and the opinion that 'vaccination was not necessary'. Seasonal influenza vaccine uptake in the pre-pandemic season 2008/09 was 52.8% among persons aged ≥60 years; 30.5% among HCW, and 43.3% among chronically ill persons. A decrease in vaccination coverage was observed across all target groups in the first post-pandemic season 2010/11 (50.6%, 25.8%, and 41.0% vaccination coverage, respectively). Seasonal influenza vaccination coverage in Germany remains in all target groups below 75%, which is a declared goal of the European Union. Our results suggest that controversial public discussions about safety and the benefits of pandemic influenza vaccination may have contributed to both a very low uptake of pandemic vaccines and a decreased uptake of seasonal influenza vaccines in the first post-pandemic season. In the upcoming years, the uptake of seasonal influenza vaccines should be carefully monitored in all target groups to identify if this trend continues and to guide public health authorities in developing more effective vaccination and communication strategies for seasonal influenza vaccination.

The priority group index: a proposed new method incorporating high risk and population burden to identify target populations for public health interventions.

PubMed

Zhang, Bo; Cohen, Joanna E; OʼConnor, Shawn

2014-01-01

Selection of priority groups is important for health interventions. However, no quantitative method has been developed. To develop a quantitative method to support the process of selecting priority groups for public health interventions based on both high risk and population health burden. Secondary data analysis of the 2010 Canadian Community Health Survey. Canadian population. Survey respondents. We identified priority groups for 3 diseases: heart disease, stroke, and chronic lower respiratory diseases. Three measures--prevalence, population counts, and adjusted odds ratios (OR)--were calculated for subpopulations (sociodemographic characteristics and other risk factors). A Priority Group Index (PGI) was calculated by summing the rank scores of these 3 measures. Of the 30 priority groups identified by the PGI (10 for each of the 3 disease outcomes), 7 were identified on the basis of high prevalence only, 5 based on population count only, 3 based on high OR only, and the remainder based on combinations of these. The identified priority groups were all in line with the literature as risk factors for the 3 diseases, such as elderly people for heart disease and stroke and those with low income for chronic lower respiratory diseases. The PGI was thus able to balance both high risk and population burden approaches in selecting priority groups, and thus it would address health inequities as well as disease burden in the overall population. The PGI is a quantitative method to select priority groups for public health interventions; it has the potential to enhance the effective use of limited public resources.

Expression profiles of miRNAs from bovine mammary glands in response to Streptococcus agalactiae-induced mastitis.

PubMed

Pu, Junhua; Li, Rui; Zhang, Chenglong; Chen, Dan; Liao, Xiangxiang; Zhu, Yihui; Geng, Xiaohan; Ji, Dejun; Mao, Yongjiang; Gong, Yunchen; Yang, Zhangping

2017-08-01

This study aimed to describe the expression profiles of microRNAs (miRNAs) from mammary gland tissues collected from dairy cows with Streptococcus agalactiae-induced mastitis and to identify differentially expressed miRNAs related to mastitis. The mammary glands of Chinese Holstein cows were challenged with Streptococcus agalactiae to induce mastitis. Small RNAs were isolated from the mammary tissues of the test and control groups and then sequenced using the Solexa sequencing technology to construct two small RNA libraries. Potential target genes of these differentially expressed miRNAs were predicted using the RNAhybrid software, and KEGG pathways associated with these genes were analysed. A total of 18 555 913 and 20 847 000 effective reads were obtained from the test and control groups, respectively. In total, 373 known and 399 novel miRNAs were detected in the test group, and 358 known and 232 novel miRNAs were uncovered in the control group. A total of 35 differentially expressed miRNAs were identified in the test group compared to the control group, including 10 up-regulated miRNAs and 25 down-regulated miRNAs. Of these miRNAs, miR-223 exhibited the highest degree of up-regulation with an approximately 3-fold increase in expression, whereas miR-26a exhibited the most decreased expression level (more than 2-fold). The RNAhybrid software predicted 18 801 genes as potential targets of these 35 miRNAs. Furthermore, several immune response and signal transduction pathways, including the RIG-I-like receptor signalling pathway, cytosolic DNA sensing pathway and Notch signal pathway, were enriched in these predicted targets. In summary, this study provided experimental evidence for the mechanism underlying the regulation of bovine mastitis by miRNAs and showed that miRNAs might be involved in signal pathways during S. agalactiae-induced mastitis.

Perioperative treatment of hemophilia A patients: blood group O patients are at risk of bleeding complications.

PubMed

Hazendonk, H C A M; Lock, J; Mathôt, R A A; Meijer, K; Peters, M; Laros-van Gorkom, B A P; van der Meer, F J M; Driessens, M H E; Leebeek, F W G; Fijnvandraat, K; Cnossen, M H

2016-03-01

ESSENTIALS: Targeting of factor VIII values is a challenge during perioperative replacement therapy in hemophilia. This study aims to identify the extent and predictors of factor VIII underdosing and overdosing. Blood group O predicts underdosing and is associated with perioperative bleeding. To increase quality of care and cost-effectiveness of treatment, refining of dosing is obligatory. Perioperative administration of factor VIII (FVIII) concentrate in hemophilia A may result in both underdosing and overdosing, leading to respectively a risk of bleeding complications and unnecessary costs. This retrospective observational study aims to identify the extent and predictors of underdosing and overdosing in perioperative hemophilia A patients (FVIII levels < 0.05 IU mL(-1)). One hundred nineteen patients undergoing 198 elective, minor, or major surgical procedures were included (median age 40 years, median body weight 75 kg). Perioperative management was evaluated by quantification of perioperative infusion of FVIII concentrate and achieved FVIII levels. Predictors of underdosing and (excessive) overdosing were analyzed by logistic regression analysis. Excessive overdosing was defined as upper target level plus ≥ 0.20 IU mL(-1). Depending on postoperative day, 7-45% of achieved FVIII levels were under and 33-75% were above predefined target ranges as stated by national guidelines. A potential reduction of FVIII consumption of 44% would have been attained if FVIII levels had been maintained within target ranges. Blood group O and major surgery were predictive of underdosing (odds ratio [OR] 6.3, 95% confidence interval [CI] 2.7-14.9; OR 3.3, 95% CI 1.4-7.9). Blood group O patients had more bleeding complications in comparison to patients with blood group non-O (OR 2.02, 95% CI 1.00-4.09). Patients with blood group non-O were at higher risk of overdosing (OR 1.5, 95% CI 1.1-1.9). Additionally, patients treated with bolus infusions were at higher risk of excessive overdosing (OR 1.8, 95% CI 1.3-2.4). Quality of care and cost-effectiveness can be improved by refining of dosing strategies based on individual patient characteristics such as blood group and mode of infusion. © 2015 International Society on Thrombosis and Haemostasis.

Prediction of homoprotein and heteroprotein complexes by protein docking and template‐based modeling: A CASP‐CAPRI experiment

PubMed Central

Velankar, Sameer; Kryshtafovych, Andriy; Huang, Shen‐You; Schneidman‐Duhovny, Dina; Sali, Andrej; Segura, Joan; Fernandez‐Fuentes, Narcis; Viswanath, Shruthi; Elber, Ron; Grudinin, Sergei; Popov, Petr; Neveu, Emilie; Lee, Hasup; Baek, Minkyung; Park, Sangwoo; Heo, Lim; Rie Lee, Gyu; Seok, Chaok; Qin, Sanbo; Zhou, Huan‐Xiang; Ritchie, David W.; Maigret, Bernard; Devignes, Marie‐Dominique; Ghoorah, Anisah; Torchala, Mieczyslaw; Chaleil, Raphaël A.G.; Bates, Paul A.; Ben‐Zeev, Efrat; Eisenstein, Miriam; Negi, Surendra S.; Weng, Zhiping; Vreven, Thom; Pierce, Brian G.; Borrman, Tyler M.; Yu, Jinchao; Ochsenbein, Françoise; Guerois, Raphaël; Vangone, Anna; Rodrigues, João P.G.L.M.; van Zundert, Gydo; Nellen, Mehdi; Xue, Li; Karaca, Ezgi; Melquiond, Adrien S.J.; Visscher, Koen; Kastritis, Panagiotis L.; Bonvin, Alexandre M.J.J.; Xu, Xianjin; Qiu, Liming; Yan, Chengfei; Li, Jilong; Ma, Zhiwei; Cheng, Jianlin; Zou, Xiaoqin; Shen, Yang; Peterson, Lenna X.; Kim, Hyung‐Rae; Roy, Amit; Han, Xusi; Esquivel‐Rodriguez, Juan; Kihara, Daisuke; Yu, Xiaofeng; Bruce, Neil J.; Fuller, Jonathan C.; Wade, Rebecca C.; Anishchenko, Ivan; Kundrotas, Petras J.; Vakser, Ilya A.; Imai, Kenichiro; Yamada, Kazunori; Oda, Toshiyuki; Nakamura, Tsukasa; Tomii, Kentaro; Pallara, Chiara; Romero‐Durana, Miguel; Jiménez‐García, Brian; Moal, Iain H.; Férnandez‐Recio, Juan; Joung, Jong Young; Kim, Jong Yun; Joo, Keehyoung; Lee, Jooyoung; Kozakov, Dima; Vajda, Sandor; Mottarella, Scott; Hall, David R.; Beglov, Dmitri; Mamonov, Artem; Xia, Bing; Bohnuud, Tanggis; Del Carpio, Carlos A.; Ichiishi, Eichiro; Marze, Nicholas; Kuroda, Daisuke; Roy Burman, Shourya S.; Gray, Jeffrey J.; Chermak, Edrisse; Cavallo, Luigi; Oliva, Romina; Tovchigrechko, Andrey

2016-01-01

ABSTRACT We present the results for CAPRI Round 30, the first joint CASP‐CAPRI experiment, which brought together experts from the protein structure prediction and protein–protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact‐sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology‐built subunit models and the smaller pair‐wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. Proteins 2016; 84(Suppl 1):323–348. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. PMID:27122118

Implementation of the guidelines for targeted temperature management after cardiac arrest: a longitudinal qualitative study of barriers and facilitators perceived by hospital resuscitation champions.

PubMed

Kim, Young-Min; Lee, Seung Joon; Jo, Sun Jin; Park, Kyu Nam

2016-01-05

To identify the barriers to and facilitators of implementing guidelines for targeted temperature management (TTM) after cardiac arrest perceived by hospital resuscitation champions and to investigate the changes in their perceptions over the early implementation period. A longitudinal qualitative study (up to 2 serial semistructured interviews over 1 year and focus groups). The individual interviews and focus groups were transcribed and coded by 2 independent assessors. Contents were analysed thematically; group interaction was also examined. 21 hospitals, including community and tertiary care centres in South Korea. 21 hospital champions (14 acting champions and 7 managerial champions). The final data set included 40 interviews and 2 focus groups. The identified barriers and facilitators could be classified into 3 major themes: (1) healthcare professionals' perceptions of the guidelines and protocols, (2) interdisciplinary and interprofessional collaboration and (3) organisational resources. Lack of resources was the most commonly agreed on barrier for the acting champions, whereas lack of interdisciplinary collaboration was the most common barrier for the managerial champions. Educational activities and sharing successfully treated cases were the most frequently identified facilitators. Most of the participants identified and agreed that cooling equipment was an important barrier as well as a facilitator of successful TTM implementation. Perception of the guidelines and protocols has improved with the accumulation of clinical experience over the study period. Healthcare professionals' internal barriers to TTM implementation may be influenced by new guidelines and can be changed with the accumulation of successful clinical experiences during the early implementation period. Promoting interprofessional and interdisciplinary collaboration through educational activities and the use of cooling equipment with an automated feedback function can improve adherence to guidelines in hospitals with limited human resources in critical care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Support group processes: Perspectives from HIV-infected women in South Africa.

PubMed

Mundell, J P; Visser, M J; Makin, J D; Forsyth, B W; Sikkema, K J

2012-01-01

This study examined the experiences and perceived benefits of support group participation among HIV-infected women in South Africa. From a qualitative analysis of responses, key psychological processes through which support groups are potentially beneficial were identified. These processes included: identification; modeling; acceptance; and empowerment. The participants' consequent life changes were explored in order to associate these processes with the positive outcomes of support group participation. Through understanding the relationship between the psychological processes within a support group setting and the potential benefits, and by targeting these processes in the development and implementation of future support group interventions, a framework is provided for achieving positive outcomes associated with support group participation.

Support group processes: Perspectives from HIV-infected women in South Africa

PubMed Central

Mundell, J.P.; Visser, M.J.; Makin, J.D.; Forsyth, B.W.; Sikkema, K.J.

2012-01-01

This study examined the experiences and perceived benefits of support group participation among HIV-infected women in South Africa. From a qualitative analysis of responses, key psychological processes through which support groups are potentially beneficial were identified. These processes included: identification; modeling; acceptance; and empowerment. The participants’ consequent life changes were explored in order to associate these processes with the positive outcomes of support group participation. Through understanding the relationship between the psychological processes within a support group setting and the potential benefits, and by targeting these processes in the development and implementation of future support group interventions, a framework is provided for achieving positive outcomes associated with support group participation. PMID:22514790

Lewis Y Antigen as a Target for Breast Cancer Therapy

DTIC Science & Technology

1996-09-01

have shown that a synthetic peptide can mimic the capsular polysaccharide of N. meningitis serogroup C (MCP) in that it induces an anti-MCP immune...intervening residue. All these sequences resemble the peptide we have identified as a mimic of the group C meningococcal polysaccharide . The immunological...Group C Polysaccharide ct(2-9)sialic acid The sequence similarities among the putative motifs suggest that antibodies raised to this peptide set might

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

[Detection and analysis of the characteristic expression of microRNAs of anal fistula patients].

PubMed

Qiu, Jianming; Yu, Jiping; Yang, Guangen; Xu, Kan; Tao, Yong; Lin, Ali; Wang, Dong

2016-07-01

To detect and analyze the characteristic miRNAs profile of anal fistula and explore their possible target genes and potential clinical significance. The anal mucosa close to the hemorrhoids were collected from three patients undergoing fistulectomy and hemorrhoidectomy (fistula group) as well as three patients receiving only hemorroidectomy(hemorrhoids group), matching with fistula group in age, gender and body weight. miRNA microarray was used to compare the expression of 1 285 human miRNAs of the anal mucosa between two groups. Cluster analysis was adopted to analyze the accumulation of the differentially expressed miRNAs(P<0.05, fold≥2.0 or ≤0.5) and their target genes were predicted with 10 softwares such as DIANAmT, miRanda, miRDB, miRWalk etc. Comprehensive scoring was performed to identify genes with highest predictive score. Gene ontology (GO) concentration technique was used to analyze the target gene-associated biological process. Immunohistochemistry was used to examine protein expression of genes with the highest score. Among 1285 miRNAs in fistula group, 13 miRNAs were differentially expressed with those in hemorrhoid group, including 2 of up-regulation and 11 of down-regulation. Paired t test showed that in fistula group, miRNA-3609 up-regulation was 5.98 folds(P=0.0231) and miR-181a-2-3p down-regulation was 0.13 folds(P=0.0067) compared to those in hemorrhoid group, which had the greatest differential expression. Cluster analysis suggested that up-regulated miR-3609 and miR-6086 had similar change trend in both groups. Among 11 down-regulated miRNAs, miR-125bp-1-3p and miR-548q had similar expression and other 9 miRNAs had similar expression as well, including miR-1185-1-3p, miR-532-3p, miR-1233-5p, miR-769-5p, miR-149-5p, miR-99b-3p, miR-141-3p, miR-138-5p, and miR-181a-2-3p. Target gene prediction analysis of above 13 genes showed that 7 miRNAs(53.8%) were eligible to predict their potential target genes, yielding totally 104 possible target genes. The rest of 6 miRNAs(46.2%) failed to predict any target gene. The highest score in prediction of target gene was chitinase 1(ChIT1) and its corresponding differential miRNA was miR-769-5p(r=-0.94286, P=0.0167). Gene ontology analysis showed that the most associated biological process related with these 104 target genes was keratinization, immune response and signal transduction. Immunohistochemistry revealed ChiT1 expression of anal mucosa in fistula group was significantly higher compared to hemorrhoid group(P<0.01). There is a characteristic miRNAs profile in anal fistula patients, which may play a role in the occurrence and development of anal fistula.

Quantifying the Evolutionary Conservation of Genes Encoding Multidrug Efflux Pumps in the ESKAPE Pathogens To Identify Antimicrobial Drug Targets.

PubMed

Brooks, Lauren E; Ul-Hasan, Sabah; Chan, Benjamin K; Sistrom, Mark J

2018-01-01

Increasing rates of antibiotic-resistant bacterial infection are one of the most pressing contemporary global health concerns. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have been identified as the leading global cause of multidrug-resistant bacterial infections, and overexpression of multidrug efflux (MEX) transport systems has been identified as one of the most critical mechanisms facilitating the evolution of multidrug resistance in ESKAPE pathogens. Despite efforts to develop efflux pump inhibitors to combat antibiotic resistance, the need persists to identify additional targets for future investigations. We evaluated evolutionary pressures on 110 MEX-encoding genes from all annotated ESKAPE organism genomes. We identify several MEX genes under stabilizing selection-representing targets which can facilitate broad-spectrum treatments with evolutionary constraints limiting the potential emergence of escape mutants. We also examine MEX systems being evaluated as drug targets, demonstrating that divergent selection may underlie some of the problems encountered in the development of effective treatments-specifically in relation to the NorA system in S. aureus. This study provides a comprehensive evolutionary context to efflux in the ESKAPE pathogens, which will provide critical context to the evaluation of efflux systems as antibiotic targets. IMPORTANCE Increasing rates of antibiotic-resistant bacterial infection are one of the most pressing contemporary global health concerns. The ESKAPE pathogen group represents the leading cause of these infections, and upregulation of efflux pump expression is a significant mechanism of resistance in these pathogens. This has resulted in substantial interest in the development of efflux pump inhibitors to combat antibiotic-resistant infections; however, no widespread treatments have been developed to date. Our study evaluates an often-underappreciated aspect of resistance-the impact of evolutionary selection. We evaluate selection on all annotated efflux genes in all sequenced ESKAPE pathogens, providing critical context for and insight into current and future development of efflux-targeting treatments for resistant bacterial infections.

Quantifying the Evolutionary Conservation of Genes Encoding Multidrug Efflux Pumps in the ESKAPE Pathogens To Identify Antimicrobial Drug Targets

PubMed Central

Ul-Hasan, Sabah; Chan, Benjamin K.; Sistrom, Mark J.

2018-01-01

ABSTRACT Increasing rates of antibiotic-resistant bacterial infection are one of the most pressing contemporary global health concerns. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have been identified as the leading global cause of multidrug-resistant bacterial infections, and overexpression of multidrug efflux (MEX) transport systems has been identified as one of the most critical mechanisms facilitating the evolution of multidrug resistance in ESKAPE pathogens. Despite efforts to develop efflux pump inhibitors to combat antibiotic resistance, the need persists to identify additional targets for future investigations. We evaluated evolutionary pressures on 110 MEX-encoding genes from all annotated ESKAPE organism genomes. We identify several MEX genes under stabilizing selection—representing targets which can facilitate broad-spectrum treatments with evolutionary constraints limiting the potential emergence of escape mutants. We also examine MEX systems being evaluated as drug targets, demonstrating that divergent selection may underlie some of the problems encountered in the development of effective treatments—specifically in relation to the NorA system in S. aureus. This study provides a comprehensive evolutionary context to efflux in the ESKAPE pathogens, which will provide critical context to the evaluation of efflux systems as antibiotic targets. IMPORTANCE Increasing rates of antibiotic-resistant bacterial infection are one of the most pressing contemporary global health concerns. The ESKAPE pathogen group represents the leading cause of these infections, and upregulation of efflux pump expression is a significant mechanism of resistance in these pathogens. This has resulted in substantial interest in the development of efflux pump inhibitors to combat antibiotic-resistant infections; however, no widespread treatments have been developed to date. Our study evaluates an often-underappreciated aspect of resistance—the impact of evolutionary selection. We evaluate selection on all annotated efflux genes in all sequenced ESKAPE pathogens, providing critical context for and insight into current and future development of efflux-targeting treatments for resistant bacterial infections. PMID:29719870

Using the theoretical domains framework to guide the development of a self-management program for individuals with spinal cord injury: Results from a national stakeholder advisory group.

PubMed

Munce, Sarah E P; Allin, Sonya; Wolfe, Dalton L; Anzai, Karen; Linassi, Gary; Noonan, Vanessa K; Jaglal, Susan B

2017-11-01

To determine the implementation considerations for a targeted self-management program for individuals with spinal cord injury (SCI) from the perspective of a national stakeholder advisory group using the Theoretical Domains Framework (TDF) as a guide. Qualitative descriptive approach. Two focus groups held at the 6 th National Spinal Cord Injury Conference (October 2-4 th , 2014) in Toronto, Ontario, Canada. A total of 25 stakeholders from across Canada participated in focus groups or "brainstorming sessions". The stakeholders included 5 clinicians, 14 researchers, 3 policy makers, and 3 individuals with SCI. Not applicable. Not applicable. All 14 theoretical domains were identified in the brainstorming sessions. No new themes or domains were identified. The need to consider the theoretical domains of Knowledge, Skills, Reinforcement, Intentions, Goals (e.g. the readiness of the individual with SCI), Environmental Context and Resources (e.g. considerations for governance and ownership of the program and a business model for sustainability), as well as Social Influences (e.g. issues of privacy and security in the context of on-line delivery) was identified. The current study provides complementary results to our previous series of studies on the implementation considerations for the development of a targeted self-management program for individuals with SCI by emphasizing the health care professional/health policy perspective. It is anticipated that such a program could not only reduce secondary complications and subsequent inappropriate health care use but it may also improve the quality of life for individuals with SCI and their caregivers.

Experimental and statistical post-validation of positive example EST sequences carrying peroxisome targeting signals type 1 (PTS1)

PubMed Central

Lingner, Thomas; Kataya, Amr R. A.; Reumann, Sigrun

2012-01-01

We recently developed the first algorithms specifically for plants to predict proteins carrying peroxisome targeting signals type 1 (PTS1) from genome sequences.1 As validated experimentally, the prediction methods are able to correctly predict unknown peroxisomal Arabidopsis proteins and to infer novel PTS1 tripeptides. The high prediction performance is primarily determined by the large number and sequence diversity of the underlying positive example sequences, which mainly derived from EST databases. However, a few constructs remained cytosolic in experimental validation studies, indicating sequencing errors in some ESTs. To identify erroneous sequences, we validated subcellular targeting of additional positive example sequences in the present study. Moreover, we analyzed the distribution of prediction scores separately for each orthologous group of PTS1 proteins, which generally resembled normal distributions with group-specific mean values. The cytosolic sequences commonly represented outliers of low prediction scores and were located at the very tail of a fitted normal distribution. Three statistical methods for identifying outliers were compared in terms of sensitivity and specificity.” Their combined application allows elimination of erroneous ESTs from positive example data sets. This new post-validation method will further improve the prediction accuracy of both PTS1 and PTS2 protein prediction models for plants, fungi, and mammals. PMID:22415050

Experimental and statistical post-validation of positive example EST sequences carrying peroxisome targeting signals type 1 (PTS1).

PubMed

Lingner, Thomas; Kataya, Amr R A; Reumann, Sigrun

2012-02-01

We recently developed the first algorithms specifically for plants to predict proteins carrying peroxisome targeting signals type 1 (PTS1) from genome sequences. As validated experimentally, the prediction methods are able to correctly predict unknown peroxisomal Arabidopsis proteins and to infer novel PTS1 tripeptides. The high prediction performance is primarily determined by the large number and sequence diversity of the underlying positive example sequences, which mainly derived from EST databases. However, a few constructs remained cytosolic in experimental validation studies, indicating sequencing errors in some ESTs. To identify erroneous sequences, we validated subcellular targeting of additional positive example sequences in the present study. Moreover, we analyzed the distribution of prediction scores separately for each orthologous group of PTS1 proteins, which generally resembled normal distributions with group-specific mean values. The cytosolic sequences commonly represented outliers of low prediction scores and were located at the very tail of a fitted normal distribution. Three statistical methods for identifying outliers were compared in terms of sensitivity and specificity." Their combined application allows elimination of erroneous ESTs from positive example data sets. This new post-validation method will further improve the prediction accuracy of both PTS1 and PTS2 protein prediction models for plants, fungi, and mammals.

Of Monkeys and Men: Immunomic Profiling of Sera from Humans and Non-Human Primates Resistant to Schistosomiasis Reveals Novel Potential Vaccine Candidates

PubMed Central

Pearson, Mark S.; Becker, Luke; Driguez, Patrick; Young, Neil D.; Gaze, Soraya; Mendes, Tiago; Li, Xiao-Hong; Doolan, Denise L.; Midzi, Nicholas; Mduluza, Takafira; McManus, Donald P.; Wilson, R. Alan; Bethony, Jeffrey M.; Nausch, Norman; Mutapi, Francisca; Felgner, Philip L.; Loukas, Alex

2015-01-01

Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to S. japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognized by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens. PMID:25999951

MicroRNA Expression Profiles as Biomarkers of Minor Salivary Gland Inflammation and Dysfunction in Sjögren's Syndrome

PubMed Central

Alevizos, Ilias; Alexander, Stefanie; Turner, R. James; Illei, Gabor G.

2013-01-01

Objective MicroRNA reflect physiologic and pathologic processes and may be used as biomarkers of concurrent pathophysiologic events in complex settings such as autoimmune diseases. We generated microRNA microarray profiles from the minor salivary glands of control subjects without Sjögren's syndrome (SS) and patients with SS who had low-grade or high-grade inflammation and impaired or normal saliva production, to identify microRNA patterns specific to salivary gland inflammation or dysfunction. Methods MicroRNA expression profiles were generated by Agilent microRNA arrays. We developed a novel method for data normalization by identifying housekeeping microRNA. MicroRNA profiles were compared by unsupervised mathematical methods to test how well they distinguish between control subjects and various subsets of patients with SS. Several bioinformatics methods were used to predict the messenger RNA targets of the differentially expressed microRNA. Results MicroRNA expression patterns accurately distinguished salivary glands from control subjects and patients with SS who had low-degree or high-degree inflammation. Using real-time quantitative polymerase chain reaction, we validated 2 microRNA as markers of inflammation in an independent cohort. Comparing microRNA from patients with preserved or low salivary flow identified a set of differentially expressed microRNA, most of which were up-regulated in the group with decreased salivary gland function, suggesting that the targets of microRNA may have a protective effect on epithelial cells. The predicted biologic targets of microRNA associated with inflammation or salivary gland dysfunction identified both overlapping and distinct biologic pathways and processes. Conclusion Distinct microRNA expression patterns are associated with salivary gland inflammation and dysfunction in patients with SS, and microRNA represent a novel group of potential biomarkers. PMID:21280008

The Association between Influenza Vaccination and Other Preventative Health Behaviors in a Cohort of Pregnant Women

ERIC Educational Resources Information Center

Scheminske, Megan; Henninger, Michelle; Irving, Stephanie A.; Thompson, Mark; Williams, Jenny; Shifflett, Pat; Ball, Sarah W.; Avalos, Lyndsay Ammon; Naleway, Allison L.

2015-01-01

Objectives: Although pregnant women are a high-priority group for seasonal influenza vaccination, vaccination rates in this population remain below target levels. Previous studies have identified sociodemographic predictors of vaccine choice, but relationships between preconception heath behaviors and seasonal influenza vaccination are poorly…

Incorporating Health and Behavioral Consequences of Child Abuse in Prevention Programs Targeting Female Adolescents.

ERIC Educational Resources Information Center

Buzi, Ruth S.; Weinman, Maxine L.; Smith, Peggy B.

1998-01-01

Examined the health and behavioral consequences of child abuse, comparing parenting and never-pregnant teens. Both groups identified major consequences of suicide, prostitution, school drop-out, crime, and substance abuse. Parenting teens expressed interest in prevention programs that would address these consequences. Recommendations for child…

77 FR 23464 - Updates to List of National System of Marine Protected Areas (MPAs)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-19

... Resources, two from the South Carolina Institute of Archaeology and Anthropology, one from the Virgin... monitoring and evaluation, targeted outreach to key user groups, and helping to identify and address MPA... Environmental Resources, the South Carolina Institute of Archaeology and Anthropology, the Virgin Islands...

Guidelines for the Integration of Instructional Television in Speech and Hearing Facilities.

ERIC Educational Resources Information Center

Borich, Gary D.

To devise an efficient instructional television system, the planner must first identify and assess objectives for target audiences; allow for construction of a flexible, expansible system; plan for exchangeable instructional tapes; observe instructional procedures for large class, small group, and remote location operations; consider types of…

Nutrition Status of HIV+ Children in Botswana

ERIC Educational Resources Information Center

Nnyepi, Maria; Bennink, Maurice R.; Jackson-Malete, Jose; Venkatesh, Sumathi; Malete, Leapetswe; Mokgatlhe, Lucky; Lyoka, Philemon; Anabwani, Gabriel M.; Makhanda, Jerry; Weatherspoon, Lorraine J.

2015-01-01

Purpose: Identifying and addressing poor nutritional status in school-aged children is often not prioritized relative to HIV/AIDS treatment. The purpose of this paper is to elucidate the benefits of integrating nutrition (assessment and culturally acceptable food supplement intervention) in the treatment strategy for this target group.…

Demography of Disadvantage in Tennessee.

ERIC Educational Resources Information Center

Jones, Lewis W., Comp.; And Others

In this report, demography conceptualizes significant characteristics to serve as a basis for more intensive study, planning, and procedures focusing on the target group. A compilation of the latest reports available and primarily tabular in form, identifies and locates Tennessee's disadvantaged people, ranking the 95 counties on each of 8…

Initial Career and Work Meanings in Seven European Countries.

ERIC Educational Resources Information Center

Claes, Rita; Quintanilla, S. Antonio R.

1994-01-01

Explores initial careers of two target groups of young adults in seven European countries. Career patterns were constructed through cluster analysis on data gathered via self-report. Six career patterns were identified. Offers suggestions for further research and implications for career counseling, career education, and organizational career…

Utilization of targeted near-infrared molecular imaging to improve pulmonary metastasectomy of osteosarcomas

NASA Astrophysics Data System (ADS)

Predina, Jarrod D.; Newton, Andrew; Deshpande, Charuhas; Low, Philip; Singhal, Sunil

2018-01-01

Pulmonary metastasectomy for osteosarcoma provides a select group of patients an opportunity for long-term survival and possible cure. Unfortunately, a complete metastasectomy is challenging due an inability to accurately identify lesions that lay below the threshold of preoperative imaging or intraoperative visual and tactile inspection. Growing evidence suggests that osteosarcomas express a number of unique molecular markers, including the folate receptor alpha. In this case report, we describe the application of a folate receptor-targeted, near-infrared optical contrast agent (OTL38) to improve osteosarcoma localization during minimally invasive pulmonary resection. In addition to localizing preoperatively identified lesions, this technology helped identify additional disease that was undetected on preoperative imaging or with traditional intraoperative techniques. This report marks the first successful utilization of a molecular imaging probe useful for osteosarcomas. This technology may provide a unique approach to improve pulmonary metastasectomy of osteosarcomas.

Financing services for developmentally disabled people: Directions for reform

PubMed Central

Tompkins, Arnold R.; Porter, Margaret E.; Harahan, Mary F.

1988-01-01

The Secretary of the Department of Health and Human Services established a working group to examine current Federal policies affecting the financing of services to persons with mental retardation and other developmental disabilities. This article summarizes the Working Group's Report to the Secretary. The working group concluded that Federal policies can act as a barrier to community and family living opportunities. Policy alternatives were identified that emphasize flexibility in order to provide appropriate services in a variety of settings, targeting services to the most severely disabled and fixing Federal costs. PMID:10318209

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.

Let's talk about smear tests: social marketing for the National Cervical Screening Programme.

PubMed

Bethune, G R; Lewis, H J

2009-09-01

The overall aim of the work was to increase participation by Māori and Pacific women in the National Cervical Screening Programme (NCSP) in New Zealand using a social marketing informed approach. Key objectives for this target group included: increasing awareness, understanding and discussion of cervical cancer and cervical screening; increasing telephone calls to the NCSP's 0800 number; and increasing uptake of cervical screening. A social marketing intervention with mixed qualitative and quantitative evaluation. Focus groups with priority women and key stakeholder interviews were used to identify a set of key messages from which television, radio and print media advertisements were developed. The advertising campaign was one element of a broader programme of activity, which involved changes to service delivery and improvement to access to services, particularly for the target groups. The campaign was evaluated in three ways: quantitative surveys conducted before, during and after the intervention; monitoring the number of calls to the NCSP's 0800 number; and monitoring NCSP monthly coverage statistics. The social marketing intervention achieved measurable behavioural impacts with its primary target audiences, delivering significant increases in screening uptake by Māori (6.8%) and Pacific women (12.7%) after 12 months. In addition, there was a secondary positive impact on other women (not the immediate target audience) whose rate of update also increased (2.7%). Overall, the intervention helped to reduce inequalities and delivered substantial increases in awareness, understanding and discussion of cervical cancer and cervical screening amongst the target groups. The results demonstrate that social marketing can be effective in targeting marginalized or under-represented groups. The intervention has not only changed the way in which women in New Zealand talk about a previously 'taboo' subject, but it has also provided a platform for significant behaviour change which will help to reduce inequalities in the burden of cervical cancer.

Feasibility and Initial Dosimetric Findings for a Randomized Trial Using Dose-Painted Multiparametric Magnetic Resonance Imaging–Defined Targets in Prostate Cancer

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

Bossart, Elizabeth L., E-mail: EBossart@med.miami.edu; Stoyanova, Radka; Sandler, Kiri

2016-06-01

Purpose: To compare dosimetric characteristics with multiparametric magnetic resonance imaging–identified imaging tumor volume (gross tumor volume, GTV), prostate clinical target volume and planning target volume, and organs at risk (OARs) for 2 treatment techniques representing 2 arms of an institutional phase 3 randomized trial of hypofractionated external beam image guided highly targeted radiation therapy. Methods and Materials: Group 1 (n=20) patients were treated before the trial inception with the standard dose prescription. Each patient had an additional treatment plan generated per the experimental arm. A total of 40 treatment plans were compared (20 plans for each technique). Group 2 (n=15)more » consists of patients currently accrued to the hypofractionated external beam image guided highly targeted radiation therapy trial. Plans were created as per the treatment arm, with additional plans for 5 of the group 2 experimental arm with a 3-mm expansion in the imaging GTV. Results: For all plans in both patient groups, planning target volume coverage ranged from 95% to 100%; GTV coverage of 89.3 Gy for the experimental treatment plans ranged from 95.2% to 99.8%. For both groups 1 and 2, the percent volumes of rectum/anus and bladder receiving 40 Gy, 65 Gy, and 80 Gy were smaller in the experimental plans than in the standard plans. The percent volume at 1 Gy per fraction and 1.625 Gy per fraction were compared between the standard and the experimental arms, and these were found to be equivalent. Conclusions: The dose per fraction to the OARs can be made equal even when giving a large simultaneous integrated boost to the GTV. The data suggest that a GTV margin may be added without significant dose effects on the OARs.« less

Combining a nontargeted and targeted metabolomics approach to identify metabolic pathways significantly altered in polycystic ovary syndrome.

PubMed

Chang, Alice Y; Lalia, Antigoni Z; Jenkins, Gregory D; Dutta, Tumpa; Carter, Rickey E; Singh, Ravinder J; Nair, K Sreekumaran

2017-06-01

Polycystic ovary syndrome (PCOS) is a condition of androgen excess and chronic anovulation frequently associated with insulin resistance. We combined a nontargeted and targeted metabolomics approach to identify pathways and metabolites that distinguished PCOS from metabolic syndrome (MetS). Twenty obese women with PCOS were compared with 18 obese women without PCOS. Both groups met criteria for MetS but could not have diabetes mellitus or take medications that treat PCOS or affect lipids or insulin sensitivity. Insulin sensitivity was derived from the frequently sampled intravenous glucose tolerance test. A nontargeted metabolomics approach was performed on fasting plasma samples to identify differentially expressed metabolites, which were further evaluated by principal component and pathway enrichment analysis. Quantitative targeted metabolomics was then applied on candidate metabolites. Measured metabolites were tested for associations with PCOS and clinical variables by logistic and linear regression analyses. This multiethnic, obese sample was matched by age (PCOS, 37±6; MetS, 40±6years) and body mass index (BMI) (PCOS, 34.6±5.1; MetS, 33.7±5.2kg/m 2 ). Principal component analysis of the nontargeted metabolomics data showed distinct group separation of PCOS from MetS controls. From the subset of 385 differentially expressed metabolites, 22% were identified by accurate mass, resulting in 19 canonical pathways significantly altered in PCOS, including amino acid, lipid, steroid, carbohydrate, and vitamin D metabolism. Targeted metabolomics identified many essential amino acids, including branched-chain amino acids (BCAA) that were elevated in PCOS compared with MetS. PCOS was most associated with BCAA (P=.02), essential amino acids (P=.03), the essential amino acid lysine (P=.02), and the lysine metabolite α-aminoadipic acid (P=.02) in models adjusted for surrogate variables representing technical variation in metabolites. No significant differences between groups were observed in concentrations of free fatty acids or vitamin D metabolites. Evaluation of the relationship of metabolites with clinical characteristics showed 1) negative associations of essential and BCAA with insulin sensitivity and sex hormone-binding globulin and 2) positive associations with homeostasis model of insulin resistance and free testosterone; metabolites were not associated with BMI or percent body fat. PCOS was associated with significant metabolic alterations not attributed exclusively to androgen-related pathways, obesity, or MetS. Concentrations of essential amino acids and BCAA are increased in PCOS, which might result from or contribute to their insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Combining a Nontargeted and Targeted Metabolomics Approach to Identify Metabolic Pathways Significantly Altered in Polycystic Ovary Syndrome

PubMed Central

Chang, Alice Y.; Lalia, Antigoni Z.; Jenkins, Gregory D.; Dutta, Tumpa; Carter, Rickey E.; Singh, Ravinder J.; Sreekumaran Nair, K.

2017-01-01

Objective Polycystic ovary syndrome (PCOS) is a condition of androgen excess and chronic anovulation frequently associated with insulin resistance. We combined a nontargeted and targeted metabolomics approach to identify pathways and metabolites that distinguished PCOS from metabolic syndrome (MetS). Methods Twenty obese women with PCOS were compared with 18 obese women without PCOS. Both groups met criteria for MetS but could not have diabetes mellitus or take medications that treat PCOS or affect lipids or insulin sensitivity. Insulin sensitivity was derived from the frequently sampled intravenous glucose tolerance test. A nontargeted metabolomics approach was performed on fasting plasma samples to identify differentially expressed metabolites, which were further evaluated by principal component and pathway enrichment analysis. Quantitative targeted metabolomics was then applied on candidate metabolites. Measured metabolites were tested for associations with PCOS and clinical variables by logistic and linear regression analyses. Results This multiethnic, obese sample was matched by age (PCOS, 37 ± 6; MetS, 40 ± 6 years) and body mass index (BMI) (PCOS, 34.6 ± 5.1; MetS, 33.7 ± 5.2 kg/m2). Principal component analysis of the nontargeted metabolomics data showed distinct group separation of PCOS from MetS controls. From the subset of 385 differentially expressed metabolites, 22% were identified by accurate mass, resulting in 19 canonical pathways significantly altered in PCOS, including amino acid, lipid, steroid, carbohydrate, and vitamin D metabolism. Targeted metabolomics identified many essential amino acids, including branched-chain amino acids (BCAA) that were elevated in PCOS compared with MetS. PCOS was most associated with BCAA (P = .02), essential amino acids (P = .03), the essential amino acid lysine (P = .02), and the lysine metabolite α-aminoadipic acid (P = .02) in models adjusted for surrogate variables representing technical variation in metabolites. No significant differences between groups were observed in concentrations of free fatty acids or vitamin D metabolites. Evaluation of the relationship of metabolites with clinical characteristics showed 1) negative associations of essential and BCAA with insulin sensitivity and sex hormone–binding globulin and 2) positive associations with homeostasis model of insulin resistance and free testosterone; metabolites were not associated with BMI or percent body fat. Conclusions PCOS was associated with significant metabolic alterations not attributed exclusively to androgen-related pathways, obesity, or MetS. Concentrations of essential amino acids and BCAA are increased in PCOS, which might result from or contribute to their insulin resistance. PMID:28521878

The role of marijuana use etiquette in avoiding targeted police enforcement

PubMed Central

REAM, GEOFFREY L.; JOHNSON, BRUCE D.; DUNLAP, ELOISE; BENOIT, ELLEN

2012-01-01

Internationally, where marijuana is illegal, users follow etiquette rules that prevent negative consequences of use. In this study, adherence to etiquette is hypothesized to reduce likelihood of marijuana-related police stop/search and arrest. Ethnographers administered group surveys to a diverse, purposive sample of 462 marijuana-using peer groups in several areas of New York City. Findings indicated that lack of etiquette was associated with dramatically higher likelihood of police stop/search or arrest only for users who were Black, male, and/or recruited from Harlem/South Bronx. If these users followed a few identified etiquette rules, their risk of police stop/search or arrest was comparable to that of other users. Implications are that etiquette represents an intentional conscientiousness about marijuana use. Groups that are specially targeted for anti-marijuana enforcement can remediate that heightened risk by following marijuana etiquette. PMID:23155303

Social marketing and student documentation of asthma care: a quasi-randomized controlled trial.

PubMed

Gimbel, Ronald W; Olsen, Cara H; Williams, Pamela M; Stephens, Mark B

2012-02-01

The study's objective was to determine the effectiveness of a social marketing intervention in influencing use of a targeted electronic medical record (EMR) template to document a standard asthma encounter. This quasi-randomized controlled trial used intervention groups exposed to an educational workshop on EMR documentation with embedded social marketing messages aimed at persuading behavior. Conducted in July 2009 to June 2010, participants in the study included third-year medical students. The primary outcome was the number of participants using a target EMR template. (Clinicaltrials.gov identifier: NCT01043113). A total of 155 participants randomized across eight clusters. Following the workshop, intervention groups were more likely to use the target asthma template than the control group (PR 3.97, 95% CI=1.34--11.79). At slightly over 30 days following the workshop, the intervention group continued to use the asthma template more often than the control group (PR 2.40, 95% CI=1.10--5.21). Stratifying by gender, intervention group females used the asthma template more after the interventions than control group females (PR 10.79, 95% CI=1.18--64.27). In follow-up at slightly over 30 days after the intervention, intervention group female participant asthma template use continued to be used more than control group females (PR 2.82, 95% CI=1.58--5.02). There were no significant differences in group use of asthma template use by intervention group males immediately after the intervention compared to control group males (PR 2.55, 95% CI=0.80--8.14) or similarly at slightly over 30 day follow-up (PR 2.18, 95% CI=0.74-6.42). Social marketing can effectively influence medical student use of EMR templates for clinical documentation in a controlled setting.

