Sample records for target significant effort

  1. Eradication of Yaws: Historical Efforts and Achieving WHO's 2020 Target

    PubMed Central

    Asiedu, Kingsley; Fitzpatrick, Christopher; Jannin, Jean

    2014-01-01

    Background Yaws, one of the 17 neglected tropical diseases (NTDs), is targeted for eradication by 2020 in resolution WHA66.12 of the World Health Assembly (2013) and the WHO roadmap on NTDs (2012). The disease frequently affects children who live in poor socioeconomic conditions. Between 1952 and 1964, WHO and the United Nations Children's Fund (UNICEF) led a global eradication campaign using injectable benzathine penicillin. Recent developments using a single dose of oral azithromycin have renewed optimism that eradication can be achieved through a comprehensive large-scale treatment strategy. We review historical efforts to eradicate yaws and argue that this goal is now technically feasible using new tools and with the favorable environment for control of NTDs. We also summarize the work of WHO's Department of Control of Neglected Tropical Diseases in leading the renewed eradication initiative and call on the international community to support efforts to achieve the 2020 eradication goal. The critical factor remains access to azithromycin. Excluding medicines, the financial cost of yaws eradication could be as little as US$ 100 million. Conclusions The development of new tools has renewed interest in eradication of yaws; with modest support, the WHO eradication target of 2020 can be achieved. PMID:25254372

  2. DOD Financial Management: Significant Efforts Still Needed for Remediating Audit Readiness Deficiencies

    DTIC Science & Technology

    2017-02-01

    19As defined in generally accepted government auditing standards, information technology controls...Financial Improvement and Audit Readiness (FIAR) Plan Status Report, while DOD continues to make progress in addressing information technology ...DOD FINANCIAL MANAGEMENT Significant Efforts Still Needed for Remediating Audit Readiness Deficiencies Report to

  3. Efforts Aimed To Reduce Attrition in Antimalarial Drug Discovery: A Systematic Evaluation of the Current Antimalarial Targets Portfolio.

    PubMed

    Chaparro, María Jesús; Calderón, Félix; Castañeda, Pablo; Fernández-Alvaro, Elena; Gabarró, Raquel; Gamo, Francisco Javier; Gómez-Lorenzo, María G; Martín, Julio; Fernández, Esther

    2018-04-13

    Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (artemisinin combination therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, able to relieve symptoms as fast as the artemisinins and/or block malaria transmission. During the past few years, the antimalarial community has focused their efforts on phenotypic screening as a pragmatic approach to identify new hits. Optimization efforts on several chemical series have been successful, and clinical candidates have been identified. In addition, recent advances in genetics and proteomics have led to the target deconvolution of phenotypic clinical candidates. New mechanisms of action will also be critical to overcome resistance and reduce attrition. Therefore, a complementary strategy focused on identifying well-validated targets to start hit identification programs is essential to reinforce the clinical pipeline. Leveraging published data, we have assessed the status quo of the current antimalarial target portfolio with a focus on the blood stage clinical disease. From an extensive list of reported Plasmodium targets, we have defined triage criteria. These criteria consider genetic, pharmacological, and chemical validation, as well as tractability/doability, and safety implications. These criteria have provided a quantitative score that has led us to prioritize those targets with the highest probability to deliver successful and differentiated new drugs.

  4. Scientometrics of drug discovery efforts: pain-related molecular targets.

    PubMed

    Kissin, Igor

    2015-01-01

    The aim of this study was to make a scientometric assessment of drug discovery efforts centered on pain-related molecular targets. The following scientometric indices were used: the popularity index, representing the share of articles (or patents) on a specific topic among all articles (or patents) on pain over the same 5-year period; the index of change, representing the change in the number of articles (or patents) on a topic from one 5-year period to the next; the index of expectations, representing the ratio of the number of all types of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed over a 5-year period; the total number of articles representing Phase I-III trials of investigational drugs over a 5-year period; and the trial balance index, a ratio of Phase I-II publications to Phase III publications. Articles (PubMed database) and patents (US Patent and Trademark Office database) on 17 topics related to pain mechanisms were assessed during six 5-year periods from 1984 to 2013. During the most recent 5-year period (2009-2013), seven of 17 topics have demonstrated high research activity (purinergic receptors, serotonin, transient receptor potential channels, cytokines, gamma aminobutyric acid, glutamate, and protein kinases). However, even with these seven topics, the index of expectations decreased or did not change compared with the 2004-2008 period. In addition, publications representing Phase I-III trials of investigational drugs (2009-2013) did not indicate great enthusiasm on the part of the pharmaceutical industry regarding drugs specifically designed for treatment of pain. A promising development related to the new tool of molecular targeting, ie, monoclonal antibodies, for pain treatment has not yet resulted in real success. This approach has not yet demonstrated clinical effectiveness (at least with nerve growth factor) much beyond conventional analgesics, when its

  5. Scientometrics of drug discovery efforts: pain-related molecular targets

    PubMed Central

    Kissin, Igor

    2015-01-01

    The aim of this study was to make a scientometric assessment of drug discovery efforts centered on pain-related molecular targets. The following scientometric indices were used: the popularity index, representing the share of articles (or patents) on a specific topic among all articles (or patents) on pain over the same 5-year period; the index of change, representing the change in the number of articles (or patents) on a topic from one 5-year period to the next; the index of expectations, representing the ratio of the number of all types of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed over a 5-year period; the total number of articles representing Phase I–III trials of investigational drugs over a 5-year period; and the trial balance index, a ratio of Phase I–II publications to Phase III publications. Articles (PubMed database) and patents (US Patent and Trademark Office database) on 17 topics related to pain mechanisms were assessed during six 5-year periods from 1984 to 2013. During the most recent 5-year period (2009–2013), seven of 17 topics have demonstrated high research activity (purinergic receptors, serotonin, transient receptor potential channels, cytokines, gamma aminobutyric acid, glutamate, and protein kinases). However, even with these seven topics, the index of expectations decreased or did not change compared with the 2004–2008 period. In addition, publications representing Phase I–III trials of investigational drugs (2009–2013) did not indicate great enthusiasm on the part of the pharmaceutical industry regarding drugs specifically designed for treatment of pain. A promising development related to the new tool of molecular targeting, ie, monoclonal antibodies, for pain treatment has not yet resulted in real success. This approach has not yet demonstrated clinical effectiveness (at least with nerve growth factor) much beyond conventional analgesics

  6. Effects of Mode of Target Task Selection on Learning about Plants in a Mobile Learning Environment: Effortful Manual Selection versus Effortless QR-Code Selection

    ERIC Educational Resources Information Center

    Gao, Yuan; Liu, Tzu-Chien; Paas, Fred

    2016-01-01

    This study compared the effects of effortless selection of target plants using quick respond (QR) code technology to effortful manual search and selection of target plants on learning about plants in a mobile device supported learning environment. In addition, it was investigated whether the effectiveness of the 2 selection methods was…

  7. A Multi-targeted Approach to Suppress Tumor-Promoting Inflammation

    PubMed Central

    Samadi, Abbas K.; Georgakilas, Alexandros G.; Amedei, Amedeo; Amin, Amr; Bishayee, Anupam; Lokeshwar, Bal L.; Grue, Brendan; Panis, Carolina; Boosani, Chandra S.; Poudyal, Deepak; Stafforini, Diana M.; Bhakta, Dipita; Niccolai, Elena; Guha, Gunjan; Rupasinghe, H.P. Vasantha; Fujii, Hiromasa; Honoki, Kanya; Mehta, Kapil; Aquilano, Katia; Lowe, Leroy; Hofseth, Lorne J.; Ricciardiello, Luigi; Ciriolo, Maria Rosa; Singh, Neetu; Whelan, Richard L.; Chaturvedi, Rupesh; Ashraf, S. Salman; Kumara, HMC Shantha; Nowsheen, Somaira; Mohammed, Sulma I.; Helferich, William G.; Yang, Xujuan

    2015-01-01

    Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes. PMID:25951989

  8. Control of robotic assistance using poststroke residual voluntary effort.

    PubMed

    Makowski, Nathaniel S; Knutson, Jayme S; Chae, John; Crago, Patrick E

    2015-03-01

    Poststroke hemiparesis limits the ability to reach, in part due to involuntary muscle co-activation (synergies). Robotic approaches are being developed for both therapeutic benefit and continuous assistance during activities of daily living. Robotic assistance may enable participants to exert less effort, thereby reducing expression of the abnormal co-activation patterns, which could allow participants to reach further. This study evaluated how well participants could perform a reaching task with robotic assistance that was either provided independent of effort in the vertical direction or in the sagittal plane in proportion to voluntary effort estimated from electromyograms (EMG) on the affected side. Participants who could not reach targets without assistance were enabled to reach further with assistance. Constant anti-gravity force assistance that was independent of voluntary effort did not reduce the quality of reach and enabled participants to exert less effort while maintaining different target locations. Force assistance that was proportional to voluntary effort on the affected side enabled participants to exert less effort and could be controlled to successfully reach targets, but participants had increased difficulty maintaining a stable position. These results suggest that residual effort on the affected side can produce an effective command signal for poststroke assistive devices.