MicroRNA profiling in the dentate gyrus in epileptic rats: The role of miR-187-3p.

PubMed

Zhang, Suya; Kou, Yubin; Hu, Chunmei; Han, Yan

2017-06-01

This study aimed to explore the role of aberrant miRNA expression in epilepsy and to identify more potential genes associated with epileptogenesis.The miRNA expression profile of GSE49850, which included 20 samples from the rat epileptic dentate gyrus at 7, 14, 30, and 90 days after electrical stimulation and 20 additional samples from sham time-matched controls, was downloaded from the Gene Expression Omnibus database. The significantly differentially expressed miRNAs were identified in stimulated samples at each time point compared to time-matched controls, respectively. The target genes of consistently differentially expressed miRNAs were screened from miRDB and microRNA.org databases, followed by Gene Ontology (GO) and pathway enrichment analysis and regulatory network construction. The overlapping target genes for consistently differentially expressed miRNAs were also identified from these 2 databases. Furthermore, the potential binding sites of miRNAs and their target genes were analyzed.Rno-miR-187-3p was consistently downregulated in stimulated groups compared with time-matched controls. The predicted target genes of rno-miR-187-3p were enriched in different GO terms and pathways. In addition, 7 overlapping target genes of rno-miR-187-3p were identified, including NFS1, PAQR4, CAND1, DCLK1, PRKAR2A, AKAP3, and KCNK10. These 7 overlapping target genes were determined to have a different number of matched binding sites with rno-miR-187-3p.Our study suggests that miR-187-3p may play an important role in epilepsy development and progression via regulating numerous target genes, such as NFS1, CAND1, DCLK1, AKAP3, and KCNK10. Determining the underlying mechanism of the role of miR-187-3p in epilepsy may make it a potential therapeutic option.

Exploring the Therapeutic Mechanism of Desmodium styracifolium on Oxalate Crystal-Induced Kidney Injuries Using Comprehensive Approaches Based on Proteomics and Network Pharmacology.

PubMed

Hou, Jiebin; Chen, Wei; Lu, Hongtao; Zhao, Hongxia; Gao, Songyan; Liu, Wenrui; Dong, Xin; Guo, Zhiyong

2018-01-01

Purpose: As a Chinese medicinal herb, Desmodium styracifolium (Osb.) Merr (DS) has been applied clinically to alleviate crystal-induced kidney injuries, but its effective components and their specific mechanisms still need further exploration. This research first combined the methods of network pharmacology and proteomics to explore the therapeutic protein targets of DS on oxalate crystal-induced kidney injuries to provide a reference for relevant clinical use. Methods: Oxalate-induced kidney injury mouse, rat, and HK-2 cell models were established. Proteins differentially expressed between the oxalate and control groups were respectively screened using iTRAQ combined with MALDI-TOF-MS. The common differential proteins of the three models were further analyzed by molecular docking with DS compounds to acquire differential targets. The inverse docking targets of DS were predicted through the platform of PharmMapper. The protein-protein interaction (PPI) relationship between the inverse docking targets and the differential proteins was established by STRING. Potential targets were further validated by western blot based on a mouse model with DS treatment. The effects of constituent compounds, including luteolin, apigenin, and genistein, were investigated based on an oxalate-stimulated HK-2 cell model. Results: Thirty-six common differentially expressed proteins were identified by proteomic analysis. According to previous research, the 3D structures of 15 major constituents of DS were acquired. Nineteen differential targets, including cathepsin D (CTSD), were found using molecular docking, and the component-differential target network was established. Inverse-docking targets including p38 MAPK and CDK-2 were found, and the network of component-reverse docking target was established. Through PPI analysis, 17 inverse-docking targets were linked to differential proteins. The combined network of component-inverse docking target-differential proteins was then constructed. The expressions of CTSD, p-p38 MAPK, and p-CDK-2 were shown to be increased in the oxalate group and decreased in kidney tissue by the DS treatment. Luteolin, apigenin, and genistein could protect oxalate-stimulated tubular cells as active components of DS. Conclusion: The potential targets including the CTSD, p38 MAPK, and CDK2 of DS in oxalate-induced kidney injuries and the active components (luteolin, apigenin, and genistein) of DS were successfully identified in this study by combining proteomics analysis, network pharmacology prediction, and experimental validation.

[Screening and identification of apolipoprotein A-I as a potential marker for hepatoblastoma in children].

PubMed

Guo, Li-Hua; Zhao, Wei; Zhang, Jun-Jie; Zhang, Qian; Fan, Ying-Zhong; Wang, Jia-Xiang

2016-12-01

To screen and identify serum biomarkers for childhood hepatoblastoma (HB). The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins. After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group. Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.

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.

Is There Any Interaction between Background Knowledge and Language Proficiency That Affects "TOEFL iBT"® Reading Performance? TOEFL iBT® Research Report. TOEFL iBT-18. ETS Research Report RR-12-22

ERIC Educational Resources Information Center

Hill, Yao Zhang; Liu, Ou Lydia

2012-01-01

This study investigated the effect of the interaction between test takers' background knowledge and language proficiency on their performance on the "TOEFL iBT"® reading section. Test takers with the target content background knowledge (the focal groups) and those without (the reference groups) were identified for each of the 5 selected…

Target vessel detection by epicardial ultrasound in off-pump coronary bypass surgery.

PubMed

Hayakawa, Masato; Asai, Tohru; Kinoshita, Takeshi; Suzuki, Tomoaki; Shiraishi, Shoichiro

2013-01-01

The detection of embedded coronary arteries is difficult especially in off-pump coronary bypass surgery. From June 2010, we introduced high-frequency epicardial ultrasound (ECUS) to assess and evaluate embedded arteries during off-pump coronary bypass surgery. Between June 2010 and June 2011, a total of 89 consecutive patients underwent isolated coronary bypass surgery at our institution. The patients consisted of 72 men and 17 women with a mean age of 67.9 years. We routinely use the VeriQC system (MediStim, Oslo, Norway) to detect the target vessels in the operation. The patients were assigned to one of two groups, depending on whether ECUS was used in the operation (n = 10, ECUS group) or not (n = 79, non-ECUS group). We analyzed the impact of introducing the ECUS in terms of operative outcome. All patients underwent revascularization using the off-pump technique without emergent conversion to cardiopulmonary bypass during surgery. The total number of distal anastomoses was 299, and 12 target vessels could not be identified either visually or on palpation. Thus, the frequency of the embedded coronary arteries was 4.01% (12/299 cases). The preoperative profiles of the two groups were not significantly different. Operation time was significantly longer in the ECUS group (P = 0.02). There were no significant differences in postoperative outcome between the two groups. In the present study, in which the target coronary arteries could not be detected either visually or on palpation in 12 (4.01%) of 299 cases, the use of high-frequency ECUS allowed all patients to undergo off-pump coronary bypass surgery without conversion to cardiopulmonary bypass during the operation. High-frequency ECUS is therefore useful in off-pump coronary bypass surgery.

Peas, please! Food familiarization through picture books helps parents introduce vegetables into preschoolers' diets.

PubMed

Owen, Laura H; Kennedy, Orla B; Hill, Claire; Houston-Price, Carmel

2018-05-26

Repeated taste exposure is an established means of increasing children's liking and intake of fruit and vegetables. However, parents find it difficult to offer children disliked foods repeatedly, often giving up after a few attempts. Studies show that familiarizing children to fruit and vegetables through picture books can increase their interest in tasting targeted foods. This study explored whether looking at picture books before providing foods to taste improved the outcomes of a home-delivered taste exposure regime. Parents of 127 toddlers (aged 21-24 months) identified two 'target' foods they wanted their child to eat (1 fruit, 1 vegetable). Families were randomly assigned to one of three groups. Parents and children in two experimental groups looked at books about either the target fruit or vegetable every day for two weeks; the control group did not receive a book. Parents in all three groups were then asked to offer their child both target foods every day during a 2-week taste-exposure phase. Parental ratings of children's liking and consumption of the foods were collected at baseline, immediately following taste-exposure (post-intervention), and 3 months later (follow-up). In all groups, liking of both foods increased following taste exposure and remained above baseline at follow-up (all ps < .001). In addition, compared to the control group who experienced only taste exposure, looking at vegetable books enhanced children's liking of their target vegetable post-intervention (p < .001) and at follow-up (p < .05), and increased consumption of the vegetable at follow-up (p < .01). Exposure to vegetable books was also associated with smaller increases in neophobia and food fussiness over the period of the study compared to controls (ps < .01), suggesting that picture books may have positive, long-term impacts on children's attitudes towards new foods. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Perceptual organization, visual attention, and objecthood.

PubMed

Kimchi, Ruth; Yeshurun, Yaffa; Spehar, Branka; Pirkner, Yossef

2016-09-01

We have previously demonstrated that the mere organization of some elements in the visual field into an object attracts attention automatically. Here, we explored three different aspects of this automatic attentional capture: (a) Does the attentional capture by an object involve a spatial component? (b) Which Gestalt organization factors suffice for an object to capture attention? (c) Does the strength of organization affect the object's ability to capture attention? Participants viewed multi-elements displays and either identified the color of one element or responded to a Vernier target. On some trials, a subset of the elements grouped by Gestalt factors into an object that was irrelevant to the task and not predictive of the target. An object effect - faster performance for targets within the object than for targets outside the object - was found even when the target appeared after the object offset, and was sensitive to target-object distance, suggesting that the capture of attention by an object is accompanied by a deployment of attention to the object location. Object effects of similar magnitude were found for objects grouped by a combination of factors (collinearity, closure, and symmetry, or closure and symmetry) or by a single factor when it was collinearity, but not symmetry, suggesting that collinearity, or closure combined with symmetry, suffices for automatic capture of attention by an object, but symmetry does not. Finally, the strength of grouping in modal completion, manipulated by varying contrast polarity between and within elements, affected the effectiveness of the attentional capture by the induced object. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sphingolipids as New Biomarkers for Assessment of Delayed-Type Hypersensitivity and Response to Triptolide

PubMed Central

Qu, Feng; Wu, Cai-Sheng; Hou, Jin-Feng; Jin, Ying; Zhang, Jin-Lan

2012-01-01

Background Hypersensitivity diseases are associated with many severe human illnesses, including leprosy and tuberculosis. Emerging evidence suggests that the pathogenesis and pathological mechanisms of treating these diseases may be attributable to sphingolipid metabolism. Methods High performance liquid chromatography-tandem mass spectrometry was employed to target and measure 43 core sphingolipids in the plasma, kidneys, livers and spleens of BALB/c mice from four experimental groups: control, delayed-type hypersensitivity (DTH) model, DTH+triptolide, and control+triptolide. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify potential biomarkers associated with variance between groups. Relationships between the identified biomarkers and disease markers were evaluated by Spearman correlation. Results As a treatment to hypersensitivity disease, triptolide significantly inhibit the ear swelling and recover the reduction of splenic index caused by DTH. The sphingolipidomic result revealed marked alterations in sphingolipid levels between groups that were associated with the effects of the disease and triptolide treatment. Based on this data, 23 potential biomarkers were identified by OPLS-DA, and seven of these biomarkers correlated markedly with the disease markers (p<0.05) by Spearman correlation. Conclusions These data indicate that differences in sphingolipid levels in plasma and tissues are related to DTH and treatment with triptolide. Restoration of proper sphingolipid levels may attribute to the therapeutic effect of triptolide treatment. Furthermore, these findings demonstrate that targeted sphingolipidomic analysis followed by multivariate analysis presents a novel strategy for the identification of biomarkers in biological samples. PMID:23300675

The nature of the language input affects brain activation during learning from a natural language

PubMed Central

Plante, Elena; Patterson, Dianne; Gómez, Rebecca; Almryde, Kyle R.; White, Milo G.; Asbjørnsen, Arve E.

2015-01-01

Artificial language studies have demonstrated that learners are able to segment individual word-like units from running speech using the transitional probability information. However, this skill has rarely been examined in the context of natural languages, where stimulus parameters can be quite different. In this study, two groups of English-speaking learners were exposed to Norwegian sentences over the course of three fMRI scans. One group was provided with input in which transitional probabilities predicted the presence of target words in the sentences. This group quickly learned to identify the target words and fMRI data revealed an extensive and highly dynamic learning network. These results were markedly different from activation seen for a second group of participants. This group was provided with highly similar input that was modified so that word learning based on syllable co-occurrences was not possible. These participants showed a much more restricted network. The results demonstrate that the nature of the input strongly influenced the nature of the network that learners employ to learn the properties of words in a natural language. PMID:26257471

Motivated social categorization: fundamental motives enhance people's sensitivity to basic social categories.

PubMed

Maner, Jon K; Miller, Saul L; Moss, Justin H; Leo, Jennifer L; Plant, E Ashby

2012-07-01

This article presents an evolutionary framework for identifying the characteristics people use to categorize members of their social world. Findings suggest that fundamental social motives lead people to implicitly categorize social targets based on whether those targets display goal-relevant phenotypic traits. A mate-search prime caused participants to categorize opposite-sex targets (but not same-sex targets) based on their level of physical attractiveness (Experiment 1). A mate-guarding prime interacted with relationship investment, causing participants to categorize same-sex targets (but not opposite-sex targets) based on their physical attractiveness (Experiment 2). A self-protection prime interacted with chronic beliefs about danger, increasing participants' tendency to categorize targets based on their racial group membership (Black or White; Experiment 3). This work demonstrates that people categorize others based on whether they display goal-relevant characteristics reflecting high levels of perceived desirability or threat. Social categorization is guided by fundamental evolved motives designed to enhance adaptive social outcomes. PsycINFO Database Record (c) 2012 APA, all rights reserved

A place for precision medicine in bladder cancer: targeting the FGFRs.

PubMed

di Martino, Erica; Tomlinson, Darren C; Williams, Sarah V; Knowles, Margaret A

2016-10-01

Bladder tumors show diverse molecular features and clinical outcome. Muscle-invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients.

A place for precision medicine in bladder cancer: targeting the FGFRs

PubMed Central

di Martino, Erica; Tomlinson, Darren C; Williams, Sarah V; Knowles, Margaret A

2016-01-01

Bladder tumors show diverse molecular features and clinical outcome. Muscle-invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients. PMID:27381494

Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group TARGET Project | Office of Cancer Genomics

Cancer.gov

TARGET researchers sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pediatric ALL cases with activated kinase signaling, including Ph-like ALL, to establish the incidence of tyrosine kinase mutations in this cohort. The study confirmed previously identified somatic mutations in JAK and FLT3, but did not find novel alterations in any additional tyrosine kinases or downstream genes. The mechanism of kinase signaling activation in this high-risk subgroup of pediatric ALL remains largely unknown.

Object aggregation using Neyman-Pearson analysis

NASA Astrophysics Data System (ADS)

Bai, Li; Hinman, Michael L.

2003-04-01

This paper presents a novel approach to: 1) distinguish military vehicle groups, and 2) identify names of military vehicle convoys in the level-2 fusion process. The data is generated from a generic Ground Moving Target Indication (GMTI) simulator that utilizes Matlab and Microsoft Access. This data is processed to identify the convoys and number of vehicles in the convoy, using the minimum timed distance variance (MTDV) measurement. Once the vehicle groups are formed, convoy association is done using hypothesis techniques based upon Neyman Pearson (NP) criterion. One characteristic of NP is the low error probability when a-priori information is unknown. The NP approach was demonstrated with this advantage over a Bayesian technique.

Toward a Clinically Meaningful Taxonomy of Violent Offenders: The Role of Anger and Thinking Styles.

PubMed

Low, Kyra; Day, Andrew

2015-05-22

Violent offender rehabilitation programs aim to reduce the risk of re-offending in known offenders by addressing a range of different treatments needs, often with core intervention targets of improving anger regulation and altering antisocial beliefs and thinking styles. Such programs have proven efficacy in reducing recidivism for some, but not all, violent offenders, and little is known about the effects of these programs on different offender types. This study investigates whether subtypes of violent offenders can be meaningfully identified and considers how this influences short-term treatment outcomes. Cluster analysis identified three distinctive violent offender groups within a sample of 305 male offenders who had been assessed for participation in a violent offender rehabilitation program. An "unregulated" group had high levels of anger experience and expression and low levels of anger control, and held beliefs that were strongly supportive of a criminal lifestyle. A "regulated" group demonstrated levels of anger and beliefs supporting criminal activity that were not in a range that warranted treatment. Finally, an "overregulated" group was assessed as the group at highest risk of violent re-offending and had low levels of anger experience and expression and an absence of beliefs supporting criminal activity. The unregulated group appeared to gain the most benefit from treatment, although it had the highest levels of criminal thinking and problematic anger. These findings nonetheless offer support for the hypothesis that violent offender treatment programs may be optimally effective when targeted at particular types of offenders. © The Author(s) 2015.

Identifying HIV most-at-risk groups in Malawi for targeted interventions. A classification tree model.

PubMed

Emina, Jacques B O; Madise, Nyovani; Kuepie, Mathias; Zulu, Eliya M; Ye, Yazoume

2013-05-28

To identify HIV-socioeconomic predictors as well as the most-at-risk groups of women in Malawi. A cross-sectional survey. Malawi The study used a sample of 6395 women aged 15-49 years from the 2010 Malawi Health and Demographic Surveys. Individual HIV status: positive or not. Findings from the Pearson χ(2) and χ(2) Automatic Interaction Detector analyses revealed that marital status is the most significant predictor of HIV. Women who are no longer in union and living in the highest wealth quintiles households constitute the most-at-risk group, whereas the less-at-risk group includes young women (15-24) never married or in union and living in rural areas. In the light of these findings, this study recommends: (1) that the design and implementation of targeted interventions should consider the magnitude of HIV prevalence and demographic size of most-at-risk groups. Preventive interventions should prioritise couples and never married people aged 25-49 years and living in rural areas because this group accounts for 49% of the study population and 40% of women living with HIV in Malawi; (2) with reference to treatment and care, higher priority must be given to promoting HIV test, monitoring and evaluation of equity in access to treatment among women in union disruption and never married or women in union aged 30-49 years and living in urban areas; (3) community health workers, households-based campaign, reproductive-health services and reproductive-health courses at school could be used as canons to achieve universal prevention strategy, testing, counselling and treatment.

Animation of graphic symbols representing verbs and prepositions: effects on transparency, name agreement, and identification.

PubMed

Schlosser, Ralf W; Shane, Howard; Sorce, James; Koul, Rajinder; Bloomfield, Emma; Debrowski, Lisa; DeLuca, Tim; Miller, Stephanie; Schneider, Danielle; Neff, Allison

2012-04-01

The effects of animation on transparency, name agreement, and identification of graphic symbols for verbs and prepositions were evaluated in preschoolers of 3 age groups. Methods A mixed-group design was used; in each age group, half of the children were randomly allocated to 1 of 2 orders of symbol formats. The 52 children were asked to guess the meaning of symbols and to identify a target symbol among foils given the spoken label. Animated symbols were more transparent than static symbols, although this was more pronounced for verbs. Animated verbs were named more accurately than static verbs, but there was no difference between animated and static prepositions. Verbs were identified more accurately compared with prepositions, but there was no difference between symbol formats. Older children guessed, named, and identified symbols more effectively than younger children. Animation enhances transparency and name agreement, especially for verbs, which reduces the instructional burden that comes with nontransparent symbols. Animation does not enhance identification accuracy. Verbs are easier to identify than prepositions. A developmental effect was observed for each measure. Limitations and implications for future research are discussed.

Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets

PubMed Central

Akala, Hoseah M.; Macharia, Rosaline W.; Juma, Dennis W.; Cheruiyot, Agnes C.; Andagalu, Ben; Brown, Mathew L.; El-Shemy, Hany A.; Nyanjom, Steven G.

2017-01-01

Malaria causes about half a million deaths annually, with Plasmodium falciparum being responsible for 90% of all the cases. Recent reports on artemisinin resistance in Southeast Asia warrant urgent discovery of novel drugs for the treatment of malaria. However, most bioactive compounds fail to progress to treatments due to safety concerns. Drug repositioning offers an alternative strategy where drugs that have already been approved as safe for other diseases could be used to treat malaria. This study screened approved drugs for antimalarial activity using an in silico chemogenomics approach prior to in vitro verification. All the P. falciparum proteins sequences available in NCBI RefSeq were mined and used to perform a similarity search against DrugBank, TTD and STITCH databases to identify similar putative drug targets. Druggability indices of the potential P. falciparum drug targets were obtained from TDR targets database. Functional amino acid residues of the drug targets were determined using ConSurf server which was used to fine tune the similarity search. This study predicted 133 approved drugs that could target 34 P. falciparum proteins. A literature search done at PubMed and Google Scholar showed 105 out of the 133 drugs to have been previously tested against malaria, with most showing activity. For further validation, drug susceptibility assays using SYBR Green I method were done on a representative group of 10 predicted drugs, eight of which did show activity against P. falciparum 3D7 clone. Seven had IC50 values ranging from 1 μM to 50 μM. This study also suggests drug-target association and hence possible mechanisms of action of drugs that did show antiplasmodial activity. The study results validate the use of proteome-wide target similarity approach in identifying approved drugs with activity against P. falciparum and could be adapted for other pathogens. PMID:29088219

Evolving molecular era of childhood medulloblastoma: time to revisit therapy.

PubMed

Khatua, Soumen

2016-01-01

Currently medulloblastoma is treated with a uniform therapeutic approach based on histopathology and clinico-radiological risk stratification, resulting in unpredictable treatment failure and relapses. Improved understanding of the biological, molecular and genetic make-up of these tumors now clearly identifies it as a compendium of four distinct subtypes (WNT, SHH, group 3 and 4). Advances in utilization of the genomic and epigenomic machinery have now delineated genetic aberrations and epigenetic perturbations in each subgroup as potential druggable targets. This has resulted in endeavors to profile targeted therapy. The challenge and future of medulloblastoma therapeutics will be to keep pace with the evolving novel biological insights and translating them into optimal targeted treatment regimens.

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.

Impact of Patient Reminders on Papanicolaou Test Completion for High-Risk Patients Identified by a Clinical Decision Support System.

PubMed

MacLaughlin, Kathy L; Kessler, Maya E; Komandur Elayavilli, Ravikumar; Hickey, Branden C; Scheitel, Marianne R; Wagholikar, Kavishwar B; Liu, Hongfang; Kremers, Walter K; Chaudhry, Rajeev

2018-05-01

A clinical decision support system (CDSS) for cervical cancer screening identifies patients due for routine cervical cancer screening. Yet, high-risk patients who require more frequent screening or earlier follow-up to address past abnormal results are not identified. We aimed to assess the effect of a complex CDSS, incorporating national guidelines for high-risk patient screening and abnormal result management, its implementation to identify patients overdue for testing, and the outcome of sending a targeted recommendation for follow-up. At three primary care clinics affiliated with an academic medical center, a reminder recommending an appointment for Papanicolaou (Pap) testing or Pap and human papillomavirus cotesting was sent to high-risk women aged 18 through 65 years (intervention group) identified by CDSS as overdue for testing. Historical control patients, who did not receive a reminder, were identified by CDSS 1 year before the date when reminders were sent to the intervention group. Test completion rates were compared between the intervention and control groups through a generalized estimating equation extension. Across the three sites, the average completion rate of recommended follow-up testing was significantly higher in the intervention group at 23.7% (61/257) than the completion rate at 3.3% (17/516) in the control group (p < 0.001). A CDSS with enhanced capabilities to identify high-risk women due for cervical cancer testing beyond routine screening intervals, with subsequent patient notification, has the potential to decrease cervical precancer and cancer by improving adherence to guideline-compliant follow-up and needed treatment.

Predictors of Bullying and Victimization in Childhood and Adolescence: A Meta-Analytic Investigation

ERIC Educational Resources Information Center

Cook, Clayton R.; Williams, Kirk R.; Guerra, Nancy G.; Kim, Tia E.; Sadek, Shelly

2010-01-01

Research on the predictors of 3 bully status groups (bullies, victims, and bully victims) for school-age children and adolescents was synthesized using meta-analytic procedures. The primary purpose was to determine the relative strength of individual and contextual predictors to identify targets for prevention and intervention. Age and how…

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...

Teaching Strategies for Effective Fifth Grade Math Intervention

ERIC Educational Resources Information Center

Zank, Alicia A.

2015-01-01

The purpose of the study is to determine what effects explicit and systematic math intervention instruction will have on student's performance on math assessments. The study will focus on a small group of fifth grade students that have been identified as needing targeted intervention (tier 2) and intensive interventions (tier 1) through the…

The Preschool Behavior Screening System: Parent, Spanish Form

ERIC Educational Resources Information Center

Rodriguez, Jennifer C.

2015-01-01

Hispanic-American youth have been identified as a high-risk group for developing behavioral and emotional difficulties. Currently, there exist few behavioral and emotional screening measures targeting young children, with even fewer accessible to the Spanish speaking populations in the U.S. The purpose of the present study was to determine whether…

Differences in Health Determinants between International and Domestic Students at a German.

ERIC Educational Resources Information Center

Kramer, Alexander; Prufer-Kramer, Luise; Stock, Christiane; Tshiananga, Jacques Tshiang

2004-01-01

The authors used a standardized questionnaire to survey 201 international and 193 German students at the University of Bielefeld, Germany, to determine differences in health practices between the 2 groups and to identify targets for health-promoting interventions. Multivariate logistic regression models revealed that long-term female international…

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…

Uveal melanoma hepatic metastases mutation spectrum analysis using targeted next-generation sequencing of 400 cancer genes.

PubMed

Luscan, A; Just, P A; Briand, A; Burin des Roziers, C; Goussard, P; Nitschké, P; Vidaud, M; Avril, M F; Terris, B; Pasmant, E

2015-04-01

Uveal melanoma (UM) is the most common malignant tumour of the eye. Diagnosis often occurs late in the course of disease, and prognosis is generally poor. Recently, recurrent somatic mutations were described, unravelling additional specific altered pathways in UM. Targeted next-generation sequencing (NGS) can now be applied to an accurate and fast identification of somatic mutations in cancer. The aim of the present study was to characterise the mutation pattern of five UM hepatic metastases with well-defined clinical and pathological features. We analysed the UM mutation spectrum using targeted NGS on 409 cancer genes. Four previous reported genes were found to be recurrently mutated. All tumours presented mutually exclusive GNA11 or GNAQ missense mutations. BAP1 loss-of-function mutations were found in three UMs. SF3B1 missense mutations were found in the two UMs with no BAP1 mutations. We then searched for additional mutation targets. We identified the Arg505Cys mutation in the tumour suppressor FBXW7. The same mutation was previously described in different cancer types, and FBXW7 was recently reported to be mutated in UM exomes. Further studies are required to confirm FBXW7 implication in UM tumorigenesis. Elucidating the molecular mechanisms underlying UM tumorigenesis holds the promise for novel and effective targeted UM therapies. 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.

A concept mapping study evaluating the UK's first NHS generic fatigue clinic.

PubMed

Hackett, Katie L; Lambson, Rebecca L; Strassheim, Victoria; Gotts, Zoe; Deary, Vincent; Newton, Julia L

2016-10-01

Fatigue is a significant and debilitating symptom affecting 25% of the population. It occurs in those with a range of chronic diseases, can be idiopathic and in 0.2-0.4% of the UK population occurs in combination with other symptoms that together constitute chronic fatigue syndrome (CFS). Until recently, NHS clinical services only focussed upon CFS and excluded the majority of fatigued patients who did not meet the CFS diagnostic criteria. The CRESTA Fatigue interdisciplinary clinic was established in 2013 in response to this unmet need. To identify the service needs of the heterogeneous group of patients accessing the CRESTA Fatigue Clinic, to prioritize these needs, to determine whether each is being met and to plan targeted service enhancements. Using a group concept mapping approach, we objectively identified the shared understanding of service users accessing this novel clinic. NHS Clinics for Research & Service in Themed Assessment (CRESTA) Fatigue Clinic, Newcastle Upon Tyne, UK. Patients (n = 30) and referrers (n = 10) to the CRESTA Fatigue Clinic contributed towards a statement generation exercise to identify ways the clinic could support service users to improve their quality of life. Patients (n = 46) participated in the sorting and rating task where resulting statements were sorted into groups similar in meaning and rated for 'importance' and 'current success'. We mapped the needs of patients attending the CRESTA Fatigue Clinic and identified which high-priority needs were being successfully met and which were not. Multidimensional scaling and hierarchical cluster analysis depicted the following eight themed clusters from the data which related to various service-user requirements: 'clinic ethos', 'communication', 'support to self-manage', 'peer support', 'allied health services', 'telemedicine', 'written information' and 'service operation'. Service improvement targets were identified within value bivariate plots of the statements. Service development concepts were grouped into thematic clusters and prioritized for both importance and current success. The resulting concept maps depict where the CRESTA Fatigue Clinic successfully addresses issues which matter to patients and highlights areas for service enhancement. Unmet needs of patients have been identified in a rigorous service evaluation, and these are currently being addressed in collaboration with a service-user group. © 2015 The Authors. Health Expectations. Published by John Wiley & Sons Ltd.

A statistically inferred microRNA network identifies breast cancer target miR-940 as an actin cytoskeleton regulator

NASA Astrophysics Data System (ADS)

Bhajun, Ricky; Guyon, Laurent; Pitaval, Amandine; Sulpice, Eric; Combe, Stéphanie; Obeid, Patricia; Haguet, Vincent; Ghorbel, Itebeddine; Lajaunie, Christian; Gidrol, Xavier

2015-02-01

MiRNAs are key regulators of gene expression. By binding to many genes, they create a complex network of gene co-regulation. Here, using a network-based approach, we identified miRNA hub groups by their close connections and common targets. In one cluster containing three miRNAs, miR-612, miR-661 and miR-940, the annotated functions of the co-regulated genes suggested a role in small GTPase signalling. Although the three members of this cluster targeted the same subset of predicted genes, we showed that their overexpression impacted cell fates differently. miR-661 demonstrated enhanced phosphorylation of myosin II and an increase in cell invasion, indicating a possible oncogenic miRNA. On the contrary, miR-612 and miR-940 inhibit phosphorylation of myosin II and cell invasion. Finally, expression profiling in human breast tissues showed that miR-940 was consistently downregulated in breast cancer tissues

Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models.

PubMed

Ng, Samuel Y; Yoshida, Noriaki; Christie, Amanda L; Ghandi, Mahmoud; Dharia, Neekesh V; Dempster, Joshua; Murakami, Mark; Shigemori, Kay; Morrow, Sara N; Van Scoyk, Alexandria; Cordero, Nicolas A; Stevenson, Kristen E; Puligandla, Maneka; Haas, Brian; Lo, Christopher; Meyers, Robin; Gao, Galen; Cherniack, Andrew; Louissaint, Abner; Nardi, Valentina; Thorner, Aaron R; Long, Henry; Qiu, Xintao; Morgan, Elizabeth A; Dorfman, David M; Fiore, Danilo; Jang, Julie; Epstein, Alan L; Dogan, Ahmet; Zhang, Yanming; Horwitz, Steven M; Jacobsen, Eric D; Santiago, Solimar; Ren, Jian-Guo; Guerlavais, Vincent; Annis, D Allen; Aivado, Manuel; Saleh, Mansoor N; Mehta, Amitkumar; Tsherniak, Aviad; Root, David; Vazquez, Francisca; Hahn, William C; Inghirami, Giorgio; Aster, Jon C; Weinstock, David M; Koch, Raphael

2018-05-22

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN-6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models.

Mapping genetic vulnerabilities reveals BTK as a novel therapeutic target in oesophageal cancer.

PubMed

Chong, Irene Yushing; Aronson, Lauren; Bryant, Hanna; Gulati, Aditi; Campbell, James; Elliott, Richard; Pettitt, Stephen; Wilkerson, Paul; Lambros, Maryou B; Reis-Filho, Jorge S; Ramessur, Anisha; Davidson, Michael; Chau, Ian; Cunningham, David; Ashworth, Alan; Lord, Christopher J

2017-08-22

Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. To identify new biomarker-defined therapeutic approaches for patients with oesophageal cancer, we integrated the genomic profiles of 17 oesophageal tumour-derived cell lines with drug sensitivity data from small molecule inhibitor profiling, identifying drug sensitivity effects associated with cancer driver gene alterations. We also interrogated recently described RNA interference screen data for these tumour cell lines to identify candidate genetic dependencies or vulnerabilities that could be exploited as therapeutic targets. By integrating the genomic features of oesophageal tumour cell lines with siRNA and drug screening data, we identified a series of candidate targets in oesophageal cancer, including a sensitivity to inhibition of the kinase BTK in MYC amplified oesophageal tumour cell lines. We found that this genetic dependency could be elicited with the clinical BTK/ERBB2 kinase inhibitor, ibrutinib. In both MYC and ERBB2 amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G 1 cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer. BTK represents a novel candidate therapeutic target in oesophageal cancer that can be targeted with ibrutinib. On the basis of this work, a proof-of-concept phase II clinical trial evaluating the efficacy of ibrutinib in patients with MYC and/or ERBB2 amplified advanced oesophageal cancer is currently underway (NCT02884453). NCT02884453; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Genome and transcriptome sequencing identifies breeding targets in the orphan crop tef (Eragrostis tef).

PubMed

Cannarozzi, Gina; Plaza-Wüthrich, Sonia; Esfeld, Korinna; Larti, Stéphanie; Wilson, Yi Song; Girma, Dejene; de Castro, Edouard; Chanyalew, Solomon; Blösch, Regula; Farinelli, Laurent; Lyons, Eric; Schneider, Michel; Falquet, Laurent; Kuhlemeier, Cris; Assefa, Kebebew; Tadele, Zerihun

2014-07-09

Tef (Eragrostis tef), an indigenous cereal critical to food security in the Horn of Africa, is rich in minerals and protein, resistant to many biotic and abiotic stresses and safe for diabetics as well as sufferers of immune reactions to wheat gluten. We present the genome of tef, the first species in the grass subfamily Chloridoideae and the first allotetraploid assembled de novo. We sequenced the tef genome for marker-assisted breeding, to shed light on the molecular mechanisms conferring tef's desirable nutritional and agronomic properties, and to make its genome publicly available as a community resource. The draft genome contains 672 Mbp representing 87% of the genome size estimated from flow cytometry. We also sequenced two transcriptomes, one from a normalized RNA library and another from unnormalized RNASeq data. The normalized RNA library revealed around 38000 transcripts that were then annotated by the SwissProt group. The CoGe comparative genomics platform was used to compare the tef genome to other genomes, notably sorghum. Scaffolds comprising approximately half of the genome size were ordered by syntenic alignment to sorghum producing tef pseudo-chromosomes, which were sorted into A and B genomes as well as compared to the genetic map of tef. The draft genome was used to identify novel SSR markers, investigate target genes for abiotic stress resistance studies, and understand the evolution of the prolamin family of proteins that are responsible for the immune response to gluten. It is highly plausible that breeding targets previously identified in other cereal crops will also be valuable breeding targets in tef. The draft genome and transcriptome will be of great use for identifying these targets for genetic improvement of this orphan crop that is vital for feeding 50 million people in the Horn of Africa.

G-protein coupled receptor expression patterns delineate medulloblastoma subgroups

PubMed Central

2013-01-01

Background Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy. Results Our study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset. Conclusions Our results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways is a secondary benefit to identifying differential GPCR expression patterns in medulloblastoma tumors. PMID:24252460

Emerging optical methods for surveillance of Barrett's oesophagus.

PubMed

Sturm, Matthew B; Wang, Thomas D

2015-11-01

The rapid rise in incidence of oesophageal adenocarcinoma has motivated the need for improved methods for surveillance of Barrett's oesophagus. Early neoplasia is flat in morphology and patchy in distribution and is difficult to detect with conventional white light endoscopy (WLE). Light offers numerous advantages for rapidly visualising the oesophagus, and advanced optical methods are being developed for wide-field and cross-sectional imaging to guide tissue biopsy and stage early neoplasia, respectively. We review key features of these promising methods and address their potential to improve detection of Barrett's neoplasia. The clinical performance of key advanced imaging technologies is reviewed, including (1) wide-field methods, such as high-definition WLE, chromoendoscopy, narrow-band imaging, autofluorescence and trimodal imaging and (2) cross-sectional techniques, such as optical coherence tomography, optical frequency domain imaging and confocal laser endomicroscopy. Some of these instruments are being adapted for molecular imaging to detect specific biological targets that are overexpressed in Barrett's neoplasia. Gene expression profiles are being used to identify early targets that appear before morphological changes can be visualised with white light. These targets are detected in vivo using exogenous probes, such as lectins, peptides, antibodies, affibodies and activatable enzymes that are labelled with fluorescence dyes to produce high contrast images. This emerging approach has potential to provide a 'red flag' to identify regions of premalignant mucosa, outline disease margins and guide therapy based on the underlying molecular mechanisms of cancer progression. 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.

Metabotyping for the development of tailored dietary advice solutions in a European population: the Food4Me study.

PubMed

O'Donovan, Clare B; Walsh, Marianne C; Woolhead, Clara; Forster, Hannah; Celis-Morales, Carlos; Fallaize, Rosalind; Macready, Anna L; Marsaux, Cyril F M; Navas-Carretero, Santiago; Rodrigo San-Cristobal, S; Kolossa, Silvia; Tsirigoti, Lydia; Mvrogianni, Christina; Lambrinou, Christina P; Moschonis, George; Godlewska, Magdalena; Surwillo, Agnieszka; Traczyk, Iwona; Drevon, Christian A; Daniel, Hannelore; Manios, Yannis; Martinez, J Alfredo; Saris, Wim H M; Lovegrove, Julie A; Mathers, John C; Gibney, Michael J; Gibney, Eileen R; Brennan, Lorraine

2017-10-01

Traditionally, personalised nutrition was delivered at an individual level. However, the concept of delivering tailored dietary advice at a group level through the identification of metabotypes or groups of metabolically similar individuals has emerged. Although this approach to personalised nutrition looks promising, further work is needed to examine this concept across a wider population group. Therefore, the objectives of this study are to: (1) identify metabotypes in a European population and (2) develop targeted dietary advice solutions for these metabotypes. Using data from the Food4Me study (n 1607), k-means cluster analysis revealed the presence of three metabolically distinct clusters based on twenty-seven metabolic markers including cholesterol, individual fatty acids and carotenoids. Cluster 2 was identified as a metabolically healthy metabotype as these individuals had the highest Omega-3 Index (6·56 (sd 1·29) %), carotenoids (2·15 (sd 0·71) µm) and lowest total saturated fat levels. On the basis of its fatty acid profile, cluster 1 was characterised as a metabolically unhealthy cluster. Targeted dietary advice solutions were developed per cluster using a decision tree approach. Testing of the approach was performed by comparison with the personalised dietary advice, delivered by nutritionists to Food4Me study participants (n 180). Excellent agreement was observed between the targeted and individualised approaches with an average match of 82 % at the level of delivery of the same dietary message. Future work should ascertain whether this proposed method could be utilised in a healthcare setting, for the rapid and efficient delivery of tailored dietary advice solutions.

Chapter 17. Extension of endogenous primers as a tool to detect micro-RNA targets.

PubMed

Vatolin, Sergei; Weil, Robert J

2008-01-01

Mammalian cells express a large number of small, noncoding RNAs, including micro-RNAs (miRNAs), that can regulate both the level of a target mRNA and the protein produced by the target mRNA. Recognition of miRNA targets is a complicated process, as a single target mRNA may be regulated by several miRNAs. The potential for combinatorial miRNA-mediated regulation of miRNA targets complicates diagnostic and therapeutic applications of miRNAs. Despite significant progress in understanding the biology of miRNAs and advances in computational predictions of miRNA targets, methods that permit direct physical identification of miRNA-mRNA complexes in eukaryotic cells are still required. Several groups have utilized coimmunoprecipitation of RNA associated with a protein(s) that is part of the RNA silencing macromolecular complex. This chapter describes a detailed but straightforward strategy that identifies miRNA targets based on the assumption that small RNAs base paired with a complementary target mRNA can be used as a primer to synthesize cDNA that may be used for cloning, identification, and functional analysis.

External factors affecting decision-making and use of evidence in an Australian public health policy environment.

PubMed

Zardo, Pauline; Collie, Alex; Livingstone, Charles

2014-05-01

This study examined external factors affecting policy and program decision-making in a specific public health policy context: injury prevention and rehabilitation compensation in the Australian state of Victoria. The aim was twofold: identify external factors that affect policy and program decision-making in this specific context; use this evidence to inform targeting of interventions aimed at increasing research use in this context. Qualitative interviews were undertaken from June 2011 to January 2012 with 33 employees from two state government agencies. Key factors identified were stakeholder feedback and action, government and ministerial input, legal feedback and action, injured persons and the media. The identified external factors were able to significantly influence policy and program decision-making processes: acting as both barriers and facilitators, depending on the particular issue at hand. The factors with the most influence were the Minister and government, lawyers, and agency stakeholders, particularly health providers, trade unions and employer groups. This research revealed that interventions aimed at increasing use of research in this context must target and harness the influence of these groups. This research provides critical insights for researchers seeking to design interventions to increase use of research in policy environments and influence decision-making in Victorian injury prevention and rehabilitation compensation. Copyright © 2014 Elsevier Ltd. All rights reserved.

The challenges of describing rehabilitation services: A discussion paper.

PubMed

Røe, Cecilie; Kirkevold, Marit; Andelic, Nada; Soberg, Helene L; Sveen, Unni; Bautz-Holter, Erik; Jahnsen, Reidun; van Walsem, Marleen R; Kildal Bragstad, Line; Gabrielsen Hjelle, Ellen; Klevberg, Gunvor; Oretorp, Per; Habberstad, Andreas; Hagfors, Jon; Væhle, Randi; Engen, Grace; Gutenbrunner, Christoph

2018-02-13

To apply the Classification of Service Organization in Rehabilitation (ICSO-R) classification of services to different target groups, include the user perspective, identify missing categories, and propose standardized descriptors for the categories from a Norwegian perspective. Expert-based consensus conferences with user involvement. Health professionals, stakeholders and users. Participants were divided into 5 panels, which applied the ICSO-R to describe the habilitation and rehabilitation services provided to children with cerebral palsy and people with Huntington's disease, acquired brain injuries (traumatic brain injuries and stroke) and painful musculoskeletal conditions. Based on the Problem/Population, Intervention, Comparison, Outcome (PICO) framework, the services were described according to the ICSO-R. Missing categories were identified. The ICSO-R was found to be feasible and applicable for describing a variety of services provided to different target groups in Norway, but the user perspective was lacking, categories were missing, and a need for standardized description of the categories was identified. The present work supports the need to produce an updated version of the ICSO-R and to encourage national and international discussion of the framework. The ICSO-R has the potential to become a tool for the standardized assessment of rehabilitation services. For such purposes, more standardized descriptions of subcategories are necessary.

Using focus groups and social marketing to strengthen promotion of group prenatal care.