  9. Effort, success, and nonuse determine arm choice

    PubMed Central

    Xiao, Yupeng; Kim, Sujin; Yoshioka, Toshinori; Gordon, James; Osu, Rieko

    2015-01-01

    How do humans choose one arm or the other to reach single targets in front of the body? Current theories of reward-driven decisionmaking predict that choice results from a comparison of “action values,” which are the expected rewards for possible actions in a given state. In addition, current theories of motor control predict that in planning arm movements, humans minimize an expected motor cost that balances motor effort and endpoint accuracy. Here, we test the hypotheses that arm choice is determined by comparison of action values comprising expected effort and expected task success for each arm, as well as a handedness bias. Right-handed subjects, in either a large or small target condition, were first instructed to use each hand in turn to shoot through an array of targets and then to choose either hand to shoot through the same targets. Effort was estimated via inverse kinematics and dynamics. A mixed-effects logistic-regression analysis showed that, as predicted, both expected effort and expected success predicted choice, as did arm use in the preceding trial. Finally, individual parameter estimation showed that the handedness bias correlated with mean difference between right- and left-arm success, leading to overall lower use of the left arm. We discuss our results in light of arm nonuse in individuals' poststroke. PMID:25948869

  10. Effortful Pitch Glide: A Potential New Exercise Evaluated by Dynamic MRI

    ERIC Educational Resources Information Center

    Miloro, Keri Vasquez; Pearson, William G., Jr.; Langmore, Susan E.

    2014-01-01

    Purpose: The purpose of this study was to compare the biomechanics of the effortful pitch glide (EPG) with swallowing using dynamic MRI. The EPG is a combination of a pitch glide and a pharyngeal squeeze maneuver for targeting laryngeal and pharyngeal muscles. The authors hypothesized that the EPG would elicit significantly greater structural…

  11. Spacecraft intercept guidance using zero effort miss steering

    NASA Astrophysics Data System (ADS)

    Newman, Brett

    The suitability of proportional navigation, or an equivalent zero effort miss formulation, for spacecraft intercepts during midcourse guidance, followed by a ballistic coast to the endgame, is addressed. The problem is formulated in terms of relative motion in a general 3D framework. The proposed guidance law for the commanded thrust vector orientation consists of the sum of two terms: (1) along the line of sight unit direction and (2) along the zero effort miss component perpendicular to the line of sight and proportional to the miss itself and a guidance gain. If the guidance law is to be suitable for longer range targeting applications with significant ballistic coasting after burnout, determination of the zero effort miss must account for the different gravitational accelerations experienced by each vehicle. The proposed miss determination techniques employ approximations for the true differential gravity effect. Theoretical results are applied to a numerical engagement scenario and the resulting performance is evaluated in terms of the miss distances determined from nonlinear simulation.

  12. Integrating High-Resolution Datasets to Target Mitigation Efforts for Improving Air Quality and Public Health in Urban Neighborhoods

    PubMed Central

    Shandas, Vivek; Voelkel, Jackson; Rao, Meenakshi; George, Linda

    2016-01-01

    Reducing exposure to degraded air quality is essential for building healthy cities. Although air quality and population vary at fine spatial scales, current regulatory and public health frameworks assess human exposures using county- or city-scales. We build on a spatial analysis technique, dasymetric mapping, for allocating urban populations that, together with emerging fine-scale measurements of air pollution, addresses three objectives: (1) evaluate the role of spatial scale in estimating exposure; (2) identify urban communities that are disproportionately burdened by poor air quality; and (3) estimate reduction in mobile sources of pollutants due to local tree-planting efforts using nitrogen dioxide. Our results show a maximum value of 197% difference between cadastrally-informed dasymetric system (CIDS) and standard estimations of population exposure to degraded air quality for small spatial extent analyses, and a lack of substantial difference for large spatial extent analyses. These results provide the foundation for improving policies for managing air quality, and targeting mitigation efforts to address challenges of environmental justice. PMID:27527205

  13. Targeted Alpha Therapy: The US DOE Tri-Lab (ORNL, BNL, LANL) Research Effort to Provide Accelerator-Produced 225Ac for Radiotherapy

    NASA Astrophysics Data System (ADS)

    John, Kevin

    2017-01-01

    Targeted radiotherapy is an emerging discipline of cancer therapy that exploits the biochemical differences between normal cells and cancer cells to selectively deliver a lethal dose of radiation to cancer cells, while leaving healthy cells relatively unperturbed. A broad overview of targeted alpha therapy including isotope production methods, and associated isotope production facility needs, will be provided. A more general overview of the US Department of Energy Isotope Program's Tri-Lab (ORNL, BNL, LANL) Research Effort to Provide Accelerator-Produced 225Ac for Radiotherapy will also be presented focusing on the accelerator-production of 225Ac and final product isolation methodologies for medical applications.

  14. Program Interruptions and Short-Stay Transfers Represent Potential Targets for Inpatient Rehabilitation Care-Improvement Efforts.

    PubMed

    Middleton, Addie; Graham, James E; Krishnan, Shilpa; Ottenbacher, Kenneth J

    2016-11-01

    The objective of this work was to present comprehensive descriptive summaries of program interruptions and short-stay transfers among Medicare fee-for-service beneficiaries receiving inpatient rehabilitation after stroke, traumatic brain injury (TBI), and traumatic spinal cord injury (SCI). Retrospective cohort study of Medicare beneficiaries with any of the 3 conditions of interest who were admitted to inpatient rehabilitation directly from an acute hospital between July 1, 2012, and November 15, 2013. In the final sample (stroke, n = 71 769; TBI, n = 7109; SCI, n = 659), program interruption rates were 0.9% (stroke), 0.8% (TBI), and 1.4% (SCI). Short-stay transfer rates were 22.3% (stroke), 21.8% (TBI), and 31.6% (SCI); 14.7% of short-stay transfers and 12.3% of interruptions resulting in a return to acute care were identified as potentially preventable among those with stroke; 10.2% of transfers and 11.7% of interruptions among those with TBI, and 3.8% of transfers and 11.1% of interruptions among those with SCI. Broad health care policies aimed at improving quality and reducing costs are currently being implemented. Reducing program interruptions and short-stay transfers during inpatient rehabilitative care represents a potential target for care-improvement efforts. Future research focused on identifying modifiable risk factors for potentially undesirable outcomes will allow for targeted preventative interventions.

  15. Program interruptions and short-stay transfers represent potential targets for inpatient rehabilitation care-improvement efforts

    PubMed Central

    Middleton, Addie; Graham, James E.; Krishnan, Shilpa; Ottenbacher, Kenneth J.

    2016-01-01

    Objective To present comprehensive descriptive summaries of program interruptions and short-stay transfers among Medicare fee-for-service beneficiaries receiving inpatient rehabilitation following stroke, traumatic brain injury (TBI), and traumatic spinal cord injury (SCI). Design Retrospective cohort study of Medicare beneficiaries with any of the three conditions of interest who were admitted to inpatient rehabilitation directly from an acute hospital between July 1, 2012 and November 15, 2013. Results In the final sample (stroke: n=71 769; TBI: n=7109; SCI: n=659), program interruption rates were 0.9% (stroke), 0.8% (TBI), and 1.4% (SCI). Short-stay transfer rates were 22.3% (stroke), 21.8% (TBI), and 31.6% (SCI). 14.7% of short-stay transfers and 12.3% of interruptions resulting in a return to acute care were identified as potentially preventable among those with stroke, 10.2% of transfers and 11.7% of interruptions among those with TBI, and 3.8% of transfers and 11.1% of interruptions among those with SCI. Conclusions Broad healthcare policies aimed at improving quality and reducing costs are currently being implemented. Reducing program interruptions and short-stay transfers during inpatient rehabilitative care represents a potential target for care-improvement efforts. Future research focused on identifying modifiable risk factors for potentially undesirable outcomes will allow for targeted preventative interventions. PMID:27631389

  16. Periodic Table Target: A Game that Introduces the Biological Significance of Chemical Element Periodicity

    ERIC Educational Resources Information Center

    Sevcik, Richard S.; McGinty, Ragan L.; Schultz, Linda D.; Alexander, Susan V.