PubMed

Vonderheid, Susan C; Carrie, S Klima; Norr, Kathleen F; Grady, Mary Alice; Westdahl, Claire M

2013-01-01

Centering Pregnancy, an innovative group model of prenatal care, shows promise to reduce persistent adverse maternal-infant outcomes and contain costs. Because this innovation requires systemwide change, clinics reported needing support enrolling women into groups and obtaining organizational buy-in. This study used the 3-step social marketing communication strategy to help clinic staff identify key customers and customer-specific barriers to adopting or supporting Centering Pregnancy. They developed targeted information to reduce barriers and built skills in communicating with different customers through role-playing. Findings provide practical information for others to use this communication strategy to improve implementation of Centering Pregnancy.

Screening of patients with bronchopulmonary diseases using methods of infrared laser photoacoustic spectroscopy and principal component analysis

NASA Astrophysics Data System (ADS)

Kistenev, Yury V.; Karapuzikov, Alexander I.; Kostyukova, Nadezhda Yu.; Starikova, Marina K.; Boyko, Andrey A.; Bukreeva, Ekaterina B.; Bulanova, Anna A.; Kolker, Dmitry B.; Kuzmin, Dmitry A.; Zenov, Konstantin G.; Karapuzikov, Alexey A.

2015-06-01

A human exhaled air analysis by means of infrared (IR) laser photoacoustic spectroscopy is presented. Eleven healthy nonsmoking volunteers (control group) and seven patients with chronic obstructive pulmonary disease (COPD, target group) were involved in the study. The principal component analysis method was used to select the most informative ranges of the absorption spectra of patients' exhaled air in terms of the separation of the studied groups. It is shown that the data of the profiles of exhaled air absorption spectrum in the informative ranges allow identifying COPD patients in comparison to the control group.

Using a pattern-centered approach to assess sexual risk-taking in study abroad students.

PubMed

Marcantonio, Tiffany; Angelone, D J; Sledjeski, Eve

2016-01-01

The purpose of this study was to examine the impact of several potential factors related to sexually risky behaviors in study abroad students. The authors utilized a pattern-centered analysis to identify specific groups that can be targeted for intervention. The sample consisted of 173 students who studied abroad in a variety of international locations for an average of 4 months. Participants completed questionnaires informed by the Triandis Theory of Interpersonal Behavior that have been predictive of risky sex in traditional traveling environments. The analyses revealed 3 different pathways for risky sexual behavior: Environmental involvement, historical condom use, and intentions to engage in risky sex. These findings can be used for identification of specific high-risk groups of students who can be targeted for predeparture prevention programs.

Barriers and facilitators to childhood obesity prevention among culturally and linguistically diverse (CALD) communities in Victoria, Australia.

PubMed

Cyril, Sheila; Nicholson, Jan M; Agho, Kingsley; Polonsky, Michael; Renzaho, Andre M

2017-06-01

Childhood obesity is rising among culturally and linguistically diverse (CALD) groups who show poor engagement in obesity prevention initiatives. We examined the barriers and facilitators to the engagement of CALD communities in obesity prevention initiatives. We used the nominal group technique to collect data from 39 participants from Vietnamese, Burmese, African, Afghani and Indian origins living in disadvantaged areas of Victoria, Australia. Data analysis revealed ranked priorities for barriers and facilitators for CALD community engagement in obesity prevention initiatives. CALD parents identified key barriers as being: competing priorities in the post-migration settlement phase; language, cultural and program accessibility barriers; low levels of food and health literacy; junk food advertisement targeting children; and lack of mandatory weight checks for schoolchildren. Key facilitators emerged as: bicultural playgroup leaders; ethnic community groups; and school-based healthy lunch box initiatives. This study has identified several policy recommendations including: the implementation of robust food taxation policies; consistent control of food advertising targeting children; improving CALD health literacy using bicultural workers; and matching health promotional materials with CALD community literacy levels. Implications for Public Health: These recommendations can directly influence public health policy to improve the engagement of CALD communities in obesity prevention services and ultimately reduce the widening obesity disparities in Australia. © 2017 The Authors.

A Framework for Identifying Selective Chemical Applications for IPM in Dryland Agriculture

PubMed Central

Umina, Paul A.; Jenkins, Sommer; McColl, Stuart; Arthur, Aston; Hoffmann, Ary A.

2015-01-01

Shifts to Integrated Pest Management (IPM) in agriculture are assisted by the identification of chemical applications that provide effective control of pests relative to broad-spectrum pesticides but have fewer negative effects on natural enemy (beneficial) groups that assist in pest control. Here, we outline a framework for identifying such applications and apply this framework to field trials involving the crop establishment phase of Australian dryland cropping systems. Several chemicals, which are not presently available to farmers in Australia, were identified as providing moderate levels of pest control and seedling protection, with the potential to be less harmful to beneficial groups including predatory mites, predatory beetles and ants. This framework highlights the challenges involved in chemically controlling pests while maintaining non-target populations when pest species are present at damaging levels. PMID:26694469

[Humoral immune diseases: Cutaneous vasculitis and auto-immune bullous dermatoses].

PubMed

Wechsler, Janine

2018-02-01

Humoral immunity is the cause of multiple diseases related to antibodies (IgA, IgG, IgM) produced by the patient. Two groups of diseases are identified. The first group is related to circulating antigen-antibody complexes. The antigens are various. They are often unknown. These immune complexes cause a vascular inflammation due to the complement fixation. Consequently, this group is dominated by inflammatory vasculitis. In the second group, the pathology is due to the fixation in situ of antibodies to a target antigen of the skin that is no more recognized by the patient. This group is represented by the auto-immune bullous dermatoses. Copyright © 2017. Published by Elsevier Masson SAS.

Social marketing targeting Indigenous peoples: a systematic review.

PubMed

Kubacki, Krzysztof; Szablewska, Natalia

2017-09-07

Social marketing is a discipline focused on the application of marketing principles to induce socially desirable behaviour change. As social marketing remains one of the main behaviour change approaches pursued by governments and international organisations, it is important to consider its use in relation to vulnerable groups that are particularly exposed to discriminatory practices, marginalisation, exclusion and destitution. The aim of this systematic review is to identify the extent to which Andreasen's (2002) six social marketing benchmark criteria were reported in social marketing interventions targeting Indigenous peoples. A total of 20 articles covering 13 social marketing interventions were identified for review. Although none of the interventions gave evidence that they addressed all six of the benchmark criteria, they appear to have been effective in challenging some of the issues faced by Indigenous peoples. However, the criteria of segmentation, exchange and competition remain underused in the identified interventions. Social marketing interventions targeting Indigenous peoples tend to rely on television and radio advertising, showing potential for more use of product, place and price to influence, facilitate and maintain socially desirable behaviour change. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A compound-based proteomic approach discloses 15-ketoatractyligenin methyl ester as a new PPARγ partial agonist with anti-proliferative ability

NASA Astrophysics Data System (ADS)

Vasaturo, Michele; Fiengo, Lorenzo; de Tommasi, Nunziatina; Sabatino, Lina; Ziccardi, Pamela; Colantuoni, Vittorio; Bruno, Maurizio; Cerchia, Carmen; Novellino, Ettore; Lupo, Angelo; Lavecchia, Antonio; Piaz, Fabrizio Dal

2017-01-01

Proteomics based approaches are emerging as useful tools to identify the targets of bioactive compounds and elucidate their molecular mechanisms of action. Here, we applied a chemical proteomic strategy to identify the peroxisome proliferator-activated receptor γ (PPARγ) as a molecular target of the pro-apoptotic agent 15-ketoatractyligenin methyl ester (compound 1). We demonstrated that compound 1 interacts with PPARγ, forms a covalent bond with the thiol group of C285 and occupies the sub-pocket between helix H3 and the β-sheet of the ligand-binding domain (LBD) of the receptor by Surface Plasmon Resonance (SPR), mass spectrometry-based studies and docking experiments. 1 displayed partial agonism of PPARγ in cell-based transactivation assays and was found to inhibit the AKT pathway, as well as its downstream targets. Consistently, a selective PPARγ antagonist (GW9662) greatly reduced the anti-proliferative and pro-apoptotic effects of 1, providing the molecular basis of its action. Collectively, we identified 1 as a novel PPARγ partial agonist and elucidated its mode of action, paving the way for therapeutic strategies aimed at tailoring novel PPARγ ligands with reduced undesired harmful side effects.

A compound-based proteomic approach discloses 15-ketoatractyligenin methyl ester as a new PPARγ partial agonist with anti-proliferative ability

PubMed Central

Vasaturo, Michele; Fiengo, Lorenzo; De Tommasi, Nunziatina; Sabatino, Lina; Ziccardi, Pamela; Colantuoni, Vittorio; Bruno, Maurizio; Cerchia, Carmen; Novellino, Ettore; Lupo, Angelo; Lavecchia, Antonio; Piaz, Fabrizio Dal

2017-01-01

Proteomics based approaches are emerging as useful tools to identify the targets of bioactive compounds and elucidate their molecular mechanisms of action. Here, we applied a chemical proteomic strategy to identify the peroxisome proliferator-activated receptor γ (PPARγ) as a molecular target of the pro-apoptotic agent 15-ketoatractyligenin methyl ester (compound 1). We demonstrated that compound 1 interacts with PPARγ, forms a covalent bond with the thiol group of C285 and occupies the sub-pocket between helix H3 and the β-sheet of the ligand-binding domain (LBD) of the receptor by Surface Plasmon Resonance (SPR), mass spectrometry-based studies and docking experiments. 1 displayed partial agonism of PPARγ in cell-based transactivation assays and was found to inhibit the AKT pathway, as well as its downstream targets. Consistently, a selective PPARγ antagonist (GW9662) greatly reduced the anti-proliferative and pro-apoptotic effects of 1, providing the molecular basis of its action. Collectively, we identified 1 as a novel PPARγ partial agonist and elucidated its mode of action, paving the way for therapeutic strategies aimed at tailoring novel PPARγ ligands with reduced undesired harmful side effects. PMID:28117438

A compound-based proteomic approach discloses 15-ketoatractyligenin methyl ester as a new PPARγ partial agonist with anti-proliferative ability.

PubMed

Vasaturo, Michele; Fiengo, Lorenzo; De Tommasi, Nunziatina; Sabatino, Lina; Ziccardi, Pamela; Colantuoni, Vittorio; Bruno, Maurizio; Cerchia, Carmen; Novellino, Ettore; Lupo, Angelo; Lavecchia, Antonio; Piaz, Fabrizio Dal

2017-01-24

Proteomics based approaches are emerging as useful tools to identify the targets of bioactive compounds and elucidate their molecular mechanisms of action. Here, we applied a chemical proteomic strategy to identify the peroxisome proliferator-activated receptor γ (PPARγ) as a molecular target of the pro-apoptotic agent 15-ketoatractyligenin methyl ester (compound 1). We demonstrated that compound 1 interacts with PPARγ, forms a covalent bond with the thiol group of C285 and occupies the sub-pocket between helix H3 and the β-sheet of the ligand-binding domain (LBD) of the receptor by Surface Plasmon Resonance (SPR), mass spectrometry-based studies and docking experiments. 1 displayed partial agonism of PPARγ in cell-based transactivation assays and was found to inhibit the AKT pathway, as well as its downstream targets. Consistently, a selective PPARγ antagonist (GW9662) greatly reduced the anti-proliferative and pro-apoptotic effects of 1, providing the molecular basis of its action. Collectively, we identified 1 as a novel PPARγ partial agonist and elucidated its mode of action, paving the way for therapeutic strategies aimed at tailoring novel PPARγ ligands with reduced undesired harmful side effects.

Plasma Glycoproteomics Reveals Sepsis Outcomes Linked to Distinct Proteins in Common Pathways

PubMed Central

DeLeon-Pennell, Kristine Y.; Nguyen, Nguyen T.; de Castro Brás, Lisandra E.; Flynn, Elizabeth R.; Cannon, Presley L.; Griswold, Michael E.; Jin, Yu-Fang; Puskarich, Michael A.; Jones, Alan E.; Lindsey, Merry L.

2015-01-01

Objective Sepsis remains a predominant cause of mortality in the ICU, yet strategies to increase survival have proved largely unsuccessful. This study aimed to identify proteins linked to sepsis outcomes using a glycoproteomic approach to target extracellular proteins that trigger downstream pathways and direct patient outcomes. Design Plasma was obtained from the LacTATEs cohort. N-linked plasma glycopeptides were quantified by solid-phase extraction coupled with mass spectrometry. Glycopeptides were assigned to proteins using RefSeq and visualized in a heat map. Protein differences were validated by immunoblotting, and proteins were mapped for biological processes using Database for Annotation, Visualization and Integrated Discovery and for functional pathways using Kyoto Encyclopedia of Genes and Genomes databases. Setting Hospitalized care. Measurements and Main Results A total of 501 glycopeptides corresponding to 234 proteins were identified. Of these, 66 glycopeptides were unique to the survivor group and corresponded to 54 proteins, 60 were unique to the nonsurvivor group and corresponded to 43 proteins, and 375 were common responses between groups and corresponded to 137 proteins. Immunoblotting showed that nonsurvivors had increased total kininogen; decreased total cathepsin-L1, vascular cell adhesion molecule, periostin, and neutrophil gelatinase–associated lipocalin; and a two-fold decrease in glycosylated clusterin (all p < 0.05). Kyoto Encyclopedia of Genes and Genomes analysis identified six enriched pathways. Interestingly, survivors relied on the extrinsic pathway of the complement and coagulation cascade, whereas nonsurvivors relied on the intrinsic pathway. Conclusion This study identifies proteins linked to patient outcomes and provides insight into unexplored mechanisms that can be investigated for the identification of novel therapeutic targets. (Crit Care Med 2015; XX:00–00) PMID:26086942

Blood grouping based on PCR methods and agarose gel electrophoresis.

PubMed

Sell, Ana Maria; Visentainer, Jeane Eliete Laguila

2015-01-01

The study of erythrocyte antigens continues to be an intense field of research, particularly after the development of molecular testing methods. More than 300 specificities have been described by the International Society for Blood Transfusion as belonging to 33 blood group systems. The polymerase chain reaction (PCR) is a central tool for red blood cells (RBC) genotyping. PCR and agarose gel electrophoresis are low cost, easy, and versatile in vitro methods for amplifying defined target DNA (RBC polymorphic region). Multiplex-PCR, AS-PCR (Specific Allele Polymerase Chain Reaction), and RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction) techniques are usually to identify RBC polymorphisms. Furthermore, it is an easy methodology to implement. This chapter describes the PCR methodology and agarose gel electrophoresis to identify the polymorphisms of the Kell, Duffy, Kidd, and MNS blood group systems.

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians: a model process.

PubMed

Whitstock, Margaret T; Pearce, Christopher M; Ridout, Stephen C; Eckermann, Elizabeth J

2011-05-21

The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients. The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug. Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug. Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Road to better health and integration: a Delphi study on health service models for Hong Kong migrants.

PubMed

Wong, William C W; Ho, Petula S Y; Liang, Jun; Holroyd, Eleanor A; Lam, Cindy L K; Pau, Agnes M Y

2014-12-19

In Hong Kong, migrants arriving from Mainland China often have multiple roles and responsibilities while adapting to new lives in their host destination. This paper explored the factors that contribute to the inequity in health services utilisation experienced by these migrants; and, identified the elements that could constitute an effective health delivery model to address the service gap. Site visits and a focus group discussion (n = 13) were held with both public and private health providers before a number of innovative health delivery models were formulated. They were then circulated among the panel in two further rounds of Delphi survey (n = 11) from March-April 2012 to systematically collect opinions and select the most endorsed health service models to serve this target population. Focus group members perceived that most migrants were unaware of, or even ignored, their own physical and mental health needs, and had low utilisation of healthcare services, because of their pre-occupation with daily chores and hardship as well as differing health values, practices and expectations. They further identified that the structural issues such as the healthcare setting or the operation of current service provisions had failed to meet migrants' health needs. Consequently, four new service models that incorporated professional advice and empowerment, which were identified as the two most important elements, were put forward. Thus, the model of having a nurse with social work training, supported by volunteer groups, was selected as the best option to familiarise and empower patients within the labyrinth of local healthcare services. Implementation of a social empowerment model by way of targeted support and specific health information is recommended. Further evaluation of this model is needed to understand its effectiveness for improving health literacy and health status in this disadvantaged group in the long term.

Morphologic and molecular study of lung cancers associated with idiopathic pulmonary fibrosis and other pulmonary fibroses.

PubMed

Guyard, Alice; Danel, Claire; Théou-Anton, Nathalie; Debray, Marie-Pierre; Gibault, Laure; Mordant, Pierre; Castier, Yves; Crestani, Bruno; Zalcman, Gérard; Blons, Hélène; Cazes, Aurélie

2017-06-15

Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS). Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group. NGS was performed using an ampliseq panel to analyze hotspots and targeted regions in 22 cancer-associated genes. ALK, ROS1 and PD-L1 expressions were assessed by immunohistochemistry. Squamous cell carcinoma was the most frequent histologic subtype in the IPF group (44%), adenocarcinoma was the most frequent subtype in the non-IPF group (62%). Forty-one mutations in 13 genes and one EGFR amplification were identified in 25 samples. Two samples had no mutation in the selected panel. Mutations were identified in TP53 (n = 20), MET (n = 4), BRAF (n = 3), FGFR3, PIK3CA, PTEN, STK11 (n = 2), SMAD4, CTNNB1, DDR2, ERBB4, FBXW7 and KRAS (n = 1) genes. No ALK and ROS1 expressions were identified. PD-L1 was expressed in 10 cases (62%) with only one (6%) case >50%. This extensive characterization of lung fibrosis-associated cancers evidenced molecular alterations which could represent either potential therapeutic targets either clues to the pathophysiology of these particular tumors. These findings support the relevance of large molecular characterization of every lung fibrosis-associated cancer.

TargetLink, a new method for identifying the endogenous target set of a specific microRNA in intact living cells.

PubMed

Xu, Yan; Chen, Yan; Li, Daliang; Liu, Qing; Xuan, Zhenyu; Li, Wen-Hong

2017-02-01

MicroRNAs are small non-coding RNAs acting as posttranscriptional repressors of gene expression. Identifying mRNA targets of a given miRNA remains an outstanding challenge in the field. We have developed a new experimental approach, TargetLink, that applied locked nucleic acid (LNA) as the affinity probe to enrich target genes of a specific microRNA in intact cells. TargetLink also consists a rigorous and systematic data analysis pipeline to identify target genes by comparing LNA-enriched sequences between experimental and control samples. Using miR-21 as a test microRNA, we identified 12 target genes of miR-21 in a human colorectal cancer cell by this approach. The majority of the identified targets interacted with miR-21 via imperfect seed pairing. Target validation confirmed that miR-21 repressed the expression of the identified targets. The cellular abundance of the identified miR-21 target transcripts varied over a wide range, with some targets expressed at a rather low level, confirming that both abundant and rare transcripts are susceptible to regulation by microRNAs, and that TargetLink is an efficient approach for identifying the target set of a specific microRNA in intact cells. C20orf111, one of the novel targets identified by TargetLink, was found to reside in the nuclear speckle and to be reliably repressed by miR-21 through the interaction at its coding sequence.

Optimizing and Validating a Brief Assessment for Identifying Children of Service Members at Risk for Psychological Health Problems Following Parent Deployment

DTIC Science & Technology

2017-09-01

these groups . In the 2014/2015 year, efforts focused on securing a commitment from the United States Marine Corps to host the study. In Winter 2014...we can reach an adjusted sample size target in the 2017/2018 project year by expanding our recruitment to incorporate deploying infantry groups ...Vocabulary Test Revised. Circle Pines, MN: American Guidance Service. George, C. & Solomon , J. (2008). The caregving system: A behavioral systems approach

Extension of On-Surface Radiation Condition (OSRC) Theory to Full-Vector Electromagnetic Wave Scattering by Three-Dimensional Conducting, Dielectric, and Coated Targets

DTIC Science & Technology

1993-08-27

rever"_? if necessary and identify by block number) FIELD SUB- GROUP Electromagnetic wave scattering, radiation boundary -. ... conditions, finite...international engineering electromagnetics symposia and in related journals has risen from a level of less than 10 per year (published primarily by my group ) to...Rzpoxs and Non -Refereed Papers: 3, as follows- I. D. S. Katz, A. Taflove, J. P. Brooks and E. Harrigan, "Large-scale methods in computational

Recovering mitochondrial DNA lineages of extinct Amerindian nations in extant homopatric Brazilian populations.

PubMed

Gonçalves, Vanessa F; Parra, Flavia C; Gonçalves-Dornelas, Higgor; Rodrigues-Carvalho, Claudia; Silva, Hilton P; Pena, Sergio Dj

2010-12-01

Brazilian Amerindians have experienced a drastic population decrease in the past 500 years. Indeed, many native groups from eastern Brazil have vanished. However, their mitochondrial mtDNA haplotypes, still persist in Brazilians, at least 50 million of whom carry Amerindian mitochondrial lineages. Our objective was to test whether, by analyzing extant rural populations from regions anciently occupied by specific Amerindian groups, we could identify potentially authentic mitochondrial lineages, a strategy we have named 'homopatric targeting'. We studied 173 individuals from Queixadinha, a small village located in a territory previously occupied by the now extinct Botocudo Amerindian nation. Pedigree analysis revealed 74 unrelated matrilineages, which were screened for Amerindian mtDNA lineages by restriction fragment length polymorphism. A cosmopolitan control group was composed of 100 individuals from surrounding cities. All Amerindian lineages identified had their hypervariable segment HVSI sequenced, yielding 13 Amerindian haplotypes in Queixadinha, nine of which were not present in available databanks or in the literature. Among these haplotypes, there was a significant excess of haplogroup C (70%) and absence of haplogroup A lineages, which were the most common in the control group. The novelty of the haplotypes and the excess of the C haplogroup suggested that we might indeed have identified Botocudo lineages. To validate our strategy, we studied teeth extracted from 14 ancient skulls of Botocudo Amerindians from the collection of the National Museum of Rio de Janeiro. We recovered mtDNA sequences from all the teeth, identifying only six different haplotypes (a low haplotypic diversity of 0.8352 ± 0.0617), one of which was present among the lineages observed in the extant individuals studied. These findings validate the technique of homopatric targeting as a useful new strategy to study the peopling and colonization of the New World, especially when direct analysis of genetic material is not possible.

Implementation of the guidelines for targeted temperature management after cardiac arrest: a longitudinal qualitative study of barriers and facilitators perceived by hospital resuscitation champions

PubMed Central

Kim, Young-Min; Lee, Seung Joon; Jo, Sun Jin; Park, Kyu Nam

2016-01-01

Objectives To identify the barriers to and facilitators of implementing guidelines for targeted temperature management (TTM) after cardiac arrest perceived by hospital resuscitation champions and to investigate the changes in their perceptions over the early implementation period. Design A longitudinal qualitative study (up to 2 serial semistructured interviews over 1 year and focus groups). The individual interviews and focus groups were transcribed and coded by 2 independent assessors. Contents were analysed thematically; group interaction was also examined. Setting 21 hospitals, including community and tertiary care centres in South Korea. Participants 21 hospital champions (14 acting champions and 7 managerial champions). Results The final data set included 40 interviews and 2 focus groups. The identified barriers and facilitators could be classified into 3 major themes: (1) healthcare professionals’ perceptions of the guidelines and protocols, (2) interdisciplinary and interprofessional collaboration and (3) organisational resources. Lack of resources was the most commonly agreed on barrier for the acting champions, whereas lack of interdisciplinary collaboration was the most common barrier for the managerial champions. Educational activities and sharing successfully treated cases were the most frequently identified facilitators. Most of the participants identified and agreed that cooling equipment was an important barrier as well as a facilitator of successful TTM implementation. Perception of the guidelines and protocols has improved with the accumulation of clinical experience over the study period. Conclusions Healthcare professionals’ internal barriers to TTM implementation may be influenced by new guidelines and can be changed with the accumulation of successful clinical experiences during the early implementation period. Promoting interprofessional and interdisciplinary collaboration through educational activities and the use of cooling equipment with an automated feedback function can improve adherence to guidelines in hospitals with limited human resources in critical care. PMID:26733568

Recovering mitochondrial DNA lineages of extinct Amerindian nations in extant homopatric Brazilian populations

PubMed Central

2010-01-01

Background Brazilian Amerindians have experienced a drastic population decrease in the past 500 years. Indeed, many native groups from eastern Brazil have vanished. However, their mitochondrial mtDNA haplotypes, still persist in Brazilians, at least 50 million of whom carry Amerindian mitochondrial lineages. Our objective was to test whether, by analyzing extant rural populations from regions anciently occupied by specific Amerindian groups, we could identify potentially authentic mitochondrial lineages, a strategy we have named 'homopatric targeting'. Results We studied 173 individuals from Queixadinha, a small village located in a territory previously occupied by the now extinct Botocudo Amerindian nation. Pedigree analysis revealed 74 unrelated matrilineages, which were screened for Amerindian mtDNA lineages by restriction fragment length polymorphism. A cosmopolitan control group was composed of 100 individuals from surrounding cities. All Amerindian lineages identified had their hypervariable segment HVSI sequenced, yielding 13 Amerindian haplotypes in Queixadinha, nine of which were not present in available databanks or in the literature. Among these haplotypes, there was a significant excess of haplogroup C (70%) and absence of haplogroup A lineages, which were the most common in the control group. The novelty of the haplotypes and the excess of the C haplogroup suggested that we might indeed have identified Botocudo lineages. To validate our strategy, we studied teeth extracted from 14 ancient skulls of Botocudo Amerindians from the collection of the National Museum of Rio de Janeiro. We recovered mtDNA sequences from all the teeth, identifying only six different haplotypes (a low haplotypic diversity of 0.8352 ± 0.0617), one of which was present among the lineages observed in the extant individuals studied. Conclusions These findings validate the technique of homopatric targeting as a useful new strategy to study the peopling and colonization of the New World, especially when direct analysis of genetic material is not possible. PMID:21122100

RKIP and HMGA2 regulate breast tumor survival and metastasis through lysyl oxidase and syndecan-2.

PubMed

Sun, M; Gomes, S; Chen, P; Frankenberger, C A; Sankarasharma, D; Chung, C H; Chada, K K; Rosner, M R

2014-07-03

Elucidating targets of physiological tumor metastasis suppressors can highlight key signaling pathways leading to invasion and metastasis. To identify downstream targets of the metastasis suppressor Raf-1 kinase inhibitory protein (RKIP/PEBP1), we utilized an integrated approach based upon statistical analysis of tumor gene expression data combined with experimental validation. Previous studies from our laboratory identified the architectural transcription factor and oncogene, high mobility group AT-hook 2 (HMGA2), as a target of inhibition by RKIP. Here we identify two signaling pathways that promote HMGA2-driven metastasis. Using both human breast tumor cells and an MMTV-Wnt mouse breast tumor model, we show that RKIP induces and HMGA2 inhibits expression of miR-200b; miR-200b directly inhibits expression of lysyl oxidase (LOX), leading to decreased invasion. RKIP also inhibits syndecan-2 (SDC2), which is aberrantly expressed in breast cancer, via downregulation of HMGA2; but this mechanism is independent of miR-200. Depletion of SDC2 induces apoptosis and suppresses breast tumor growth and metastasis in mouse xenografts. RKIP, LOX and SDC2 are coordinately regulated and collectively encompass a prognostic signature for metastasis-free survival in ER-negative breast cancer patients. Taken together, our findings reveal two novel signaling pathways targeted by the metastasis suppressor RKIP that regulate remodeling of the extracellular matrix and tumor survival.

Towards 90-90-90 Target: Factors Influencing Availability, Access, and Utilization of HIV Services—A Qualitative Study in 19 Ugandan Districts

PubMed Central

Tumwebaze, Flora; Akakimpa, Denis; Kityo, Cissy; Mugyenyi, Peter; Abongomera, George

2018-01-01

Background UNAIDS has set a new target 90-90-90 by 2020. To achieve this target, current programs need to address challenges that limit access, availability, and utilization of HIV testing and treatment services. Therefore, the aim of this study was to identify the barriers that influence access, availability, and utilization of HIV services in rural Uganda within the setting of a large donor funded program. Methods We conducted key informant interviews with stakeholders at the district level, staff of existing HIV/AIDS projects, and health facilities in 19 districts. Data were also collected from focus group discussions comprised of clients presenting for HIV care and treatment. Data were transcribed and analyzed using content analysis. Results. Barriers identified were as follows: (1) drug shortages including antiretroviral drugs at health facilities. Some patients were afraid to start ART because of worrying about shortages; (2) distance and (3) staffing shortages; (4) stigma persistence; (5) lack of social and economic support initiatives that enhance retention in treatment. Conclusions In conclusion, our study has identified several factors that influence access, availability, and utilization of HIV services. Programs need to address drug and staff shortages, HIV stigma, and long distances to health facilities to broaden access and utilization in order to realize the UNAIDS target. PMID:29750175

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 distributed computational search strategy for the identification of diagnostics targets: application to finding aptamer targets for methicillin-resistant staphylococci.

PubMed

Flanagan, Keith; Cockell, Simon; Harwood, Colin; Hallinan, Jennifer; Nakjang, Sirintra; Lawry, Beth; Wipat, Anil

2014-06-30

The rapid and cost-effective identification of bacterial species is crucial, especially for clinical diagnosis and treatment. Peptide aptamers have been shown to be valuable for use as a component of novel, direct detection methods. These small peptides have a number of advantages over antibodies, including greater specificity and longer shelf life. These properties facilitate their use as the detector components of biosensor devices. However, the identification of suitable aptamer targets for particular groups of organisms is challenging. We present a semi-automated processing pipeline for the identification of candidate aptamer targets from whole bacterial genome sequences. The pipeline can be configured to search for protein sequence fragments that uniquely identify a set of strains of interest. The system is also capable of identifying additional organisms that may be of interest due to their possession of protein fragments in common with the initial set. Through the use of Cloud computing technology and distributed databases, our system is capable of scaling with the rapidly growing genome repositories, and consequently of keeping the resulting data sets up-to-date. The system described is also more generically applicable to the discovery of specific targets for other diagnostic approaches such as DNA probes, PCR primers and antibodies.

A distributed computational search strategy for the identification of diagnostics targets: Application to finding aptamer targets for methicillin-resistant staphylococci.

PubMed

Flanagan, Keith; Cockell, Simon; Harwood, Colin; Hallinan, Jennifer; Nakjang, Sirintra; Lawry, Beth; Wipat, Anil

2014-06-01

The rapid and cost-effective identification of bacterial species is crucial, especially for clinical diagnosis and treatment. Peptide aptamers have been shown to be valuable for use as a component of novel, direct detection methods. These small peptides have a number of advantages over antibodies, including greater specificity and longer shelf life. These properties facilitate their use as the detector components of biosensor devices. However, the identification of suitable aptamer targets for particular groups of organisms is challenging. We present a semi-automated processing pipeline for the identification of candidate aptamer targets from whole bacterial genome sequences. The pipeline can be configured to search for protein sequence fragments that uniquely identify a set of strains of interest. The system is also capable of identifying additional organisms that may be of interest due to their possession of protein fragments in common with the initial set. Through the use of Cloud computing technology and distributed databases, our system is capable of scaling with the rapidly growing genome repositories, and consequently of keeping the resulting data sets up-to-date. The system described is also more generically applicable to the discovery of specific targets for other diagnostic approaches such as DNA probes, PCR primers and antibodies.

MicroRNA-124-3p expression and its prospective functional pathways in hepatocellular carcinoma: A quantitative polymerase chain reaction, gene expression omnibus and bioinformatics study.

PubMed

He, Rong-Quan; Yang, Xia; Liang, Liang; Chen, Gang; Ma, Jie

2018-04-01

The present study aimed to explore the potential clinical significance of microRNA (miR)-124-3p expression in the hepatocarcinogenesis and development of hepatocellular carcinoma (HCC), as well as the potential target genes of functional HCC pathways. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the expression of miR-124-3p in 101 HCC and adjacent non-cancerous tissue samples. Additionally, the association between miR-124-3p expression and clinical parameters was also analyzed. Differentially expressed genes identified following miR-124-3p transfection, the prospective target genes predicted in silico and the key genes of HCC obtained from Natural Language Processing (NLP) were integrated to obtain potential target genes of miR-124-3p in HCC. Relevant signaling pathways were assessed with protein-protein interaction (PPI) networks, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein Annotation Through Evolutionary Relationships (PANTHER) pathway enrichment analysis. miR-124-3p expression was significantly reduced in HCC tissues compared with expression in adjacent non-cancerous liver tissues. In HCC, miR-124-3p was demonstrated to be associated with clinical stage. The mean survival time of the low miR-124-3p expression group was reduced compared with that of the high expression group. A total of 132 genes overlapped from differentially expressed genes, miR-124-3p predicted target genes and NLP identified genes. PPI network construction revealed a total of 109 nodes and 386 edges, and 20 key genes were identified. The major enriched terms of three GO categories included regulation of cell proliferation, positive regulation of cellular biosynthetic processes, cell leading edge, cytosol and cell projection, protein kinase activity, transcription activator activity and enzyme binding. KEGG analysis revealed pancreatic cancer, prostate cancer and non-small cell lung cancer as the top three terms. Angiogenesis, the endothelial growth factor receptor signaling pathway and the fibroblast growth factor signaling pathway were identified as the most significant terms in the PANTHER pathway analysis. The present study confirmed that miR-124-3p acts as a tumor suppressor in HCC. miR-124-3p may target multiple genes, exerting its effect spatiotemporally, or in combination with a diverse range of processes in HCC. Functional characterization of miR-124-3p targets will offer novel insight into the molecular changes that occur in HCC progression.

Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial.

PubMed

Schmidt, Barbara; Whyte, Robin K; Asztalos, Elizabeth V; Moddemann, Diane; Poets, Christian; Rabi, Yacov; Solimano, Alfonso; Roberts, Robin S

2013-05-22

The goal of oxygen therapy is to deliver sufficient oxygen to the tissues while minimizing oxygen toxicity and oxidative stress. It remains uncertain what values of arterial oxygen saturations achieve this balance in preterm infants. To compare the effects of targeting lower or higher arterial oxygen saturations on the rate of death or disability in extremely preterm infants. Randomized, double-blind trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel in which 1201 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days were enrolled within 24 hours after birth between December 2006 and August 2010. Follow-up assessments began in October 2008 and ended in August 2012. Study participants were monitored until postmenstrual ages of 36 to 40 weeks with pulse oximeters that displayed saturations of either 3% above or below the true values. Caregivers adjusted the concentration of oxygen to achieve saturations between 88% and 92%, which produced 2 treatment groups with true target saturations of 85% to 89% (n = 602) or 91% to 95% (n = 599). Alarms were triggered when displayed saturations decreased to 86% or increased to 94%. The primary outcome was a composite of death, gross motor disability, cognitive or language delay, severe hearing loss, or bilateral blindness at a corrected age of 18 months. Secondary outcomes included retinopathy of prematurity and brain injury. Of the 578 infants with adequate data for the primary outcome who were assigned to the lower target range, 298 (51.6%) died or survived with disability compared with 283 of the 569 infants (49.7%) assigned to the higher target range (odds ratio adjusted for center, 1.08; 95% CI, 0.85 to 1.37; P = .52). The rates of death were 16.6% for those in the 85% to 89% group and 15.3% for those in the 91% to 95% group (adjusted odds ratio, 1.11; 95% CI, 0.80 to 1.54; P = .54). Targeting lower saturations reduced the postmenstrual age at last use of oxygen therapy (adjusted mean difference, -0.8 weeks; 95% CI, -1.5 to -0.1; P = .03) but did not alter any other outcomes. In extremely preterm infants, targeting oxygen saturations of 85% to 89% compared with 91% to 95% had no significant effect on the rate of death or disability at 18 months. These results may help determine the optimal target oxygen saturation. ISRCTN Identifier: 62491227; ClinicalTrials.gov Identifier: NCT00637169.

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.

A Novel Uveolymphatic Drainage Pathway-Possible New Target for Glaucoma Treatment.

PubMed

Tomczyk-Socha, Martyna; Turno-Kręcicka, Anna

2017-12-01

Glaucoma is a heterogeneous group of ophthalmic diseases leading to irreversible damage to the optic nerve. While the overall mechanism responsible for glaucoma remains obscure, the most important risk factor is elevated intraocular pressure. The current therapies, whether pharmacological or surgical, are primarily symptomatic with the aim to lower the intraocular pressure (IOP). Poorer response to treatment is associated, for example, with pseudoexfoliation glaucoma, which is determined by blocking the trabecular meshwork (TM) both by pigment grains and the pseudoexfoliation material. It was thought that aqueous humor is drained from the eye by two main pathways: conventional outflow through the TM and Schlemm's canal; and unconventional outflow through the ciliary body through uveal tissue. In 2009 Yucel et al. described and proved the presence of a third pathway for aqueous humor drainage using two specific lymphatic markers: podoplanin, and lymphatic vessel endothelial hyaluronan receptor-1 to identify lymphatic channels in the human ciliary body. The discovery identifies a novel target for IOP-lowering therapies. The most promising group are prostaglandins, which are widely prescribed for glaucoma patients. An intriguing new possibility in glaucoma therapy is using ANGPT agonist. It is still not known if the lymphatic drainage in glaucoma is decreased or dysfunctional and whether lymphatic stimulation can help in removing the improperly accumulated substances, as is seen in pseudoexfoliation glaucoma. However, this new target for glaucoma treatment appears very promising.

The Animadora Project: Identifying factors related to the promotion of physical activity among Mexican Americans with diabetes

PubMed Central

Ingram, Maia; Ruis, Maricruz; Mayorga, Maria Theresa; Rosales, Cecilia

2015-01-01

Purpose There is a dearth of information about factors related to physical activity among Mexican Americans with diabetes. Self efficacy and social support are associated with physical activity, however little is known about their role within different cultural groups. Design Focus groups were used to identify factors that motivate walking. Setting Two Mexican American communities located in Tucson, Arizona. Subjects Individuals who attended diabetes education. Intervention A community-based provider organized walking groups with people who previously attended diabetes classes. Walkers participated in focus groups exploring themes related to their experience. Measures Self efficacy, social support, and collective efficacy. Grounded theory was used to analyze focus group results using two rounds of analysis; the first identifying references to self efficacy and social support and the second adding collective efficacy as a theoretical basis for walking. Results Among 43 eligible participants, 20 participated in focus groups. Social support was expressed as commitment and companionship. Walkers demonstrated a high level of self efficacy for walking. Development of group identity/social cohesion was also a motivator to walk. Collective efficacy emerged as an applicable theoretical model encompassing these themes and their interrelationship. Conclusion Collective efficacy, or the belief that the group can improve their lives through collective effort, is a viable theoretical construct in the development of physical activity interventions targeting Mexican Americans with diabetes. PMID:19601479

Influences on Adoption of Greenhouse Gas Reduction Targets among US States, 1998-2008

PubMed Central

Cale, Tabitha M.; Reams, Margaret A.

2016-01-01

While the United States has not established federal regulations for greenhouse gas (GHG) reduction targets, many US states have adopted their own standards and guidelines. In this study we examine state adoption of targets for GHG reductions during the ten-year period of 1998–2008, and identify factors that explain variation in target adoption. Potential influences are drawn from research from the public policy formulation and diffusion literature, and from studies specific to climate policy adoption. Potential influences on GHG reduction efforts among US states include socioeconomic attributes of residents, political and ideological orientations of citizens and state government, interest group activities, environmental pressures, and proximity to other states that have adopted GHG reduction targets. The findings of the multinomial logistic regression analysis indicate that states are more likely to adopt GHG reduction targets if they share a border with another state with a similar climate program and if their citizens are more ideologically liberal. Other factors including socioeconomic resources and interest group activities were not found to be associated with policy adoption. The findings yield insights into the conditions under which states are more likely to take action to reduce GHG’s, and are relevant both to state policy makers and residents with an interest in climate planning, and for researchers attempting to estimate future greenhouse gas reduction scenarios. PMID:27471657

Opening minds in Canada: targeting change.

PubMed

Stuart, Heather; Chen, Shu-Ping; Christie, Romie; Dobson, Keith; Kirsh, Bonnie; Knaak, Stephanie; Koller, Michelle; Krupa, Terry; Lauria-Horner, Bianca; Luong, Dorothy; Modgill, Geeta; Patten, Scott B; Pietrus, Mike; Szeto, Andrew; Whitley, Rob

2014-10-01

To summarize the ongoing activities of the Opening Minds (OM) Anti-Stigma Initiative of the Mental Health Commission of Canada regarding the 4 groups targeted (youth, health care providers, media, and workplaces), highlight some of the key methodological challenges, and review lessons learned. The approach used by OM is rooted in community development philosophy, with clearly defined target groups, contact-based education as the central organizing element across interventions, and a strong evaluative component so that best practices can be identified, replicated, and disseminated. Contact-based education occurs when people who have experienced a mental illness share their personal story of recovery and hope. Results have been generally positive. Contact-based education has the capacity to reduce prejudicial attitudes and improve social acceptance of people with a mental illness across various target groups and sectors. Variations in program outcomes have contributed to our understanding of active ingredients. Contact-based education has become a cornerstone of the OM approach to stigma reduction. A story of hope and recovery told by someone who has experienced a mental illness is powerful and engaging, and a critical ingredient in the fight against stigma. Building partnerships with existing community programs and promoting systematic evaluation using standardized approaches and instruments have contributed to our understanding of best practices in the field of anti-stigma programming. The next challenge will be to scale these up so that they may have a national impact.

Spy: a new group of eukaryotic DNA transposons without target site duplications.

PubMed

Han, Min-Jin; Xu, Hong-En; Zhang, Hua-Hao; Feschotte, Cédric; Zhang, Ze

2014-06-24

Class 2 or DNA transposons populate the genomes of most eukaryotes and like other mobile genetic elements have a profound impact on genome evolution. Most DNA transposons belong to the cut-and-paste types, which are relatively simple elements characterized by terminal-inverted repeats (TIRs) flanking a single gene encoding a transposase. All eukaryotic cut-and-paste transposons so far described are also characterized by target site duplications (TSDs) of host DNA generated upon chromosomal insertion. Here, we report a new group of evolutionarily related DNA transposons called Spy, which also include TIRs and DDE motif-containing transposase but surprisingly do not create TSDs upon insertion. Instead, Spy transposons appear to transpose precisely between 5'-AAA and TTT-3' host nucleotides, without duplication or modification of the AAATTT target sites. Spy transposons were identified in the genomes of diverse invertebrate species based on transposase homology searches and structure-based approaches. Phylogenetic analyses indicate that Spy transposases are distantly related to IS5, ISL2EU, and PIF/Harbinger transposases. However, Spy transposons are distinct from these and other DNA transposon superfamilies by their lack of TSD and their target site preference. Our findings expand the known diversity of DNA transposons and reveal a new group of eukaryotic DDE transposases with unusual catalytic properties. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Targeting BTK through microRNA in chronic lymphocytic leukemia

PubMed Central

Bottoni, Arianna; Rizzotto, Lara; Lai, Tzung-Huei; Liu, Chaomei; Smith, Lisa L.; Mantel, Rose; Reiff, Sean; El-Gamal, Dalia; Larkin, Karilyn; Johnson, Amy J.; Lapalombella, Rosa; Lehman, Amy; Plunkett, William; Byrd, John C.; Blachly, James S.; Woyach, Jennifer A.