    2008-01-01

    Periodic Table Target, a game for middle school or high school students, familiarizes students with the form of the periodic table and the biological significance of different elements. The Periodic Table Target game board is constructed as a class project, and the game is played to reinforce the content. Students are assigned several elements…

  17. Objective Assessment of Listening Effort: Coregistration of Pupillometry and EEG.

    PubMed

    Miles, Kelly; McMahon, Catherine; Boisvert, Isabelle; Ibrahim, Ronny; de Lissa, Peter; Graham, Petra; Lyxell, Björn

    2017-01-01

    Listening to speech in noise is effortful, particularly for people with hearing impairment. While it is known that effort is related to a complex interplay between bottom-up and top-down processes, the cognitive and neurophysiological mechanisms contributing to effortful listening remain unknown. Therefore, a reliable physiological measure to assess effort remains elusive. This study aimed to determine whether pupil dilation and alpha power change, two physiological measures suggested to index listening effort, assess similar processes. Listening effort was manipulated by parametrically varying spectral resolution (16- and 6-channel noise vocoding) and speech reception thresholds (SRT; 50% and 80%) while 19 young, normal-hearing adults performed a speech recognition task in noise. Results of off-line sentence scoring showed discrepancies between the target SRTs and the true performance obtained during the speech recognition task. For example, in the SRT80% condition, participants scored an average of 64.7%. Participants' true performance levels were therefore used for subsequent statistical modelling. Results showed that both measures appeared to be sensitive to changes in spectral resolution (channel vocoding), while pupil dilation only was also significantly related to their true performance levels (%) and task accuracy (i.e., whether the response was correctly or partially recalled). The two measures were not correlated, suggesting they each may reflect different cognitive processes involved in listening effort. This combination of findings contributes to a growing body of research aiming to develop an objective measure of listening effort.

  18. Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

    DOE PAGES

    Cucinotta, Francis A.; Cacao, Eliedonna

    2017-05-12

    Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-setmore » for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.« less

  19. Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

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

    Cucinotta, Francis A.; Cacao, Eliedonna

    Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-setmore » for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.« less

  20. Prioritizing multiple therapeutic targets in parallel using automated DNA-encoded library screening

    NASA Astrophysics Data System (ADS)

    Machutta, Carl A.; Kollmann, Christopher S.; Lind, Kenneth E.; Bai, Xiaopeng; Chan, Pan F.; Huang, Jianzhong; Ballell, Lluis; Belyanskaya, Svetlana; Besra, Gurdyal S.; Barros-Aguirre, David; Bates, Robert H.; Centrella, Paolo A.; Chang, Sandy S.; Chai, Jing; Choudhry, Anthony E.; Coffin, Aaron; Davie, Christopher P.; Deng, Hongfeng; Deng, Jianghe; Ding, Yun; Dodson, Jason W.; Fosbenner, David T.; Gao, Enoch N.; Graham, Taylor L.; Graybill, Todd L.; Ingraham, Karen; Johnson, Walter P.; King, Bryan W.; Kwiatkowski, Christopher R.; Lelièvre, Joël; Li, Yue; Liu, Xiaorong; Lu, Quinn; Lehr, Ruth; Mendoza-Losana, Alfonso; Martin, John; McCloskey, Lynn; McCormick, Patti; O'Keefe, Heather P.; O'Keeffe, Thomas; Pao, Christina; Phelps, Christopher B.; Qi, Hongwei; Rafferty, Keith; Scavello, Genaro S.; Steiginga, Matt S.; Sundersingh, Flora S.; Sweitzer, Sharon M.; Szewczuk, Lawrence M.; Taylor, Amy; Toh, May Fern; Wang, Juan; Wang, Minghui; Wilkins, Devan J.; Xia, Bing; Yao, Gang; Zhang, Jean; Zhou, Jingye; Donahue, Christine P.; Messer, Jeffrey A.; Holmes, David; Arico-Muendel, Christopher C.; Pope, Andrew J.; Gross, Jeffrey W.; Evindar, Ghotas

    2017-07-01

    The identification and prioritization of chemically tractable therapeutic targets is a significant challenge in the discovery of new medicines. We have developed a novel method that rapidly screens multiple proteins in parallel using DNA-encoded library technology (ELT). Initial efforts were focused on the efficient discovery of antibacterial leads against 119 targets from Acinetobacter baumannii and Staphylococcus aureus. The success of this effort led to the hypothesis that the relative number of ELT binders alone could be used to assess the ligandability of large sets of proteins. This concept was further explored by screening 42 targets from Mycobacterium tuberculosis. Active chemical series for six targets from our initial effort as well as three chemotypes for DHFR from M. tuberculosis are reported. The findings demonstrate that parallel ELT selections can be used to assess ligandability and highlight opportunities for successful lead and tool discovery.

  1. Targeting of Repeated Sequences Unique to a Gene Results in Significant Increases in Antisense Oligonucleotide Potency

    PubMed Central

    Vickers, Timothy A.; Freier, Susan M.; Bui, Huynh-Hoa; Watt, Andrew; Crooke, Stanley T.

    2014-01-01

    A new strategy for identifying potent RNase H-dependent antisense oligonucleotides (ASOs) is presented. Our analysis of the human transcriptome revealed that a significant proportion of genes contain unique repeated sequences of 16 or more nucleotides in length. Activities of ASOs targeting these repeated sites in several representative genes were compared to those of ASOs targeting unique single sites in the same transcript. Antisense activity at repeated sites was also evaluated in a highly controlled minigene system. Targeting both native and minigene repeat sites resulted in significant increases in potency as compared to targeting of non-repeated sites. The increased potency at these sites is a result of increased frequency of ASO/RNA interactions which, in turn, increases the probability of a productive interaction between the ASO/RNA heteroduplex and human RNase H1 in the cell. These results suggest a new, highly efficient strategy for rapid identification of highly potent ASOs. PMID:25334092

  2. Community-Engaged Strategies to Promote Relevance of Research Capacity-Building Efforts Targeting Community Organizations.

    PubMed

    Cunningham, Jennifer; Miller, Stephania T; Joosten, Yvonne; Elzey, Jared D; Israel, Tiffany; King, Christine; Luther, Patrick; Vaughn, Yolanda; Wilkins, Consuelo H

    2015-10-01

    The study goal is to highlight strategies for promoting relevance of research capacity-building efforts targeting community organizations (CO)s. Two community partners, representing two COs, were invited to participate in CO research development trainings, Community Research Forums (Forum)s. Their contributions were documented via Forum document review. Forum participants, representatives from other COs, completed post-Forum surveys to identify additional training needs and rate Forum impact relative to their training expectations. A content-based analysis and descriptive statistics were used to summarize needs assessment- and impact-related survey responses, respectively. Community partners were involved in eight Forum-related activities including marketing (planning), facilitation (implementation), and manuscript coauthorship (dissemination). Eighty-one individuals, representing 55 COs, attended the Forums. Needs assessment responses revealed a desire for additional assistance with existing Forum topics (e.g., defining research priorities) and a need for new ones (e.g., promoting organizational buy in for research). Ninety-one percent of participants agreed that the Forum demonstrated the value of research to COs and how to create a research agenda. Including community partners in all Forum phases ensured that CO perspectives were integrated throughout. Post-Forum needs and impact assessment results will help in tailoring, where needed, future training topics and strategies, respectively. © 2015 Wiley Periodicals, Inc.

  3. Targeting Vasculature in Urologic Tumors: Mechanistic and Therapeutic Significance

    PubMed Central

    Sakamoto, Shinichi; Ryan, A. Jacqueline; Kyprianou, Natasha

    2008-01-01

    Recent advances toward understanding the molecular mechanisms regulating cancer initiation and progression provide new insights into the therapeutic value of targeting tumor vascularity by interfering with angiogenic signaling pathways. The functional contribution of key angiogenic factors toward increased vascularity characterizing metastatic tumors and their therapeutic exploitation is considered in three major urologic malignancies, renal, bladder, and prostate cancer. With the realization that the success of the therapeutic efficacy of the various anti-angiogenic approaches for the treatment of urologic tumors has yet to be proven clinically, the challenge remains to select critical angiogenesis pathways that can be targeted for an individual tumor. Here we discuss the major mechanisms that support formation of vasculature in renal, bladder, and prostate tumors and the current results of targeting of specific molecules/regulators for therapeutic intervention against metastastic disease. PMID:17668426

  4. Targeting women or transforming institutions? Policy lessons from NGO anti-poverty efforts.

    PubMed

    Kabeer, N

    1995-05-01

    Some research has found that the extent of gender-based discrimination in market-based institutions and unfair advantages within domestic and market institutions meant women were less successful in translating education and work into income and purchasing power. Anti-poverty programs functioned without specifically addressing the implications for women and children. Women-in-development efforts attempted to compensate for prior deficiencies by promotion of income generation schemes for women. In this article, the suggestion is made for policy makers to design projects with goals, objectives, and strategies that are clear, consistent, and well-informed about gender. Efforts should be made to avoid debates about women-only versus integrated projects. The experiences of nongovernmental organizations (NGOs) in the South Asian context offer lessons in good policy efforts to address all forms of marginalization. The definition of women's needs must be provided by women themselves; openness and flexibility are recommended. Participatory approaches serve the aims of needs identification, involvement in democratic processes, and awareness of constraints on women's use of resources. In credit lending, constraints were overcome by compensating for the absence of material collateral, guaranteeing physical access, simplifying procedures, and subsidizing access rather than interest rates. Underlying structural conditions that reinforce inequalities by gender are in need of change. Empowerment of women would assure that marginalization would not occur.