2016-01-01

Bruton’s tyrosine kinase (BTK) is a critical mediator of survival in B-cell neoplasms. Although BTK inhibitors have transformed therapy in chronic lymphocytic leukemia (CLL), patients with high-risk genetics are at risk for relapse and have a poor prognosis. Identification of novel therapeutic strategies for this group of patients is an urgent unmet clinical need, and therapies that target BTK via alternative mechanisms may fill this niche. Herein, we identify a set of microRNAs (miRs) that target BTK in primary CLL cells and show that the histone deacetylase (HDAC) repressor complex is recruited to these miR promoters to silence their expression. Targeting the HDACs by using either RNA interference against HDAC1 in CLL or a small molecule inhibitor (HDACi) in CLL and mantle cell lymphoma restored the expression of the BTK-targeting miRs with loss of BTK protein and downstream signaling and consequent cell death. We have also made the novel and clinically relevant discovery that inhibition of HDAC induces the BTK-targeting miRs in ibrutinib-sensitive and resistant CLL to effectively reduce both wild-type and C481S-mutant BTK. This finding identifies a novel strategy that may be promising as a therapeutic modality to eliminate the C481S-mutant BTK clone that drives resistance to ibrutinib and provides the rationale for a combination strategy that includes ibrutinib to dually target BTK to suppress its prosurvival signaling. PMID:27756747

Targeting BTK through microRNA in chronic lymphocytic leukemia.

PubMed

Bottoni, Arianna; Rizzotto, Lara; Lai, Tzung-Huei; Liu, Chaomei; Smith, Lisa L; Mantel, Rose; Reiff, Sean; El-Gamal, Dalia; Larkin, Karilyn; Johnson, Amy J; Lapalombella, Rosa; Lehman, Amy; Plunkett, William; Byrd, John C; Blachly, James S; Woyach, Jennifer A; Sampath, Deepa

2016-12-29

Bruton's tyrosine kinase (BTK) is a critical mediator of survival in B-cell neoplasms. Although BTK inhibitors have transformed therapy in chronic lymphocytic leukemia (CLL), patients with high-risk genetics are at risk for relapse and have a poor prognosis. Identification of novel therapeutic strategies for this group of patients is an urgent unmet clinical need, and therapies that target BTK via alternative mechanisms may fill this niche. Herein, we identify a set of microRNAs (miRs) that target BTK in primary CLL cells and show that the histone deacetylase (HDAC) repressor complex is recruited to these miR promoters to silence their expression. Targeting the HDACs by using either RNA interference against HDAC1 in CLL or a small molecule inhibitor (HDACi) in CLL and mantle cell lymphoma restored the expression of the BTK-targeting miRs with loss of BTK protein and downstream signaling and consequent cell death. We have also made the novel and clinically relevant discovery that inhibition of HDAC induces the BTK-targeting miRs in ibrutinib-sensitive and resistant CLL to effectively reduce both wild-type and C481S-mutant BTK. This finding identifies a novel strategy that may be promising as a therapeutic modality to eliminate the C481S-mutant BTK clone that drives resistance to ibrutinib and provides the rationale for a combination strategy that includes ibrutinib to dually target BTK to suppress its prosurvival signaling. © 2016 by The American Society of Hematology.

Delivering an Optimised Behavioural Intervention (OBI) to people with low back pain with high psychological risk; results and lessons learnt from a feasibility randomised controlled trial of Contextual Cognitive Behavioural Therapy (CCBT) vs. Physiotherapy.

PubMed

Pincus, Tamar; Anwar, Shamaila; McCracken, Lance M; McGregor, Alison; Graham, Liz; Collinson, Michelle; McBeth, John; Watson, Paul; Morley, Stephen; Henderson, Juliet; Farrin, Amanda J

2015-06-16

Low Back Pain (LBP) remains a common and costly problem. Psychological obstacles to recovery have been identified, but psychological and behavioural interventions have produced only moderate improvements. Reviews of trials have suggested that the interventions lack clear theoretical basis, are often compromised by low dose, lack of fidelity, and delivery by non-experts. In addition, interventions do not directly target known risk mechanisms. We identified a theory driven intervention (Contexual Cognitive Behavioural Therapy, CCBT) that directly targets an evidence-based risk mechanism (avoidance and ensured dose and delivery were optimised. This feasibility study was designed to test the credibility and acceptability of optimised CCBT against physiotherapy for avoidant LBP patients, and to test recruitment, delivery of the intervention and response rates prior to moving to a full definitive trial. A randomised controlled feasibility trial with patients randomised to receive CCBT or physiotherapy. CCBT was delivered by trained supervised psychologists on a one to one basis and comprised up to 8 one-hour sessions. Physiotherapy comprised back to fitness group exercises with at least 60 % of content exercise-based. Patients were eligible to take part if they had back pain for more than 3 months, and scored above a threshold indicating fear avoidance, catastrophic beliefs and distress. 89 patients were recruited. Uptake rates were above those predicted. Scores for credibility and acceptability of the interventions met the set criteria. Response rates at three and six months fell short of the 75 % target. Problems associated with poor response rates were identified and successfully resolved, rates increased to 77 % at 3 months, and 68 % at 6 months. Independent ratings of treatment sessions indicated that CCBT was delivered to fidelity. Numbers were too small for formal analysis. Although average scores for acceptance were higher in the CCBT group than in the group attending physiotherapy (increase of 7.9 versus 5.1) and change in disability and pain from baseline to 6 months were greater in the CCBT group than in the physiotherapy group, these findings should be interpreted with caution. CCBT is a credible and acceptable intervention for LBP patients who exhibit psychological obstacles to recovery. ISRCTN43733490 , registered 15/12/2010.

Reaching Hard-to-Reach Individuals: Nonselective Versus Targeted Outbreak Response Vaccination for Measles

PubMed Central

Minetti, Andrea; Hurtado, Northan; Grais, Rebecca F.; Ferrari, Matthew

2014-01-01

Current mass vaccination campaigns in measles outbreak response are nonselective with respect to the immune status of individuals. However, the heterogeneity in immunity, due to previous vaccination coverage or infection, may lead to potential bias of such campaigns toward those with previous high access to vaccination and may result in a lower-than-expected effective impact. During the 2010 measles outbreak in Malawi, only 3 of the 8 districts where vaccination occurred achieved a measureable effective campaign impact (i.e., a reduction in measles cases in the targeted age groups greater than that observed in nonvaccinated districts). Simulation models suggest that selective campaigns targeting hard-to-reach individuals are of greater benefit, particularly in highly vaccinated populations, even for low target coverage and with late implementation. However, the choice between targeted and nonselective campaigns should be context specific, achieving a reasonable balance of feasibility, cost, and expected impact. In addition, it is critical to develop operational strategies to identify and target hard-to-reach individuals. PMID:24131555

Guidelines for integrating population education into primary education and literacy programmes.

PubMed

1989-01-01

In recent seminars and workshops in the Asia and Pacific region the integration of population education into primary schools and literacy programs were the main topics. In most of the countries in this area separate courses in population education appear to be unfeasible for primary and secondary schools. In the nonformal area experience has indicated that population education acquires more meaning and relevance if it is integrated into an ongoing development program. The integration approach requires knowledge of the contents of the accommodating subjects or programs and knowledge of the contents of the accommodating subjects or programs and knowledge of the contents of population education. Guidelines suggested include the following steps in developing an integrated curriculum and instructional materials. First determine the needs, characteristics and other background information needed on the target group. Next prioritize the problems and needs of the target group, and formulate educational objectives from the identified needs and problems. Next determine and sequence the curriculum contents and then determine specific population education objectives and contents for integration, and what specific materials have to be developed. Then identify the specific type of format of materials to be developed, and write the first draft of the material. Also prepare illustrations and other art and graphic materials. Then the draft material should be reviewed and translated into the language of the target audience if needed. The materials should then be pretested, or field tested, using a sample of the intended users. To make sure the materials are reaching the target groups and being used effectively, a user's guide should be prepared and teachers and facilitators, as well as supervisors, should be prepared on the use of the material. In addition, a distribution and utilization plan should be prepared. Nonformal education materials can be distributed through libraries, reading center, residences of village leaders, neighborhood stores, and direct mail. The material distribution and utilization should be monitored and evaluated.

Improving ovarian cancer imaging with LHRH-NBs: an experimental study.

PubMed

Li, Wenjuan; Zhang, Lingping; Zhu, Yuanfang; Zhang, Jinyi; Shen, Li; Huang, Shuying; Fang, Shanyu

2016-09-01

Our previous study used freeze-drying and biotin-avidin binding methods and obtained nontargeted nanobubbles (N-NBs) and ovarian cancer-targeting nanobubbles (LHRH-NBs, luteinizing hormone-releasing hormone nanobubbles). Our study also identified the physical and chemical properties of these two contrast agents, and validated the targeting ability and underlying mechanisms of LHRH-NBs in vitro. The present study investigated the imaging of N-NBs and LHRH-NBs in nude mice and their binding with tissues. The nude mice models of xenografts were divided into three groups, N-NB, LHRH-NB, and SonoVue. These contrast agents were injected via the caudal vein to observe the imaging of ovarian cancer. Fluorescence microscope was used to observe the penetration of N-NBs and LHRH-NBs through the vascular endothelial gaps. Immunofluorescence was used to observe the penetration of N-NBs and LHRH-NBs through vascular endothelial gaps and binding to the tumor cells. The imaging intensity and duration were not significantly different between N-NBs and LHRH-NBs. The imaging intensity in the N-NB and LHRH-NB groups was not significantly different compared with the SonoVue group; however, the imaging duration in the N-NB and LHRH-NB groups was significantly longer than in the SonoVue group (P < 0.001). Both N-NBs and LHRH-NBs penetrated through the vascular endothelial gaps. After penetrating through the vascular endothelial gapes, LHRH-NBs could target and bind to the tumor cells. N-NBs and LHRH-NBs are of good imaging effectiveness and relatively long imaging duration. LHRH-NB is a potent contrast agent for imaging ovarian cancer, while achieving targeted delivery of drugs to the site of ovarian cancer.

Development of Seasonal Influenza Vaccination Recommendations: Relevance and Influence of the Evidence on the Decision-Making Process in France and the Netherlands.

PubMed

Silva, Maria Laura; Paget, W John; Mosnier, Anne; Buthion, Valérie; Cohen, Jean Marie; Perrier, Lionel; Späth, Hans Martin

2016-01-01

Target groups for seasonal influenza vaccination are defined at the country level and are based on several factors. However, little is known about the national decision-making procedures. The purpose of this study was to compare the evidence used for the development of recommendations and its impact on the choice of target groups in France and the Netherlands. A preliminary documentary analysis identified institutions to include in the assessment: governmental authorities, research institutions, associations, and manufacturers. At least one expert from each group was invited to our study. Thirty-three semi-structured interviews were conducted in 2013 (16 France, 17 the Netherlands). We used NVivo10® to perform a thematic content analysis. Clinical/epidemiological studies were the evidence most used in both countries. Economic models were increasingly being used; these had greater influence on the decision making in the Netherlands than in France, probably because of the presence of a modeler. Generally, the quality of the evidence used was poor, although no systematic use of standard protocol for its assessment was observed. A general protocol was sometimes used in France; however, the personal judgment of the experts was crucial for the assessment in both countries. There were differences in the target groups, for example, pregnant women, recommended only in France. France and the Netherlands use similar evidence for developing vaccination recommendations, although different decisions are sometimes made regarding target groups. This could be associated with the lack of systematic standard appraisals, increasing the influence of the experts' judgment on decision making. The development of standards for the appraisal of evidence is recommended. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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.

Timing variability of reach trajectories in left versus right hemisphere stroke.

PubMed

Freitas, Sandra Maria Sbeghen Ferreira; Gera, Geetanjali; Scholz, John Peter

2011-10-24

This study investigated trajectory timing variability in right and left stroke survivors and healthy controls when reaching to a centrally located target under a fixed target condition or when the target could suddenly change position after reach onset. Trajectory timing variability was investigated with a novel method based on dynamic programming that identifies the steps required to time warp one trial's acceleration time series to match that of a reference trial. Greater trajectory timing variability of both hand and joint motions was found for the paretic arm of stroke survivors compared to their non-paretic arm or either arm of controls. Overall, the non-paretic left arm of the LCVA group and the left arm of controls had higher timing variability than the non-paretic right arm of the RCVA group and right arm of controls. The shoulder and elbow joint warping costs were consistent predictors of the hand's warping cost for both left and right arms only in the LCVA group, whereas the relationship between joint and hand warping costs was relatively weak in control subjects and less consistent across arms in the RCVA group. These results suggest that the left hemisphere may be more involved in trajectory timing, although the results may be confounded by skill differences between the arms in these right hand dominant participants. On the other hand, arm differences did not appear to be related to differences in targeting error. The paretic left arm of the RCVA exhibited greater trajectory timing variability than the paretic right arm of the LCVA group. This difference was highly correlated with the level of impairment of the arms. Generally, the effect of target uncertainty resulted in slightly greater trajectory timing variability for all participants. The results are discussed in light of previous studies of hemispheric differences in the control of reaching, in particular, left hemisphere specialization for temporal control of reaching movements. Copyright © 2011 Elsevier B.V. All rights reserved.

TIMING VARIABILITY OF REACH TRAJECTORIES IN LEFT VERSUS RIGHT HEMISPHERE STROKE

PubMed Central

Freitas, Sandra Maria Sbeghen Ferreira; Gera, Geetanjali; Scholz, John Peter

2011-01-01

This study investigated trajectory timing variability in right and left stroke survivors and healthy controls when reaching to a centrally located target under a fixed target condition or when the target could suddenly change position after reach onset. Trajectory timing variability was investigated with a novel method based on dynamic programming that identifies the steps required to time warp one trial’s acceleration time series to match that of a reference trial. Greater trajectory timing variability of both hand and joint motions was found for the paretic arm of stroke survivors compared to their non-paretic arm or either arm of controls. Overall, the non-paretic left arm of the LCVA group and the left arm of controls had higher timing variability than the non-paretic right arm of the RCVA group and right arm of controls. The shoulder and elbow joint warping costs were consistent predictors of the hand’s warping cost for both left and right arms only in the LCVA group, whereas the relationship between joint and hand warping costs was relatively weak in control subjects and less consistent across arms in the RCVA group. These results suggest that the left hemisphere may be more involved in trajectory timing, although the results may be confounded by skill differences between the arms in these right hand dominant participants. On the other hand, arm differences did not appear to be related to differences in targeting error. The paretic left arm of the RCVA exhibited greater trajectory timing variability than the paretic right arm of the LCVA group. This difference was highly correlated with the level of impairment of the arms. Generally, the effect of target uncertainty resulted in slightly greater trajectory timing variability for all participants. The results are discussed in light of previous studies of hemispheric differences in the control of reaching, in particular, left hemisphere specialization for temporal control of reaching movements. PMID:21920508

Falling through the Social Safety Net: Food Stamp Use and Nonuse among Older Impoverished Americans

ERIC Educational Resources Information Center

Fuller-Thomson, Esme; Redmond, Melissa

2008-01-01

Purpose: Older adults are less likely than any other age group to use the federal Food Stamp Program. The personal and social costs of elderly diet insufficiency include disease exacerbation, depression, and increased hospitalization. In order to improve targeting and outreach efforts, this study identifies the characteristics of eligible older…

A Primary Prevention Program to Reduce Bulimia and Anorexia Nervosa.

ERIC Educational Resources Information Center

Cullari, Salvatore; Redmon, William K.

This paper presents a theoretical model for a primary prevention program for bulimia and anorexia nervosa to be used with adolescents and young women considered most at risk of developing these eating disorders. Characteristics of potential anorexics and bulimics are identified to aid in the selection of target groups for the program. It is…

A Meta-Analytic Review of the Penn Resiliency Program's Effect on Depressive Symptoms

ERIC Educational Resources Information Center

Brunwasser, Steven M.; Gillham, Jane E.; Kim, Eric S.

2009-01-01

The purpose of this review was to evaluate whether the Penn Resiliency Program (PRP), a group cognitive-behavioral intervention, is effective in targeting depressive symptoms in youths. We identified 17 controlled evaluations of PRP (N = 2,498) in which depressive symptoms had been measured via an online search of PsycInfo, Medline, ERIC, and…

Using a Pattern-Centered Approach to Assess Sexual Risk-Taking in Study Abroad Students

ERIC Educational Resources Information Center

Marcantonio, Tiffany; Angelone, D. J.; Sledjeski, Eve

2016-01-01

Objectives: The purpose of this study was to examine the impact of several potential factors related to sexually risky behaviors in study abroad students. The authors utilized a pattern-centered analysis to identify specific groups that can be targeted for intervention. Participants: The sample consisted of 173 students who studied abroad in a…

Quality and Equity in the Mongolian Education Sector

ERIC Educational Resources Information Center

Steiner-Khamsi, Gita; Gerelmaa, Amgaabazar

2008-01-01

This case study identifies four targets groups that are specific to the achievement of the EFA Millennium Development Goals in Mongolia: boys, out-of-school children, vulnerable children and minorities, and children of herders. Boys from herder families in remote rural areas are at the greatest risk of drop-out or non-enrollment. The case study…

Psychopathy among Pedophilic and Nonpedophilic Child Molesters

ERIC Educational Resources Information Center

Strassberg, Donald S.; Eastvold, Angela; Kenney, J. Wilson; Suchy, Yana

2012-01-01

Objective: Among men who commit sexual offenses against children, at least 2 distinct groups can be identified on the basis of the age of the primary targets of their sexual interest; pedophiles and nonpedophiles. Method: In the present report, across 2 independent samples of both types of child molesters as well as controls, a total of 104 men…

Demographic Trends as a Stimulus to Extended Post-Secondary Education in the Federal Republic of Germany.

ERIC Educational Resources Information Center

Brandes, Uwe; Raters, Ernst

1981-01-01

The effect of a sharp fall in the birth rate on German universities and the need to identify new target student groups are considered. The implementation of extended education and three matters of significance in promoting it (prospective audience, organization, and use of appropriate distance-study materials) are discussed. (Author/MLW)

A Computer-Based Training System for American Antique Chair Styles.

ERIC Educational Resources Information Center

See, Maha

A computer-based training (CBT) system was designed to train learners to recognize six styles of 18th century American antique chairs. The project consisted of five phases. The first phase consisted of a needs analysis to determine the training needs for the target population. Three groups of learners were identified: antique sales personnel,…

Neptune: a bioinformatics tool for rapid discovery of genomic variation in bacterial populations

PubMed Central

Marinier, Eric; Zaheer, Rahat; Berry, Chrystal; Weedmark, Kelly A.; Domaratzki, Michael; Mabon, Philip; Knox, Natalie C.; Reimer, Aleisha R.; Graham, Morag R.; Chui, Linda; Patterson-Fortin, Laura; Zhang, Jian; Pagotto, Franco; Farber, Jeff; Mahony, Jim; Seyer, Karine; Bekal, Sadjia; Tremblay, Cécile; Isaac-Renton, Judy; Prystajecky, Natalie; Chen, Jessica; Slade, Peter

2017-01-01

Abstract The ready availability of vast amounts of genomic sequence data has created the need to rethink comparative genomics algorithms using ‘big data’ approaches. Neptune is an efficient system for rapidly locating differentially abundant genomic content in bacterial populations using an exact k-mer matching strategy, while accommodating k-mer mismatches. Neptune’s loci discovery process identifies sequences that are sufficiently common to a group of target sequences and sufficiently absent from non-targets using probabilistic models. Neptune uses parallel computing to efficiently identify and extract these loci from draft genome assemblies without requiring multiple sequence alignments or other computationally expensive comparative sequence analyses. Tests on simulated and real datasets showed that Neptune rapidly identifies regions that are both sensitive and specific. We demonstrate that this system can identify trait-specific loci from different bacterial lineages. Neptune is broadly applicable for comparative bacterial analyses, yet will particularly benefit pathogenomic applications, owing to efficient and sensitive discovery of differentially abundant genomic loci. The software is available for download at: http://github.com/phac-nml/neptune. PMID:29048594

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

Effective identification of Lactobacillus casei group species: genome-based selection of the gene mutL as the target of a novel multiplex PCR assay.

PubMed

Bottari, Benedetta; Felis, Giovanna E; Salvetti, Elisa; Castioni, Anna; Campedelli, Ilenia; Torriani, Sandra; Bernini, Valentina; Gatti, Monica

2017-07-01

Lactobacillus casei,Lactobacillus paracasei and Lactobacillusrhamnosus form a closely related taxonomic group (the L. casei group) within the facultatively heterofermentative lactobacilli. Strains of these species have been used for a long time as probiotics in a wide range of products, and they represent the dominant species of nonstarter lactic acid bacteria in ripened cheeses, where they contribute to flavour development. The close genetic relationship among those species, as well as the similarity of biochemical properties of the strains, hinders the development of an adequate selective method to identify these bacteria. Despite this being a hot topic, as demonstrated by the large amount of literature about it, the results of different proposed identification methods are often ambiguous and unsatisfactory. The aim of this study was to develop a more robust species-specific identification assay for differentiating the species of the L. casei group. A taxonomy-driven comparative genomic analysis was carried out to select the potential target genes whose similarity could better reflect genome-wide diversity. The gene mutL appeared to be the most promising one and, therefore, a novel species-specific multiplex PCR assay was developed to rapidly and effectively distinguish L. casei, L. paracasei and L. rhamnosus strains. The analysis of a collection of 76 wild dairy isolates, previously identified as members of the L. casei group combining the results of multiple approaches, revealed that the novel designed primers, especially in combination with already existing ones, were able to improve the discrimination power at the species level and reveal previously undiscovered intraspecific biodiversity.

How dietary intake methodology is adapted for use in European immigrant population groups - a review.

PubMed

Ngo, Joy; Gurinovic, Mirjana; Frost-Andersen, Lene; Serra-Majem, Lluís

2009-07-01

Immigrants comprise a noteworthy segment of the European population whose numbers are increasing. Research on the dietary habits of immigrants is critical for correctly providing diet counselling and implementing effective interventions. The aim of the present study was to identify the presently used methods and adaptations required for measuring dietary intake in European immigrant groups. A comprehensive review strategy included a structured MEDLINE search, related references and key expert consultations. The review targeted adults from non-European union (European union-15 countries) ethnic groups having the largest populations in Europe. As studies evaluating nutrient intake were scarce, papers evaluating intake at the level of foods were included. Forty-six papers were selected. Although Eastern Europe, Turkey, Africa (North, Sub-Saharan and Afro-Caribbean), Asia and Latin America represented the most numerous immigrant groups, papers on dietary intake were not available for all populations. Interview-administered FFQ and repeated 24 hour recalls were the most frequently applied instruments. Inclusion of ethnic foods and quantification of specific portion sizes of traditional foods and dishes in assessment tools as well as food composition databases were commonly identified problems. For FFQ, food list elaboration required particular consideration to reflect key ethnic foods and relative contribution to nutrient intake. Extra efforts were observed to overcome cultural barriers to study participation. Evaluating dietary intake of immigrant populations requires special attention to various methodological aspects (sampling, recruiting, instruments used, method of administration, food composition database, acculturation, etc.) so as to adequately address the range of socio-cultural factors inherent in these nutritionally at risk target groups.

Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation

PubMed Central

Manousopoulou, A; Koutmani, Y; Karaliota, S; Woelk, C H; Manolakos, E S; Karalis, K; Garbis, S D

2016-01-01

Objective: This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. Methods: Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. Results: Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. Conclusions: High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms mediating a sustained ‘perpetual cycle' of appetite enhancement were observed. The GlyR protein may constitute a novel treatment target for the reduction of central orexigenic signals in obesity. PMID:27110685

Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation.

PubMed

Manousopoulou, A; Koutmani, Y; Karaliota, S; Woelk, C H; Manolakos, E S; Karalis, K; Garbis, S D

2016-04-25

This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms mediating a sustained 'perpetual cycle' of appetite enhancement were observed. The GlyR protein may constitute a novel treatment target for the reduction of central orexigenic signals in obesity.

HMPAS: Human Membrane Protein Analysis System

PubMed Central

2013-01-01

Background Membrane proteins perform essential roles in diverse cellular functions and are regarded as major pharmaceutical targets. The significance of membrane proteins has led to the developing dozens of resources related with membrane proteins. However, most of these resources are built for specific well-known membrane protein groups, making it difficult to find common and specific features of various membrane protein groups. Methods We collected human membrane proteins from the dispersed resources and predicted novel membrane protein candidates by using ortholog information and our membrane protein classifiers. The membrane proteins were classified according to the type of interaction with the membrane, subcellular localization, and molecular function. We also made new feature dataset to characterize the membrane proteins in various aspects including membrane protein topology, domain, biological process, disease, and drug. Moreover, protein structure and ICD-10-CM based integrated disease and drug information was newly included. To analyze the comprehensive information of membrane proteins, we implemented analysis tools to identify novel sequence and functional features of the classified membrane protein groups and to extract features from protein sequences. Results We constructed HMPAS with 28,509 collected known membrane proteins and 8,076 newly predicted candidates. This system provides integrated information of human membrane proteins individually and in groups organized by 45 subcellular locations and 1,401 molecular functions. As a case study, we identified associations between the membrane proteins and diseases and present that membrane proteins are promising targets for diseases related with nervous system and circulatory system. A web-based interface of this system was constructed to facilitate researchers not only to retrieve organized information of individual proteins but also to use the tools to analyze the membrane proteins. Conclusions HMPAS provides comprehensive information about human membrane proteins including specific features of certain membrane protein groups. In this system, user can acquire the information of individual proteins and specified groups focused on their conserved sequence features, involved cellular processes, and diseases. HMPAS may contribute as a valuable resource for the inference of novel cellular mechanisms and pharmaceutical targets associated with the human membrane proteins. HMPAS is freely available at http://fcode.kaist.ac.kr/hmpas. PMID:24564858

Identification of educational and infrastructural barriers to prompt antibiotic delivery in febrile neutropenia: a quality improvement initiative.

PubMed

Burry, Erica; Punnett, Angela; Mehta, Ashley; Thull-Freedman, Jennifer; Robinson, Lisa; Gupta, Sumit

2012-09-01

Antibiotic administration within 60 minutes of presentation for medical care may be used as a treatment target for febrile neutropenia (FN); however, anecdotal evidence suggests this target is often missed. Few studies have examined the prevalence or causes of delay. We describe the median time to antibiotic administration at our institution, predictors of delay, and barriers to prompt administration to inform quality improvement strategies. A random sample of 50 episodes of FN presenting to the emergency department (ED) between 2008 and 2009 were reviewed. Times between triage, MD assessment, lab results, and antibiotic administration were recorded. Patient and ED variables were examined as possible predictors of delay. In parallel, lean methodology was used to identify system inefficiencies. A trained moderator conducted group interviews with interdisciplinary representatives involved in the emergency care of neutropenic patients to identify process barriers to prompt antibiotics. The median time from triage to antibiotics was 216 minutes (interquartile range [IQR] = 151-274 minutes). The greatest delay occurred following the reporting of lab results (152 minutes, IQR = 84-210 minutes). Only fall season predicted a longer time to antibiotics (P = 0.03). The lean process identified unnecessary areas of delay between departments. Time to antibiotic administration exceeded 1 hour. The chart review and lean process suggested targets for educational and infrastructural interventions, including an ED pre-printed order sheet, targeted combined subspecialty education between emergency and hematology/oncology staff, and family education. A mixed methodology approach represents a model for improving process efficiency and meeting "best-practice" targets in medicine. Copyright © 2011 Wiley Periodicals, Inc.

Cortisol inhibits mTOR signaling in avascular necrosis of the femoral head.

PubMed

Liao, Yun; Su, Rui; Zhang, Ping; Yuan, Bo; Li, Ling

2017-10-18

ANFH is a major health problem, to which long lasting and definitive treatments are lacking. The aim of this study is to study RNA alterations attributed to cortisol-induced ANFH. Rat models were stratified into three groups: in vitro group (n = 20) for molecular biological assays, control group (n = 3), and ANFH group induced using lipopolysaccharide and dexamethasone (n = 3). Bone marrow-derived endothelial progenitor cells (BM-EPCs) were extracted from the rats. An RNA expression array was performed on BM-EPCs, and enriched genes were subject to pathway analysis. In vitro studies following findings of array results were also performed using the isolated BM-EPCs. Significant alterations in mammalian target of rapamycin (mTOR) and HIF signaling pathways were identified in BM-EPCs of ANFH. By applying cortisol and dexamethasone to BM-EPCs, significant changes in mTOR and HIF elements were identified. The alteration of HIF pathways appeared to be downstream of mTOR signaling. Glucocorticoid receptor (GR) expression was related to glucocorticoid-dependent mRNA expression of mTOR/HIF genes. mTOR-dependent angiogenesis but not anabolism was the target of GR in ANFH. Inhibition of mTOR signaling also induced apoptosis of BM-EPCs via CHOP-dependent DR5 induction in response to GR stimulation. Decreased mTOR signaling in response to GR stimulation leading to downregulated HIF pathway as well as increased apoptosis could be the pathophysiology.

Sedation-analgesia with propofol and remifentanil: concentrations required to avoid gag reflex in upper gastrointestinal endoscopy.

PubMed

Borrat, Xavier; Valencia, José Fernando; Magrans, Rudys; Gimenez-Mila, Marc; Mellado, Ricard; Sendino, Oriol; Perez, Maria; Nunez, Matilde; Jospin, Mathieu; Jensen, Erik Weber; Troconiz, Inaki; Gambus, Pedro L

2015-07-01

The purpose of this study was to identify optimal target propofol and remifentanil concentrations to avoid a gag reflex in response to insertion of an upper gastrointestinal endoscope. Patients presenting for endoscopy received target-controlled infusions (TCI) of both propofol and remifentanil for sedation-analgesia. Patients were randomized to 4 groups of fixed target effect-site concentrations: remifentanil 1 ng•mL (REMI 1) or 2 ng•mL (REMI 2) and propofol 2 μg•mL (PROP 2) or 3 μg•mL (PROP 3). For each group, the other drug (propofol for the REMI groups and vice versa) was increased or decreased using the "up-down" method based on the presence or absence of a gag response in the previous patient. A modified isotonic regression method was used to estimate the median effective Ce,50 from the up-down method in each group. A concentration-effect (sigmoid Emax) model was built to estimate the corresponding Ce,90 for each group. These data were used to estimate propofol bolus doses and remifentanil infusion rates that would achieve effect-site concentrations between Ce,50 and Ce,90 when a TCI system is not available for use. One hundred twenty-four patients were analyzed. To achieve between a 50% and 90% probability of no gag response, propofol TCIs were between 2.40 and 4.23 μg•mL (that could be achieved with a bolus of 1 mg•kg) when remifentanil TCI was fixed at 1 ng•mL, and target propofol TCIs were between 2.15 and 2.88 μg•mL (that could be achieved with a bolus of 0.75 mg•kg) when remifentanil TCI was fixed at 2 ng•mL. Remifentanil ranges were 1.00 to 4.79 ng•mL and 0.72 to 3.19 ng•mL when propofol was fixed at 2 and 3 μg•mL, respectively. We identified a set of propofol and remifentanil TCIs that blocked the gag response to endoscope insertion in patients undergoing endoscopy. Propofol bolus doses and remifentanil infusion rates designed to achieve similar effect-site concentrations can be used to prevent gag response when TCI is not available.

Identifying HIV most-at-risk groups in Malawi for targeted interventions. A classification tree model

PubMed Central

Emina, Jacques B O; Madise, Nyovani; Kuepie, Mathias; Zulu, Eliya M; Ye, Yazoume

2013-01-01

Objectives To identify HIV-socioeconomic predictors as well as the most-at-risk groups of women in Malawi. Design A cross-sectional survey. Setting Malawi Participants The study used a sample of 6395 women aged 15–49 years from the 2010 Malawi Health and Demographic Surveys. Interventions N/A Primary and secondary outcome measures Individual HIV status: positive or not. Results Findings from the Pearson χ2 and χ2 Automatic Interaction Detector analyses revealed that marital status is the most significant predictor of HIV. Women who are no longer in union and living in the highest wealth quintiles households constitute the most-at-risk group, whereas the less-at-risk group includes young women (15–24) never married or in union and living in rural areas. Conclusions In the light of these findings, this study recommends: (1) that the design and implementation of targeted interventions should consider the magnitude of HIV prevalence and demographic size of most-at-risk groups. Preventive interventions should prioritise couples and never married people aged 25–49 years and living in rural areas because this group accounts for 49% of the study population and 40% of women living with HIV in Malawi; (2) with reference to treatment and care, higher priority must be given to promoting HIV test, monitoring and evaluation of equity in access to treatment among women in union disruption and never married or women in union aged 30–49 years and living in urban areas; (3) community health workers, households-based campaign, reproductive-health services and reproductive-health courses at school could be used as canons to achieve universal prevention strategy, testing, counselling and treatment. PMID:23793677

Understanding effects in reviews of implementation interventions using the Theoretical Domains Framework.

PubMed

Little, Elizabeth A; Presseau, Justin; Eccles, Martin P

2015-06-17

Behavioural theory can be used to better understand the effects of behaviour change interventions targeting healthcare professional behaviour to improve quality of care. However, the explicit use of theory is rarely reported despite interventions inevitably involving at least an implicit idea of what factors to target to implement change. There is a quality of care gap in the post-fracture investigation (bone mineral density (BMD) scanning) and management (bisphosphonate prescription) of patients at risk of osteoporosis. We aimed to use the Theoretical Domains Framework (TDF) within a systematic review of interventions to improve quality of care in post-fracture investigation. Our objectives were to explore which theoretical factors the interventions in the review may have been targeting and how this might be related to the size of the effect on rates of BMD scanning and osteoporosis treatment with bisphosphonate medication. A behavioural scientist and a clinician independently coded TDF domains in intervention and control groups. Quantitative analyses explored the relationship between intervention effect size and total number of domains targeted, and as number of different domains targeted. Nine randomised controlled trials (RCTs) (10 interventions) were analysed. The five theoretical domains most frequently coded as being targeted by the interventions in the review included "memory, attention and decision processes", "knowledge", "environmental context and resources", "social influences" and "beliefs about consequences". Each intervention targeted a combination of at least four of these five domains. Analyses identified an inverse relationship between both number of times and number of different domains coded and the effect size for BMD scanning but not for bisphosphonate prescription, suggesting that the more domains the intervention targeted, the lower the observed effect size. When explicit use of theory to inform interventions is absent, it is possible to retrospectively identify the likely targeted factors using theoretical frameworks such as the TDF. In osteoporosis management, this suggested that several likely determinants of healthcare professional behaviour appear not yet to have been considered in implementation interventions. This approach may serve as a useful basis for using theory-based frameworks such as the TDF to retrospectively identify targeted factors within systematic reviews of implementation interventions in other implementation contexts.

Key beliefs related to decisions for physical activity engagement among first-in-family students transitioning to university.

PubMed

Cowie, Eloise; Hamilton, Kyra

2014-08-01

The current study investigated key beliefs related to decisions for physical activity (PA) engagement among first-in-family (FIF) students transitioning to university. FIF students (n = 157) completed an online questionnaire assessing standard theory of planned behaviour constructs and belief-based items. One week later, participants completed a follow-up questionnaire assessing self-reported PA during the previous week. Results identified a range of behavioural, normative, and control beliefs that were significantly correlated with both PA intention and behaviour. Various key beliefs were also identified in relation to FIF students' decisions to be regularly physically active, with behavioural beliefs such as "take up too much time", normative beliefs including "friends outside of university", and control beliefs such as "cost", identified. Finally, frequencies of those who strongly or fully accepted these beliefs were analysed, demonstrating that typically, a large number of FIF students did not hold the beliefs, and as such, these are relevant to target in resultant interventions. The current study effectively highlights a number of key beliefs that can be targeted in programs aimed at encouraging FIF students' PA. Further, the study addresses a gap in the literature of targeting FIF students, a cohort at risk for inactivity, and utilises a sound theoretical framework to identify the unique set of beliefs guiding decisions for PA for this at-risk community group.

Bioinformatic identification and experimental validation of miRNAs from foxtail millet (Setaria italica).

PubMed

Han, Jun; Xie, Hao; Sun, Qingpeng; Wang, Jun; Lu, Min; Wang, Weixiang; Guo, Erhu; Pan, Jinbao

2014-08-10

MiRNAs are a novel group of non-coding small RNAs that negatively regulate gene expression. Many miRNAs have been identified and investigated extensively in plant species with sequenced genomes. However, few miRNAs have been identified in foxtail millet (Setaria italica), which is an ancient cereal crop of great importance for dry land agriculture. In this study, 271 foxtail millet miRNAs belonging to 44 families were identified using a bioinformatics approach. Twenty-three pairs of sense/antisense miRNAs belonging to 13 families, and 18 miRNA clusters containing members of 8 families were discovered in foxtail millet. We identified 432 potential targets for 38 miRNA families, most of which were predicted to be involved in plant development, signal transduction, metabolic pathways, disease resistance, and environmental stress responses. Gene ontology (GO) analysis revealed that 101, 56, and 23 target genes were involved in molecular functions, biological processes, and cellular components, respectively. We investigated the expression patterns of 43 selected miRNAs using qRT-PCR analysis. All of the miRNAs were expressed ubiquitously with many exhibiting different expression levels in different tissues. We validated five predicted targets of four miRNAs using the RNA ligase mediated rapid amplification of cDNA end (5'-RLM-RACE) method. Copyright © 2014 Elsevier B.V. All rights reserved.

Using Opinions and Knowledge to Identify Natural Groups of Gambling Employees.

PubMed

Gray, Heather M; Tom, Matthew A; LaPlante, Debi A; Shaffer, Howard J

2015-12-01

Gaming industry employees are at higher risk than the general population for health conditions including gambling disorder. Responsible gambling training programs, which train employees about gambling and gambling-related problems, might be a point of intervention. However, such programs tend to use a "one-size-fits-all" approach rather than multiple tiers of instruction. We surveyed employees of one Las Vegas casino (n = 217) and one online gambling operator (n = 178) regarding their gambling-related knowledge and opinions prior to responsible gambling training, to examine the presence of natural knowledge groups among recently hired employees. Using k-means cluster analysis, we observed four natural groups within the Las Vegas casino sample and two natural groups within the online operator sample. We describe these natural groups in terms of opinion/knowledge differences as well as distributions of demographic/occupational characteristics. Gender and language spoken at home were correlates of cluster group membership among the sample of Las Vegas casino employees, but we did not identify demographic or occupational correlates of cluster group membership among the online gambling operator employees. Gambling operators should develop more sophisticated training programs that include instruction that targets different natural knowledge groups.

'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.

Implementing rapid HIV testing in outreach and community settings: results from an advancing HIV prevention demonstration project conducted in seven U.S. cities.

PubMed

Bowles, Kristina E; Clark, Hollie A; Tai, Eric; Sullivan, Patrick S; Song, Binwei; Tsang, Jenny; Dietz, Craig A; Mir, Julita; Mares-DelGrasso, Azul; Calhoun, Cindy; Aguirre, Daisy; Emerson, Cicily; Heffelfinger, James D

2008-01-01

The goals of this project were to assess the feasibility of conducting rapid human immunodeficiency virus (HIV) testing in outreach and community settings to increase knowledge of HIV serostatus among groups disproportionately affected by HIV and to identify effective nonclinical venues for recruiting people in the targeted populations. Community-based organizations (CBOs) in seven U.S. cities conducted rapid HIV testing in outreach and community settings, including public parks, homeless shelters, and bars. People with reactive preliminary positive test results received confirmatory testing, and people confirmed to be HIV-positive were referred to health-care and prevention services. A total of 23,900 people received rapid HIV testing. Of the 267 people (1.1%) with newly diagnosed HIV infection, 75% received their confirmatory test results and 64% were referred to care. Seventy-six percent were from racial/ethnic minority groups, and 58% identified themselves as men who have sex with men, 72% of whom reported having multiple sex partners in the past year. Venues with the highest proportion of new HIV diagnoses were bathhouses, social service organizations, and needle-exchange programs. The acceptance rate for testing was 60% among sites collecting this information. Findings from this demonstration project indicate that offering rapid HIV testing in outreach and community settings is a feasible approach for reaching members of minority groups and people at high risk for HIV infection. The project identified venues that would be important to target and offered lessons that could be used by other CBOs to design and implement similar programs in the future.

Communicating with parents of obese children: which channels are most effective?

PubMed

Randle, Melanie; Okely, Anthony D; Dolnicar, Sara

2017-04-01

One of the strategies proven most successful in curbing rising rates of childhood obesity involves targeting parents as agents of change. Prior studies have focused on what messages to communicate, but few have investigated how they should be communicated. To identify the channels most effective for communicating with parents of overweight and obese children and understand whether their use of parenting information sources differs from others in the community. This study utilizes data from the Longitudinal Study of Australian Children (LSAC). Families were included if weight and height information was available for parents and children at three data collection points: Waves 1, 2 and 4 (collected 2004, 2006 and 2010, respectively, n = 5107). A priori and a posteriori segmentation methods identified groups of parents that were similar in the sources used to obtain information about parenting, and examined whether some segments were more likely to have obese children. Four segments were identified that differed in their information source use: the 'personal networks', 'books', 'official sources' and 'mixed approach' segments. The 'official sources' and 'mixed approach' segments were most likely to have obese children, and they used doctors, government/community organizations and friends to obtain information on parenting. These segments were also less educated and had lower employment. Messages are most likely to reach families with obese children if communicated through doctors, government publications and community organizations. Further, messages targeting social groupings of parents will leverage the power of advice from friends, which is another valuable information source for this group. © 2016 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

Carbohydrate Microarrays Identify Blood Group Precursor Cryptic Epitopes as Potential Immunological Targets of Breast Cancer

PubMed Central

Wang, Denong; Tang, Jin; Liu, Shaoyi

2015-01-01

Using carbohydrate microarrays, we explored potential natural ligands of antitumor monoclonal antibody HAE3. This antibody was raised against a murine mammary tumor antigen but was found to cross-react with a number of human epithelial tumors in tissues. Our carbohydrate microarray analysis reveals that HAE3 is specific for an O-glycan cryptic epitope that is normally hidden in the cores of blood group substances. Using HAE3 to screen tumor cell surface markers by flow cytometry, we found that the HAE3 glycoepitope, gpHAE3, was highly expressed by a number of human breast cancer cell lines, including some triple-negative cancers that lack the estrogen, progesterone, and Her2/neu receptors. Taken together, we demonstrate that HAE3 recognizes a conserved cryptic glycoepitope of blood group precursors, which is nevertheless selectively expressed and surface-exposed in certain breast tumor cells. The potential of this class of O-glycan cryptic antigens in breast cancer subtyping and targeted immunotherapy warrants further investigation. PMID:26539555

Comparison of motives underlying food choice and barriers to healthy eating among low medium income consumers in Uruguay.