  5. Anticipated emotions and effort allocation in weight goal striving.

    PubMed

    Nelissen, Rob M A; de Vet, Emely; Zeelenberg, Marcel

    2011-02-01

    This study aimed to investigate the influence of anticipated emotions on preventive health behaviour if specified at the level of behavioural outcomes. Consistent with predictions from a recently developed model of goal pursuit, we hypothesized that the impact of emotions on effort levels depended on the perceived proximity to the goal. Participants with weight-loss intentions were randomly selected from an Internet panel and completed questionnaires at three points in time, baseline (T1; N= 725), 2 weeks later at T2 (N= 582) and again 2 months later at T3 (N= 528). Questionnaires assessed anticipated emotions (at T1) and experienced emotions (at T2) towards goal attainment and non-attainment. Goal proximity, goal desirability, and effort levels in striving for weight loss were assessed at both T1 and T2. Current and target weights were reported at all three assessments. In line with predictions, we found that negative anticipated emotions towards goal non-attainment resulted in increased effort but only if people perceived themselves in close proximity to their goal. Effort, in turn, predicted weight loss and goal achievement. The current data bear important practical implications as they identify anticipated emotions as targets of behaviour change interventions aimed to stimulate effort in striving for broad, health-related goals like weight loss. ©2010 The British Psychological Society.

  6. Using a Geographic Information System to Improve Childhood Lead-Screening Efforts

    PubMed Central

    2013-01-01

    The Idaho Division of Public Health conducted a pilot study to produce a lead-exposure–risk map to help local and state agencies better target childhood lead-screening efforts. Priority lead-screening areas, at the block group level, were created by using county tax assessor data and geographic information system software. A series of maps were produced, indicating childhood lead-screening prevalence in areas in which there was high potential for exposure to lead. These maps could enable development of more systematically targeted and cost-effective childhood lead-screening efforts. PMID:23764346

  7. How do feelings influence effort? An empirical study of entrepreneurs' affect and venture effort.

    PubMed

    Foo, Maw-Der; Uy, Marilyn A; Baron, Robert A

    2009-07-01

    How do feelings influence the effort of entrepreneurs? To obtain data on this issue, the authors implemented experience sampling methodology in which 46 entrepreneurs used cell phones to provide reports on their affect, future temporal focus, and venture effort twice daily for 24 days. Drawing on the affect-as-information theory, the study found that entrepreneurs' negative affect directly predicts entrepreneurs' effort toward tasks that are required immediately. Results were consistent for within-day and next-day time lags. Extending the theory, the study found that positive affect predicts venture effort beyond what is immediately required and that this relationship is mediated by future temporal focus. The mediating effects were significant only for next-day outcomes. Implications of findings on the nature of the affect-effort relationship for different time lags are discussed.

  8. Characterizing Fishing Effort and Spatial Extent of Coastal Fisheries

    PubMed Central

    Stewart, Kelly R.; Lewison, Rebecca L.; Dunn, Daniel C.; Bjorkland, Rhema H.; Kelez, Shaleyla; Halpin, Patrick N.; Crowder, Larry B.

    2010-01-01

    Biodiverse coastal zones are often areas of intense fishing pressure due to the high relative density of fishing capacity in these nearshore regions. Although overcapacity is one of the central challenges to fisheries sustainability in coastal zones, accurate estimates of fishing pressure in coastal zones are limited, hampering the assessment of the direct and collateral impacts (e.g., habitat degradation, bycatch) of fishing. We compiled a comprehensive database of fishing effort metrics and the corresponding spatial limits of fisheries and used a spatial analysis program (FEET) to map fishing effort density (measured as boat-meters per km2) in the coastal zones of six ocean regions. We also considered the utility of a number of socioeconomic variables as indicators of fishing pressure at the national level; fishing density increased as a function of population size and decreased as a function of coastline length. Our mapping exercise points to intra and interregional ‘hotspots’ of coastal fishing pressure. The significant and intuitive relationships we found between fishing density and population size and coastline length may help with coarse regional characterizations of fishing pressure. However, spatially-delimited fishing effort data are needed to accurately map fishing hotspots, i.e., areas of intense fishing activity. We suggest that estimates of fishing effort, not just target catch or yield, serve as a necessary measure of fishing activity, which is a key link to evaluating sustainability and environmental impacts of coastal fisheries. PMID:21206903

  9. Characterizing fishing effort and spatial extent of coastal fisheries.

    PubMed

    Stewart, Kelly R; Lewison, Rebecca L; Dunn, Daniel C; Bjorkland, Rhema H; Kelez, Shaleyla; Halpin, Patrick N; Crowder, Larry B

    2010-12-29

    Biodiverse coastal zones are often areas of intense fishing pressure due to the high relative density of fishing capacity in these nearshore regions. Although overcapacity is one of the central challenges to fisheries sustainability in coastal zones, accurate estimates of fishing pressure in coastal zones are limited, hampering the assessment of the direct and collateral impacts (e.g., habitat degradation, bycatch) of fishing. We compiled a comprehensive database of fishing effort metrics and the corresponding spatial limits of fisheries and used a spatial analysis program (FEET) to map fishing effort density (measured as boat-meters per km²) in the coastal zones of six ocean regions. We also considered the utility of a number of socioeconomic variables as indicators of fishing pressure at the national level; fishing density increased as a function of population size and decreased as a function of coastline length. Our mapping exercise points to intra and interregional 'hotspots' of coastal fishing pressure. The significant and intuitive relationships we found between fishing density and population size and coastline length may help with coarse regional characterizations of fishing pressure. However, spatially-delimited fishing effort data are needed to accurately map fishing hotspots, i.e., areas of intense fishing activity. We suggest that estimates of fishing effort, not just target catch or yield, serve as a necessary measure of fishing activity, which is a key link to evaluating sustainability and environmental impacts of coastal fisheries.

  10. Visually directed vs. software-based targeted biopsy compared to transperineal template mapping biopsy in the detection of clinically significant prostate cancer.

    PubMed

    Valerio, Massimo; McCartan, Neil; Freeman, Alex; Punwani, Shonit; Emberton, Mark; Ahmed, Hashim U

    2015-10-01

    Targeted biopsy based on cognitive or software magnetic resonance imaging (MRI) to transrectal ultrasound registration seems to increase the detection rate of clinically significant prostate cancer as compared with standard biopsy. However, these strategies have not been directly compared against an accurate test yet. The aim of this study was to obtain pilot data on the diagnostic ability of visually directed targeted biopsy vs. software-based targeted biopsy, considering transperineal template mapping (TPM) biopsy as the reference test. Prospective paired cohort study included 50 consecutive men undergoing TPM with one or more visible targets detected on preoperative multiparametric MRI. Targets were contoured on the Biojet software. Patients initially underwent software-based targeted biopsies, then visually directed targeted biopsies, and finally systematic TPM. The detection rate of clinically significant disease (Gleason score ≥3+4 and/or maximum cancer core length ≥4mm) of one strategy against another was compared by 3×3 contingency tables. Secondary analyses were performed using a less stringent threshold of significance (Gleason score ≥4+3 and/or maximum cancer core length ≥6mm). Median age was 68 (interquartile range: 63-73); median prostate-specific antigen level was 7.9ng/mL (6.4-10.2). A total of 79 targets were detected with a mean of 1.6 targets per patient. Of these, 27 (34%), 28 (35%), and 24 (31%) were scored 3, 4, and 5, respectively. At a patient level, the detection rate was 32 (64%), 34 (68%), and 38 (76%) for visually directed targeted, software-based biopsy, and TPM, respectively. Combining the 2 targeted strategies would have led to detection rate of 39 (78%). At a patient level and at a target level, software-based targeted biopsy found more clinically significant diseases than did visually directed targeted biopsy, although this was not statistically significant (22% vs. 14%, P = 0.48; 51.9% vs. 44.3%, P = 0.24). Secondary

  11. Prediction of fishing effort distributions using boosted regression trees.

    PubMed

    Soykan, Candan U; Eguchi, Tomoharu; Kohin, Suzanne; Dewar, Heidi

    2014-01-01

    Concerns about bycatch of protected species have become a dominant factor shaping fisheries management. However, efforts to mitigate bycatch are often hindered by a lack of data on the distributions of fishing effort and protected species. One approach to overcoming this problem has been to overlay the distribution of past fishing effort with known locations of protected species, often obtained through satellite telemetry and occurrence data, to identify potential bycatch hotspots. This approach, however, generates static bycatch risk maps, calling into question their ability to forecast into the future, particularly when dealing with spatiotemporally dynamic fisheries and highly migratory bycatch species. In this study, we use boosted regression trees to model the spatiotemporal distribution of fishing effort for two distinct fisheries in the North Pacific Ocean, the albacore (Thunnus alalunga) troll fishery and the California drift gillnet fishery that targets swordfish (Xiphias gladius). Our results suggest that it is possible to accurately predict fishing effort using < 10 readily available predictor variables (cross-validated correlations between model predictions and observed data -0.6). Although the two fisheries are quite different in their gears and fishing areas, their respective models had high predictive ability, even when input data sets were restricted to a fraction of the full time series. The implications for conservation and management are encouraging: Across a range of target species, fishing methods, and spatial scales, even a relatively short time series of fisheries data may suffice to accurately predict the location of fishing effort into the future. In combination with species distribution modeling of bycatch species, this approach holds promise as a mitigation tool when observer data are limited. Even in data-rich regions, modeling fishing effort and bycatch may provide more accurate estimates of bycatch risk than partial observer coverage