PubMed

Ares, Gastón; Machín, Leandro; Girona, Alejandra; Curutchet, María Rosa; Giménez, Ana

2017-05-18

Interventions aimed at changing dietary patterns should be designed based on the main motives underlying the food choices of specific target populations. The aim of the present study was to identify motives underlying food choice and barriers to healthy eating among consumers in two socioeconomic levels in Uruguay. Eleven focus groups were carried out with a total of 76 participants. Six of the groups involved low income participants and the others were conducted with middle income participants. Discussions were held around frequently consumed products, motives underlying food choices and barriers to healthy eating. Results confirmed the strong influence of income level on motives underlying food choice and barriers to the adoption of healthy eating. Low income participants described their choices as mainly driven by economic factors and satiety, whereas convenience was the main determinant of food selection for middle income participants. Implications for the design of public policies targeted at each group are discussed.

Factors differentiating callous-unemotional children with and without conduct problems.

PubMed

Wall, Tina D; Frick, Paul J; Fanti, Kostas A; Kimonis, Eva R; Lordos, Alexandros

2016-08-01

Callous-unemotional (CU) traits are a risk factor for a severe, aggressive, and persistent pattern of conduct problems (CP). This study investigated characteristics that might differentiate children with elevated CU traits with and without CP in an effort to identify factors that may reduce the risk for CP in children with limited prosocial emotions. Utilizing a sample of 1,366 children from Cyprus, five groups were identified for further study based on latent profile analysis: low-risk (67.2%), high-CP/low-CU (7.9%), high-CU (9.4%), moderate-CP/CU (8.4%), and high-CP/CU (7.2%). The identified groups were compared on behavioral and social measures. There were significant main effects of group for: impulsivity and executive functioning; parenting; and connectedness to school. The high-CU group had significantly lower hyperactivity-impulsivity and executive functioning deficits, significantly higher self-regulation, and their mothers reported more maternal involvement and positive parenting than those in the high-CP/CU group. Also, the high-CU group showed more school connectedness than those in the high-CP/CU group. These findings highlight several factors in the child and in his or her social environment that are associated with CU traits in the absence of serious CP and that may suggest targets for intervention for youth who may lack prosocial emotions. © 2016 Association for Child and Adolescent Mental Health.

AmpliVar: mutation detection in high-throughput sequence from amplicon-based libraries.

PubMed

Hsu, Arthur L; Kondrashova, Olga; Lunke, Sebastian; Love, Clare J; Meldrum, Cliff; Marquis-Nicholson, Renate; Corboy, Greg; Pham, Kym; Wakefield, Matthew; Waring, Paul M; Taylor, Graham R

2015-04-01

Conventional means of identifying variants in high-throughput sequencing align each read against a reference sequence, and then call variants at each position. Here, we demonstrate an orthogonal means of identifying sequence variation by grouping the reads as amplicons prior to any alignment. We used AmpliVar to make key-value hashes of sequence reads and group reads as individual amplicons using a table of flanking sequences. Low-abundance reads were removed according to a selectable threshold, and reads above this threshold were aligned as groups, rather than as individual reads, permitting the use of sensitive alignment tools. We show that this approach is more sensitive, more specific, and more computationally efficient than comparable methods for the analysis of amplicon-based high-throughput sequencing data. The method can be extended to enable alignment-free confirmation of variants seen in hybridization capture target-enrichment data. © 2015 WILEY PERIODICALS, INC.

Recent advances in the development of p21-activated kinase inhibitors.

PubMed

Coleman, Natalia; Kissil, Joseph

2012-04-01

The p21-activated kinases (PAKs) are downstream effectors of the small G-proteins of the Rac and cdc42 family and have been implicated as essential for cell proliferation and survival. Recent studies have also demonstrated the promise of PAKs as therapeutic targets in various types of cancers. The PAKs are divided into two major groups (group I and II) based on sequence similarities. Although the different roles the PAK groups might play are not well understood, recent efforts have focused on the identification of kinase inhibitors that can discriminate between the two groups. In this review these efforts and newly identified inhibitors will be described and future directions discussed.

Rationalizing fragment based drug discovery for BACE1: insights from FB-QSAR, FB-QSSR, multi objective (MO-QSPR) and MIF studies

NASA Astrophysics Data System (ADS)

Manoharan, Prabu; Vijayan, R. S. K.; Ghoshal, Nanda

2010-10-01

The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values. A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR) method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability algorithm to identify the optimal level of independent variables ( X) that could confer a trade-off between selectivity and activity. The results obtained from FB-QSAR were further substantiated using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion, the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate some prospective novel, potent and selective BACE1 inhibitors.

Rationalizing fragment based drug discovery for BACE1: insights from FB-QSAR, FB-QSSR, multi objective (MO-QSPR) and MIF studies.

PubMed

Manoharan, Prabu; Vijayan, R S K; Ghoshal, Nanda

2010-10-01

The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values. A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR) method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability algorithm to identify the optimal level of independent variables (X) that could confer a trade-off between selectivity and activity. The results obtained from FB-QSAR were further substantiated using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion, the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate some prospective novel, potent and selective BACE1 inhibitors.

Motives underlying food consumption in the Western Balkans: consumers' profiles and public health strategies.

PubMed

Mardon, Julie; Thiel, Elise; Laniau, Martine; Sijtsema, Siet; Zimmermann, Karin; Barjolle, Dominique

2015-07-01

This study aims to identify subgroups of consumers based on the health motives underlying their food choice in Western Balkan Countries. The survey (n = 2943) was based on the Food Choice Questionnaire (FCQ) and elicited information on socio-demographic characteristics, consumption frequency of healthy food products, nutrition knowledge and impulsiveness. Analysis of the FCQ data focused on items of "health and natural content" and "weight control" factors to identify clusters. The biggest group of the sample was weight control and health-concerned individuals (34 %), mainly urban women older than 50. The second group of respondents (31 %) was moderately motivated about health and weight. A third group was health concerned but paid less attention to weight control (21 %), mainly comprising men and people living with children. The last group consisted of unconcerned young men (14 %) eating less fruit and showing higher impulsiveness. Western Balkan consumers differ in the importance they attach to health and natural content and weight control. This insight is needed to target interventions.

Identifying New Members of Nearby Moving Groups

NASA Astrophysics Data System (ADS)

Holmbeck, Erika; Vican, Laura

2014-06-01

Our group has assembled a sample of 14,000 stars of spectral types B9-M9 with measured UVW Galactic space velocities and lying within 125 pc of Earth. We have identified candidate members of three nearby young (less than 100 Myr) moving groups. For stars of spectral types G5 and later, we have used the Kast spectrometer on the Shane 3m telescope at Lick Observatory to measure lithium abundance in order to determine stellar ages. With the data we have obtained from this run, we will be able to establish whether our candidates are bona fide members of the moving groups in question. I will be presenting the preliminary results from this survey, including spectra of the ~50 stars observed thus far. These nearby young stars will make excellent targets for direct imaging followup surveys, since any giant planets around young stars will still be warm, and will therefore be bright enough to detect with instruments like GPI.

Peer group self-identification as a predictor of relational and physical aggression among high school students.

PubMed

Pokhrel, Pallav; Sussman, Steven; Black, David; Sun, Ping

2010-05-01

Adolescent peer group self-identification refers to adolescents' affiliation with reputation-based peer groups such as "Goths" or "Jocks." These groups tend to vary on normative characteristics, including the group members' attitudes and behaviors. This article examined whether adolescents' baseline peer group self-identification predicted their self-reported relational and physical aggression 1 year later. Self-report data were collected from 1614 students from 9 regular and 9 continuation (alternative) high schools in Southern California, at baseline and 1-year follow-up. Subjects' mean baseline age was 15.21 years (SD = 1.18) and 51.6% of the subjects were female. Findings indicated that compared with self-identified "Regular" or "Normal" students, adolescents who identified with high-risk peer groups (eg, "Druggies,"Goths") tended to report higher relational and physical aggression 1 year later, controlling for baseline aggression and demographic variables. In addition, adolescents' self-identification with high-status peer groups (eg, "Jocks,"Populars") was predictive of higher relational aggression 1 year later. Gender and school type (ie, regular vs continuation) were not found to moderate these effects. It appears that peer group self-identification is a salient predictor of physical and relational aggression across gender and school type. Adolescents who identify with high-risk peer groups tend to report higher levels of physical as well as relational aggression in the future. In addition, adolescents who affiliate with elite groups tend to become more relationally aggressive over time. School-based prevention programs targeting aggression may benefit from addressing the impacts of peer group self-identification on adolescents' aggressive behavior.

OTX2 activity at distal regulatory elements shapes the chromatin landscape of Group 3 medulloblastoma

PubMed Central

Boulay, Gaylor; Awad, Mary E.; Riggi, Nicolo; Archer, Tenley C.; Iyer, Sowmya; Boonseng, Wannaporn E.; Rossetti, Nikki E; Naigles, Beverly; Rengarajan, Shruthi; Volorio, Angela; Kim, James C.; Mesirov, Jill P.; Tamayo, Pablo; Pomeroy, Scott L.; Aryee, Martin J.; Rivera, Miguel N.

2017-01-01

Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as Wnt, SHH, Group 3 and Group 4. Here we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2 bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1. These sites are responsive to OTX2 and NEUROD1 knockdown and could also be generated de novo upon ectopic OTX2 expression in primary cells, showing that OTX2 cooperates with NEUROD1 and plays a major role in maintaining and possibly establishing regulatory elements as a pioneer factor. Among OTX2 target genes we identified the kinase NEK2, whose knockdown and pharmacological inhibition decreased cell viability. Our studies thus show that OTX2 controls the regulatory landscape of Group 3 medulloblastoma through cooperative activity at enhancer elements and contributes to the expression of critical target genes. PMID:28213356

Exploratory Temporal and Spatial Analysis of Myocardial Infarction Hospitalizations in Calgary, Canada

PubMed Central

Liu, Xiaoxiao; Bertazzon, Stefania

2017-01-01

Spatial and temporal analyses are critical to understand the pattern of myocardial infarction (MI) hospitalizations over space and time, and to identify their underlying determinants. In this paper, we analyze MI hospitalizations in Calgary from 2004 to 2013, stratified by age and gender. First, a seasonal trend decomposition analyzes the seasonality; then a linear regression models the trend component. Moran’s I and hot spot analyses explore the spatial pattern. Though exploratory, results show that most age and gender groups feature a statistically significant decline over the 10 years, consistent with previous studies in Canada. Decline rates vary across ages and genders, with the slowest decline observed for younger males. Each gender exhibits a seasonal pattern with peaks in both winter and summer. Spatially, MI hot spots are identified in older communities, and in socioeconomically and environmentally disadvantaged communities. In the older communities, higher MI rates appear to be more highly associated with demographics. Conversely, worse air quality appears to be locally associated with higher MI incidence in younger age groups. The study helps identify areas of concern, where MI hot spots are identified for younger age groups, suggesting the need for localized public health policies to target local risk factors. PMID:29232910

Electronic symptom reporting between patient and provider for improved health care service quality: a systematic review of randomized controlled trials. part 1: state of the art.

PubMed

Johansen, Monika Alise; Henriksen, Eva; Horsch, Alexander; Schuster, Tibor; Berntsen, Gro K Rosvold

2012-10-03

Over the last two decades, the number of studies on electronic symptom reporting has increased greatly. However, the field is very heterogeneous: the choices of patient groups, health service innovations, and research targets seem to involve a broad range of foci. To move the field forward, it is necessary to build on work that has been done and direct further research to the areas holding most promise. Therefore, we conducted a comprehensive review of randomized controlled trials (RCTs) focusing on electronic communication between patient and provider to improve health care service quality, presented in two parts. Part 2 investigates the methodological quality and effects of the RCTs, and demonstrates some promising benefits of electronic symptom reporting. To give a comprehensive overview of the most mature part of this emerging field regarding (1) patient groups, (2) health service innovations, and (3) research targets relevant to electronic symptom reporting. We searched Medline, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and IEEE Xplore for original studies presented in English-language articles published from 1990 to November 2011. Inclusion criteria were RCTs of interventions where patients or parents reported health information electronically to the health care system for health care purposes and were given feedback. Of 642 records identified, we included 32 articles representing 29 studies. The included articles were published from 2002, with 24 published during the last 5 years. The following five patient groups were represented: respiratory and lung diseases (12 studies), cancer (6), psychiatry (6), cardiovascular (3), and diabetes (1). In addition to these, 1 study had a mix of three groups. All included studies, except 1, focused on long-term conditions. We identified four categories of health service innovations: consultation support (7 studies), monitoring with clinician support (12), self-management with clinician support (9), and therapy (1). Most of the research (21/29, 72%) was conducted within four combinations: consultation support innovation in the cancer group (5/29, 17%), monitoring innovation in the respiratory and lung diseases group (8/29, 28%), and self-management innovations in psychiatry (4/29, 14%) and in the respiratory and lung diseases group (4/29, 14%). Research targets in the consultation support studies focused on increased patient centeredness, while monitoring and self-management mainly aimed at documenting health benefits. All except 1 study aiming for reduced health care costs were in the monitoring group. RCT-based research on electronic symptom reporting has developed enormously since 2002. Research including additional patient groups or new combinations of patient groups with the four identified health service innovations can be expected in the near future. We suggest that developing a generic model (not diagnosis specific) for electronic patient symptom reporting for long-term conditions may benefit the field.

Electronic Symptom Reporting Between Patient and Provider for Improved Health Care Service Quality: A Systematic Review of Randomized Controlled Trials. Part 1: State of the Art

PubMed Central

Henriksen, Eva; Horsch, Alexander; Schuster, Tibor; Berntsen, Gro K Rosvold

2012-01-01

Background Over the last two decades, the number of studies on electronic symptom reporting has increased greatly. However, the field is very heterogeneous: the choices of patient groups, health service innovations, and research targets seem to involve a broad range of foci. To move the field forward, it is necessary to build on work that has been done and direct further research to the areas holding most promise. Therefore, we conducted a comprehensive review of randomized controlled trials (RCTs) focusing on electronic communication between patient and provider to improve health care service quality, presented in two parts. Part 2 investigates the methodological quality and effects of the RCTs, and demonstrates some promising benefits of electronic symptom reporting. Objective To give a comprehensive overview of the most mature part of this emerging field regarding (1) patient groups, (2) health service innovations, and (3) research targets relevant to electronic symptom reporting. Methods We searched Medline, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and IEEE Xplore for original studies presented in English-language articles published from 1990 to November 2011. Inclusion criteria were RCTs of interventions where patients or parents reported health information electronically to the health care system for health care purposes and were given feedback. Results Of 642 records identified, we included 32 articles representing 29 studies. The included articles were published from 2002, with 24 published during the last 5 years. The following five patient groups were represented: respiratory and lung diseases (12 studies), cancer (6), psychiatry (6), cardiovascular (3), and diabetes (1). In addition to these, 1 study had a mix of three groups. All included studies, except 1, focused on long-term conditions. We identified four categories of health service innovations: consultation support (7 studies), monitoring with clinician support (12), self-management with clinician support (9), and therapy (1). Most of the research (21/29, 72%) was conducted within four combinations: consultation support innovation in the cancer group (5/29, 17%), monitoring innovation in the respiratory and lung diseases group (8/29, 28%), and self-management innovations in psychiatry (4/29, 14%) and in the respiratory and lung diseases group (4/29, 14%). Research targets in the consultation support studies focused on increased patient centeredness, while monitoring and self-management mainly aimed at documenting health benefits. All except 1 study aiming for reduced health care costs were in the monitoring group. Conclusion RCT-based research on electronic symptom reporting has developed enormously since 2002. Research including additional patient groups or new combinations of patient groups with the four identified health service innovations can be expected in the near future. We suggest that developing a generic model (not diagnosis specific) for electronic patient symptom reporting for long-term conditions may benefit the field. PMID:23032300

Overeating phenotypes in overweight and obese children.

PubMed

Boutelle, Kerri N; Peterson, Carol B; Crosby, Ross D; Rydell, Sarah A; Zucker, Nancy; Harnack, Lisa

2014-05-01

The purpose of this study was to identify overeating phenotypes and their correlates in overweight and obese children. One hundred and seventeen treatment-seeking overweight and obese 8-12year-old children and their parents completed the study. Children completed an eating in the absence of hunger (EAH) paradigm, the Eating Disorder Examination interview, and measurements of height and weight. Parents and children completed questionnaires that evaluated satiety responsiveness, food responsiveness, negative affect eating, external eating and eating in the absence of hunger. Latent profile analysis was used to identify heterogeneity in overeating phenotypes in the child participants. Latent classes were then compared on measures of demographics, obesity status and nutritional intake. Three latent classes of overweight and obese children were identified: High Satiety Responsive, High Food Responsive, and Moderate Satiety and Food Responsive. Results indicated that the High Food Responsive group had higher BMI and BMI-Z scores compared to the High Satiety Responsive group. No differences were found among classes in demographics or nutritional intake. This study identified three overeating phenotypes, supporting the heterogeneity of eating patterns associated with overweight and obesity in treatment-seeking children. These finding suggest that these phenotypes can potentially be used to identify high risk groups, inform prevention and intervention targets, and develop specific treatments for these behavioral phenotypes. Copyright © 2014. Published by Elsevier Ltd.

Docking and scoring protein complexes: CAPRI 3rd Edition.

PubMed

Lensink, Marc F; Méndez, Raúl; Wodak, Shoshana J

2007-12-01

The performance of methods for predicting protein-protein interactions at the atomic scale is assessed by evaluating blind predictions performed during 2005-2007 as part of Rounds 6-12 of the community-wide experiment on Critical Assessment of PRedicted Interactions (CAPRI). These Rounds also included a new scoring experiment, where a larger set of models contributed by the predictors was made available to groups developing scoring functions. These groups scored the uploaded set and submitted their own best models for assessment. The structures of nine protein complexes including one homodimer were used as targets. These targets represent biologically relevant interactions involved in gene expression, signal transduction, RNA, or protein processing and membrane maintenance. For all the targets except one, predictions started from the experimentally determined structures of the free (unbound) components or from models derived by homology, making it mandatory for docking methods to model the conformational changes that often accompany association. In total, 63 groups and eight automatic servers, a substantial increase from previous years, submitted docking predictions, of which 1994 were evaluated here. Fifteen groups submitted 305 models for five targets in the scoring experiment. Assessment of the predictions reveals that 31 different groups produced models of acceptable and medium accuracy-but only one high accuracy submission-for all the targets, except the homodimer. In the latter, none of the docking procedures reproduced the large conformational adjustment required for correct assembly, underscoring yet again that handling protein flexibility remains a major challenge. In the scoring experiment, a large fraction of the groups attained the set goal of singling out the correct association modes from incorrect solutions in the limited ensembles of contributed models. But in general they seemed unable to identify the best models, indicating that current scoring methods are probably not sensitive enough. With the increased focus on protein assemblies, in particular by structural genomics efforts, the growing community of CAPRI predictors is engaged more actively than ever in the development of better scoring functions and means of modeling conformational flexibility, which hold promise for much progress in the future. (c) 2007 Wiley-Liss, Inc.

Keeping the nursing shortage from becoming a nursing crisis.

PubMed

Erickson, Jeanette Ives; Holm, Lauren J; Chelminiak, Lee

2004-02-01

Healthcare organizations are experiencing an unprecedented shortage of qualified nurses. How can we increase our understanding of how the potential labor pool views the nursing profession and identify recruitment themes to encourage young people and adult career switchers to choose a career in nursing? The authors discuss the results of a study that was conducted to gain a better understanding of the dynamics of career selection among these two target groups and identify what types of communication would motivate young people and career switchers to be drawn to the nursing profession.

Educators' Guide to Ally Week

ERIC Educational Resources Information Center

Gay, Lesbian and Straight Education Network (GLSEN), 2010

2010-01-01

An ally is an individual who speaks out and stands up for a person or group that is targeted and/or discriminated against. An ally works to end oppression by supporting and advocating for people who are stigmatized, or treated unfairly because of who they are. In this context, Allies are referred to as people who do not identify as LGBT (lesbian,…

Cockpit resource management at USAir

NASA Technical Reports Server (NTRS)

Sellards, Robert

1987-01-01

The current USAir CRM program is presented. The lessons learned and the program issues are combined. The training material was developed after an extensive literature search and pilot interview survey to determine the problem. The investigation led to the design, implementation, and evaluation of a behavioral science awareness training program. The need was found, and the target population was identified as the pilot group.

Response to Intervention: Evaluation Report and Executive Summary

ERIC Educational Resources Information Center

Gorard, Stephen; Siddiqui, Nadia; See, Beng Huat

2014-01-01

Response to Intervention (RTI) is a targeted programme that uses a tiered approach to identify the needs of low achieving pupils. The approach begins with whole class teaching (Tier 1), followed by small group tuition (Tier 2) for those who need more attention, and one to one tutoring (Tier 3) for those who do not respond to the small group…

An Observational Study of the Lecture Delivery Style Characteristics of High and Low Rated Lectures.

ERIC Educational Resources Information Center

Albanese, Mark A.; And Others

This study identifies distinguishing differences in lecture delivery styles of lecturers rated by students in a large multi-instructor course: the Introduction to Clinical Medicine Course (ICM). The 20 lowest- and highest-rated lecturers of the 1982 and 1983 ICM courses served as the target group. Non-student raters observing the 1984 lectures…

Young Offenders in New South Wales, Australia and the Need for Remedial Sexual Health Education

ERIC Educational Resources Information Center

Mistler, Grant; Kirkwood, Kristie; Potter, Emily; Cashin, Andrew

2008-01-01

The 2005-2008 Australian National Sexually Transmissible Infections Strategy identifies young people as a key target group in need of sexual health education, screening and management. For young people who are in contact with the New South Wales (NSW) juvenile justice system, a dire need for remedial sexual health education exists. NSW young…

Best Friends: Children Use Mutual Gaze to Identify Friendships in Others

ERIC Educational Resources Information Center

Nurmsoo, Erika; Einav, Shiri; Hood, Bruce M.

2012-01-01

This study examined children's ability to use mutual eye gaze as a cue to friendships in others. In Experiment 1, following a discussion about friendship, 4-, 5-, and 6-year-olds were shown animations in which three cartoon children looked at one another, and were told that one target character had a best friend. Although all age groups accurately…

Research on Mail Surveys: Response Rates and Methods in Relation to Population Group and Time.

ERIC Educational Resources Information Center

Boser, Judith A.; Green, Kathy

The purpose of this review was to look for trends across time in response rates and variables studied for published mail surveys and to compare response rates and variables studied for different target populations. Studies were identified in databases in four fields: education, psychology, business and marketing, and sociology. A total of 225…

A Survey of Marketing and Market Research Activities in Two and Four-Year Colleges and Universities.

ERIC Educational Resources Information Center

Smith, Janet D.; And Others

A survey of marketing and market research activities in large, urban, two- and four-year colleges was conducted to identify the nature of marketing problems faced by institutions; current and preferred emphasis placed on market research activities; modes of assessing the needs of target groups and developing appropriate programs; the location of…

Reverse screening methods to search for the protein targets of chemopreventive compounds

NASA Astrophysics Data System (ADS)

Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan

2018-05-01

This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and grasp the types of calculations used in protein target fishing. In addition, we review the main features of these methods, programs and databases and provide a variety of examples illustrating the application of one or a combination of reverse screening methods for accurate target prediction.

Reverse Screening Methods to Search for the Protein Targets of Chemopreventive Compounds.

PubMed

Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan

2018-01-01

This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget, and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB, and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and grasp the types of calculations used in protein target fishing. In addition, we review the main features of these methods, programs and databases and provide a variety of examples illustrating the application of one or a combination of reverse screening methods for accurate target prediction.

Reverse Screening Methods to Search for the Protein Targets of Chemopreventive Compounds

PubMed Central

Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan

2018-01-01

This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget, and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB, and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and grasp the types of calculations used in protein target fishing. In addition, we review the main features of these methods, programs and databases and provide a variety of examples illustrating the application of one or a combination of reverse screening methods for accurate target prediction. PMID:29868550

Closing the Aboriginal child injury gap: targets for injury prevention.

PubMed

Möller, Holger; Falster, Kathleen; Ivers, Rebecca; Falster, Michael O; Clapham, Kathleen; Jorm, Louisa

2017-02-01

To describe the leading mechanisms of hospitalised unintentional injury in Australian Aboriginal children and identify the injury mechanisms with the largest inequalities between Aboriginal and non-Aboriginal children. We used linked hospital and mortality data to construct a whole of population birth cohort including 1,124,717 children (1,088,645 non-Aboriginal and 35,749 Aboriginal) born in the state of New South Wales (NSW), Australia, between 1 July 2000 and 31 December 2012. Injury hospitalisation rates were calculated per person years at risk for injury mechanisms coded according to the ICD10-AM classification. The leading injury mechanisms in both groups of children were falls from playground equipment. For 66 of the 69 injury mechanisms studied, Aboriginal children had a higher rate of hospitalisation compared with non-Aboriginal children. The largest relative inequalities were observed for injuries due to exposure to fire and flame, and the largest absolute inequalities for injuries due to falls from playground equipment. Aboriginal children in NSW experience a significant higher burden of unintentional injury compared with their non-Aboriginal counterparts. Implications for Public Health: We suggest the implementation of targeted injury prevention measures aimed at injury mechanism and age groups identified in this study. © 2016 The Authors.

Sentence stress in children with dysarthria and cerebral palsy.

PubMed

Kuschmann, Anja; Lowit, Anja

2018-03-08

This study aimed to advance our understanding of how children with dysarthria and cerebral palsy (CP) realise sentence stress acoustically, and how well listeners could identify the position of the stressed word within these utterances. Seven children with CP and eight typically developing children participated in the experiment. Stress on target words in two sentence positions was elicited through a picture-based question-answer paradigm. Acoustic parameters of stress [duration, intensity and fundamental frequency (F0)] were measured and compared between stressed and unstressed target words. For the perception experiment, ten listeners were asked to determine the position of the stressed word in the children's productions. Acoustic measures showed that at group level the typically developing children used all three acoustic parameters to mark sentence stress, whereas the children with CP showed changes in duration only. Individual performance variations were evident in both groups. Perceptually, listeners were significantly better at identifying the stressed words in the utterances produced by the typically developing children than those of the children with CP. The results suggest that children with CP can manipulate temporal speech properties to mark stress. This ability to modulate acoustic-prosodic features could be harnessed in intervention to enhance children's functional communication.

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

Fingerprint Analysis: Moving Toward Multiattribute Determination via Individual Markers.

PubMed

Brunelle, Erica; Huynh, Crystal; Alin, Eden; Eldridge, Morgan; Le, Anh Minh; Halámková, Lenka; Halámek, Jan

2018-01-02

Forensic science will be forever revolutionized if law enforcement can identify personal attributes of a person of interest solely from a fingerprint. For the past 2 years, the goal of our group has been to establish a way to identify originator attributes, specifically biological sex, from a single analyte. To date, an enzymatic assay and two chemical assays have been developed for the analysis of multiple analytes. In this manuscript, two additional assays have been developed. This time, however, the assays utilize only one amino acid each. The enzymatic assay targets alanine and employs alanine transaminase (ALT), pyruvate oxidase (POx), and horseradish peroxidase (HRP). The other, a chemical assay, is known as the Sakaguchi test and targets arginine. It is important to note that alanine has a significantly higher concentration than arginine in the fingerprint content of both males and females. Both assays proved to be capable of accurately differentiating between male and female fingerprints, regardless of their respective average concentration. The ability to target a single analyte will transform forensic science as each originator attribute can be correlated to a different analyte. This would then lead to the possibility of identifying multiple attributes from a single fingerprint sample. Ultimately, this would allow for a profile of a person of interest to be established without the need for time-consuming lab processes.

Models for discovery of targeted therapy in genetic epileptic encephalopathies.

PubMed

Maljevic, Snezana; Reid, Christopher A; Petrou, Steven

2017-10-01

Epileptic encephalopathies are severe disorders emerging in the first days to years of life that commonly include refractory seizures, various types of movement disorders, and different levels of developmental delay. In recent years, many de novo occurring variants have been identified in individuals with these devastating disorders. To unravel disease mechanisms, the functional impact of detected variants associated with epileptic encephalopathies is investigated in a range of cellular and animal models. This review addresses efforts to advance and use such models to identify specific molecular and cellular targets for the development of novel therapies. We focus on ion channels as the best-studied group of epilepsy genes. Given the clinical and genetic heterogeneity of epileptic encephalopathy disorders, experimental models that can reflect this complexity are critical for the development of disease mechanisms-based targeted therapy. The convergence of technological advances in gene sequencing, stem cell biology, genome editing, and high throughput functional screening together with massive unmet clinical needs provides unprecedented opportunities and imperatives for precision medicine in epileptic encephalopathies. © 2017 International Society for Neurochemistry.

[Techniques for rapid production of monoclonal antibodies for use with antibody technology].

PubMed

Kamada, Haruhiko

2012-01-01

A monoclonal antibody (Mab), due to its specific binding ability to a target protein, can potentially be one of the most useful tools for the functional analysis of proteins in recent proteomics-based research. However, the production of Mab is a very time-consuming and laborious process (i.e., preparation of recombinant antigens, immunization of animals, preparation of hybridomas), making it the rate-limiting step in using Mabs in high-throughput proteomics research, which heavily relies on comprehensive and rapid methods. Therefore, there is a great demand for new methods to efficiently generate Mabs against a group of proteins identified by proteome analysis. Here, we describe a useful method called "Antibody proteomic technique" for the rapid generations of Mabs to pharmaceutical target, which were identified by proteomic analyses of disease samples (ex. tumor tissue, etc.). We also introduce another method to find profitable targets on vasculature, which is called "Vascular proteomic technique". Our results suggest that this method for the rapid generation of Mabs to proteins may be very useful in proteomics-based research as well as in clinical applications.

Eating Patterns and Health Outcomes in Patients With Type 2 Diabetes.

PubMed

Aguiar Sarmento, Roberta; Peçanha Antonio, Juliana; Lamas de Miranda, Ingrid; Bellicanta Nicoletto, Bruna; Carnevale de Almeida, Jussara

2018-01-01

To evaluate the relationship between eating patterns and therapeutic target's achieving in patients with type 2 diabetes. In this cross-sectional study, patients underwent clinical, laboratory, and nutritional evaluations. Dietary intake was assessed by a quantitative food frequency questionnaire and eating patterns identified by cluster analysis. The therapeutic targets were as follows: blood pressure, <140/90 mm Hg; BMI, <25 kg/m 2 (<27 kg/m 2 for elderly); waist circumference, <94 cm for men and <80 cm for women; fasting plasma glucose, <130 mg/dL; HbA1c, <7%; triglycerides, <150 mg/dL; HDL-cholesterol, >40 mg/dL for men and >50 mg/dL for women; LDL-cholesterol, <100 mg/dL. One hundred ninety seven patients were studied. We identified two eating patterns: "unhealthy" (n = 100)-high consumption of refined carbohydrates, ultra-processed foods, sweets and desserts ( P < 0.05); and "healthy" (n = 97)-high intake of whole carbohydrates, dairy, white meat, fish, fruits and vegetables ( P < 0.05). The healthy group more frequently achieved therapeutic targets for fasting plasma glucose, HbA1c, and LDL-cholesterol than the unhealthy group. Poisson regression confirmed the association of healthy eating pattern with attaining the therapeutic target for fasting plasma glucose [PR, 1.59 (95% CI, 1.01 to 2.34); P = 0.018], HbA1c [PR, 2.09 (95% CI, 1.17 to 3.74); P = 0.013], and LDL-cholesterol [PR, 1.37 (95% CI, 1.01 to 1.86); P = 0.042]. A healthy eating pattern, including the frequent intake of whole carbohydrates, dairy, white meat, fish, fruits, and vegetables, is associated with reduced fasting plasma glucose, HbA1c, and LDL cholesterol levels in patients with type 2 diabetes.

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.

Using the Information-Motivation-Behavioral Skills Model to Guide the Development of an HIV Prevention Smartphone Application for High-Risk MSM

PubMed Central

Aliabadi, Negar; Carballo-Dieguez, Alex; Bakken, Suzanne; Rojas, Marlene; Brown, William; Carry, Monique; Mosley, Jocelyn Patterson; Gelaude, Deborah; Schnall, Rebecca

2016-01-01

HIV remains a significant public health problem among men who have sex with men (MSM). MSM comprise 2% of the U.S. population, but constitute 56% of persons living with HIV. Mobile health technology is a promising tool for HIV prevention. The purpose of this study was to identify the desired content, features and functions of a mobile application (app) for HIV prevention in high-risk MSM. We conducted five focus group sessions with 33 MSM. Focus group recordings were transcribed and coded using themes informed by the information-motivation-behavioral (IMB) skills model. Participants identified information needs related to HIV prevention: HIV testing and prophylaxis distribution centers, support groups/peers, and HIV/STI disease/treatment information. Areas of motivation to target for the app included: attitudes and intentions. Participants identified behavioral skills to address with an app: using condoms correctly, negotiating safer sex, recognizing signs of HIV/STI. Findings from this work provide insight into the desired content of a mobile app for HIV prevention in high-risk MSM. PMID:26595265

Evaluation of targeted exome sequencing for 28 protein-based blood group systems, including the homologous gene systems, for blood group genotyping.

PubMed

Schoeman, Elizna M; Lopez, Genghis H; McGowan, Eunike C; Millard, Glenda M; O'Brien, Helen; Roulis, Eileen V; Liew, Yew-Wah; Martin, Jacqueline R; McGrath, Kelli A; Powley, Tanya; Flower, Robert L; Hyland, Catherine A

2017-04-01

Blood group single nucleotide polymorphism genotyping probes for a limited range of polymorphisms. This study investigated whether massively parallel sequencing (also known as next-generation sequencing), with a targeted exome strategy, provides an extended blood group genotype and the extent to which massively parallel sequencing correctly genotypes in homologous gene systems, such as RH and MNS. Donor samples (n = 28) that were extensively phenotyped and genotyped using single nucleotide polymorphism typing, were analyzed using the TruSight One Sequencing Panel and MiSeq platform. Genes for 28 protein-based blood group systems, GATA1, and KLF1 were analyzed. Copy number variation analysis was used to characterize complex structural variants in the GYPC and RH systems. The average sequencing depth per target region was 66.2 ± 39.8. Each sample harbored on average 43 ± 9 variants, of which 10 ± 3 were used for genotyping. For the 28 samples, massively parallel sequencing variant sequences correctly matched expected sequences based on single nucleotide polymorphism genotyping data. Copy number variation analysis defined the Rh C/c alleles and complex RHD hybrids. Hybrid RHD*D-CE-D variants were correctly identified, but copy number variation analysis did not confidently distinguish between D and CE exon deletion versus rearrangement. The targeted exome sequencing strategy employed extended the range of blood group genotypes detected compared with single nucleotide polymorphism typing. This single-test format included detection of complex MNS hybrid cases and, with copy number variation analysis, defined RH hybrid genes along with the RHCE*C allele hitherto difficult to resolve by variant detection. The approach is economical compared with whole-genome sequencing and is suitable for a red blood cell reference laboratory setting. © 2017 AABB.

Dietary patterns among a national random sample of British adults

PubMed Central

Pryer, J; Nichols, R; Elliott, P; Thakrar, B; Brunner, E; Marmot, M

2001-01-01

STUDY OBJECTIVES—To identify groups within the UK male and female population who report similar patterns of diet.
DESIGN—National representative dietary survey, using seven day weighed dietary records, of men and women aged 16-64 years living in private households in Great Britain in 1986-7. Cluster analysis was used to aggregate participants into diet groups.
SETTING—Great Britain.
PARTICIPANTS—1087 men and 1110 women.
RESULTS—93% of men and 86% of women fell into one of four distinct diet groups. Among men the most prevalent diet group was "beer and convenience food" (34% of the male population); second was "traditional British diet" (18%); third was "healthier but sweet diet" (17.5%) and fourth was "healthier diet " (17%). Among women, the most prevalent diet group was " traditional British diet" (32%); second, was "healthy cosmopolitan diet" (25%); third was a "convenience food diet" (21%); and fourth was "healthier but sweet diet" (15%). There were important differences in nutrient profile, sociodemographic and behavioural characteristics between diet groups.
CONCLUSIONS—Cluster analysis identified four diet groups among men and four among women, which differed not only in terms of reported dietary intakes, but also with respect to nutrient, social and behavioural profiles. The groups identified could provide a useful basis for development, monitoring and targeting of public health nutrition policy in the UK.


Keywords: diet; cluster analysis; sociodemographic variables PMID:11112948

CRISPR/Cas9-mediated gene knockout screens and target identification via whole-genome sequencing uncover host genes required for picornavirus infection.

PubMed

Kim, Heon Seok; Lee, Kyungjin; Bae, Sangsu; Park, Jeongbin; Lee, Chong-Kyo; Kim, Meehyein; Kim, Eunji; Kim, Minju; Kim, Seokjoong; Kim, Chonsaeng; Kim, Jin-Soo

2017-06-23

Several groups have used genome-wide libraries of lentiviruses encoding small guide RNAs (sgRNAs) for genetic screens. In most cases, sgRNA expression cassettes are integrated into cells by using lentiviruses, and target genes are statistically estimated by the readout of sgRNA sequences after targeted sequencing. We present a new virus-free method for human gene knockout screens using a genome-wide library of CRISPR/Cas9 sgRNAs based on plasmids and target gene identification via whole-genome sequencing (WGS) confirmation of authentic mutations rather than statistical estimation through targeted amplicon sequencing. We used 30,840 pairs of individually synthesized oligonucleotides to construct the genome-scale sgRNA library, collectively targeting 10,280 human genes ( i.e. three sgRNAs per gene). These plasmid libraries were co-transfected with a Cas9-expression plasmid into human cells, which were then treated with cytotoxic drugs or viruses. Only cells lacking key factors essential for cytotoxic drug metabolism or viral infection were able to survive. Genomic DNA isolated from cells that survived these challenges was subjected to WGS to directly identify CRISPR/Cas9-mediated causal mutations essential for cell survival. With this approach, we were able to identify known and novel genes essential for viral infection in human cells. We propose that genome-wide sgRNA screens based on plasmids coupled with WGS are powerful tools for forward genetics studies and drug target discovery. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Development of a smoking prevention mass media program using diagnostic and formative research.

PubMed

Worden, J K; Flynn, B S; Geller, B M; Chen, M; Shelton, L G; Secker-Walker, R H; Solomon, D S; Solomon, L J; Couchey, S; Costanza, M C

1988-09-01

The process of developing a mass media campaign to prevent smoking among adolescents is described in detail. This campaign supplements a school smoking prevention program and shares educational objectives with the school program but is otherwise independent. It comprises various television and radio 30- and 60-sec "spot" messages. The campaign development process includes identifying educational objectives and strategies for appealing to young people; conducting diagnostic surveys and focus groups to determine target audience interests and perceptions about smoking and media content; suggesting approaches to producers to create preliminary television and radio messages for testing; conducting formative pretests with target groups to select optimal messages and suggest improvements to those messages; producing final messages for media presentation; and developing a media exposure plan to place messages in local media at optimal times for reception by target audiences. The media campaign is being evaluated in a 5-year project with 5,500 adolescents in four communities to determine the additional effect of mass media over a school program alone in preventing smoking.

Imbalance in chemical space: How to facilitate the identification of protein-protein interaction inhibitors.

PubMed

Kuenemann, Mélaine A; Labbé, Céline M; Cerdan, Adrien H; Sperandio, Olivier

2016-04-01

Protein-protein interactions (PPIs) play vital roles in life and provide new opportunities for therapeutic interventions. In this large data analysis, 3,300 inhibitors of PPIs (iPPIs) were compared to 17 reference datasets of collectively ~566,000 compounds (including natural compounds, existing drugs, active compounds on conventional targets, etc.) using a chemoinformatics approach. Using this procedure, we showed that comparable classes of PPI targets can be formed using either the similarity of their ligands or the shared properties of their binding cavities, constituting a proof-of-concept that not only can binding pockets be used to group PPI targets, but that these pockets certainly condition the properties of their corresponding ligands. These results demonstrate that matching regions in both chemical space and target space can be found. Such identified classes of targets could lead to the design of PPI-class-specific chemical libraries and therefore facilitate the development of iPPIs to the stage of drug candidates.

Multiplexed Thiol Reactivity Profiling for Target Discovery of Electrophilic Natural Products.

PubMed

Tian, Caiping; Sun, Rui; Liu, Keke; Fu, Ling; Liu, Xiaoyu; Zhou, Wanqi; Yang, Yong; Yang, Jing

2017-11-16

Electrophilic groups, such as Michael acceptors, expoxides, are common motifs in natural products (NPs). Electrophilic NPs can act through covalent modification of cysteinyl thiols on functional proteins, and exhibit potent cytotoxicity and anti-inflammatory/cancer activities. Here we describe a new chemoproteomic strategy, termed multiplexed thiol reactivity profiling (MTRP), and its use in target discovery of electrophilic NPs. We demonstrate the utility of MTRP by identifying cellular targets of gambogic acid, an electrophilic NP that is currently under evaluation in clinical trials as anticancer agent. Moreover, MTRP enables simultaneous comparison of seven structurally diversified α,β-unsaturated γ-lactones, which provides insights into the relative proteomic reactivity and target preference of diverse structural scaffolds coupled to a common electrophilic motif and reveals various potential druggable targets with liganded cysteines. We anticipate that this new method for thiol reactivity profiling in a multiplexed manner will find broad application in redox biology and drug discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Uncovering the Mechanisms of Chinese Herbal Medicine (MaZiRenWan) for Functional Constipation by Focused Network Pharmacology Approach.

PubMed

Huang, Tao; Ning, Ziwan; Hu, Dongdong; Zhang, Man; Zhao, Ling; Lin, Chengyuan; Zhong, Linda L D; Yang, Zhijun; Xu, Hongxi; Bian, Zhaoxiang

2018-01-01

MaZiRenWan (MZRW, also known as Hemp Seed Pill) is a Chinese Herbal Medicine which has been demonstrated to safely and effectively alleviate functional constipation (FC) in a randomized, placebo-controlled clinical study with 120 subjects. However, the underlying pharmacological actions of MZRW for FC, are still largely unknown. We systematically analyzed the bioactive compounds of MZRW and mechanism-of-action biological targets through a novel approach called "focused network pharmacology." Among the 97 compounds identified by UPLC-QTOF-MS/MS in MZRW extract, 34 were found in rat plasma, while 10 were found in rat feces. Hierarchical clustering analysis suggest that these compounds can be classified into component groups, in which compounds are highly similar to each other and most of them are from the same herb. Emodin, amygdalin, albiflorin, honokiol, and naringin were selected as representative compounds of corresponding component groups. All of them were shown to induce spontaneous contractions of rat colonic smooth muscle in vitro . Network analysis revealed that biological targets in acetylcholine-, estrogen-, prostaglandin-, cannabinoid-, and purine signaling pathways are able to explain the prokinetic effects of representative compounds and corresponding component groups. In conclusion, MZRW active components enhance colonic motility, possibly by acting on multiple targets and pathways.

Uncovering the Mechanisms of Chinese Herbal Medicine (MaZiRenWan) for Functional Constipation by Focused Network Pharmacology Approach

PubMed Central

Huang, Tao; Ning, Ziwan; Hu, Dongdong; Zhang, Man; Zhao, Ling; Lin, Chengyuan; Zhong, Linda L. D.; Yang, Zhijun; Xu, Hongxi; Bian, Zhaoxiang

2018-01-01

MaZiRenWan (MZRW, also known as Hemp Seed Pill) is a Chinese Herbal Medicine which has been demonstrated to safely and effectively alleviate functional constipation (FC) in a randomized, placebo-controlled clinical study with 120 subjects. However, the underlying pharmacological actions of MZRW for FC, are still largely unknown. We systematically analyzed the bioactive compounds of MZRW and mechanism-of-action biological targets through a novel approach called “focused network pharmacology.” Among the 97 compounds identified by UPLC-QTOF-MS/MS in MZRW extract, 34 were found in rat plasma, while 10 were found in rat feces. Hierarchical clustering analysis suggest that these compounds can be classified into component groups, in which compounds are highly similar to each other and most of them are from the same herb. Emodin, amygdalin, albiflorin, honokiol, and naringin were selected as representative compounds of corresponding component groups. All of them were shown to induce spontaneous contractions of rat colonic smooth muscle in vitro. Network analysis revealed that biological targets in acetylcholine-, estrogen-, prostaglandin-, cannabinoid-, and purine signaling pathways are able to explain the prokinetic effects of representative compounds and corresponding component groups. In conclusion, MZRW active components enhance colonic motility, possibly by acting on multiple targets and pathways. PMID:29632490

Efficacy and acceptability of a home-based, family-inclusive intervention for veterans with TBI: A randomized controlled trial.

PubMed

Winter, Laraine; Moriarty, Helene J; Robinson, Keith; Piersol, Catherine V; Vause-Earland, Tracey; Newhart, Brian; Iacovone, Delores Blazer; Hodgson, Nancy; Gitlin, Laura N

2016-01-01

Traumatic brain injury (TBI) often undermines community re-integration, impairs functioning and produces other symptoms. This study tested an innovative programme for veterans with TBI, the Veterans' In-home Programme (VIP), delivered in veterans' homes, involving a family member and targeting the environment (social and physical) to promote community re-integration, mitigate difficulty with the most troubling TBI symptoms and facilitate daily functioning. Interviews and intervention sessions were conducted in homes or by telephone. Eighty-one veterans with TBI at a VA polytrauma programme and a key family member. This was a 2-group randomized controlled trial. Control-group participants received usual-care enhanced by two attention-control telephone calls. Follow-up interviews occurred up to 4 months after baseline interview. VIP's efficacy was evaluated using measures of community re-integration, target outcomes reflecting veterans' self-identified problems and self-rated functional competence. At follow-up, VIP participants had significantly higher community re-integration scores and less difficulty managing targeted outcomes, compared to controls. Self-rated functional competence did not differ between groups. In addition, VIP's acceptability was high. A home-based, family-inclusive service for veterans with TBI shows promise for improving meaningful outcomes and warrants further research and clinical application.

Contradictions in digital health engagement: An activity tracker's ambiguous influence on vulnerable young adults' engagement in own health.

PubMed

Kanstrup, Anne Marie; Bertelsen, Pernille; Jensen, Martin B

2018-01-01

Activity trackers are designed to support individuals in monitoring and increasing their physical activity. The use of activity trackers among individuals diagnosed with depression and anxiety has not yet been examined. This pilot study investigates how this target group engages with an activity tracker during a 10-week health intervention aimed to increase their physical activity level and improve their physical and mental health. Two groups of 11 young adults (aged 18-29 years) diagnosed with depression or anxiety participated in the digital health intervention. The study used mixed methods to investigate the research question. Quantitative health data were used to assess the intervention's influence on the participants' health and qualitative data provided insights into the participants' digital health experience. The study demonstrated an ambiguous influence from the use of an activity tracker with positive physical and mental health results, but a fading and even negative digital health engagement and counterproductive competition. The ambiguous results identify a need for (1) developing strategies for health professionals to provide supervised use of activity trackers and support the target groups' abilities to convert health information about physical activity into positive health strategies, and (2) designing alternatives for health promoting IT targeted users who face challenges and need motivation beyond self-tracking and competition.

Targeting community-dwelling urinary incontinence sufferers: a multi-disciplinary community based model for conservative continence services.

PubMed

St John, Winsome; Wallis, Marianne; James, Heather; McKenzie, Shona; Guyatt, Sheridan

2004-10-01

This paper presents an argument that there is a need to provide services that target community-dwelling incontinence sufferers, and presents a demonstration case study of a multi-disciplinary, community-based conservative model of service delivery: The Waterworx Model. Rationale for approaches taken, implementation of the model, evaluation and lessons learned are discussed. In this paper community-dwelling sufferers of urinary incontinence are identified as an underserved group, and useful information is provided for those wishing to establish services for them. The Waterworx Model of continence service delivery incorporates three interrelated approaches. Firstly, client access is achieved by using community-based services via clinic and home visits, creating referral pathways and active promotion of services. Secondly, multi-disciplinary client care is provided by targeting a specific client group, multi-disciplinary assessment, promoting client self-management and developing client knowledge and health literacy. Finally, interdisciplinary collaboration and linkages is facilitated by developing multidisciplinary assessment tools, using interdisciplinary referrals, staff development, multi-disciplinary management and providing professional education. Implementation of the model achieved greater client access, improvement in urinary incontinence and client satisfaction. Our experiences suggest that those suffering urinary incontinence and living in the community are an underserved group and that continence services should be community focussed, multi-disciplinary, generalist in nature.

Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging.

PubMed

Due, Deborah L; Huettel, Scott A; Hall, Warren G; Rubin, David C

2002-06-01

The authors sought to increase understanding of the brain mechanisms involved in cigarette addiction by identifying neural substrates modulated by visual smoking cues in nicotine-deprived smokers. Event-related functional magnetic resonance imaging (fMRI) was used to detect brain activation after exposure to smoking-related images in a group of nicotine-deprived smokers and a nonsmoking comparison group. Subjects viewed a pseudo-random sequence of smoking images, neutral nonsmoking images, and rare targets (photographs of animals). Subjects pressed a button whenever a rare target appeared. In smokers, the fMRI signal was greater after exposure to smoking-related images than after exposure to neutral images in mesolimbic dopamine reward circuits known to be activated by addictive drugs (right posterior amygdala, posterior hippocampus, ventral tegmental area, and medial thalamus) as well as in areas related to visuospatial attention (bilateral prefrontal and parietal cortex and right fusiform gyrus). In nonsmokers, no significant differences in fMRI signal following exposure to smoking-related and neutral images were detected. In most regions studied, both subject groups showed greater activation following presentation of rare target images than after exposure to neutral images. In nicotine-deprived smokers, both reward and attention circuits were activated by exposure to smoking-related images. Smoking cues are processed like rare targets in that they activate attentional regions. These cues are also processed like addictive drugs in that they activate mesolimbic reward regions.

Opening Minds in Canada: Targeting Change

PubMed Central

Stuart, Heather; Chen, Shu-Ping; Christie, Romie; Dobson, Keith; Kirsh, Bonnie; Knaak, Stephanie; Koller, Michelle; Krupa, Terry; Lauria-Horner, Bianca; Luong, Dorothy; Modgill, Geeta; Patten, Scott B; Pietrus, Mike; Szeto, Andrew; Whitley, Rob

2014-01-01

Objective: To summarize the ongoing activities of the Opening Minds (OM) Anti-Stigma Initiative of the Mental Health Commission of Canada regarding the 4 groups targeted (youth, health care providers, media, and workplaces), highlight some of the key methodological challenges, and review lessons learned. Method: The approach used by OM is rooted in community development philosophy, with clearly defined target groups, contact-based education as the central organizing element across interventions, and a strong evaluative component so that best practices can be identified, replicated, and disseminated. Contact-based education occurs when people who have experienced a mental illness share their personal story of recovery and hope. Results: Results have been generally positive. Contact-based education has the capacity to reduce prejudicial attitudes and improve social acceptance of people with a mental illness across various target groups and sectors. Variations in program outcomes have contributed to our understanding of active ingredients. Conclusions: Contact-based education has become a cornerstone of the OM approach to stigma reduction. A story of hope and recovery told by someone who has experienced a mental illness is powerful and engaging, and a critical ingredient in the fight against stigma. Building partnerships with existing community programs and promoting systematic evaluation using standardized approaches and instruments have contributed to our understanding of best practices in the field of anti-stigma programming. The next challenge will be to scale these up so that they may have a national impact. PMID:25565697

Healthcare teams as complex adaptive systems: Focus on interpersonal interaction.

PubMed

Pype, Peter; Krystallidou, Demi; Deveugele, Myriam; Mertens, Fien; Rubinelli, Sara; Devisch, Ignaas

2017-11-01

The aim of this study is to test the feasibility of a tool to objectify the functioning of healthcare teams operating in the complexity zone, and to evaluate its usefulness in identifying areas for team quality improvement. We distributed The Complex Adaptive Leadership (CAL™) Organisational Capability Questionnaire (OCQ) to all members of one palliative care team (n=15) and to palliative care physicians in Flanders, Belgium (n=15). Group discussions were held on feasibility aspects and on the low scoring topics. Data was analysed calculating descriptive statistics (sum score, mean and standard deviation). The one sample T-Test was used to detect differences within each group. Both groups of participants reached mean scores ranging from good to excellent. The one sample T test showed statistically significant differences between participants' sum scores within each group (p<0,001). Group discussion led to suggestions for quality improvement e.g. enhanced feedback strategies between team members. The questionnaire used in our study shows to be a feasible and useful instrument for the evaluation of the palliative care teams' day-to-day operations and to identify areas for quality improvement. The CAL™OCQ is a promising instrument to evaluate any healthcare team functioning. A group discussion on the questionnaire scores can serve as a starting point to identify targets for quality improvement initiatives. Copyright © 2017 Elsevier B.V. All rights reserved.

Sensibility of grey particle production system to energy and centrality in 60A and 200A GeV 16O-Nucleus interactions

NASA Astrophysics Data System (ADS)

Abdelsalam, A.; El–Nagdy, M. S.; Badawy, B. M.; Osman, W.; Fayed, M.

2016-06-01

The grey particle production following 60 A and 200A GeV 16O interactions with emulsion nuclei is investigated at different centralities. The evaporated target fragment multiplicity is voted as a centrality parameter. The target size effect is examined over a wide range, where the C, N and O nuclei present the light target group while the Br and Ag nuclei are the heavy group. In the framework of the nuclear limiting fragmentation hypothesis, the grey particle multiplicity characteristics depend only on the target size and centrality while the projectile size and energy are not effective. The grey particle is suggested to be a multisource production system. The emission direction in the 4π space depends upon the production source. Either the exponential decay or the Poisson’s peaking curves are the usual characteristic shapes of the grey particle multiplicity distributions. The decay shape is suggested to be a characteristic feature of the source singularity while the peaking shape is a multisource super-position. The sensibility to the centrality varies from a source to other. The distribution shape is identified at each centrality region according to the associated source contribution. In general, the multiplicity characteristics seem to be limited w.r.t. the collision system centrality using light target nuclei. The selection of the black particle multiplicity as a centrality parameter is successful through the collision with the heavy target nuclei. In the collision with the light target nuclei it may be qualitatively better to vote another centrality parameter.

Genetic Epidemiology of Cigarette Smoke–Induced Lung Disease

PubMed Central

2012-01-01

Chronic obstructive pulmonary disease (COPD) and lung cancer represent two diseases that share a strong risk factor in smoking, and COPD increases risk of lung cancer even after adjusting for the effects of smoking. These diseases not only occur jointly within an individual but also there is evidence of shared occurrence within families. Understanding the genetic contributions to these diseases, both individually and jointly, is needed to identify the highest risk group for screening and targeted prevention, as well as aiding in the development of targeted treatments. The chromosomal regions that have been identified as being associated either jointly or independently with lung cancer, COPD, nicotine addiction, and lung function are presented. Studies jointly measuring genetic variation in lung cancer and COPD have been limited by the lack of detailed COPD diagnosis and severity data in lung cancer populations, the lack of lung cancer–specific phenotypes (histology and tumor markers) in COPD populations, and the lack of inclusion of minorities. African Americans, who smoke fewer cigarettes per day and have different linkage disequilibrium and disease patterns than whites, and Asians, also with different patterns of exposure to lung carcinogens and linkage patterns, will provide invaluable information to better understand shared and independent genetic contributions to lung cancer and COPD to more fully define the highest risk group of individuals who will most benefit from screening and to develop molecular signatures to aid in targeted treatment and prevention efforts. PMID:22550237

CargoTIPS: an innovative approach to combating cargo theft

NASA Astrophysics Data System (ADS)

Toth, Gail E.

1998-12-01

Cargo theft has been estimated by the Federal Bureau o Investigations to be 6 billion annually, while others believe it to be more than 10 billion annually. Opportunistic thieves, street gangs, traditional organized crime groups, and new organized crime groups have been targeting cargo. They steal from warehouses, terminals, equipment, truck stops, or any place where freight comes to a rest. With zero inventory levels, our trailers have become virtual warehouses on wheels and easy targets for thieves. Without information and communication cargo thieves can thrive. The industry and law enforcement are forced into being reactive instead of developing proactive policies and procedures. Cargo thieves cross town lines, county lines, state lines and country borders. This makes communication within the law enforcement community imperative. CargoTIPS (cargo theft information processing system) was developed in response to the need for cargo theft information. The system allows us to collect cargo theft statistics to analyze the problem, assess the threat and develop a response on a national level. CargoTIPS includes a bulletin board, which allows users to communicate with each other, pass on alerts or seek information. The system is also used as an investigative tool. CargoTIPS can identify the mode of transportation (truck, small parcel, air, rail or ocean). It was designed to take in international data. Currently the system has identified that food products are the number one targeted commodity, followed by electronic products and third, computers and computer parts.

Capacity building efforts and perceptions for wildlife surveillance to detect zoonotic pathogens: comparing stakeholder perspectives.

PubMed

Schwind, Jessica S; Goldstein, Tracey; Thomas, Kate; Mazet, Jonna A K; Smith, Woutrina A

2014-07-04

The capacity to conduct zoonotic pathogen surveillance in wildlife is critical for the recognition and identification of emerging health threats. The PREDICT project, a component of United States Agency for International Development's Emerging Pandemic Threats program, has introduced capacity building efforts to increase zoonotic pathogen surveillance in wildlife in global 'hot spot' regions where zoonotic disease emergence is likely to occur. Understanding priorities, challenges, and opportunities from the perspectives of the stakeholders is a key component of any successful capacity building program. A survey was administered to wildlife officials and to PREDICT-implementing in-country project scientists in 16 participating countries in order to identify similarities and differences in perspectives between the groups regarding capacity needs for zoonotic pathogen surveillance in wildlife. Both stakeholder groups identified some human-animal interfaces (i.e. areas of high contact between wildlife and humans with the potential risk for disease transmission), such as hunting and markets, as important for ongoing targeting of wildlife surveillance. Similarly, findings regarding challenges across stakeholder groups showed some agreement in that a lack of sustainable funding across regions was the greatest challenge for conducting wildlife surveillance for zoonotic pathogens (wildlife officials: 96% and project scientists: 81%). However, the opportunity for improving zoonotic pathogen surveillance capacity identified most frequently by wildlife officials as important was increasing communication or coordination among agencies, sectors, or regions (100% of wildlife officials), whereas the most frequent opportunities identified as important by project scientists were increasing human capacity, increasing laboratory capacity, and the growing interest or awareness regarding wildlife disease or surveillance programs (all identified by 69% of project scientists). A One Health approach to capacity building applied at local and global scales will have the greatest impact on improving zoonotic pathogen surveillance in wildlife. This approach will involve increasing communication and cooperation across ministries and sectors so that experts and stakeholders work together to identify and mitigate surveillance gaps. Over time, this transdisciplinary approach to capacity building will help overcome existing challenges and promote efficient targeting of high risk interfaces for zoonotic pathogen transmission.

Effects and molecular mechanisms of intrauterine infection/inflammation on lung development.

PubMed

Pan, Jiarong; Zhan, Canyang; Yuan, Tianming; Wang, Weiyan; Shen, Ying; Sun, Yi; Wu, Tai; Gu, Weizhong; Chen, Lihua; Yu, Huimin

2018-05-10

Intrauterine infection/inflammation plays an important role in the development of lung injury and bronchopulmonary dysplasia (BPD) in preterm infants, While a multifactorial genesis is likely, mechanisms involved in BPD after intrauterine infection/inflammation are largely unknown. Recent studies have suggested microRNAs (miRNAs) are likely to play a role. Therefore, this study aimed to study the effects and mechanisms of intrauterine infection/inflammation on lung development, and to identify miRNAs related to lung injury and BPD. An animal model of intrauterine infection/inflammation was established with pregnant SD rats endocervically inoculated with E.coli. The fetal and neonatal rats were observed at embryonic day (E) 17, 19, 21 and postnatal day (P) 1, 3, 7, 14, respectively. Body weight, lung weight, the expression levels of NLRP3, TNF-α, IL-lβ, IL-6, VEGF, Collagen I, SP-A, SP-B and SP-C in the lung tissues of fetal and neonatal rats were measured. Expression profiles of 1218 kinds of miRNAs in the lungs of neonatal rats were detected by miRNA microarray technique. Target genes of the identified miRNAs were predicted through online software. Intrauterine infection/inflammation compromised not only weight development but also lung development of the fetal and neonatal rats. The results showed significantly increased expression of NLRP3, TNF-α, IL-1β, IL-6, Collagen I, and significantly decreased expression of VEGF, SP-A, SP-B and SP-C in the fetal and neonatal rat lung tissues in intrauterine infection group compared to the control group at different observation time point (P < 0.05). Forty-three miRNAs with significant differential expression were identified. Possible target genes regulated by the identified miRNAs are very rich. Intrauterine infection/inflammation results in lung histological changes which are very similar to those observed in BPD. Possible mechanisms may include NLRP3 inflammasome activation followed by inflammatory cytokines expression up-regulated, inhibiting the expression of pulmonary surfactant proteins, interfering with lung interstitial development. There are many identified miRNAs which target a wide range of genes and may play an important role in the processes of lung injury and BPD.

Identifying clusters of falls-related hospital admissions to inform population targets for prioritising falls prevention programmes

PubMed Central

Finch, Caroline F; Stephan, Karen; Shee, Anna Wong; Hill, Keith; Haines, Terry P; Clemson, Lindy; Day, Lesley

2015-01-01

Background There has been limited research investigating the relationship between injurious falls and hospital resource use. The aims of this study were to identify clusters of community-dwelling older people in the general population who are at increased risk of being admitted to hospital following a fall and how those clusters differed in their use of hospital resources. Methods Analysis of routinely collected hospital admissions data relating to 45 374 fall-related admissions in Victorian community-dwelling older adults aged ≥65 years that occurred during 2008/2009 to 2010/2011. Fall-related admission episodes were identified based on being admitted from a private residence to hospital with a principal diagnosis of injury (International Classification of Diseases (ICD)-10-AM codes S00 to T75) and having a first external cause of a fall (ICD-10-AM codes W00 to W19). A cluster analysis was performed to identify homogeneous groups using demographic details of patients and information on the presence of comorbidities. Hospital length of stay (LOS) was compared across clusters using competing risks regression. Results Clusters based on area of residence, demographic factors (age, gender, marital status, country of birth) and the presence of comorbidities were identified. Clusters representing hospitalised fallers with comorbidities were associated with longer LOS compared with other cluster groups. Clusters delineated by demographic factors were also associated with increased LOS. Conclusions All patients with comorbidity, and older women without comorbidities, stay in hospital longer following a fall and hence consume a disproportionate share of hospital resources. These findings have important implications for the targeting of falls prevention interventions for community-dwelling older people. PMID:25618735

DNA-based stable isotope probing coupled with cultivation methods implicates Methylophaga in hydrocarbon degradation

PubMed Central

Mishamandani, Sara; Gutierrez, Tony; Aitken, Michael D.

2014-01-01

Marine hydrocarbon-degrading bacteria perform a fundamental role in the oxidation and ultimate removal of crude oil and its petrochemical derivatives in coastal and open ocean environments. Those with an almost exclusive ability to utilize hydrocarbons as a sole carbon and energy source have been found confined to just a few genera. Here we used stable isotope probing (SIP), a valuable tool to link the phylogeny and function of targeted microbial groups, to investigate hydrocarbon-degrading bacteria in coastal North Carolina sea water (Beaufort Inlet, USA) with uniformly labeled [13C]n-hexadecane. The dominant sequences in clone libraries constructed from 13C-enriched bacterial DNA (from n-hexadecane enrichments) were identified to belong to the genus Alcanivorax, with ≤98% sequence identity to the closest type strain—thus representing a putative novel phylogenetic taxon within this genus. Unexpectedly, we also identified 13C-enriched sequences in heavy DNA fractions that were affiliated to the genus Methylophaga. This is a contentious group since, though some of its members have been proposed to degrade hydrocarbons, substantive evidence has not previously confirmed this. We used quantitative PCR primers targeting the 16S rRNA gene of the SIP-identified Alcanivorax and Methylophaga to determine their abundance in incubations amended with unlabeled n-hexadecane. Both showed substantial increases in gene copy number during the experiments. Subsequently, we isolated a strain representing the SIP-identified Methylophaga sequences (99.9% 16S rRNA gene sequence identity) and used it to show, for the first time, direct evidence of hydrocarbon degradation by a cultured Methylophaga sp. This study demonstrates the value of coupling SIP with cultivation methods to identify and expand on the known diversity of hydrocarbon-degrading bacteria in the marine environment. PMID:24578702

Critical differences between elective and emergency surgery: identifying domains for quality improvement in emergency general surgery.

PubMed

Columbus, Alexandra B; Morris, Megan A; Lilley, Elizabeth J; Harlow, Alyssa F; Haider, Adil H; Salim, Ali; Havens, Joaquim M

2018-04-01

The objective of our study was to characterize providers' impressions of factors contributing to disproportionate rates of morbidity and mortality in emergency general surgery to identify targets for care quality improvement. Emergency general surgery is characterized by a high-cost burden and disproportionate morbidity and mortality. Factors contributing to these observed disparities are not comprehensively understood and targets for quality improvement have not been formally developed. Using a grounded theory approach, emergency general surgery providers were recruited through purposive-criterion-based sampling to participate in semi-structured interviews and focus groups. Participants were asked to identify contributors to emergency general surgery outcomes, to define effective care for EGS patients, and to describe operating room team structure. Interviews were performed to thematic saturation. Transcripts were iteratively coded and analyzed within and across cases to identify emergent themes. Member checking was performed to establish credibility of the findings. A total of 40 participants from 5 academic hospitals participated in either individual interviews (n = 25 [9 anesthesia, 12 surgery, 4 nursing]) or focus groups (n = 2 [15 nursing]). Emergency general surgery was characterized by an exceptionally high level of variability, which can be subcategorized as patient-variability (acute physiology and comorbidities) and system-variability (operating room resources and workforce). Multidisciplinary communication is identified as a modifier to variability in emergency general surgery; however, nursing is often left out of early communication exchanges. Critical variability in emergency general surgery may impact outcomes. Patient-variability and system-variability, with focus on multidisciplinary communication, represent potential domains for quality improvement in this field. Copyright © 2017 Elsevier Inc. All rights reserved.

Social media use and HIV transmission risk behavior among ethnically diverse HIV-positive gay men: results of an online study in three U.S. states.

PubMed

Hirshfield, Sabina; Grov, Christian; Parsons, Jeffrey T; Anderson, Ian; Chiasson, Mary Ann

2015-10-01

Though Black and Hispanic men who have sex with men (MSM) are at an increased risk for HIV, few HIV risk reduction interventions that target HIV-positive MSM, and even fewer that use technology, have been designed to target these groups. Despite similar rates of social media and technology use across racial/ethnic groups, online engagement of minority MSM for HIV prevention efforts is low. Since minority MSM tend to have less representation in online HIV prevention studies, the goals of this online anonymous study of HIV-positive gay-identified men were to test the feasibility of conducting targeted recruitment by race/ethnicity and sexual orientation, to assess technology and social media use, and to assess global HIV transmission risk. In 2011, an anonymous online survey was conducted among 463 members of an HIV-positive personals website. Emails were sent to a subset of HIV-positive male members who self-identified as gay. While 57 % were White, substantial proportions of participants were Black (20 %) or Hispanic (18 %). Median age was 46 (range 18-79). Men who reported using 3 or more websites or apps to meet sex partners were significantly more likely to report anal intercourse (AOR 4.43, p < .001) and condomless anal sex (CAS) (AOR 2.70, p < .05) in the past 3 months. The only predictor of CAS with HIV-negative or unknown status partners was being under age 30 (AOR 3.38, p < .01). This study helped to inform online targeted recruitment techniques, access to technology and social media use, and sexual risk among a diverse sample of HIV-positive gay men. Efficacy trials of technology-based HIV prevention interventions targeting high-risk minority HIV-positive MSM are warranted.

Management of inherited thrombophilia in pregnancy

PubMed Central

Ormesher, Laura; Simcox, Louise; Tower, Clare; Greer, Ian A

2016-01-01

Adverse pregnancy outcomes, such as pregnancy loss and pre-eclampsia, are associated with thrombotic mechanisms and thrombophilia. Antithrombotic interventions, particularly low-molecular-weight heparin, have been investigated in women identified by previous pregnancy outcome; however, the results have been inconsistent. This may reflect heterogeneity of both the study groups and the disease processes resulting in inadequate stratification to guide antithrombotic interventions. Furthermore, the variation in gestation at initiation of low-molecular-weight heparin treatment might be important. Despite limited evidence of efficacy, low-molecular-weight heparin is often used in an attempt to prevent these complications, owing to the lack of other effective treatments and its perceived safety in pregnancy. Research is required to better understand the disease processes, identify possible biomarkers and thereby more homogeneous groups for targeted treatment. PMID:27638899

An investigation of the psychological characteristics of stalkers: empathy, problem-solving, attachment and borderline personality features.

PubMed

Lewis, S F; Fremouw, W J; Del Ben, K; Farr, C

2001-01-01

This study examined the psychological characteristics of a sample of self-reported stalkers in comparison with a control group, on measures of empathy, problem-solving skills, attachment, and borderline personality features. Stalkers were identified by their endorsement of specific behavioral items, consistent with a widely adopted definition of stalking, denoting behaviors that: (a) are repeatedly directed toward an identified target; (b) are intrusive and unwanted; and (c) evoke fear in the victim. Stalkers scored significantly higher than controls on measures of insecure attachment and borderline personality features, suggesting that the stalking group demonstrates a general pattern of inadequate interpersonal attachment, has limited abilities to form and maintain appropriate relationships, is emotionally labile and unstable, and experiences ambivalence regarding their interpersonal relationships. Treatment implications are discussed herein.

Effects of intensive glucose lowering in type 2 diabetes.

PubMed

Gerstein, Hertzel C; Miller, Michael E; Byington, Robert P; Goff, David C; Bigger, J Thomas; Buse, John B; Cushman, William C; Genuth, Saul; Ismail-Beigi, Faramarz; Grimm, Richard H; Probstfield, Jeffrey L; Simons-Morton, Denise G; Friedewald, William T

2008-06-12

Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.) 2008 Massachusetts Medical Society

Effects of Intensive Glucose Lowering in Type 2 Diabetes

PubMed Central

2015-01-01

Background Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Methods In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. Results At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P = 0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). Conclusions As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.) PMID:18539917

Expression of cancer-associated simple mucin-type O-glycosylated antigens in parasites.

PubMed

Osinaga, Eduardo

2007-01-01

Simple mucin-type O-glycan structures, such as Tn, TF, sialyl-Tn and Tk antigens, are among of the most specific human cancer-associated structures. These antigens are involved in several types of receptor-ligand interactions, and they are potential targets for immunotherapy. In the last few years several simple mucin-type O-glycan antigens were identified in different species belonging to the main two helminth parasite phyla, and sialyl-Tn bearing glycoproteins were detected in Trypanosoma cruzi. These results are of interest to understand new aspects in parasite glycoimmunology and may help identify new biological characteristics of parasites as well of the host-parasite relationship. Considering that different groups reported a negative correlation between certain parasite infections and cancer development, we could hypothesize that simple mucin-type O-glycosylated antigens obtained from parasites could be good potential targets for cancer immunotherapy.

Application of the Athlete's Performance Passport for Doping Control: A Case Report.

PubMed

Iljukov, Sergei; Bermon, Stephane; Schumacher, Yorck O

2018-01-01

The efficient use of testing resources is a key issue in the fight against doping. The longitudinal tracking of sporting performances to identify unusual improvements possibly caused by doping, so-called "athlete's performance passport" (APP) is a new concept to improve targeted anti-doping testing. In fact, unusual performances by an athlete would trigger a more thorough testing program. In the present case report, performance data is modeled using the critical power concept for a group of athletes based on their past performances. By these means, an athlete with unusual deviations from his predicted performances was identified. Subsequent target testing using blood testing and the athlete biological passport resulted in an anti-doping rule violation procedure and suspension of the athlete. This case demonstrates the feasibility of the APP approach where athlete's performance is monitored and might serve as an example for the practical implementation of the method.

Application of the Athlete's Performance Passport for Doping Control: A Case Report

PubMed Central

Iljukov, Sergei; Bermon, Stephane; Schumacher, Yorck O.

2018-01-01

The efficient use of testing resources is a key issue in the fight against doping. The longitudinal tracking of sporting performances to identify unusual improvements possibly caused by doping, so-called “athlete's performance passport” (APP) is a new concept to improve targeted anti-doping testing. In fact, unusual performances by an athlete would trigger a more thorough testing program. In the present case report, performance data is modeled using the critical power concept for a group of athletes based on their past performances. By these means, an athlete with unusual deviations from his predicted performances was identified. Subsequent target testing using blood testing and the athlete biological passport resulted in an anti-doping rule violation procedure and suspension of the athlete. This case demonstrates the feasibility of the APP approach where athlete's performance is monitored and might serve as an example for the practical implementation of the method. PMID:29651247

Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation.

PubMed

Webhofer, C; Gormanns, P; Tolstikov, V; Zieglgänsberger, W; Sillaber, I; Holsboer, F; Turck, C W

2011-12-13

Currently used antidepressants elevate monoamine levels in the synaptic cleft. There is good reason to assume that this is not the only source for antidepressant therapeutic activities and that secondary downstream effects may be relevant for alleviating symptoms of depression. We attempted to elucidate affected biochemical pathways downstream of monoamine reuptake inhibition by interrogating metabolomic profiles in DBA/2Ola mice after chronic paroxetine treatment. Metabolomic changes were investigated using gas chromatography-mass spectrometry profiling and group differences were analyzed by univariate and multivariate statistics. Pathways affected by antidepressant treatment were related to energy metabolism, amino acid metabolism and hormone signaling. The identified pathways reveal further antidepressant therapeutic action and represent targets for drug development efforts. A comparison of the central nervous system with blood plasma metabolite alterations identified GABA, galactose-6-phosphate and leucine as biomarker candidates for assessment of antidepressant treatment effects in the periphery.

Monitoring Neural Activity with Bioluminescence during Natural Behavior

PubMed Central

Naumann, Eva A.; Kampff, Adam R.; Prober, David A.; Schier, Alexander F.; Engert, Florian

2010-01-01

Existing techniques for monitoring neural activity in awake, freely behaving vertebrates are invasive and difficult to target to genetically identified neurons. Here we describe the use of bioluminescence to non-invasively monitor the activity of genetically specified neurons in freely behaving zebrafish. Transgenic fish expressing the Ca2+-sensitive photoprotein GFP-apoAequorin (GA) in most neurons generated large and fast bioluminescent signals related to neural activity, neuroluminescence, that could be recorded continuously for many days. To test the limits of this technique, GA was specifically targeted to the hypocretin-positive neurons of the hypothalamus. We found that neuroluminescence generated by this group of ~20 neurons was associated with periods of increased locomotor activity and identified two classes of neural activity corresponding to distinct swim latencies. Thus, our neuroluminescence assay can report, with high temporal resolution and sensitivity, the activity of small subsets of neurons during unrestrained behavior. PMID:20305645

Compensatory strategies during manual wheelchair propulsion in response to weakness in individual muscle groups: A simulation study.

PubMed

Slowik, Jonathan S; McNitt-Gray, Jill L; Requejo, Philip S; Mulroy, Sara J; Neptune, Richard R

2016-03-01

The considerable physical demand placed on the upper extremity during manual wheelchair propulsion is distributed among individual muscles. The strategy used to distribute the workload is likely influenced by the relative force-generating capacities of individual muscles, and some strategies may be associated with a higher injury risk than others. The objective of this study was to use forward dynamics simulations of manual wheelchair propulsion to identify compensatory strategies that can be used to overcome weakness in individual muscle groups and identify specific strategies that may increase injury risk. Identifying these strategies can provide rationale for the design of targeted rehabilitation programs aimed at preventing the development of pain and injury in manual wheelchair users. Muscle-actuated forward dynamics simulations of manual wheelchair propulsion were analyzed to identify compensatory strategies in response to individual muscle group weakness using individual muscle mechanical power and stress as measures of upper extremity demand. The simulation analyses found the upper extremity to be robust to weakness in any single muscle group as the remaining groups were able to compensate and restore normal propulsion mechanics. The rotator cuff muscles experienced relatively high muscle stress levels and exhibited compensatory relationships with the deltoid muscles. These results underline the importance of strengthening the rotator cuff muscles and supporting muscles whose contributions do not increase the potential for impingement (i.e., the thoracohumeral depressors) and minimize the risk of upper extremity injury in manual wheelchair users. Copyright © 2016 Elsevier Ltd. All rights reserved.

Compensatory Strategies during Manual Wheelchair Propulsion in Response to Weakness in Individual Muscle Groups: A Simulation Study

PubMed Central

Slowik, Jonathan S.; McNitt-Gray, Jill L.; Requejo, Philip S.; Mulroy, Sara J.; Neptune, Richard R.

2016-01-01

Background The considerable physical demand placed on the upper extremity during manual wheelchair propulsion is distributed among the individual muscles. The strategy used to distribute the workload is likely influenced by the relative force-generating capacities of individual muscles, and some strategies may be associated with a higher injury risk than others. The objective of this study was to use forward dynamics simulations of manual wheelchair propulsion to identify compensatory strategies that can be used to overcome weakness in individual muscle groups and identify specific strategies that may increase injury risk. Identifying these strategies can provide rationale for the design of targeted rehabilitation programs aimed at preventing the development of pain and injury in manual wheelchair users. Methods Muscle-actuated forward dynamics simulations of manual wheelchair propulsion were analyzed to identify compensatory strategies in response to individual muscle group weakness, using individual muscle mechanical power and stress as measures of upper extremity demand. Findings The simulation analyses found the upper extremity to be robust to weakness in any single muscle group as the remaining groups were able to compensate and restore normal propulsion mechanics. The rotator cuff muscles experienced relatively high muscle stress levels and exhibited compensatory relationships with the deltoid muscles. Interpretation These results underline the importance of strengthening the rotator cuff muscles and supporting muscles whose contributions do not increase the potential for impingement (i.e., the thoracohumeral depressors) and minimize the risk of upper extremity injury in manual wheelchair users. PMID:26945719

Targeted Ovarian Cancer Education for Hispanic Women: A Pilot Program in Arizona.

PubMed

Schlumbrecht, Matthew; Yarian, Ranay; Salmon, Kristine; Niven, Christine; Singh, Diljeet

2016-06-01

In disadvantaged populations, including Hispanics, there is a deficit in understanding of cancer risk factors, symptoms, prevention, and treatment. The objective of this study was to assess ovarian cancer knowledge in a population of Hispanic women in Arizona, identify deficiencies, and to evaluate the utility of an educational program developed specifically for this community's needs. A de novo questionnaire about ovarian cancer was distributed to Hispanic women enrolled in family literacy programs at Mesa Public Schools. Following this assessment, a video educational program was developed, with emphasis on areas of greatest knowledge deficits, and post-intervention assessment administered. Chi square, Wilcoxon rank sum, and Kruskal-Wallis tests were used for analysis. 167 questionnaires were completed in the pretest group and 102 in the post-intervention group. Between groups, there were no differences in age (p = 0.49), education (p = 0.68), or annual income (p = 0.26). In the pretest group, 45 % of questions were answered correctly versus 84 % in the post-test group (p < 0.01). 24.2 % of the initial respondents correctly identified ovarian cancer symptoms versus 85.6 of post-test respondents (p < 0.01). With the program, there was an increase in the number of correct post-test responses for each question and symptom (p < 0.01), except those about hereditary risk of ovarian cancer (p = 0.62) and pelvic anatomy (p = 0.16). Following identification of an ovarian cancer knowledge deficit in this cohort of Hispanic women, an educational tool targeting specific deficiencies successfully increased cancer knowledge and awareness of symptoms. Similar efforts in this and other minority populations should be continued.

Web-Based Communication Strategies Designed to Improve Intention to Minimize Risk for Colorectal Cancer: Randomized Controlled Trial

PubMed Central

Flight, Ingrid; Zajac, Ian T; Turnbull, Deborah; Young, Graeme P; Olver, Ian

2018-01-01

Background People seek information on the Web for managing their colorectal cancer (CRC) risk but retrieve much personally irrelevant material. Targeting information pertinent to this cohort via a frequently asked question (FAQ) format could improve outcomes. Objective We identified and prioritized colorectal cancer information for men and women aged 35 to 74 years (study 1) and built a website containing FAQs ordered by age and gender. In study 2, we conducted a randomized controlled trial (RCT) to test whether targeted FAQs were more influential on intention to act on CRC risk than the same information accessed via a generic topic list. Secondary analyses compared preference for information delivery, usability, relevance, and likelihood of recommendation of FAQ and LIST websites. Methods Study 1 determined the colorectal cancer information needs of Australians (N=600) by sex and age group (35-49, 50-59, 60-74) through a Web-based survey. Free-text responses were categorized as FAQs: the top 5 issues within each of the 6 cohorts were identified. Study 2 (N=240) compared the impact of presentation as targeted FAQ links to information with links presented as a generic list (LIST) and a CONTROL (no information) condition. We also tested preference for presentation of access to information as FAQ or LIST by adding a CHOICE condition (a self-selected choice of FAQs or a list of information topics). Results Study 1 showed considerable consistency in information priorities among all 6 cohorts with 2 main concerns: treatment of CRC and risk factors. Some differences included a focus on general risk factors, excluding diet and lifestyle, in the younger cohort, and on the existence of a test for CRC in the older cohorts. Study 2 demonstrated that, although respondents preferred information access ordered by FAQs over a list, presentation in this format had limited impact on readiness to act on colorectal cancer risk compared with the list or a no-information control (P=.06). Both FAQ and LIST were evaluated as equally usable. Those aged 35 to 49 years rated the information less relevant to them and others in their age group, and information ordered by FAQs was rated, across all age groups and both sexes, as less relevant to people outside the age group targeted within the FAQs. Conclusions FAQs are preferred over a list as a strategy for presenting access to information about CRC. They may improve intention to act on risk, although further research is required. Future research should aim to identify better the characteristics of information content and presentation that optimize perceived relevance and fully engage the target audience. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12618000137291; https://www.anzctr.org. au/Trial/Registration/TrialReview.aspx?id=374129 (Archived by WebCite at http://www.webcitation.org/6x2Mr6rPC) PMID:29434013

The impact of nurse-driven targeted HIV screening in 8 emergency departments: study protocol for the DICI-VIH cluster-randomized two-period crossover trial.

PubMed

Leblanc, Judith; Rousseau, Alexandra; Hejblum, Gilles; Durand-Zaleski, Isabelle; de Truchis, Pierre; Lert, France; Costagliola, Dominique; Simon, Tabassome; Crémieux, Anne-Claude

2016-02-01

In 2010, to reduce late HIV diagnosis, the French national health agency endorsed non-targeted HIV screening in health care settings. Despite these recommendations, non-targeted screening has not been implemented and only physician-directed diagnostic testing is currently performed. A survey conducted in 2010 in 29 French Emergency Departments (EDs) showed that non-targeted nurse-driven screening was feasible though only a few new HIV diagnoses were identified, predominantly among high-risk groups. A strategy targeting high-risk groups combined with current practice could be shown to be feasible, more efficient and cost-effective than current practice alone. DICI-VIH (acronym for nurse-driven targeted HIV screening) is a multicentre, cluster-randomized, two-period crossover trial. The primary objective is to compare the effectiveness of 2 strategies for diagnosing HIV among adult patients visiting EDs: nurse-driven targeted HIV screening combined with current practice (physician-directed diagnostic testing) versus current practice alone. Main secondary objectives are to compare access to specialist consultation and how early HIV diagnosis occurs in the course of the disease between the 2 groups, and to evaluate the implementation, acceptability and cost-effectiveness of nurse-driven targeted screening. The 2 strategies take place during 2 randomly assigned periods in 8 EDs of metropolitan Paris, where 42 % of France's new HIV patients are diagnosed every year. All patients aged 18 to 64, not presenting secondary to HIV exposure are included. During the intervention period, patients are invited to fill a 7-item questionnaire (country of birth, sexual partners and injection drug use) in order to select individuals who are offered a rapid test. If the rapid test is reactive, a follow-up visit with an infectious disease specialist is scheduled within 72 h. Assuming an 80 % statistical power and a 5 % type 1 error, with 1.04 and 3.38 new diagnoses per 10,000 patients in the control and targeted groups respectively, a sample size of 140,000 patients was estimated corresponding to 8,750 patients per ED and per period. Inclusions started in June 2014. Results are expected by mid-2016. The DICI-VIH study is the first large randomized controlled trial designed to assess nurse-driven targeted HIV screening. This study can provide valuable information on HIV screening in health care settings. ClinicalTrials.gov: NCT02127424 (29 April 2014).

A new disaster victim identification management strategy targeting "near identification-threshold" cases: Experiences from the Boxing Day tsunami.