  12. Brain Stimulation Over the Frontopolar Cortex Enhances Motivation to Exert Effort for Reward.

    PubMed

    Soutschek, Alexander; Kang, Pyungwon; Ruff, Christian C; Hare, Todd A; Tobler, Philippe N

    2018-07-01

    Loss of motivation is a characteristic feature of several psychiatric and neurological disorders. However, the neural mechanisms underlying human motivation are far from being understood. Here, we investigate the role that the frontopolar cortex (FPC) plays in motivating cognitive and physical effort exertion by computing subjective effort equivalents. We manipulated neural processing with transcranial direct current stimulation targeting the FPC while 141 healthy participants decided whether or not to engage in cognitive or physical effort to obtain rewards. We found that brain stimulation targeting the FPC increased the amount of both types of effort participants were willing to exert for rewards. Our findings provide important insights into the neural mechanisms involved in motivating effortful behavior. Moreover, they suggest that considering the motivation-related activity of the FPC could facilitate the development of treatments for the loss of motivation commonly seen in psychiatric and other neurological disorders. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Exoatmospheric intercepts using zero effort miss steering for midcourse guidance

    NASA Astrophysics Data System (ADS)

    Newman, Brett

    The suitability of proportional navigation, or an equivalent zero effort miss formulation, for exatmospheric intercepts during midcourse guidance, followed by a ballistic coast to the endgame, is addressed. The problem is formulated in terms of relative motion in a general, three dimensional framework. The proposed guidance law for the commanded thrust vector orientation consists of the sum of two terms: (1) along the line of sight unit direction and (2) along the zero effort miss component perpendicular to the line of sight and proportional to the miss itself and a guidance gain. If the guidance law is to be suitable for longer range targeting applications with significant ballistic coasting after burnout, determination of the zero effort miss must account for the different gravitational accelerations experienced by each vehicle. The proposed miss determination techniques employ approximations for the true differential gravity effect and thus, are less accurate than a direct numerical propagation of the governing equations, but more accurate than a baseline determination, which assumes equal accelerations for both vehicles. Approximations considered are constant, linear, quadratic, and linearized inverse square models. Theoretical results are applied to a numerical engagement scenario and the resulting performance is evaluated in terms of the miss distances determined from nonlinear simulation.

  14. When can efforts to control nuisance and invasive species backfire?

    USGS Publications Warehouse

    Zipkin, E.F.; Kraft, C.E.; Cooch, E.G.; Sullivan, P.J.

    2009-01-01

    Population control through harvest has the potential to reduce the abundance of nuisance and invasive species. However, demographic structure and density-dependent processes can confound removal efforts and lead to undesirable consequences, such as overcompensation (an increase in abundance in response to harvest) and instability (population cycling or chaos). Recent empirical studies have demonstrated the potential for increased mortality (such as that caused by harvest) to lead to overcompensation and instability in plant, insect, and fish populations. We developed a general population model with juvenile and adult stages to help determine the conditions under which control harvest efforts can produce unintended outcomes. Analytical and simulation analyses of the model demonstrated that the potential for overcompensation as a result of harvest was significant for species with high fecundity, even when annual stage-specific survivorship values were fairly low. Population instability as a result of harvest occurred less frequently and was only possible with harvest strategies that targeted adults when both fecundity and adult survivorship were high. We considered these results in conjunction with current literature on nuisance and invasive species to propose general guidelines for assessing the risks associated with control harvest based on life history characteristics of target populations. Our results suggest that species with high per capita fecundity (over discrete breeding periods), short juvenile stages, and fairly constant survivorship rates are most likely to respond undesirably to harvest. It is difficult to determine the extent to which overcompensation and instability could occur during real-world removal efforts, and more empirical removal studies should be undertaken to evaluate population-level responses to control harvests. Nevertheless, our results identify key issues that have been seldom acknowledged and are potentially generic across taxa

  15. When can efforts to control nuisance and invasive species backfire?

    PubMed

    Zipkin, Elise F; Kraft, Clifford E; Cooch, Evan G; Sullivan, Patrick J

    2009-09-01

    Population control through harvest has the potential to reduce the abundance of nuisance and invasive species. However, demographic structure and density-dependent processes can confound removal efforts and lead to undesirable consequences, such as overcompensation (an increase in abundance in response to harvest) and instability (population cycling or chaos). Recent empirical studies have demonstrated the potential for increased mortality (such as that caused by harvest) to lead to overcompensation and instability in plant, insect, and fish populations. We developed a general population model with juvenile and adult stages to help determine the conditions under which control harvest efforts can produce unintended outcomes. Analytical and simulation analyses of the model demonstrated that the potential for overcompensation as a result of harvest was significant for species with high fecundity, even when annual stage-specific survivorship values were fairly low. Population instability as a result of harvest occurred less frequently and was only possible with harvest strategies that targeted adults when both fecundity and adult survivorship were high. We considered these results in conjunction with current literature on nuisance and invasive species to propose general guidelines for assessing the risks associated with control harvest based on life history characteristics of target populations. Our results suggest that species with high per capita fecundity (over discrete breeding periods), short juvenile stages, and fairly constant survivorship rates are most likely to respond undesirably to harvest. It is difficult to determine the extent to which overcompensation and instability could occur during real-world removal efforts, and more empirical removal studies should be undertaken to evaluate population-level responses to control harvests. Nevertheless, our results identify key issues that have been seldom acknowledged and are potentially generic across taxa.

  16. Leverage front-line expertise to maximize trauma prevention efforts.

    PubMed

    2012-06-01

    The trauma prevention program at Geisinger Wyoming Valley (GWV) Medical Center in Wilkes-Barre, PA, has enlisted the assistance of an experienced paramedic and ED tech to spend part of his time targeting prevention education toward populations that have been experiencing high rates of traumatic injuries. While community outreach has long been a priority for the trauma prevention program, the new position is enabling GWV to boost the magnitude of its prevention efforts, and to reach out to referring facilities as well. Program administrators say a similar outreach effort aimed at EMS providers has strengthened relationships and helped to improve trauma care at the facility. The new trauma injury prevention outreach coordinator has focused his first efforts on fall prevention and curbing motor vehicle accidents among very young and very mature driving populations. Data from GWV's trauma registry suggest that its fall prevention efforts are having an effect. The incidence of falls among patients over the age 65 is down by about 10% at the facility since it began targeting education at the community's senior population. Administrators say a monthly lecture series aimed at the prehospital community has gone a long way toward nurturing ties with EMS providers. Called "EMS Night Out," the series covers a range of topics, but the most popular programs involve case reviews.

  17. Cryogenci DT and D2 Targets for Inertial Confinement Fusion

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

    Sangster, T.C.; Betti, R.; Craxton, R.S.

    Ignition target designs for inertial confinement fusion on the National Ignition Facility (NIF) are based on a spherical ablator containing a solid, cryogenic-fuel layer of deuterium and tritium. The need for solid-fuel layers was recognized more than 30 years ago and considerable effort has resulted in the production of cryogenic targets that meet most of the critical fabrication tolerances for ignition on the NIf. Significant progress with the formation and characterization of cryogenic targets for both direct and x-ray drive will be described. Results from recent cryogenic implosions will also be presented.

  18. Negative Effect of Acoustic Panels on Listening Effort in a Classroom Environment.

    PubMed

    Amlani, Amyn M; Russo, Timothy A

    monosyllabic words. After each list in the primary task was completed, participants were asked to recall the string of five digits verbatim. Word-recognition and digit-recall performance decreased with the presence of acoustic panels and as the distance from the target signal to a given seat location increased. The results were validated using the STI, as indicated by a decrease in the transmission of the target signal in the presence of acoustic panel and as the distance to a given seat location increased. The inclusion of acoustic panels reduced the negative effects of noise and reverberation in a classroom environment, resulting in an acoustic climate that complied with the ANSI-recommended guidelines for classroom design. Results, however, revealed that participants required an increased amount of mental effort when the classroom was modified with acoustic treatment compared to no acoustic treatment. Independent of acoustic treatment, mental effort was greatest at seat locations beyond the critical distance (CD). With the addition of acoustic panels, mental effort was found to increase significantly at seat locations beyond the CD compared to the unmodified room condition. Overall, results indicate that increasing the distance between the teacher and child has a detrimental impact on mental effort and, ultimately, academic performance. American Academy of Audiology

  19. Motivated to do well: an examination of the relationships between motivation, effort, and cognitive performance in schizophrenia.

    PubMed

    Foussias, G; Siddiqui, I; Fervaha, G; Mann, S; McDonald, K; Agid, O; Zakzanis, K K; Remington, G

    2015-08-01

    The uncertain relationship between negative symptoms, and specifically motivational deficits, with cognitive dysfunction in schizophrenia is in need of further elucidation as it pertains to the interpretation of cognitive test results. Findings to date have suggested a possible mediating role of motivational deficits on cognitive test measures, although findings from formal examinations of effort using performance validity measures have been inconsistent. The aim of this study was to examine the relationships between motivation, effort exerted during cognitive testing, and cognitive performance in schizophrenia. Sixty-nine outpatients with schizophrenia or schizoaffective disorder were evaluated for psychopathology, severity of motivational deficits, effort exerted during cognitive testing, and cognitive performance. Motivation and degree of effort exerted during cognitive testing were significantly related to cognitive performance, specifically verbal fluency, verbal and working memory, attention and processing speed, and reasoning and problem solving. Further, effort accounted for 15% of the variance in cognitive performance, and partially mediated the relationship between motivation and cognitive performance. Examining cognitive performance profiles for individuals exerting normal or reduced effort revealed significant differences in global cognition, as well as attention/processing speed and reasoning and problem solving. These findings suggest that cognitive domains may be differentially affected by impairments in motivation and effort, and highlight the importance of understanding the interplay between motivation and cognitive performance deficits, which may guide the appropriate selection of symptom targets for promoting recovery in patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Rebinding the Ties that Bind: Government Efforts to Preserve and Promote Marriage

    ERIC Educational Resources Information Center

    Brotherson, Sean E.; Duncan, William C.

    2004-01-01

    Governmental efforts to strengthen marriage through a variety of approaches have become increasingly common in the last decade. Societal trends related to family formation, marriage, and divorce have shaped interest in marriage and its stability as a social institution. The public sector has targeted efforts at key stages in the life history of…

  1. A methodology to link national and local information for spatial targeting of ammonia mitigation efforts

    NASA Astrophysics Data System (ADS)

    Carnell, E. J.; Misselbrook, T. H.; Dore, A. J.; Sutton, M. A.; Dragosits, U.

    2017-09-01

    The effects of atmospheric nitrogen (N) deposition are evident in terrestrial ecosystems worldwide, with eutrophication and acidification leading to significant changes in species composition. Substantial reductions in N deposition from nitrogen oxides emissions have been achieved in recent decades. By contrast, ammonia (NH3) emissions from agriculture have not decreased substantially and are typically highly spatially variable, making efficient mitigation challenging. One solution is to target NH3 mitigation measures spatially in source landscapes to maximize the benefits for nature conservation. The paper develops an approach to link national scale data and detailed local data to help identify suitable measures for spatial targeting of local sources near designated Special Areas of Conservation (SACs). The methodology combines high-resolution national data on emissions, deposition and source attribution with local data on agricultural management and site conditions. Application of the methodology for the full set of 240 SACs in England found that agriculture contributes ∼45 % of total N deposition. Activities associated with cattle farming represented 54 % of agricultural NH3 emissions within 2 km of the SACs, making them a major contributor to local N deposition, followed by mineral fertiliser application (21 %). Incorporation of local information on agricultural management practices at seven example SACs provided the means to correct outcomes compared with national-scale emission factors. The outcomes show how national scale datasets can provide information on N deposition threats at landscape to national scales, while local-scale information helps to understand the feasibility of mitigation measures, including the impact of detailed spatial targeting on N deposition rates to designated sites.

  2. Assessment of the significance of patent-derived information for the early identification of compound-target interaction hypotheses.

    PubMed

    Senger, Stefan

    2017-04-21

    Patents are an important source of information for effective decision making in drug discovery. Encouragingly, freely accessible patent-chemistry databases are now in the public domain. However, at present there is still a wide gap between relatively low coverage-high quality manually-curated data sources and high coverage data sources that use text mining and automated extraction of chemical structures. To secure much needed funding for further research and an improved infrastructure, hard evidence is required to demonstrate the significance of patent-derived information in drug discovery. Surprisingly little such evidence has been reported so far. To address this, the present study attempts to quantify the relevance of patents for formulating and substantiating hypotheses for compound-target interactions. A manually-curated set of 130 compound-target interaction pairs annotated with what are considered to be the earliest patent and publication has been produced. The analysis of this set revealed that in stark contrast to what has been reported for novel chemical structures, only about 10% of the compound-target interaction pairs could be found in publications in the scientific literature within one year of being reported in patents. The average delay across all interaction pairs is close to 4 years. In an attempt to benchmark current capabilities, it was also examined how much of the benefit of using patent-derived information can be retained when a bioannotated version of SureChEMBL is used as secondary source for the patent literature. Encouragingly, this approach found the patents in the annotated set for 72% of the compound-target interaction pairs. Similarly, the effect of using the bioactivity database ChEMBL as secondary source for the scientific literature was studied. Here, the publications from the annotated set were only found for 46% of the compound-target interaction pairs. Patent-derived information is a significant enabler for formulating compound-target

  3. The neural correlates of cognitive effort in anxiety: effects on processing efficiency.

    PubMed

    Ansari, Tahereh L; Derakshan, Nazanin

    2011-03-01

    We investigated the neural correlates of cognitive effort/pre-target preparation (Contingent Negative Variation activity; CNV) in anxiety using a mixed antisaccade task that manipulated the interval between offset of instructional cue and onset of target (CTI). According to attentional control theory (Eysenck et al., 2007) we predicted that anxiety should result in increased levels of compensatory effort, as indicated by greater frontal CNV, to maintain comparable levels of performance under competing task demands. Our results showed that anxiety resulted in faster antisaccade latencies during medium compared with short and long CTIs. Accordingly, high-anxious individuals compared with low-anxious individuals showed greater levels of CNV activity at frontal sites during medium CTI suggesting that they exerted greater cognitive effort and invested more attentional resources in preparation for the task goal. Our results are the first to demonstrate the neural correlates of processing efficiency and compensatory effort in anxiety and are discussed within the framework of attentional control theory. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. The Effort Paradox: Effort Is Both Costly and Valued.

    PubMed

    Inzlicht, Michael; Shenhav, Amitai; Olivola, Christopher Y

    2018-04-01

    According to prominent models in cognitive psychology, neuroscience, and economics, effort (be it physical or mental) is costly: when given a choice, humans and non-human animals alike tend to avoid effort. Here, we suggest that the opposite is also true and review extensive evidence that effort can also add value. Not only can the same outcomes be more rewarding if we apply more (not less) effort, sometimes we select options precisely because they require effort. Given the increasing recognition of effort's role in motivation, cognitive control, and value-based decision-making, considering this neglected side of effort will not only improve formal computational models, but also provide clues about how to promote sustained mental effort across time. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Examining human resources' efforts to develop a culturally competent workforce.

    PubMed

    Whitman, Marilyn V; Valpuesta, Domingo

    2010-01-01

    The increasing diversification of the nation's population poses significant challenges in providing care that meets the needs of culturally diverse patients. Human resource management plays a vital role in developing a more culturally competent workforce. This exploratory study examines current efforts by human resource directors (HRDs) in Alabama's general hospitals to recruit more diverse candidates, train staff, and make language access resources available. A questionnaire was developed based on the Office of Minority Health's Culturally and Linguistically Appropriate Services standards. The HRDs of the 101 Alabama general hospitals served as the study's target population. A sample of 61 responses, or 60.4% of the population, was obtained. The findings indicate that most HRDs are focusing their efforts on recruiting racially/ethnically diverse candidates and training clerical and nursing staff to care for culturally and linguistically diverse patients. Less effort is being focused on recruiting candidates who speak a different language, and only 44.3% have a trained interpreter on the staff. The HRDs who indicated that they work closely with organizations that provide support to diverse groups were more likely to recruit diverse employees and have racially/ethnically and linguistically diverse individuals in leadership positions. It is crucial that health care organizations take the necessary steps to diversify their workforce to broaden access, improve the quality and equity of care, and capture a greater market share.

  6. Emerging therapeutic targets for treatment of leishmaniasis.

    PubMed

    Sundar, Shyam; Singh, Bhawana

    2018-06-01

    Parasitic diseases that pose a threat to human life include leishmaniasis - caused by protozoan parasite Leishmania species. Existing drugs have limitations due to deleterious side effects like teratogenicity, high cost and drug resistance. This calls for the need to have an insight into therapeutic aspects of disease. Areas covered: We have identified different drug targets via. molecular, imuunological, metabolic as well as by system biology approaches. We bring these promising drug targets into light so that they can be explored to their maximum. In an effort to bridge the gaps between existing knowledge and prospects of drug discovery, we have compiled interesting studies on drug targets, thereby paving the way for establishment of better therapeutic aspects. Expert opinion: Advancements in technology shed light on many unexplored pathways. Further probing of well established pathways led to the discovery of new drug targets. This review is a comprehensive report on current and emerging drug targets, with emphasis on several metabolic targets, organellar biochemistry, salvage pathways, epigenetics, kinome and more. Identification of new targets can contribute significantly towards strengthening the pipeline for disease elimination.