PubMed

Wright, Kirsty; Mundorff, Amy; Chaseling, Janet; Forrest, Alexander; Maguire, Christopher; Crane, Denis I

2015-05-01

The international disaster victim identification (DVI) response to the Boxing Day tsunami, led by the Royal Thai Police in Phuket, Thailand, was one of the largest and most complex in DVI history. Referred to as the Thai Tsunami Victim Identification operation, the group comprised a multi-national, multi-agency, and multi-disciplinary team. The traditional DVI approach proved successful in identifying a large number of victims quickly. However, the team struggled to identify certain victims due to incomplete or poor quality ante-mortem and post-mortem data. In response to these challenges, a new 'near-threshold' DVI management strategy was implemented to target presumptive identifications and improve operational efficiency. The strategy was implemented by the DNA Team, therefore DNA kinship matches that just failed to reach the reporting threshold of 99.9% were prioritized, however the same approach could be taken by targeting, for example, cases with partial fingerprint matches. The presumptive DNA identifications were progressively filtered through the Investigation, Dental and Fingerprint Teams to add additional information necessary to either strengthen or conclusively exclude the identification. Over a five-month period 111 victims from ten countries were identified using this targeted approach. The new identifications comprised 87 adults, 24 children and included 97 Thai locals. New data from the Fingerprint Team established nearly 60% of the total near-threshold identifications and the combined DNA/Physical method was responsible for over 30%. Implementing the new strategy, targeting near-threshold cases, had positive management implications. The process initiated additional ante-mortem information collections, and established a much-needed, distinct "end-point" for unresolved cases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

CRISPR Genome-Wide Screening Identifies Dependence on the Proteasome Subunit PSMC6 for Bortezomib Sensitivity in Multiple Myeloma.

PubMed

Shi, Chang-Xin; Kortüm, K Martin; Zhu, Yuan Xiao; Bruins, Laura A; Jedlowski, Patrick; Votruba, Patrick G; Luo, Moulun; Stewart, Robert A; Ahmann, Jonathan; Braggio, Esteban; Stewart, A Keith

2017-12-01

Bortezomib is highly effective in the treatment of multiple myeloma; however, emergent drug resistance is common. Consequently, we employed CRISPR targeting 19,052 human genes to identify unbiased targets that contribute to bortezomib resistance. Specifically, we engineered an RPMI8226 multiple myeloma cell line to express Cas9 infected by lentiviral vector CRISPR library and cultured derived cells in doses of bortezomib lethal to parental cells. Sequencing was performed on surviving cells to identify inactivated genes responsible for drug resistance. From two independent whole-genome screens, we selected 31 candidate genes and constructed a second CRISPR sgRNA library, specifically targeting each of these 31 genes with four sgRNAs. After secondary screening for bortezomib resistance, the top 20 "resistance" genes were selected for individual validation. Of these 20 targets, the proteasome regulatory subunit PSMC6 was the only gene validated to reproducibly confer bortezomib resistance. We confirmed that inhibition of chymotrypsin-like proteasome activity by bortezomib was significantly reduced in cells lacking PSMC6. We individually investigated other members of the PSMC group (PSMC1 to 5) and found that deficiency in each of those subunits also imparts bortezomib resistance. We found 36 mutations in 19S proteasome subunits out of 895 patients in the IA10 release of the CoMMpass study (https://themmrf.org). Our findings demonstrate that the PSMC6 subunit is the most prominent target required for bortezomib sensitivity in multiple myeloma cells and should be examined in drug-refractory populations. Mol Cancer Ther; 16(12); 2862-70. ©2017 AACR . ©2017 American Association for Cancer Research.

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.

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.

A Public Health Model for the Molecular Surveillance of HIV Transmission in San Diego, California

PubMed Central

May, Susanne; Tweeten, Samantha; Drumright, Lydia; Pacold, Mary E.; Kosakovsky Pond, Sergei L.; Pesano, Rick L.; Lie, Yolanda S.; Richman, Douglas D.; Frost, Simon D.W.; Woelk, Christopher H.; Little, Susan J.

2009-01-01

Background Current public health efforts often use molecular technologies to identify and contain communicable disease networks, but not for HIV. Here, we investigate how molecular epidemiology can be used to identify highly-related HIV networks within a population and how voluntary contact tracing of sexual partners can be used to selectively target these networks. Methods We evaluated the use of HIV-1 pol sequences obtained from participants of a community-recruited cohort (n=268) and a primary infection research cohort (n=369) to define highly related transmission clusters and the use of contact tracing to link other individuals (n=36) within these clusters. The presence of transmitted drug resistance was interpreted from the pol sequences (Calibrated Population Resistance v3.0). Results Phylogenetic clustering was conservatively defined when the genetic distance between any two pol sequences was <1%, which identified 34 distinct transmission clusters within the combined community-recruited and primary infection research cohorts containing 160 individuals. Although sequences from the epidemiologically-linked partners represented approximately 5% of the total sequences, they clustered with 60% of the sequences that clustered from the combined cohorts (O.R. 21.7; p=<0.01). Major resistance to at least one class of antiretroviral medication was found in 19% of clustering sequences. Conclusions Phylogenetic methods can be used to identify individuals who are within highly related transmission groups, and contact tracing of epidemiologically-linked partners of recently infected individuals can be used to link into previously-defined transmission groups. These methods could be used to implement selectively targeted prevention interventions. PMID:19098493

Transcriptome profiling of equine vitamin E deficient neuroaxonal dystrophy identifies upregulation of liver X receptor target genes

PubMed Central

Finno, Carrie J.; Bordbari, Matthew H.; Valberg, Stephanie J.; Lee, David; Herron, Josi; Hines, Kelly; Monsour, Tamer; Scott, Erica; Bannasch, Danika L.; Mickelson, James; Xu, Libin

2016-01-01

Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord. Differential gene expression analysis identified 157 significantly (FDR<0.05) dysregulated transcripts within the spinal cord of eNAD-affected horses. Statistical enrichment analysis identified significant downregulation of the ionotropic and metabotropic group III glutamate receptor, synaptic vesicle trafficking and cholesterol biosynthesis pathways. Gene co-expression analysis identified one module of upregulated genes significantly associated with the eNAD phenotype that included the liver X receptor (LXR) targets CYP7A1, APOE, PLTP and ABCA1. Validation of CYP7A1 and APOE dysregulation was performed in an independent biologic group and CYP7A1 was found to be additionally upregulated in the medulla oblongata of eNAD horses. Evidence of LXR activation supports a role for modulation of oxysterol-dependent LXR transcription factor activity by tocopherols. We hypothesize that the protective role of α-TOH in eNAD may reside in its ability to prevent oxysterol accumulation and subsequent activation of the LXR in order to decrease lipid peroxidation associated neurodegeneration. PMID:27751910

In-situ Click Reaction Coupled with Quantitative Proteomics for Identifying Protein Targets of Catechol Estrogens.

PubMed

Liang, Huei-Chen; Liu, Yi-Chen; Chen, Hsin; Ku, Ming Chun; Do, Quynh-Trang; Wang, Chih-Yen; Tzeng, Shun-Fen; Chen, Shu-Hui

2018-06-13

Catechol estrogens (CEs) are metabolic electrophiles that actively undergo covalent interaction with cellular proteins, influencing molecular function. There is no feasible method to identify their binders in a living system. Herein, we developed a click chemistry-based approach using ethinylestradiol (EE2) as the precursor probe coupled with quantitative proteomics to identify protein targets of CEs and classify their binding strengths. Using in-situ metabolic conversion and click reaction in liver microsomes, CEs-protein complex was captured by the probe, digested by trypsin, stable isotope labeled via reductive amination, and analyzed by liquid chromatography-mass spectrometry (LC-MS). A total of 334 liver proteins were repeatedly identified (n  2); 274 identified proteins were classified as strong binders based on precursor mass mapping. The binding strength was further scaled by D/H ratio (activity probe/solvent): 259 strong binders had D/H > 5.25; 46 weak binders had 5.25 > D/H > 1; 5 non-specific binders (keratins) had D/H < 1. These results were confirmed using spiked covalent control (strong binder) and noncovalent control (weak binder), as well as in vitro testing of cytochrome c (D/H = 5.9) which showed covalent conjugation with CEs. Many identified strong binders, such as glutathione transferase, catechol-O-methyl transferase, superoxide dismutase, catalase, glutathione peroxidase, and cytochrome c, are involved in cellular redox processes or detoxification activities. CE conjugation was shown to suppress the superoxide oxidase activity of cytochrome c, suggesting that CEs modification may alter the redox action of cellular proteins. Due to structural similarity and inert alkyne group, EE2 probe is very likely to capture protein targets of CEs in general. Thus, this strategy can be adopted to explore the biological impact of CEs modification in living systems.

Smoking Patterns and Their Relationship to Drinking Among First-Year College Students

PubMed Central

2014-01-01

Introduction: Unlike older smokers, young adult smokers frequently engage in light and intermittent smoking. It remains unclear how stable such smoking patterns are over time, as substantial variability exists between these smokers. This study identified subgroups of college student smokers based on the trajectory of their smoking frequency during the first year of college, thereby examining stability versus instability over time. We then tested if the interplay between drinking and smoking differed in the identified groups to determine the relative role drinking may play in intermittent versus more regular smoking. Methods: Incoming college students at 3 institutions completed online biweekly surveys of their daily substance use throughout the first year of college. Students who reported smoking at least 1 cigarette during this year (n = 266) were included in analyses (70% female, 74% White). Results: Group-based trajectory modeling identified 5 groups of smokers, 3 of which maintained their smoking frequency throughout the year (77%), and 2 groups of infrequent smokers showed significant trends (11% increasing, 12% decreasing). Notably, nondaily smoking was maintained at different specific frequencies (e.g., 1 vs. 3 days per week). Identified groups differed in the relationship between drinking and smoking, where cooccurrence was particularly strong among infrequent smokers, and trends in smoking quantity differed between groups. Conclusions: While there was a diversity of smoking patterns in the sample, patterns of intermittent smoking remain relatively stable for a majority of students throughout the year. Intervention messages targeting drinking and smoking should be tailored on the basis of smoking frequency. PMID:24415586

Polymorphism discovery and allele frequency estimation using high-throughput DNA sequencing of target-enriched pooled DNA samples

PubMed Central

2012-01-01

Background The central role of the somatotrophic axis in animal post-natal growth, development and fertility is well established. Therefore, the identification of genetic variants affecting quantitative traits within this axis is an attractive goal. However, large sample numbers are a pre-requisite for the identification of genetic variants underlying complex traits and although technologies are improving rapidly, high-throughput sequencing of large numbers of complete individual genomes remains prohibitively expensive. Therefore using a pooled DNA approach coupled with target enrichment and high-throughput sequencing, the aim of this study was to identify polymorphisms and estimate allele frequency differences across 83 candidate genes of the somatotrophic axis, in 150 Holstein-Friesian dairy bulls divided into two groups divergent for genetic merit for fertility. Results In total, 4,135 SNPs and 893 indels were identified during the resequencing of the 83 candidate genes. Nineteen percent (n = 952) of variants were located within 5' and 3' UTRs. Seventy-two percent (n = 3,612) were intronic and 9% (n = 464) were exonic, including 65 indels and 236 SNPs resulting in non-synonymous substitutions (NSS). Significant (P < 0.01) mean allele frequency differentials between the low and high fertility groups were observed for 720 SNPs (58 NSS). Allele frequencies for 43 of the SNPs were also determined by genotyping the 150 individual animals (Sequenom® MassARRAY). No significant differences (P > 0.1) were observed between the two methods for any of the 43 SNPs across both pools (i.e., 86 tests in total). Conclusions The results of the current study support previous findings of the use of DNA sample pooling and high-throughput sequencing as a viable strategy for polymorphism discovery and allele frequency estimation. Using this approach we have characterised the genetic variation within genes of the somatotrophic axis and related pathways, central to mammalian post-natal growth and development and subsequent lactogenesis and fertility. We have identified a large number of variants segregating at significantly different frequencies between cattle groups divergent for calving interval plausibly harbouring causative variants contributing to heritable variation. To our knowledge, this is the first report describing sequencing of targeted genomic regions in any livestock species using groups with divergent phenotypes for an economically important trait. PMID:22235840

Jejunal long noncoding RNAs are associated with glycemic control via gut-brain axis after bariatric surgery in diabetic mice.

PubMed

Liang, Yongjun; Yu, Bo; Wang, Yueqian; Qiao, Zhengdong; Cao, Ting; Zhang, Peng

2018-06-01

Metabolic and bariatric surgery is effective in ameliorating type 2 diabetes, although its underlying mechanisms are largely unknown. Our previous study indicated that the distinctly expressed duodenal long noncoding RNAs (lncRNAs) induced by the duodenal-jejunal bypass (DJB) might play a role in improving glycemic control via the enteropancreatic axis. Therefore, the physiologic role of the jejunum in metabolic regulation after DJB requires investigation. To investigate the alterations in the jejunal Roux limb lncRNA expression signatures after DJB and analyze the functional pathways associated with metabolic improvement on a genome-wide scale in high-fat diet-induced diabetic mice. University medical center. Diabetic mice induced by high-fat diet were randomly assigned into 2 groups undergoing either DJB or sham surgery. The lncRNA and messenger (m)RNA expression profiles of the Roux limb segment of the jejunum in both groups were investigated using microarray. To identify the functional characteristics of the distinctly expressed lncRNAs, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted. The lncRNA-mRNA and lncRNA-transcription factor interaction networks were constructed based on Pearson correlation analysis. Compared with the sham group, 827 dysregulated (fold change ≥2.0) jejunal lncRNAs were identified in the DJB group. Both Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology enrichment analysis revealed that 601 lncRNA-co-expressed mRNAs (fold change ≥2.0) were associated with neuromodulation-related pathways or biological processes, including serotonergic, glutamatergic, and dopaminergic synapses. In addition, hormonal regulation-related pathways, especially steroid biosynthesis, were also enriched. The results were further confirmed by bioinformatic analysis of target genes or transcription factors predicted on the basis of dysregulated jejunal lncRNAs. Furthermore, the NONMMUT023781 lncRNA may simultaneously target the Adcy8 mRNA both in cis and in trans and participate in neuromodulation and hormonal regulation. Alterations of jejunal Roux limb lncRNA and mRNA expression profiles trigger both neuromodulation and endocrine-related pathways, which play a critical role in type 2 diabetes remission after metabolic and bariatric surgery via the gut-brain axis. NONMMTU023781 and Adcy8 were identified as potential targets, which warrant further research. Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Have adults lost their sense of play? An observational study of the social dynamics of physical (in)activity in German and Hawaiian leisure settings.

PubMed

Thiel, Ansgar; Thedinga, Hendrik K; Thomas, Samantha L; Barkhoff, Harald; Giel, Katrin E; Schweizer, Olesia; Thiel, Syra; Zipfel, Stephan

2016-08-02

Physical inactivity is one of the biggest health problems nowadays. Recent research shows that socio-cultural barriers to physical activity are mostly related to modern lifestyles. However, there is a lack of research on how social and group dynamics influence engagement in physical activity. Furthermore, there are few cross-cultural studies that have compared the social dynamics of (in)activity in different cultural settings. This paper therefore aims to analyse how social group dynamics influence physical activity and inactivity in informal social environments and whether physical activity is influenced by the socio-cultural settings. The paper presents the qualitative data collected within a covert participant observation study. Data was collected by keeping observational notes in order to record typical, regular patterns regarding physical (in)activity related behaviour of groups at an artificial open air swimming pool in Germany and a natural pond in Hawai'i. The data collection period was eight and a half months. Data was interpreted based on constant comparative analysis in order to identify most generative patterns in the field notes. Group structures appear to play a significant role regarding the activity of the group members. In this study, we identified four key factors that influence group based physical activity: 1) Physical activity seems to be a group disturbing behaviour particularly in larger groups of adults; 2) Physical activity appears to be more functional and less joyful in adults than in children; 3) Group activity is influenced by (in)activity anchors, including 'domestication' of a group's site, obesity, and controlling parents. 4) Physical activity is to a certain extent socially contagious, particularly with regard to playful activities. Successful promotion of physical activity should target the social structures of inactive individuals' groups. In this regard, one of the main problems is that fun and wellbeing, as very important targets of public health strategies for the adult population, appear not to be compatible with physical activity. Developing strategies to reframe physical activity rather as 'fun' and less as functional may be one way to engage inactive individuals in physical activity in leisure settings.

Formative assessment in the development of an obesity prevention component for the expanded food and nutrition education program in Texas.

PubMed

Thompson, Debbe; Cullen, Karen Weber; Reed, Debra B; Konzelmann, Karen; Smalling, Aggie Lara

2011-01-01

This study conducted formative research (surveys, focus groups) to assess the nutrition education needs of clients in the Texas Expanded Food and Nutrition Education Program prior to curriculum revision. Participants were current Expanded Food and Nutrition Education Program participants in 3 Texas cities (Austin, Houston, San Antonio). Data were used to tailor the curriculum to the target population. This research provides evidence that members of the target audience can provide valuable insights into a particular topic. Formative work prior to intervention development should be conducted to identify key issues regarding a particular topic and to evaluate potential educational approaches.

Ligand-directed profiling of organelles with internalizing phage libraries

PubMed Central

Dobroff, Andrey S.; Rangel, Roberto; Guzman-Roja, Liliana; Salmeron, Carolina C.; Gelovani, Juri G.; Sidman, Richard L.; Bologa, Cristian G.; Oprea, Tudor I.; Brinker, C. Jeffrey; Pasqualini, Renata; Arap, Wadih

2015-01-01

Phage display is a resourceful tool to, in an unbiased manner, discover and characterize functional protein-protein interactions, to create vaccines, and to engineer peptides, antibodies, and other proteins as targeted diagnostic and/or therapeutic agents. Recently, our group has developed a new class of internalizing phage (iPhage) for ligand-directed targeting of organelles and/or to identify molecular pathways within live cells. This unique technology is suitable for applications ranging from fundamental cell biology to drug development. Here we describe the method for generating and screening the iPhage display system, and explain how to select and validate candidate internalizing homing peptide. PMID:25640897

Interaction of multiple networks modulated by the working memory training based on real-time fMRI

NASA Astrophysics Data System (ADS)

Shen, Jiahui; Zhang, Gaoyan; Zhu, Chaozhe; Yao, Li; Zhao, Xiaojie

2015-03-01

Neuroimaging studies of working memory training have identified the alteration of brain activity as well as the regional interactions within the functional networks such as central executive network (CEN) and default mode network (DMN). However, how the interaction within and between these multiple networks is modulated by the training remains unclear. In this paper, we examined the interaction of three training-induced brain networks during working memory training based on real-time functional magnetic resonance imaging (rtfMRI). Thirty subjects assigned to the experimental and control group respectively participated in two times training separated by seven days. Three networks including silence network (SN), CEN and DMN were identified by the training data with the calculated function connections within each network. Structural equation modeling (SEM) approach was used to construct the directional connectivity patterns. The results showed that the causal influences from the percent signal changes of target ROI to the SN were positively changed in both two groups, as well as the causal influence from the SN to CEN was positively changed in experimental group but negatively changed in control group from the SN to DMN. Further correlation analysis of the changes in each network with the behavioral improvements showed that the changes in SN were stronger positively correlated with the behavioral improvement of letter memory task. These findings indicated that the SN was not only a switch between the target ROI and the other networks in the feedback training but also an essential factor to the behavioral improvement.

Comparative genomics identification of a novel set of temporally regulated hedgehog target genes in the retina.

PubMed

McNeill, Brian; Perez-Iratxeta, Carol; Mazerolle, Chantal; Furimsky, Marosh; Mishina, Yuji; Andrade-Navarro, Miguel A; Wallace, Valerie A

2012-03-01

The hedgehog (Hh) signaling pathway is involved in numerous developmental and adult processes with many links to cancer. In vertebrates, the activity of the Hh pathway is mediated primarily through three Gli transcription factors (Gli1, 2 and 3) that can serve as transcriptional activators or repressors. The identification of Gli target genes is essential for the understanding of the Hh-mediated processes. We used a comparative genomics approach using the mouse and human genomes to identify 390 genes that contained conserved Gli binding sites. RT-qPCR validation of 46 target genes in E14.5 and P0.5 retinal explants revealed that Hh pathway activation resulted in the modulation of 30 of these targets, 25 of which demonstrated a temporal regulation. Further validation revealed that the expression of Bok, FoxA1, Sox8 and Wnt7a was dependent upon Sonic Hh (Shh) signaling in the retina and their regulation is under positive and negative controls by Gli2 and Gli3, respectively. We also show using chromatin immunoprecipitation that Gli2 binds to the Sox8 promoter, suggesting that Sox8 is an Hh-dependent direct target of Gli2. Finally, we demonstrate that the Hh pathway also modulates the expression of Sox9 and Sox10, which together with Sox8 make up the SoxE group. Previously, it has been shown that Hh and SoxE group genes promote Müller glial cell development in the retina. Our data are consistent with the possibility for a role of SoxE group genes downstream of Hh signaling on Müller cell development. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Discrimination of dementia with Lewy bodies from Alzheimer's disease using voxel-based morphometry of white matter by statistical parametric mapping 8 plus diffeomorphic anatomic registration through exponentiated Lie algebra.

PubMed

Nakatsuka, Tomoya; Imabayashi, Etsuko; Matsuda, Hiroshi; Sakakibara, Ryuji; Inaoka, Tsutomu; Terada, Hitoshi

2013-05-01

The purpose of this study was to identify brain atrophy specific for dementia with Lewy bodies (DLB) and to evaluate the discriminatory performance of this specific atrophy between DLB and Alzheimer's disease (AD). We retrospectively reviewed 60 DLB and 30 AD patients who had undergone 3D T1-weighted MRI. We randomly divided the DLB patients into two equal groups (A and B). First, we obtained a target volume of interest (VOI) for DLB-specific atrophy using correlation analysis of the percentage rate of significant whole white matter (WM) atrophy calculated using the Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) based on statistical parametric mapping 8 (SPM8) plus diffeomorphic anatomic registration through exponentiated Lie algebra, with segmented WM images in group A. We then evaluated the usefulness of this target VOI for discriminating the remaining 30 DLB patients in group B from the 30 AD patients. Z score values in this target VOI obtained from VSRAD were used as the determinant in receiver operating characteristic (ROC) analysis. Specific target VOIs for DLB were determined in the right-side dominant dorsal midbrain, right-side dominant dorsal pons, and bilateral cerebellum. ROC analysis revealed that the target VOI limited to the midbrain exhibited the highest area under the ROC curves of 0.75. DLB patients showed specific atrophy in the midbrain, pons, and cerebellum. Midbrain atrophy demonstrated the highest power for discriminating DLB and AD. This approach may be useful for determining the contributions of DLB and AD pathologies to the dementia syndrome.

Slowing down after a mild traumatic brain injury: a strategy to improve cognitive task performance?

PubMed

Ozen, Lana J; Fernandes, Myra A

2012-01-01

Long-term persistent attention and memory difficulties following a mild traumatic brain injury (TBI) often go undetected on standard neuropsychological tests, despite complaints by mild TBI individuals. We conducted a visual Repetition Detection working memory task to digits, in which we manipulated task difficulty by increasing cognitive load, to identify subtle deficits long after a mild TBI. Twenty-six undergraduate students with a self-report of one mild TBI, which occurred at least 6 months prior, and 31 non-head-injured controls took part in the study. Participants were not informed until study completion that the study's purpose was to examine cognitive changes following a mild TBI, to reduce the influence of "diagnosis threat" on performance. Neuropsychological tasks did not differentiate the groups, though mild TBI participants reported higher state anxiety levels. On our working memory task, the mild TBI group took significantly longer to accurately detect repeated targets on our task, suggesting that slowed information processing is a long-term consequence of mild TBI. Accuracy was comparable in the low-load condition and, unexpectedly, mild TBI performance surpassed that of controls in the high-load condition. Temporal analysis of target identification suggested a strategy difference between groups: mild TBI participants made a significantly greater number of accurate responses following the target's offset, and significantly fewer erroneous distracter responses prior to target onset, compared with controls. Results suggest that long after a mild TBI, high-functioning young adults invoke a strategy of delaying their identification of targets in order to maintain, and facilitate, accuracy on cognitively demanding tasks. © The Author 2011. Published by Oxford University Press. All rights reserved.

Treatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the Femoropopliteal Arteries

PubMed Central

Laird, John R.; Tepe, Gunnar; Brodmann, Marianne; Zeller, Thomas; Scheinert, Dierk; Metzger, Christopher; Micari, Antonio; Sachar, Ravish; Jaff, Michael R.; Wang, Hong; Hasenbank, Melissa S.; Krishnan, Prakash

2018-01-01

Background— Randomized controlled trials have reported favorable 1-year outcomes with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral arterial disease when compared with standard percutaneous transluminal angioplasty (PTA). Evidence remains limited on the durability of the treatment effect with DCBs in the longer term. Methods and Results— IN.PACT SFA is a single-blind, randomized trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 patients with symptomatic (Rutherford 2–4) femoropopliteal lesions up to 18 cm in length. Patients were randomized 2:1 to receive treatment with DCB or PTA. The 36-month assessments included primary patency, freedom from clinically driven target lesion revascularization, major adverse events, and functional outcomes. At 36 months, primary patency remained significantly higher among patients treated with DCB compared with PTA (69.5% versus 45.1%; log rank P<0.001). The rates of clinically driven target lesion revascularization were 15.2% and 31.1% (P=0.002) for the DCB and PTA groups, respectively. Functional outcomes were similarly improved between treatment groups even though subjects in the DCB group required significantly fewer reinterventions versus those in the PTA group (P<0.001 for target lesion revascularization, P=0.001 for target vessel revascularization). There were no device- or procedure-related deaths as adjudicated by an independent Clinical Events Committee. Conclusions— Three-year results demonstrate a durable and superior treatment effect among patients treated with DCB versus standard PTA, with significantly higher primary patency and lower clinically driven target lesion revascularization, resulting in similar functional improvements with reduced need for repeat interventions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01175850 for IN.PACT SFA phase I in the European Union and NCT01566461 for IN.PACT SFA phase II in the United States. PMID:29326153

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors

PubMed Central

Naganathan, Saranga; Grunbeck, Amy; Tian, He; Huber, Thomas; Sakmar, Thomas P.

2013-01-01

To facilitate structural and dynamic studies of G protein-coupled receptor (GPCR) signaling complexes, new approaches are required to introduce informative probes or labels into expressed receptors that do not perturb receptor function. We used amber codon suppression technology to genetically-encode the unnatural amino acid, p-azido-L-phenylalanine (azF) at various targeted positions in GPCRs heterologously expressed in mammalian cells. The versatility of the azido group is illustrated here in different applications to study GPCRs in their native cellular environment or under detergent solubilized conditions. First, we demonstrate a cell-based targeted photocrosslinking technology to identify the residues in the ligand-binding pocket of GPCR where a tritium-labeled small-molecule ligand is crosslinked to a genetically-encoded azido amino acid. We then demonstrate site-specific modification of GPCRs by the bioorthogonal Staudinger-Bertozzi ligation reaction that targets the azido group using phosphine derivatives. We discuss a general strategy for targeted peptide-epitope tagging of expressed membrane proteins in-culture and its detection using a whole-cell-based ELISA approach. Finally, we show that azF-GPCRs can be selectively tagged with fluorescent probes. The methodologies discussed are general, in that they can in principle be applied to any amino acid position in any expressed GPCR to interrogate active signaling complexes. PMID:24056801

Peer Group Self-Identification as a Predictor of Relational and Physical Aggression Among High School Students

PubMed Central

Pokhrel, Pallav; Sussman, Steven; Black, David; Sun, Ping

2011-01-01

BACKGROUND Adolescent peer group self-identification refers to adolescents’ affiliation with reputation-based peer groups such as “Goths” or “Jocks.” These groups tend to vary on normative characteristics, including the group members’ attitudes and behaviors. This article examined whether adolescents’ baseline peer group self-identification predicted their self-reported relational and physical aggression 1 year later. METHODS Self-report data were collected from 1614 students from 9 regular and 9 continuation (alternative) high schools in Southern California, at baseline and 1-year follow-up. Subjects’ mean baseline age was 15.21 years (SD = 1.18) and 51.6% of the subjects were female. RESULTS Findings indicated that compared with self-identified “Regular” or “Normal” students, adolescents who identified with high-risk peer groups (eg, “Druggies,” “Goths”) tended to report higher relational and physical aggression 1 year later, controlling for baseline aggression and demographic variables. In addition, adolescents’ self-identification with high-status peer groups (eg, “Jocks,” “Populars”) was predictive of higher relational aggression 1 year later. Gender and school type (ie, regular vs continuation) were not found to moderate these effects. CONCLUSIONS It appears that peer group self-identification is a salient predictor of physical and relational aggression across gender and school type. Adolescents who identify with high-risk peer groups tend to report higher levels of physical as well as relational aggression in the future. In addition, adolescents who affiliate with elite groups tend to become more relationally aggressive over time. School-based prevention programs targeting aggression may benefit from addressing the impacts of peer group self-identification on adolescents’ aggressive behavior. PMID:20529198

Orbital Monitoring of the AstraLux Large M-dwarf Multiplicity Sample

NASA Astrophysics Data System (ADS)

Janson, Markus; Bergfors, Carolina; Brandner, Wolfgang; Bonnefoy, Mickaël; Schlieder, Joshua; Köhler, Rainer; Hormuth, Felix; Henning, Thomas; Hippler, Stefan

2014-10-01

Orbital monitoring of M-type binaries is essential for constraining their fundamental properties. This is particularly useful in young systems, where the extended pre-main-sequence evolution can allow for precise isochronal dating. Here, we present the continued astrometric monitoring of the more than 200 binaries of the AstraLux Large Multiplicity Survey, building both on our previous work, archival data, and new astrometric data spanning the range of 2010-2012. The sample is very young overall—all included stars have known X-ray emission, and a significant fraction (18%) of them have recently also been identified as members of young moving groups in the solar neighborhood. We identify ~30 targets that both have indications of being young and for which an orbit either has been closed or appears possible to close in a reasonable time frame (a few years to a few decades). One of these cases, GJ 4326, is, however, identified as probably being substantially older than has been implied from its apparent moving group membership, based on astrometric and isochronal arguments. With further astrometric monitoring, these targets will provide a set of empirical isochrones, against which theoretical isochrones can be calibrated, and which can be used to evaluate the precise ages of nearby young moving groups. Based on observations collected at the European Southern Observatory, Chile, under observing programs 081.C-0314(A), 082.C-0053(A), and 084.C-0812(A), and on observations collected at the Centro Astronómico Hispano Alemán (CAHA) at Calar Alto, operated jointly by the Max-Planck Institute for Astronomy and the Instituto de Astrofísica de Andalucía (CSIC).

Hydrogen peroxide-induced reduction of delayed rectifier potassium current in hippocampal neurons involves oxidation of sulfhydryl groups.

PubMed

Hasan, Sonia M K; Redzic, Zoran B; Alshuaib, Waleed B

2013-07-03

This study examined the effect of H2O2 on the delayed rectifier potassium current (IKDR) in isolated hippocampal neurons. Whole-cell voltage-clamp experiments were performed on freshly dissociated hippocampal CA1 neurons of SD rats before and after treatment with H2O2. To reveal the mechanism behind H2O2-induced changes in IKDR, cells were treated with different oxidizing and reducing agents. External application of membrane permeable H2O2 reduced the amplitude and voltage-dependence of IKDR in a concentration dependent manner. Desferoxamine (DFO), an iron-chelator that prevents hydroxyl radical (OH) generation, prevented H2O2-induced reduction in IKDR. Application of the sulfhydryl-oxidizing agent 5,5 dithio-bis-nitrobenzoic acid (DTNB) mimicked the effect of H2O2. Sulfhydryl-reducing agents dithiothreitol (DTT) and glutathione (GSH) alone did not affect IKDR; however, DTT and GSH reversed and prevented the H2O2-induced inhibition of IKDR, respectively. Membrane impermeable agents GSH and DTNB showed effects only when added intracellularly identifying intracellular sulfhydryl groups as potential targets for hydroxyl-mediated oxidation. However, the inhibitory effects of DTNB and H2O2 at the positive test potentials were completely and partially abolished by DTT, respectively, suggesting an additional mechanism of action for H2O2, that is not shared by DTNB. In summary, this study provides evidence for the redox modulation of IKDR, identifies hydroxyl radical as an intermediate oxidant responsible for the H2O2-induced decrease in current amplitude and identifies intracellular sulfhydryl groups as an oxidative target. Copyright © 2013 Elsevier B.V. All rights reserved.

Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies

PubMed Central

Lehmann, Brian D.; Bauer, Joshua A.; Chen, Xi; Sanders, Melinda E.; Chakravarthy, A. Bapsi; Shyr, Yu; Pietenpol, Jennifer A.

2011-01-01

Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and subtyping is necessary to better identify molecular-based therapies. In this study, we analyzed gene expression (GE) profiles from 21 breast cancer data sets and identified 587 TNBC cases. Cluster analysis identified 6 TNBC subtypes displaying unique GE and ontologies, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem–like (MSL), and a luminal androgen receptor (LAR) subtype. Further, GE analysis allowed us to identify TNBC cell line models representative of these subtypes. Predicted “driver” signaling pathways were pharmacologically targeted in these cell line models as proof of concept that analysis of distinct GE signatures can inform therapy selection. BL1 and BL2 subtypes had higher expression of cell cycle and DNA damage response genes, and representative cell lines preferentially responded to cisplatin. M and MSL subtypes were enriched in GE for epithelial-mesenchymal transition, and growth factor pathways and cell models responded to NVP-BEZ235 (a PI3K/mTOR inhibitor) and dasatinib (an abl/src inhibitor). The LAR subtype includes patients with decreased relapse-free survival and was characterized by androgen receptor (AR) signaling. LAR cell lines were uniquely sensitive to bicalutamide (an AR antagonist). These data may be useful in biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies. PMID:21633166

The 5As: A practical taxonomy for the determinants of vaccine uptake.

PubMed

Thomson, Angus; Robinson, Karis; Vallée-Tourangeau, Gaëlle

2016-02-17

Suboptimal vaccine uptake in both childhood and adult immunisation programs limits their full potential impact on global health. A recent progress review of the Global Vaccine Action Plan stated that "countries should urgently identify barriers and bottlenecks and implement targeted approaches to increase and sustain coverage". However, vaccination coverage may be determined by a complex mix of demographic, structural, social and behavioral factors. To develop a practical taxonomy to organise the myriad possible root causes of a gap in vaccination coverage rates, we performed a narrative review of the literature and tested whether all non-socio-demographic determinants of coverage could be organised into 4 dimensions: Access, Affordability, Awareness and Acceptance. Forty-three studies were reviewed, from which we identified 23 primary determinants of vaccination uptake. We identified a fifth domain, Activation, which captured interventions such as SMS reminders which effectively nudge people towards getting vaccinated. The 5As taxonomy captured all identified determinants of vaccine uptake. This intuitive taxonomy has already facilitated mutual understanding of the primary determinants of suboptimal coverage within inter-sectorial working groups, a first step towards them developing targeted and effective solutions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of a Pharmacy Technician-Driven Program to Improve Vaccination Rates at an Academic Medical Center.

PubMed

Hill, John D; Anderegg, Sammuel V; Couldry, Rick J

2017-10-01

Background: Influenza and pneumococcal disease contribute substantially to the burden of preventable disease in the United States. Despite quality measures tied to immunization rates, health systems have struggled to achieve these targets in the inpatient setting. Pharmacy departments have had success through implementation of pharmacist standing order programs (SOP); however, these initiatives are labor-intensive and have not resulted in 100% immunization rates. Objective: The objective of this study was to evaluate a pilot utilizing pharmacy technician interventions, in combination with a nursing SOP, to improve vaccination rates of hospitalized patients for influenza and pneumococcal disease. Methods: A process was developed for pharmacy technicians to identify patients who were not previously screened or immunized during the weekend days on the Cardiovascular Progressive Care unit at the University of Kansas Health-System. Targeted pharmacy technician interventions consisted of phone call reminders and face-to-face discussions with nursing staff. The primary study outcome was the change in immunization compliance rates between the control and intervention groups. Results: Influenza vaccine rates showed a statistically significant increase from 72.2% (52 of 72) of patients during the control group to 92.9% (65 of 70, P = .001) of patients during the intervention group. A pneumococcal vaccination rate of 81.3% (61 of 75) was observed in the control group, compared with 84.3% (59 of 70) of patients in the intervention group ( P = .638). Conclusion: An improvement in inpatient influenza immunization rates can be achieved through targeted follow-up performed by pharmacy technicians, in combination with a nursing-driven SOP.

Efficacy of Stent-Retriever Thrombectomy in Magnetic Resonance Imaging Versus Computed Tomographic Perfusion-Selected Patients in SWIFT PRIME Trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

PubMed

Menjot de Champfleur, Nicolas; Saver, Jeffrey L; Goyal, Mayank; Jahan, Reza; Diener, Hans-Christoph; Bonafe, Alain; Levy, Elad I; Pereira, Vitor M; Cognard, Christophe; Yavagal, Dileep R; Albers, Gregory W

2017-06-01

The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI). Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP. MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital ( P =0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group ( P =0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI [Thrombolysis in Cerebral Infarction] score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI, P =0.02; CTP, P =0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups. Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461. © 2017 American Heart Association, Inc.

Lunch and Recess: The "Eye of the Storm"--Using Targeted Interventions for Students with Behavioral Problems

ERIC Educational Resources Information Center

Cuccaro, Carlo; Geitner, Geri

2007-01-01

A group of fifth-grade students who had persistent problems at lunch and recess were identified and provided with direct instruction in pro-social skills. These skills were taught by the authors in a two-week program that they called the "Alternative to Lunch Program for Students" (ALPS). This action research study measured the impact of…

Advancing Cyber Intelligence Practices Through the SEI’s Consortium

DTIC Science & Technology

2015-01-27

blogsjsocial media Extracurricular Activities Vu lnerabilities from these individuals roles with non-target entities-non-profits, activist groups, or...information to identify, track, and predict cyber capabilities, intentions, and activities to offer courses of action that enhance decision making 7 SEI...8 SEI Webinar Series January 27, 2015 © 2015 Carnegie Mellon University Offerings Steering Committee: Guide Consortium activities and plan for

Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation.

PubMed

Chan, Kwok Keung; Wong, Corinne Kung Yen; Lui, Vincent Chi Hang; Tam, Paul Kwong Hang; Sham, Mai Har

2003-10-15

SOX10 is a member of the SOX gene family related by homology to the high-mobility group (HMG) box region of the testis-determining gene SRY. Mutations of the transcription factor gene SOX10 lead to Waardenburg-Hirschsprung syndrome (Waardenburg-Shah syndrome, WS4) in humans. A number of SOX10 mutations have been identified in WS4 patients who suffer from different extents of intestinal aganglionosis, pigmentation, and hearing abnormalities. Some patients also exhibit signs of myelination deficiency in the central and peripheral nervous systems. Although the molecular bases for the wide range of symptoms displayed by the patients are still not clearly understood, a few target genes for SOX10 have been identified. We have analyzed the impact of six different SOX10 mutations on the activation of SOX10 target genes by yeast one-hybrid and mammalian cell transfection assays. To investigate the transactivation activities of the mutant proteins, three different SOX target binding sites were introduced into luciferase reporter gene constructs and examined in our series of transfection assays: consensus HMG domain protein binding sites; SOX10 binding sites identified in the RET promoter; and Sox10 binding sites identified in the P0 promoter. We found that the same mutation could have different transactivation activities when tested with different target binding sites and in different cell lines. The differential transactivation activities of the SOX10 mutants appeared to correlate with the intestinal and/or neurological symptoms presented in the patients. Among the six mutant SOX10 proteins tested, much reduced transactivation activities were observed when tested on the SOX10 binding sites from the RET promoter. Of the two similar mutations X467K and 1400del12, only the 1400del12 mutant protein exhibited an increase of transactivation through the P0 promoter. While the lack of normal SOX10 mediated activation of RET transcription may lead to intestinal aganglionosis, overexpression of genes coding for structural myelin proteins such as P0 due to mutant SOX10 may explain the dysmyelination phenotype observed in the patients with an additional neurological disorder. Copyright 2003 Wiley-Liss, Inc.

Preventing stroke: a narrative review of community interventions for improving hypertension control in black adults.

PubMed

Connell, Patricia; Wolfe, Charles; McKevitt, Christopher

2008-03-01

Incidence rates for stroke and hypertension are higher in black ethnic groups of African descent in the USA and UK than in white groups, suggesting a need for targeted intervention. We conduct a narrative review of published research evidence on community interventions to manage hypertension among black ethnic groups, and explore the concept of cultural sensitivity in these interventions. Data sources comprised computer-aided searches of published studies over the years 1981 to March 2006, on community strategies for improving hypertension control targeting black groups, and further references from these articles. Twenty-seven relevant studies were identified. Health education was associated with improvements in knowledge about hypertension, while education combined with individualised support for patients to self-manage hypertension, including goal setting and monitoring to enhance patient self-management of hypertension, and family support in managing hypertension were associated with reductions in blood pressure levels and improvements in blood pressure control. Collaboration with black communities, using local or minority ethnic staff, conducting preliminary research with target groups to investigate perceptions and canvass ideas for the intervention design were common methods assumed to achieve cultural sensitivity. Studies, however, provided insufficient robust evidence of the effectiveness of these strategies in terms of quantifiable outcomes, although this criterion is contested, with social justice arguments being offered instead. Implicit assumptions about homogeneity and shared interests within the 'community', and representation of 'community' views have implications for the effectiveness of interventions. These findings highlight areas for the future development of interventions to reduce hypertension rates in black groups, and factors that need to be robustly investigated and explicitly addressed in intervention design.

Using a community-based definition of poverty for targeting poor households for premium subsidies in the context of a community health insurance in Burkina Faso.

PubMed

Savadogo, Germain; Souarès, Aurelia; Sié, Ali; Parmar, Divya; Bibeau, Gilles; Sauerborn, Rainer

2015-02-06

One of the biggest challenges in subsidizing premiums of poor households for community health insurance is the identification and selection of these households. Generally, poverty assessments in developing countries are based on monetary terms. The household is regarded as poor if its income or consumption is lower than a predefined poverty cut-off. These measures fail to recognize the multi-dimensional character of poverty, ignoring community members' perception and understanding of poverty, leaving them voiceless and powerless in the identification process. Realizing this, the steering committee of Nouna's health insurance devised a method to involve community members to better define 'perceived' poverty, using this as a key element for the poor selection. The community-identified poor were then used to effectively target premium subsidies for the insurance scheme. The study was conducted in the Nouna's Health District located in northwest Burkina Faso. Participants in each village were selected to take part in focus-group discussions (FGD) organized in 41 villages and 7 sectors of Nouna's town to discuss criteria and perceptions of poverty. The discussions were audio recorded, transcribed and analyzed in French using the software NVivo 9. From the FGD on poverty and the subjective definitions and perceptions of the community members, we found that poverty was mainly seen as scarcity of basic needs, vulnerability, deprivation of capacities, powerlessness, voicelessness, indecent living conditions, and absence of social capital and community networks for support in times of need. Criteria and poverty groups as described by community members can be used to identify poor who can then be targeted for subsidies. Policies targeting the poorest require the establishment of effective selection strategies. These policies are well-conditioned by proper identification of the poor people. Community perceptions and criteria of poverty are grounded in reality, to better appreciate the issue. It is crucial to take these perceptions into account in undertaking community development actions which target the poor. For most community-based health insurance schemes with limited financial resources, using a community-based definition of poverty in the targeting of the poorest might be a less costly alternative.