  7. Listening Effort Through Depth of Processing in School-Age Children.

    PubMed

    Hsu, Benson Cheng-Lin; Vanpoucke, Filiep; van Wieringen, Astrid

    A reliable and practical measure of listening effort is crucial in the aural rehabilitation of children with communication disorders. In this article, we propose a novel behavioral paradigm designed to measure listening effort in school-age children based on different depths and levels of verbal processing. The paradigm consists of a classic word recognition task performed in quiet and in noise coupled to one of three additional tasks asking the children to judge the color of simple pictures or a certain semantic category of the presented words. The response time (RT) from the categorization tasks is considered the primary indicator of listening effort. The listening effort paradigm was evaluated in a group of 31 normal-hearing, normal-developing children 7 to 12 years of age. A total of 146 Dutch nouns were selected for the experiment after surveying 14 local Dutch-speaking children. Windows-based custom software was developed to administer the behavioral paradigm from a conventional laptop computer. A separate touch screen was used as a response interface to gather the RT data from the participants. Verbal repetition of each presented word was scored by the tester and a percentage-correct word recognition score (WRS) was calculated for each condition. Randomized lists of target words were presented in one of three signal to noise ratios (SNR) to examine the effect of background noise on the two outcome measures of WRS and RT. Three novel categorization tasks, each corresponding to a different depth or elaboration level of semantic processing, were developed to examine the effect of processing level on either WRS or RT. It was hypothesized that, while listening effort as measured by RT would be affected by both noise and processing level, WRS performance would be affected by changes in noise level only. The RT measure was also hypothesized to increase more from an increase in noise level in categorization conditions demanding a deeper or more elaborate form of

  8. Use of a vision model to quantify the significance of factors effecting target conspicuity

    NASA Astrophysics Data System (ADS)

    Gilmore, M. A.; Jones, C. K.; Haynes, A. W.; Tolhurst, D. J.; To, M.; Troscianko, T.; Lovell, P. G.; Parraga, C. A.; Pickavance, K.

    2006-05-01

    When designing camouflage it is important to understand how the human visual system processes the information to discriminate the target from the background scene. A vision model has been developed to compare two images and detect differences in local contrast in each spatial frequency channel. Observer experiments are being undertaken to validate this vision model so that the model can be used to quantify the relative significance of different factors affecting target conspicuity. Synthetic imagery can be used to design improved camouflage systems. The vision model is being used to compare different synthetic images to understand what features in the image are important to reproduce accurately and to identify the optimum way to render synthetic imagery for camouflage effectiveness assessment. This paper will describe the vision model and summarise the results obtained from the initial validation tests. The paper will also show how the model is being used to compare different synthetic images and discuss future work plans.

  9. TS-Chemscore, a Target-Specific Scoring Function, Significantly Improves the Performance of Scoring in Virtual Screening.

    PubMed

    Wang, Wen-Jing; Huang, Qi; Zou, Jun; Li, Lin-Li; Yang, Sheng-Yong

    2015-07-01

    Most of the scoring functions currently used in structure-based drug design belong to 'universal' scoring functions, which often give a poor correlation between the calculated scores and experimental binding affinities. In this investigation, we proposed a simple strategy to construct target-specific scoring functions based on known 'universal' scoring functions. This strategy was applied to Chemscore, a widely used empirical scoring function, which led to a new scoring function, termed TS-Chemscore. TS-Chemscore was validated on 14 protein targets, which cover a wide range of biological target categories. The results showed that TS-Chemscore significantly improved the correlation between the calculated scores and experimental binding affinities compared with the original Chemscore. TS-Chemscore was then applied in virtual screening to retrieve novel JAK3 and YopH inhibitors. Top 30 compounds for each target were selected for experimental validation. Six active compounds for JAK3 and four for YopH were obtained. These compounds were out of the lists of top 30 compounds sorted by Chemscore. Collectively, TS-Chemscore established in this study showed a better performance in virtual screening than its counterpart Chemscore. © 2014 John Wiley & Sons A/S.

  10. Gene-carried hepatoma targeting complex induced high gene transfection efficiency with low toxicity and significant antitumor activity.

    PubMed

    Zhao, Qing-Qing; Hu, Yu-Lan; Zhou, Yang; Li, Ni; Han, Min; Tang, Gu-Ping; Qiu, Feng; Tabata, Yasuhiko; Gao, Jian-Qing

    2012-01-01

    The success of gene transfection is largely dependent on the development of a vehicle or vector that can efficiently deliver a gene to cells with minimal toxicity. A liver cancer-targeted specific peptide (FQHPSF sequence) was successfully synthesized and linked with chitosan-linked polyethylenimine (CP) to form a new targeted gene delivery vector called CPT (CP/peptide). The structure of CPT was confirmed by (1)H nuclear magnetic resonance spectroscopy and ultraviolet spectrophotometry. The particle size of CPT/ DNA complexes was measured using laser diffraction spectrometry and the cytotoxicity of the copolymer was evaluated by methylthiazol tetrazolium method. The transfection efficiency evaluation of the CP copolymer was performed using luciferase activity assay. Cellular internalization of the CP/DNA complex was observed under confocal laser scanning microscopy. The targeting specificity of the polymer coupled to peptide was measured by competitive inhibition transfection study. The liver targeting specificity of the CPT copolymer in vivo was demonstrated by combining the copolymer with a therapeutic gene, interleukin-12, and assessed by its abilities in suppressing the growth of ascites tumor in mouse model. The results showed that the liver cancer-targeted specific peptide was successfully synthesized and linked with CP to form a new targeted gene delivery vector called CPT. The composition of CPT was confirmed and the vector showed low cytotoxicity and strong targeting specificity to liver tumors in vitro. The in vivo study results showed that interleukin-12 delivered by the new gene vector CPT/DNA significantly enhanced the antitumor effect on ascites tumor-bearing imprinting control region mice as compared with polyethylenimine (25 kDa), CP, and other controls, which further demonstrate the targeting specificity of the new synthesized polymer. The synthesized CPT copolymer was proven to be an effective liver cancer-targeted vector for therapeutic gene

  11. Speech effort measurement and stuttering: investigating the chorus reading effect.

    PubMed

    Ingham, Roger J; Warner, Allison; Byrd, Anne; Cotton, John

    2006-06-01

    The purpose of this study was to investigate chorus reading's (CR's) effect on speech effort during oral reading by adult stuttering speakers and control participants. The effect of a speech effort measurement highlighting strategy was also investigated. Twelve persistent stuttering (PS) adults and 12 normally fluent control participants completed 1-min base rate readings (BR-nonchorus) and CRs within a BR/CR/BR/CR/BR experimental design. Participants self-rated speech effort using a 9-point scale after each reading trial. Stuttering frequency, speech rate, and speech naturalness measures were also obtained. Instructions highlighting speech effort ratings during BR and CR phases were introduced after the first CR. CR improved speech effort ratings for the PS group, but the control group showed a reverse trend. Both groups' effort ratings were not significantly different during CR phases but were significantly poorer than the control group's effort ratings during BR phases. The highlighting strategy did not significantly change effort ratings. The findings show that CR will produce not only stutter-free and natural sounding speech but also reliable reductions in speech effort. However, these reductions do not reach effort levels equivalent to those achieved by normally fluent speakers, thereby conditioning its use as a gold standard of achievable normal fluency by PS speakers.

  12. Discovery of functional monoclonal antibodies targeting G-protein-coupled receptors and ion channels.

    PubMed

    Wilkinson, Trevor C I

    2016-06-15

    The development of recombinant antibody therapeutics is a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Despite this growth, however, certain classes of important molecular targets have remained intractable to therapeutic antibodies due to complexity of the target molecules. These complex target molecules include G-protein-coupled receptors and ion channels which represent a large potential target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these target proteins. Given this opportunity, substantial effort has been applied to address the technical challenges of targeting these complex membrane proteins with monoclonal antibodies. In this review recent progress made in the strategies for discovery of functional monoclonal antibodies for these challenging membrane protein targets is addressed. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  13. COMPARATIVE DIVERSITY OF FECAL BACTERIA IN AGRICULTURALLY SIGNIFICANT ANIMALS TO IDENTIFY ALTERNATIVE TARGETS FOR MICROBIAL SOURCE TRACKING

    EPA Science Inventory

    Animals of agricultural significance contribute a large percentage of fecal pollution to waterways via runoff contamination. The premise of microbial source tracking is to utilize fecal bacteria to identify target populations which are directly correlated to specific animal feces...

  14. Targeting adults who provide alcohol to underage youth: results from a national survey of local law enforcement agencies.

    PubMed

    Jones-Webb, Rhonda; Toomey, Traci L; Lenk, Kathleen M; Nelson, Toben F; Erickson, Darin J

    2015-06-01

    We investigated what local enforcement agencies are doing to target adults who provide alcohol to underage youth; what types of enforcement activities are being conducted to target adult providers; and factors that encourage enforcement activities that target adult providers. We surveyed 1,056 local law enforcement agencies in the US and measured whether or not the agency conducted enforcement activities that target adults who provide alcohol to underage youth. We also measured whether certain agency and jurisdiction characteristics were associated with enforcement activities that target adults who provide alcohol to underage youth. Less than half (42%) of local enforcement agencies conducted enforcement efforts targeting adults who provide alcohol to underage youth. Agencies that conducted the enforcement activities targeting adult providers were significantly more likely to have a full time officer specific to alcohol enforcement, a division specific to alcohol enforcement, a social host law, and to perceive underage drinking was very common. Results suggest that targeting social providers (i.e., adults over 21 years of age) will require greater law enforcement resources, implementation of underage drinking laws (e.g., social host policies), and changing perceptions among law enforcement regarding underage drinking. Future studies are needed to identify the most effective enforcement efforts and to examine how enforcement efforts are prospectively linked to alcohol consumption.