The Interaction of Sexual Identity With Sexual Behavior and Its Influence on HIV Risk Among Latino Men: Results of a Community Survey in Northern San Diego County, California

PubMed Central

Zellner, Jennifer A.; Sañudo, Fernando; Fernández-Cerdeño, Araceli; Sipan, Carol L.; Hovell, Melbourne F.; Carrillo, Héctor

2009-01-01

Objectives. We examined the sexual behavior, sexual identities, and HIV risk factors of a community sample of Latino men to inform efforts to reduce Latinos' HIV risk. Methods. In 2005 and 2006, 680 Latino men in San Diego County, California, in randomly selected, targeted community venues, completed an anonymous, self-administered survey. Results. Most (92.3%) respondents self-identified as heterosexual, with 2.2%, 4.9%, and 0.6% self-identifying as bisexual, gay, or other orientation, respectively. Overall, 4.8% of heterosexually identified men had a lifetime history of anal intercourse with other men. Compared with behaviorally heterosexual men, heterosexually identified men who had sex with both men and women were more likely to have had a sexually transmitted infection, to have unprotected sexual intercourse with female partners, and to report having sex while under the influence of alcohol or other drugs. Bisexually identified men who had sex with men and women did not differ from behaviorally heterosexual men in these risk factors. Conclusions. Latino men who have a heterosexual identity and bisexual practices are at greater risk of HIV infection, and efforts to reduce HIV risk among Latinos should target this group. PMID:19008512

Opportunistic mammography screening provides effective detection rates in a limited resource healthcare system.

PubMed

Teh, Yew-Ching; Tan, Gie-Hooi; Taib, Nur Aishah; Rahmat, Kartini; Westerhout, Caroline Judy; Fadzli, Farhana; See, Mee-Hoong; Jamaris, Suniza; Yip, Cheng-Har

2015-05-15

Breast cancer is the leading cause of cancer deaths in women world-wide. In low and middle income countries, where there are no population-based mammographic screening programmes, late presentation is common, and because of inadequate access to optimal treatment, survival rates are poor. Mammographic screening is well-studied in high-income countries in western populations, and because it has been shown to reduce breast cancer mortality, it has become part of the healthcare systems in such countries. However the performance of mammographic screening in a developing country is largely unknown. This study aims to evaluate the performance of mammographic screening in Malaysia, a middle income country, and to compare the stage and surgical treatment of screen-detected and symptomatic breast cancer. A retrospective review of 2510 mammograms performed from Jan to Dec 2010 in a tertiary medical centre is carried out. The three groups identified are the routine (opportunistic) screening group, the targeted (high risk) screening group and the diagnostic group. The performance indicators of each group is calculated, and stage at presentation and treatment between the screening and diagnostic group is analyzed. The cancer detection rate in the opportunistic screening group, targeted screening group, and the symptomatic group is 0.5 %, 1.25 % and 26 % respectively. The proportion of ductal carcinoma in situ is 23.1 % in the two screening groups compared to only 2.5 % in the diagnostic group. Among the opportunistic screening group, the cancer detection rate was 0.2 % in women below 50 years old compared to 0.65 % in women 50 years and above. The performance indicators are within international standards. Early-staged breast cancer (Stage 0-2) were 84.6 % in the screening groups compared to 61.1 % in the diagnostic group. From the results, in a setting with resource constraints, targeted screening of high risk individuals will give a higher yield, and if more resources are available, population-based screening of women 50 and above is effective. Opportunistic mammographic screening is feasible and effective in a middle income country with performance indicators within international standards. Waiting until women are symptomatic will lead to more advanced cancers.

Visual target modulation of functional connectivity networks revealed by self-organizing group ICA.

PubMed

van de Ven, Vincent; Bledowski, Christoph; Prvulovic, David; Goebel, Rainer; Formisano, Elia; Di Salle, Francesco; Linden, David E J; Esposito, Fabrizio

2008-12-01

We applied a data-driven analysis based on self-organizing group independent component analysis (sogICA) to fMRI data from a three-stimulus visual oddball task. SogICA is particularly suited to the investigation of the underlying functional connectivity and does not rely on a predefined model of the experiment, which overcomes some of the limitations of hypothesis-driven analysis. Unlike most previous applications of ICA in functional imaging, our approach allows the analysis of the data at the group level, which is of particular interest in high order cognitive studies. SogICA is based on the hierarchical clustering of spatially similar independent components, derived from single subject decompositions. We identified four main clusters of components, centered on the posterior cingulate, bilateral insula, bilateral prefrontal cortex, and right posterior parietal and prefrontal cortex, consistently across all participants. Post hoc comparison of time courses revealed that insula, prefrontal cortex and right fronto-parietal components showed higher activity for targets than for distractors. Activation for distractors was higher in the posterior cingulate cortex, where deactivation was observed for targets. While our results conform to previous neuroimaging studies, they also complement conventional results by showing functional connectivity networks with unique contributions to the task that were consistent across subjects. SogICA can thus be used to probe functional networks of active cognitive tasks at the group-level and can provide additional insights to generate new hypotheses for further study. Copyright 2007 Wiley-Liss, Inc.

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.

Heterogeneity of neutrophil antibodies in patients with primary Sjögren's syndrome.

PubMed

Lamour, A; Le Corre, R; Pennec, Y L; Cartron, J; Youinou, P

1995-11-01

Our aims were to determine the prevalence of neutrophil antibodies in patients with primary Sjögren's syndrome (pSS), identify their target antigen(s), and evaluate their functional significance. Neutrophil antibodies were detected using an indirect immunofluorescence (IIIF) test and an enzyme-linked immunosorbent assay (ELISA), using recombinant human Fc-gamma receptor (Fc gamma RIIIb) as a capture agent. Luminol-dependent chemiluminescence was then measured by an established technique. Antibodies to neutrophils were detected in 30 of 66 patients (45%) and categorized on the basis of positivity for the two assays: IIF+/ELISA+ (group A: five patients), IIF+/ELISA- (group B: five patients), and IFF-/ELISA+ (group C: 20 patients). All positive sera contained antibodies directed to the neutrophil specific Fc gamma RIIIb, and none of them bound to NAnull neutrophils. The titer of neutrophil-reactive antibodies (groups A and B) showed no correlation with the neutrophil count, but these autoantibodies did reduce the cell ability to generate a respiratory burst. Thus, neutrophil antibodies are common in patients with pSS. Their main target appears to be Fc gamma RIII, and this may partly account for the dysfunction in Fc gamma R-mediated clearance by the reticuloendothelial system reported in these patients.

Conservative versus liberal oxygenation targets in critically ill children: the randomised multiple-centre pilot Oxy-PICU trial.

PubMed

Peters, Mark J; Jones, Gareth A L; Wiley, Daisy; Wulff, Jerome; Ramnarayan, Padmanabhan; Ray, Samiran; Inwald, David; Grocott, Michael; Griksaitis, Michael; Pappachan, John; O'Neill, Lauran; Eaton, Simon; Mouncey, Paul R; Harrison, David A; Rowan, Kathryn M

2018-06-04

Oxygen saturation monitoring for children receiving respiratory support is standard worldwide. No randomised clinical trials have compared peripheral oxygen saturation (SpO 2 ) targets for critically ill children. The harm of interventions to raise SpO 2 to > 94% may exceed their benefits. We undertook an open, parallel-group randomised trial of children > 38 weeks completed gestation and < 16 years of age receiving invasive or non-invasive respiratory support and supplemental oxygen who were admitted urgently to one of three paediatric intensive care units. A 'research without prior consent' approach was employed. Children were randomly assigned to a liberal oxygenation group (SpO 2 targets > 94%) or a conservative oxygenation group (SpO 2  = 88-92% inclusive). Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between-group separation of SpO 2 and safety. The Oxy-PICU trial was registered before recruitment: ClinicalTrials.gov identifier NCT03040570. A total of 159 children met the inclusion criteria, of whom 119 (75%) were randomised between April and July 2017, representing a rate of 10 patients per month per site. The mean time to randomisation from first contact with an intensive care team was 1.9 (SD 2.2) h. Consent to continue in the study was obtained in 107 cases (90%); the children's parents/legal representatives were supportive of the consent process. The median (interquartile range, IQR) of time-weighted individual mean SpO 2 was 94.9% (92.6-97.1) in the conservative oxygenation group and 97.5% (96.2-98.4) in the liberal group [difference 2.7%, 95% confidence interval (95% CI) 1.3-4.0%, p < 0.001]. Median (IQR) time-weighted individual mean FiO 2 was 0.28 (0.24-0.37) in the conservative group and 0.37 (0.30-0.42) in the liberal group (difference 0.08, 95% CI 0.03-0.13, p < 0.001). There were no significant between-group differences in length of stay, duration of organ support or mortality. Two prespecified serious adverse events (cardiac arrests) occurred, both in the liberal oxygenation group. A definitive clinical trial of peripheral oxygen saturation targets is feasible in critically ill children.

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.

Is Angiosome-Targeted Angioplasty Effective for Limb Salvage and Wound Healing in Diabetic Foot? : A Meta-Analysis.

PubMed

Chae, Kum Ju; Shin, Jin Yong

2016-01-01

Given that the efficacy of employing angiosome-targeted angioplasty in the treatment of diabetic foot remains controversial, this study was conducted to examine its efficacy. We performed a systematic literature review and meta-analysis using core databases, extracting the treatment modality of angiosome-targeted angioplasty as the predictor variable, and limb salvage, wound healing, and revision rate as the outcome variables. We used the Newcastle-Ottawa Scale to assess the study quality, along with the Cochrane Risk of Bias Tool. We evaluated publication bias using a funnel plot. The search strategy identified 518 publications. After screening these, we selected four articles for review. The meta-analysis revealed that overall limb salvage and wound healing rates were significantly higher (Odds ratio = 2.209, 3.290, p = 0.001, p<0.001) in patients who received angiosome-targeted angioplasty than in those who received nonangiosome-targeted angioplasty. The revision rate between the angiosome and nonangiosome groups was not significantly different (Odds ratio = 0.747, p = 0.314). Although a further randomized controlled trial is required for confirmation, angiosome-targeted angioplasty in diabetic foot was more effective than nonangiosome-targeted angioplasty with respect to wound healing and limb salvage.

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

A systematic review of suicide prevention interventions targeting indigenous peoples in Australia, United States, Canada and New Zealand

PubMed Central

2013-01-01

Background Indigenous peoples of Australia, Canada, United States and New Zealand experience disproportionately high rates of suicide. As such, the methodological quality of evaluations of suicide prevention interventions targeting these Indigenous populations should be rigorously examined, in order to determine the extent to which they are effective for reducing rates of Indigenous suicide and suicidal behaviours. This systematic review aims to: 1) identify published evaluations of suicide prevention interventions targeting Indigenous peoples in Australia, Canada, United States and New Zealand; 2) critique their methodological quality; and 3) describe their main characteristics. Methods A systematic search of 17 electronic databases and 13 websites for the period 1981–2012 (inclusive) was undertaken. The reference lists of reviews of suicide prevention interventions were hand-searched for additional relevant studies not identified by the electronic and web search. The methodological quality of evaluations of suicide prevention interventions was assessed using a standardised assessment tool. Results Nine evaluations of suicide prevention interventions were identified: five targeting Native Americans; three targeting Aboriginal Australians; and one First Nation Canadians. The main intervention strategies employed included: Community Prevention, Gatekeeper Training, and Education. Only three of the nine evaluations measured changes in rates of suicide or suicidal behaviour, all of which reported significant improvements. The methodological quality of evaluations was variable. Particular problems included weak study designs, reliance on self-report measures, highly variable consent and follow-up rates, and the absence of economic or cost analyses. Conclusions There is an urgent need for an increase in the number of evaluations of preventive interventions targeting reductions in Indigenous suicide using methodologically rigorous study designs across geographically and culturally diverse Indigenous populations. Combining and tailoring best evidence and culturally-specific individual strategies into one coherent suicide prevention program for delivery to whole Indigenous communities and/or population groups at high risk of suicide offers considerable promise. PMID:23663493

A systematic review of suicide prevention interventions targeting indigenous peoples in Australia, United States, Canada and New Zealand.

PubMed

Clifford, Anton C; Doran, Christopher M; Tsey, Komla

2013-05-13

Indigenous peoples of Australia, Canada, United States and New Zealand experience disproportionately high rates of suicide. As such, the methodological quality of evaluations of suicide prevention interventions targeting these Indigenous populations should be rigorously examined, in order to determine the extent to which they are effective for reducing rates of Indigenous suicide and suicidal behaviours. This systematic review aims to: 1) identify published evaluations of suicide prevention interventions targeting Indigenous peoples in Australia, Canada, United States and New Zealand; 2) critique their methodological quality; and 3) describe their main characteristics. A systematic search of 17 electronic databases and 13 websites for the period 1981-2012 (inclusive) was undertaken. The reference lists of reviews of suicide prevention interventions were hand-searched for additional relevant studies not identified by the electronic and web search. The methodological quality of evaluations of suicide prevention interventions was assessed using a standardised assessment tool. Nine evaluations of suicide prevention interventions were identified: five targeting Native Americans; three targeting Aboriginal Australians; and one First Nation Canadians. The main intervention strategies employed included: Community Prevention, Gatekeeper Training, and Education. Only three of the nine evaluations measured changes in rates of suicide or suicidal behaviour, all of which reported significant improvements. The methodological quality of evaluations was variable. Particular problems included weak study designs, reliance on self-report measures, highly variable consent and follow-up rates, and the absence of economic or cost analyses. There is an urgent need for an increase in the number of evaluations of preventive interventions targeting reductions in Indigenous suicide using methodologically rigorous study designs across geographically and culturally diverse Indigenous populations. Combining and tailoring best evidence and culturally-specific individual strategies into one coherent suicide prevention program for delivery to whole Indigenous communities and/or population groups at high risk of suicide offers considerable promise.

Development and Application of a Stepwise Assessment Process for Rational Redesign of Sequential Skills-Based Courses.

PubMed

Gallimore, Casey E; Porter, Andrea L; Barnett, Susanne G

2016-10-25

Objective. To develop and apply a stepwise process to assess achievement of course learning objectives related to advanced pharmacy practice experiences (APPEs) preparedness and inform redesign of sequential skills-based courses. Design. Four steps comprised the assessment and redesign process: (1) identify skills critical for APPE preparedness; (2) utilize focus groups and course evaluations to determine student competence in skill performance; (3) apply course mapping to identify course deficits contributing to suboptimal skill performance; and (4) initiate course redesign to target exposed deficits. Assessment. Focus group participants perceived students were least prepared for skills within the Accreditation Council for Pharmacy Education's pre-APPE core domains of Identification and Assessment of Drug-related Problems and General Communication Abilities. Course mapping identified gaps in instruction, performance, and assessment of skills within aforementioned domains. Conclusions. A stepwise process that identified strengths and weaknesses of a course, was used to facilitate structured course redesign. Strengths of the process included input and corroboration from both preceptors and students. Limitations included feedback from a small number of pharmacy preceptors and increased workload on course coordinators.

Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.

PubMed

Barnes, Tristan A; Amir, Eitan; Templeton, Arnoud J; Gomez-Garcia, Susana; Navarro, Beatriz; Seruga, Bostjan; Ocana, Alberto

2017-05-01

New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. Drugs approved for solid tumor treatment between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes (group 1), anti-angiogenics (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the registration trials and pooled in a meta-analysis. Odds ratios for toxic death, treatment discontinuation and grade 3-4 toxicity were compared to control groups. The Micromedex Red Book was used to calculate the monthly price. Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a greater degree with groups 1 and 2 than with groups 3 and 4, (pooled HR: 0.54, 0.56, 0.63, and 0.76 for groups 1-4 respectively, p for difference <0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR: 0.77, 0.78, 0.68, and 0.83 for groups 1-4 respectively, p for difference=0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no significant difference between groups. There was no meaningful correlation between pricing and efficacy. Compared to control groups, immunotherapeutics and drugs targeting oncogenes or angiogenesis improve efficacy to a greater degree than chemotherapy. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coomassie Brilliant Blue G-250 Dye: An Application for Forensic Fingerprint Analysis.

PubMed

Brunelle, Erica; Le, Anh Minh; Huynh, Crystal; Wingfield, Kelly; Halámková, Lenka; Agudelo, Juliana; Halámek, Jan

2017-04-04

The Bradford reagent, comprised of the Coomassie Brilliant Blue G-250 dye, methanol, and phosphoric acid, has been traditionally used for quantifying proteins. Use of this reagent in the Bradford assay relies on the binding of the Coomassie Blue G-250 dye to proteins. However, the ability of the dye to react with a small group of amino acids (arginine, histidine, lysine, phenylalanine, tyrosine, and tryptophan) makes it a viable chemical assay for fingerprint analysis in order to identify the biological sex of the fingerprint originator. It is recognized that the identification of biological sex has been readily accomplished using two other methods; however, both of those systems are reliant upon a large group of amino acids, 23 to be precise. The Bradford assay, described here, was developed specifically to aid in the transition from targeting large groups of amino acids, as demonstrated in the previous studies, to targeting only a single amino acid without compromising the intensity of the response and/or the ability to differentiate between two attributes. In this work, we aim to differentiate between female fingerprints and male fingerprints.

Measurement of attitudes toward commercial development of geothermal energy in Federal Region IX. Final report

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

Not Available

1981-06-01

A survey was conducted of ten target study groups and subgroups for Klamath Falls, Oregon, and Susanville, California: local government, current and potential industry at the site, relocators to the site, current and potential financial community, regulators, and current and potential promoters and developers. The results of benchmark attitudinal measurement is presented separately for each target group. A literature review was conducted and Macro-environmental attitudes of a sample of local government and industry personnel at the sites were assessed. An assessment of capabilities was made which involved two measurements. The first was a measurement of a sample of promoters, developers,more » and industrial service companies active at the site to determine infrastructure capabilities required by industry for geothermal plants. The second measurement involved analyzing a sample of industry management in the area and defining their requirements for plant retrofit and expansion. Finally, the processes used by the study group to analyze information to reach commitment and regulatory decisions that significantly impact on geothermal energy projects at the site were identified and defined.« less

Switching on After Nine: Black gay-identified men's perceptions of sexual identities and partnerships in South African towns.

PubMed

Mantell, Joanne E; Tocco, Jack Ume; Osmand, Thomas; Sandfort, Theo; Lane, Tim

2016-01-01

There is considerable diversity, fluidity and complexity in the expressions of sexuality and gender among men who have sex with men (MSM). Some non-gay identified MSM are known colloquially by gay-identified men in Mpumalanga, Province, South Africa, as 'After-Nines' because they do not identify as gay and present as straight during the day but also have sex with other men at night. Based on, key informant interviews and focus group discussions in two districts in Mpumalanga, we explored Black gay-identified men's perceptions of and relationships with After-Nine men, focusing on sexual and gender identities and their social consequences. Gay-identified men expressed ambivalence about their After-Nine partners, desiring them for their masculinity, yet often feeling dissatisfied and exploited in their relationships with them. The exchange of sex for commodities, especially alcohol, was common. Gay men's characterisation of After-Nines as men who ignore them during the day but have sex with them at night highlights the diversity of how same-sex practicing men perceive themselves and their sexual partners. Sexual health promotion programmes targeting 'MSM' must understand this diversity to effectively support the community in developing strategies for reaching and engaging different groups of gay and non-gay identified men.

Effect of circulating exosomes from transition cows on Madin-Darby bovine kidney cell function.

PubMed

Crookenden, M A; Walker, C G; Peiris, H; Koh, Y; Almughlliq, F; Vaswani, K; Reed, S; Heiser, A; Loor, J J; Kay, J K; Meier, S; Donkin, S S; Murray, A; Dukkipati, V S R; Roche, J R; Mitchell, M D

2017-07-01

The greatest risk of metabolic and infectious disease in dairy cows is during the transition from pregnancy to lactating (i.e., the transition period). The objective of this experiment was to determine the effects of extracellular vesicles (microvesicles involved in cell-to-cell signaling) isolated from transition cows on target cell function. We previously identified differences in the protein profiles of exosomes isolated from cows divergent in metabolic health status. Therefore, we hypothesized that these exosomes would affect target tissues differently. To investigate this, 2 groups of cows (n = 5/group) were selected based on the concentration of β-hydroxybutyrate and fatty acids in plasma and triacylglycerol concentration in liver at wk 1 and 2 postcalving. Cows with high concentrations of β-hydroxybutyrate, fatty acids, and triacylglycerol were considered at increased risk of clinical disease during the transition period (high-risk group; n = 5) and were compared with cows that had low concentrations of the selected health indicators (low-risk group; n = 5). At 2 time points during the transition period (postcalving at wk 1 and 4), blood was sampled and plasma exosomes were isolated from the high-risk and low-risk cows. The exosomes were applied at concentrations of 10 and 1 µg/mL to 5 × 10 3 Madin-Darby bovine kidney cells grown to 50% confluence in 96-well plates. Results indicate a numerical increase in cell proliferation when exosomes from high-risk cows were applied compared with those from low-risk cows. Consistent with an effect on cell proliferation, quantitative reverse transcriptase PCR indicated a trend for upregulation of 3 proinflammatory genes (granulocyte colony-stimulating factor, ciliary neurotrophic factor, and CD27 ligand) with the application of high-risk exosomes, which are involved in cellular growth and survival. Proteomic analysis indicated 2 proteins in the low-risk group that were not identified in the high-risk group (endoplasmin and catalase), which may also be indicative of the metabolic state of origin. It is likely that the metabolic state of the transition cow affects cellular function through exosomal messaging; however, more in-depth research into cross-talk between exosomes and target cells is required to determine whether exosomes influence Madin-Darby bovine kidney cells in this manner. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Pilot study of a brief intervention based on the theory of planned behaviour and self-identity to increase chlamydia testing among young people living in deprived areas.

PubMed

Booth, Amy R; Norman, Paul; Goyder, Elizabeth; Harris, Peter R; Campbell, Michael J

2014-09-01

This study sought to estimate the effects of a novel intervention, compared with usual chlamydia testing promotion, on chlamydia test uptake and intentions among young people living in deprived areas. The intervention was based on the theory of planned behaviour, augmented with self-identity, and targeted the significant predictors of chlamydia testing intentions identified in the previous research. Cluster randomization was used to allocate college tutor groups (intervention n = 10; control n = 11) to the intervention or control group. The sample comprised 253 participants (intervention n = 145, control n = 108). The primary outcome was test offer uptake at the end of the session. Other outcomes measured at immediate follow-up were intention, attitude, subjective norm, perceived behavioural control, and self-identity. Generalized estimating equations, controlling for cluster effects and sexual activity, found a small but non-significant effect of condition on test offer uptake, OR = 1.65 (95% CI 0.70, 3.88) p = .25, with 57.5% of intervention participants accepting the offer of a test compared with 40.2% of control participants. Using the same analysis procedure, small-to-medium intervention effects were found on other outcome variables, including a significant effect on attitudes towards chlamydia testing, OR = 1.37 (95% CI 1.00, 1.87), p = .05. The results provide encouraging initial evidence that this theory-based intervention, targeting the key determinants of chlamydia testing, may help to improve chlamydia testing uptake in a high-risk group. They support the conduct of a larger trial to evaluate the effectiveness of the intervention. What is already known on this subject? Young people living in areas of increased socio-economic deprivation have been identified as a high-risk group for chlamydia. Previous research within an extended model of the theory of planned behaviour (TPB) found that attitude, subjective norm, perceived behavioural control, and self-identity all significantly predicted chlamydia testing intentions in this high-risk group. What does this study add? Development and testing of a novel, TPB-based intervention targeting predictors of chlamydia testing intentions. The intervention led to significantly more positive attitudes towards chlamydia testing. Preliminary indication that a TPB-based intervention may help to improve chlamydia testing in a high-risk group. © 2013 The British Psychological Society.

Attitudes and beliefs about deceased organ donation in the Arabic-speaking community in Australia: a focus group study.

PubMed

Ralph, Angelique F; Alyami, Ali; Allen, Richard D M; Howard, Kirsten; Craig, Jonathan C; Chadban, Steve J; Irving, Michelle; Tong, Allison

2016-01-19

To describe the beliefs and attitudes to organ donation in the Arabic-speaking community. Arabic-speaking participants were purposively recruited to participate in 6 focus groups. Transcripts were analysed thematically. 53 participants, aged 19-77 years, and originating from 8 countries, participated in 1 of 6 focus groups. Participants identified as Christian (73%), Islam (26%), Buddhist (2%) or did not identify with any religion (2%). 6 themes (with subthemes) were identified; religious conviction; invisibility of organ donation; medical suspicion; owning the decision; and reciprocal benefit. Although organ donation is considered a generous life-saving 'gift', representative members of the Arabic-speaking community in Australia were unfamiliar with, unnerved by and sceptical about the donation process. Making positive decisions about organ donation would likely require resolving tensions between respecting family, community and religious values versus their individual autonomy. Providing targeted education about the process and benefits of organ donation within the Arabic community may clarify ambiguities surrounding cultural and religious-based views on organ donation, reduce taboos and suspicion towards donation, and in turn, lead to increased organ donation rates. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Characterizing violence in health care in British Columbia.

PubMed

Kling, Rakel N; Yassi, Annalee; Smailes, Elizabeth; Lovato, Chris Y; Koehoorn, Mieke

2009-08-01

The high rate of violence in the healthcare sector supports the need for greater surveillance efforts. The purpose of this study was to use a province-wide workplace incident reporting system to calculate rates and identify risk factors for violence in the British Columbia healthcare industry by occupational groups, including nursing. Data were extracted for a 1-year period (2004-2005) from the Workplace Health Indicator Tracking and Evaluation database for all employee reports of violence incidents for four of the six British Columbia health authorities. Risk factors for violence were identified through comparisons of incident rates (number of incidents/100,000 worked hours) by work characteristics, including nursing occupations and work units, and by regression models adjusted for demographic factors. Across health authorities, three groups at particularly high risk for violence were identified: very small healthcare facilities [rate ratios (RR) = 6.58, 95% CI =3.49, 12.41], the care aide occupation (RR = 10.05, 95% CI = 6.72, 15.05), and paediatric departments in acute care hospitals (RR = 2.22, 95% CI = 1.05, 4.67). The three high-risk groups warrant targeted prevention or intervention efforts be implemented. The identification of high-risk groups supports the importance of a province-wide surveillance system for public health planning.

Screening for tuberculosis in an urban shelter for homeless in Switzerland: a prospective study.

PubMed

Janssens, Jean-Paul; Wuillemin, Timothee; Adler, Dan; Jackson, Yves

2017-05-16

Whereas high risk groups such as asylum seekers are systematically screened for active tuberculosis (TB) upon entry in Switzerland, this strategy does not apply to homeless persons despite a reported high risk. Geneva health and social authorities implemented an intersectoral project to screen for active TB in homeless persons. We aimed to assess acceptability of this program and prevalence of active TB in this group. This prospective study targeted all homeless adults registering for shelter accommodation in Geneva during winter 2015. Applicants were proposed a questionnaire-based screening ( www.tb-screen.ch ) exploring epidemiological and clinical risk factors for active TB. Participants with a positive score underwent diagnostic procedures at Geneva University Hospital. Enhanced TB surveillance targeting homeless persons in the community was continued 3 months after the study termination. Overall, 726/832 (87.3%) homeless persons accepted the screening procedure. Most were young male migrants without access to care in Switzerland. Male gender (adjusted OR: 2.14; 95% confidence interval: 1.27-3.62), age below 25 years (aOR: 4.16; 95% CI: 1.27-13.64) and short duration of homelessness (aOR: 1.75; 95% CI: 1.06-2.87) were predictors of acceptance. Thirty (4.1%) had positive screening scores but none of the 24 who underwent further testing had active TB. Post-study surveillance did not identify any incident case in Geneva. Active TB screening targeting highly mobile homeless persons in shelters was well accepted and feasible. The participants' sociodemographic profile highlighted the heterogeneity of homeless groups in Europe and the null TB prevalence the variability of their active TB risks. These findings underline the feasibility of health programs targeting this hard to reach group and the need for close monitoring of this social group considering the rapid changes in international mobility patterns to tailor preventive and screening strategies to the local context.

"Don't wait for them to come to you, you go to them". A qualitative study of recruitment approaches in community based walking programmes in the UK.

PubMed

Matthews, Anne; Brennan, Graham; Kelly, Paul; McAdam, Chloe; Mutrie, Nanette; Foster, Charles

2012-08-10

This study aimed to examine the experiences of walking promotion professionals on the range and effectiveness of recruitment strategies used within community based walking programmes within the United Kingdom. Two researchers recruited and conducted semi-structured interviews with managers and project co-ordinators of community based walking programmes, across the UK, using a purposive sampling frame. Twenty eight interviews were conducted, with community projects targeting participants by age, physical activity status, socio-demographic characteristics (i.e. ethnic group) or by health status. Three case studies were also conducted with programmes aiming to recruit priority groups and also demonstrating innovative recruitment methods. Data analysis adopted an approach using analytic induction. Two types of programmes were identified: those with explicit health aims and those without. Programme aims which required targeting of specific groups adopted more specific recruitment methods. The selection of recruitment method was dependent on the respondent's awareness of 'what works' and the resource capacity at their disposal. Word of mouth was perceived to be the most effective means of recruitment but using this approach took time and effort to build relationships with target groups, usually through a third party. Perceived effectiveness of recruitment was assessed by number of participants rather than numbers of the right participants. Some programmes, particularly those targeting younger adult participants, recruited using new social communication media. Where adopted, social marketing recruitment strategies tended to promote the 'social' rather than the 'health' benefits of walking. Effective walking programme recruitment seems to require trained, strategic, labour intensive, word-of-mouth communication, often in partnerships, in order to understand needs and develop trust and motivation within disengaged sedentary communities. Walking promotion professionals require better training and resources to deliver appropriate recruitment strategies to reach priority groups.

Analysis of nucleotide diphosphate sugar dehydrogenases reveals family and group-specific relationships.

PubMed

Freas, Nicholas; Newton, Peter; Perozich, John

2016-01-01

UDP-glucose dehydrogenase (UDPGDH), UDP-N-acetyl-mannosamine dehydrogenase (UDPNAMDH) and GDP-mannose dehydrogenase (GDPMDH) belong to a family of NAD (+)-linked 4-electron-transfering oxidoreductases called nucleotide diphosphate sugar dehydrogenases (NDP-SDHs). UDPGDH is an enzyme responsible for converting UDP-d-glucose to UDP-d-glucuronic acid, a product that has different roles depending on the organism in which it is found. UDPNAMDH and GDPMDH convert UDP-N-acetyl-mannosamine to UDP-N-acetyl-mannosaminuronic acid and GDP-mannose to GDP-mannuronic acid, respectively, by a similar mechanism to UDPGDH. Their products are used as essential building blocks for the exopolysaccharides found in organisms like Pseudomonas aeruginosa and Staphylococcus aureus. Few studies have investigated the relationships between these enzymes. This study reveals the relationships between the three enzymes by analysing 229 amino acid sequences. Eighteen invariant and several other highly conserved residues were identified, each serving critical roles in maintaining enzyme structure, coenzyme binding or catalytic function. Also, 10 conserved motifs that included most of the conserved residues were identified and their roles proposed. A phylogenetic tree demonstrated relationships between each group and verified group assignment. Finally, group entropy analysis identified novel conservations unique to each NDP-SDH group, including residue positions critical to NDP-sugar substrate interaction, enzyme structure and intersubunit contact. These positions may serve as targets for future research. UDP-glucose dehydrogenase (UDPGDH, EC 1.1.1.22).

Therapeutic Inhibition of miR-4260 Suppresses Colorectal Cancer via Targeting MCC and SMAD4.

PubMed

Xiao, Junjie; Lv, Dongchao; Zhou, Jinzhe; Bei, Yihua; Chen, Ting; Hu, Muren; Zhou, Qiulian; Fu, Siyi; Huang, Qi

2017-01-01

Dysregulation of microRNAs (miRNAs, miRs) and their putative target genes have been increasingly reported to contribute to colorectal cancer. However, miRNAs that directly target the mutated in colorectal cancer (MCC) gene, a tumor suppressor which is downregulated or inactivated in colorectal cancer, remain largely unknown. By using an array-based miRNA analysis, we identified a group of miRNAs that were dysregulated in human metastatic versus non-metastatic colorectal cancer tissues. One of these miRNAs, miR-4260, was predicted to target MCC in the miRDB database. Results using human HCT116 and HT29 colorectal cancer cell lines showed that miR-4260 mimic enhanced cell proliferation and migration and reduced apoptosis induced by the chemotherapeutic agent 5-fluorouracil while miR-4260 inhibitor had inverse effects. Furthermore, miR-4260 negatively regulated MCC as well as SMAD4 by directly binding to the 3'untranslational region (3'UTR). Using siRNAs targeting MCC or SMAD4, we showed that upregulation of MCC and SMAD4 was essential to mediate the functional roles of miR-4260 inhibitor in colorectal cancer cells. Our in vivo experiments indicated that inhibition of miR-4260 reduced colorectal tumor growth in nude mice subcutaneously implanted with HCT116 cells. Significantly, miR-4260 was increased in human colorectal cancer tissues with simultaneous downregulation of MCC and SMAD4, strongly suggesting the clinical relevance of targeting miR-4260 in the treatment of colorectal cancer. In summary, we identified miR-4260 as a novel oncomiR for colorectal cancer that targets MCC and SMAD4. Inhibition of miR-4260 can, therefore, be a potential therapeutic strategy for colorectal cancer.

Cellular, synaptic and biochemical features of resilient cognition in Alzheimer’s disease

PubMed Central

Arnold, Steven. E.; Louneva, Natalia; Cao, Kajia; Wang, Li-San; Han, Li-Ying; Wolk, David A.; Negash, Selamawit; Leurgans, Sue E.; Schneider, Julie A.; Buchman, Aron S.; Wilson, Robert S.; Bennett, David A.

2012-01-01

While neuritic plaques and neurofibrillary tangles in older adults are correlated with cognitive impairment and severity of dementia, it has long been recognized that the relationship is imperfect as some people exhibit normal cognition despite high levels of AD pathology. We compared the cellular, synaptic and biochemical composition of midfrontal cortices in female subjects from the Religious Orders Study who were stratified into three subgroups: 1) pathological AD with normal cognition (“AD-Resilient”), 2) pathological AD with AD-typical dementia (“AD-Dementia)” and 3) pathologically normal with normal cognition (“Normal Comparison”). The AD-Resilient group exhibited preserved densities of synaptophysin-labeled presynaptic terminals and synaptopodin-labeled dendritic spines compared to the AD-Dementia group, and increased densities of GFAP astrocytes compared to both the AD-Dementia and Normal Comparison group. Further, in a discovery antibody microarray protein analysis we identified a number of candidate protein abnormalities that were associated with diagnostic group. These data characterize cellular and synaptic features and identify novel biochemical targets that may be associated with resilient cognitive brain aging in the setting of pathological AD. PMID:22554416

Early Risk Factors of Overweight Developmental Trajectories during Middle Childhood

PubMed Central

Pryor, Laura E.; Brendgen, Mara; Tremblay, Richard E.; Pingault, Jean-Baptiste; Liu, Xuecheng; Dubois, Lise; Touchette, Evelyne; Falissard, Bruno; Boivin, Michel; Côté, Sylvana M.

2015-01-01

Background Research is needed to identify early life risk factors associated with different developmental paths leading to overweight by adolescence. Objectives To model heterogeneity in overweight development during middle childhood and identify factors associated with differing overweight trajectories. Methods Data was drawn from the Quebec Longitudinal Study of Child Development (QLSCD; 1998-2010). Trained research assistants measured height and weight according to a standardized protocol and conducted yearly home interviews with the child’s caregiver (mother in 98% of cases). Information on several putative early life risk factors for the development of overweight were obtained, including factors related to the child’s perinatal, early behavioral family and social environment. Group-based trajectories of the probability of overweight (6-12 years) were identified with a semiparametric method (n=1678). Logistic regression analyses were used to identify early risk factors (5 months- 5 years) associated with each trajectory. Results Three trajectories of overweight were identified: “early-onset overweight” (11.0 %), “late-onset overweight” (16.6%) and “never overweight” (72.5%). Multinomial analyses indicated that children in the early and late-onset group, compared to the never overweight group, had 3 common types of risk factors: parental overweight, preschool overweight history, and large size for gestational age. Maternal overprotection (OR= 1.12, CI: 1.01-1.25), short nighttime sleep duration (OR=1.66, CI: 1.07-2.57), and immigrant status (OR=2.01, CI: 1.05-3.84) were factors specific to the early-onset group. Finally, family food insufficiency (OR=1.81, CI: 1.00-3.28) was weakly associated with membership in the late-onset trajectory group. Conclusions The development of overweight in childhood follows two different trajectories, which have common and distinct risk factors that could be the target of early preventive interventions. PMID:26121682

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

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.

Murine Anti-vaccinia Virus D8 Antibodies Target Different Epitopes and Differ in Their Ability to Block D8 Binding to CS-E

PubMed Central

Matho, Michael H.; de Val, Natalia; Miller, Gregory M.; Brown, Joshua; Schlossman, Andrew; Meng, Xiangzhi; Crotty, Shane; Peters, Bjoern; Xiang, Yan; Hsieh-Wilson, Linda C.; Ward, Andrew B.; Zajonc, Dirk M.

2014-01-01

The IMV envelope protein D8 is an adhesion molecule and a major immunodominant antigen of vaccinia virus (VACV). Here we identified the optimal D8 ligand to be chondroitin sulfate E (CS-E). CS-E is characterized by a disaccharide moiety with two sulfated hydroxyl groups at positions 4′ and 6′ of GalNAc. To study the role of antibodies in preventing D8 adhesion to CS-E, we have used a panel of murine monoclonal antibodies, and tested their ability to compete with CS-E for D8 binding. Among four antibody specificity groups, MAbs of one group (group IV) fully abrogated CS-E binding, while MAbs of a second group (group III) displayed widely varying levels of CS-E blocking. Using EM, we identified the binding site for each antibody specificity group on D8. Recombinant D8 forms a hexameric arrangement, mediated by self-association of a small C-terminal domain of D8. We propose a model in which D8 oligomerization on the IMV would allow VACV to adhere to heterogeneous population of CS, including CS-C and potentially CS-A, while overall increasing binding efficiency to CS-E. PMID:25474621

Murine anti-vaccinia virus D8 antibodies target different epitopes and differ in their ability to block D8 binding to CS-E.

PubMed

Matho, Michael H; de Val, Natalia; Miller, Gregory M; Brown, Joshua; Schlossman, Andrew; Meng, Xiangzhi; Crotty, Shane; Peters, Bjoern; Xiang, Yan; Hsieh-Wilson, Linda C; Ward, Andrew B; Zajonc, Dirk M

2014-12-01

The IMV envelope protein D8 is an adhesion molecule and a major immunodominant antigen of vaccinia virus (VACV). Here we identified the optimal D8 ligand to be chondroitin sulfate E (CS-E). CS-E is characterized by a disaccharide moiety with two sulfated hydroxyl groups at positions 4' and 6' of GalNAc. To study the role of antibodies in preventing D8 adhesion to CS-E, we have used a panel of murine monoclonal antibodies, and tested their ability to compete with CS-E for D8 binding. Among four antibody specificity groups, MAbs of one group (group IV) fully abrogated CS-E binding, while MAbs of a second group (group III) displayed widely varying levels of CS-E blocking. Using EM, we identified the binding site for each antibody specificity group on D8. Recombinant D8 forms a hexameric arrangement, mediated by self-association of a small C-terminal domain of D8. We propose a model in which D8 oligomerization on the IMV would allow VACV to adhere to heterogeneous population of CS, including CS-C and potentially CS-A, while overall increasing binding efficiency to CS-E.

Unsheltered Homelessness Among Veterans: Correlates and Profiles.

PubMed

Byrne, Thomas; Montgomery, Ann Elizabeth; Fargo, Jamison D

2016-02-01

We identified correlates of unsheltered status among Veterans experiencing homelessness and described distinct subgroups within the unsheltered homeless Veteran population using data from a screening instrument for homelessness that is administered to all Veterans accessing outpatient care at a Veterans Health Administration (VHA) facility. Correlates of unsheltered homelessness included male gender, white race, older age, lower levels of VHA eligibility, substance use disorders, frequent use of VHA inpatient and infrequent use of VHA outpatient services, and residing in the West. We identified six distinct subgroups of unsheltered Veterans; the tri-morbid frequent users represented the highest need group, but the largest group was comprised of Veterans who made highly infrequent use of VHA healthcare services. Differences between sheltered and unsheltered Veterans and heterogeneity within the unsheltered Veteran population should be considered in targeting housing and other interventions.

Life Course Typology of Adults Who Experienced Sexual Violence

PubMed Central

Draucker, Claire Burke; Martsolf, Donna S.

2011-01-01

Two qualitative methodologies were used to develop a life course typology of individuals who had been exposed to sexual violence. Interview narratives of 121 adult women and men who participated in qualitative study of women’s and men’s responses to sexual violence provided the data. The authors combined a narrative approach (holistic-content and holistic-form analysis) to describe the life courses of the participants and a qualitative person-oriented approach (cross-case analysis) to identify meaningful sub-groups within the total sample. The six groups are: (a) life of turmoil, (b) life of struggles, (c) diminished life, (d) taking control of life, (e), finding peace in life, and (f) getting life back to normal. This work exemplifies a promising strategy for identifying sub-groups of violence-exposed individuals within a heterogeneous sample. Such a typology could aid the development of treatment approaches that consider both the substance and the structure of an individual’s life course, rather than target one specific type of violence. PMID:19762554

Cigarette promotional offers: who takes advantage?

PubMed

White, Victoria M; White, Martha M; Freeman, Karen; Gilpin, Elizabeth A; Pierce, John P

2006-03-01

Promotional offers on cigarettes (e.g., dollar-off, multipack discounts) composed the largest share of tobacco industry marketing expenditures, totaling $8.9 billion, or 72% of the total budget in 2002. Internal industry documents indicate that young adults, potential quitters, and other price-sensitive groups are the targets of these marketing tactics. How effective they are in actually reaching these groups in the general population of smokers has not yet been investigated. Data were from 4618 current smokers responding to the large, random-digit-dialed population-based 2002 California Tobacco Survey. The characteristics were identified of smokers who reported that they used these offers "every time I see one." Thirty-five percent of smokers used promotional offers every time they saw one. Multivariate analyses identified young adults, women, African Americans, those with higher daily cigarette consumption, and those worried about cigarette costs as more likely to use promotional offers at every opportunity. Smokers most committed to quitting were no more likely to use promotional offers than those with no intention to quit. Cigarette brand was highly correlated with age and race/ethnicity, and therefore was not included in the multivariate analysis. Those who smoked menthol cigarettes and Camels, more often young adults and African Americans, were much more likely than those of other brands to use promotional offers. With the exception of smokers intending to quit, cigarette promotional offers are effectively reaching most industry-targeted groups. Importantly, young adults, who have the greatest long-term customer potential, are responding.