  15. Generating Electricity during Walking with a Lower Limb-Driven Energy Harvester: Targeting a Minimum User Effort

    PubMed Central

    Shepertycky, Michael; Li, Qingguo

    2015-01-01

    Background Much research in the field of energy harvesting has sought to develop devices capable of generating electricity during daily activities with minimum user effort. No previous study has considered the metabolic cost of carrying the harvester when determining the energetic effects it has on the user. When considering device carrying costs, no energy harvester to date has demonstrated the ability to generate a substantial amount of electricity (> 5W) while maintaining a user effort at the same level or lower than conventional power generation methods (e.g. hand crank generator). Methodology/Principal Findings We developed a lower limb-driven energy harvester that is able to generate approximately 9W of electricity. To quantify the performance of the harvester, we introduced a new performance measure, total cost of harvesting (TCOH), which evaluates a harvester’s overall efficiency in generating electricity including the device carrying cost. The new harvester captured the motion from both lower limbs and operated in the generative braking mode to assist the knee flexor muscles in slowing the lower limbs. From a testing on 10 participants under different walking conditions, the harvester achieved an average TCOH of 6.1, which is comparable to the estimated TCOH for a conventional power generation method of 6.2. When generating 5.2W of electricity, the TCOH of the lower limb-driven energy harvester (4.0) is lower than that of conventional power generation methods. Conclusions/Significance These results demonstrated that the lower limb-driven energy harvester is an energetically effective option for generating electricity during daily activities. PMID:26039493

  16. Pathophysiological significance and therapeutic targeting of germinal center kinase in diffuse large B-cell lymphoma.

    PubMed

    Matthews, Julie Marie; Bhatt, Shruti; Patricelli, Matthew P; Nomanbhoy, Tyzoon K; Jiang, Xiaoyu; Natkunam, Yasodha; Gentles, Andrew J; Martinez, Ezequiel; Zhu, Daxing; Chapman, Jennifer Rose; Cortizas, Elena; Shyam, Ragini; Chinichian, Shideh; Advani, Ranjana; Tan, Li; Zhang, Jianming; Choi, Hwan Geun; Tibshirani, Robert; Buhrlage, Sara J; Gratzinger, Dita; Verdun, Ramiro; Gray, Nathanael S; Lossos, Izidore S

    2016-07-14

    Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, yet 40% to 50% of patients will eventually succumb to their disease, demonstrating a pressing need for novel therapeutic options. Gene expression profiling has identified messenger RNAs that lead to transformation, but critical events transforming cells are normally executed by kinases. Therefore, we hypothesized that previously unrecognized kinases may contribute to DLBCL pathogenesis. We performed the first comprehensive analysis of global kinase activity in DLBCL, to identify novel therapeutic targets, and discovered that germinal center kinase (GCK) was extensively activated. GCK RNA interference and small molecule inhibition induced cell-cycle arrest and apoptosis in DLBCL cell lines and primary tumors in vitro and decreased the tumor growth rate in vivo, resulting in a significantly extended lifespan of mice bearing DLBCL xenografts. GCK expression was also linked to adverse clinical outcome in a cohort of 151 primary DLBCL patients. These studies demonstrate, for the first time, that GCK is a molecular therapeutic target in DLBCL tumors and that inhibiting GCK may significantly extend DLBCL patient survival. Because the majority of DLBCL tumors (∼80%) exhibit activation of GCK, this therapy may be applicable to most patients. © 2016 by The American Society of Hematology.

  17. Effort-Based Reinforcement Processing and Functional Connectivity Underlying Amotivation in Medicated Patients with Depression and Schizophrenia.

    PubMed

    Park, Il Ho; Lee, Boung Chul; Kim, Jae-Jin; Kim, Joong Il; Koo, Min-Seung

    2017-04-19

    Amotivation is a common phenotype of major depressive disorder and schizophrenia, which are clinically distinct disorders. Effective treatment targets and strategies can be discovered by examining the dopaminergic reward network function underlying amotivation between these disorders. We conducted an fMRI study in healthy human participants and medicated patients with depression and schizophrenia using an effort-based reinforcement task. We examined regional activations related to reward type (positive and negative reinforcement), effort level, and their composite value, as well as resting-state functional connectivities within the meso-striatal-prefrontal pathway. We found that integrated reward and effort values of low effort-positive reinforcement and high effort-negative reinforcement were behaviorally anticipated and represented in the putamen and medial orbitofrontal cortex activities. Patients with schizophrenia and depression did not show anticipation-related and work-related reaction time reductions, respectively. Greater amotivation severity correlated with smaller work-related putamen activity changes according to reward type in schizophrenia and effort level in depression. Patients with schizophrenia showed feedback-related putamen hyperactivity of low effort compared with healthy controls and depressed patients. The strength of medial orbitofrontal-striatal functional connectivity predicted work-related reaction time reduction of high effort negative reinforcement in healthy controls and amotivation severity in both patients with schizophrenia and those with depression. Patients with depression showed deficient medial orbitofrontal-striatal functional connectivity compared with healthy controls and patients with schizophrenia. These results indicate that amotivation in depression and schizophrenia involves different pathophysiology in the prefrontal-striatal circuitry. SIGNIFICANCE STATEMENT Amotivation is present in both depression and schizophrenia

  18. Exploring Spatiotemporal Trends in Commercial Fishing Effort of an Abalone Fishing Zone: A GIS-Based Hotspot Model

    PubMed Central

    Jalali, M. Ali; Ierodiaconou, Daniel; Gorfine, Harry; Monk, Jacquomo; Rattray, Alex

    2015-01-01

    Assessing patterns of fisheries activity at a scale related to resource exploitation has received particular attention in recent times. However, acquiring data about the distribution and spatiotemporal allocation of catch and fishing effort in small scale benthic fisheries remains challenging. Here, we used GIS-based spatio-statistical models to investigate the footprint of commercial diving events on blacklip abalone (Haliotis rubra) stocks along the south-west coast of Victoria, Australia from 2008 to 2011. Using abalone catch data matched with GPS location we found catch per unit of fishing effort (CPUE) was not uniformly spatially and temporally distributed across the study area. Spatial autocorrelation and hotspot analysis revealed significant spatiotemporal clusters of CPUE (with distance thresholds of 100’s of meters) among years, indicating the presence of CPUE hotspots focused on specific reefs. Cumulative hotspot maps indicated that certain reef complexes were consistently targeted across years but with varying intensity, however often a relatively small proportion of the full reef extent was targeted. Integrating CPUE with remotely-sensed light detection and ranging (LiDAR) derived bathymetry data using generalized additive mixed model corroborated that fishing pressure primarily coincided with shallow, rugose and complex components of reef structures. This study demonstrates that a geospatial approach is efficient in detecting patterns and trends in commercial fishing effort and its association with seafloor characteristics. PMID:25992800

  19. Coworker incivility and incivility targets' work effort and counterproductive work behaviors: the moderating role of supervisor social support.

    PubMed

    Sakurai, Kenji; Jex, Steve M

    2012-04-01

    This study addresses the relationships between coworker incivility and both work effort and counterproductive work behaviors (CWBs). It was expected that employees who experienced high levels of incivility from their coworkers would report reductions in work effort and higher levels of CWBs. Also, based on the emotion-centered model of work behaviors (Spector & Fox, 2002), it was expected that negative emotions would mediate the relationships between coworker incivility and both work effort and CWBs. Finally, we examined supervisor social support as a moderator of relationships between negative emotions and both work effort and CWBs. Two hundred nine full-time university employees completed a two-wave survey over a two-month time period. Results supported the hypothesized mediated relationships. It was also found that supervisor social support moderated the relationship between negative emotions and work effort but not the relationship between negative emotions and CWBs. Study implications and limitations are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  20. Improving patient outcomes to targeted therapies in melanoma.

    PubMed

    Eroglu, Zeynep; Smalley, Keiran S M; Sondak, Vernon K

    2016-06-01

    The arrival of targeted therapies has led to significant improvements in clinical outcomes for patients with BRAFV600 mutated advanced melanoma over the past five years. In several clinical trials, BRAF and MEK inhibitors have shown improvement in progression free and overall survival, along with much higher tumor response rates in comparison to chemotherapy, with the combination of these drugs superior to monotherapy. These agents are also being tested in earlier-stage patients, in addition to alternative dosing regimens and in combinations with other therapeutics. Efforts are also ongoing to expand the success found with targeted therapies to other subtypes of melanoma, including NRAS and c-kit mutated melanomas, uveal melanomas, and BRAF/NRAS wild type melanomas. Expert Commentary: We aim to provide an overview of clinical outcomes with targeted therapies in melanoma patients.

  1. Motor Effort Alters Changes of Mind in Sensorimotor Decision Making

    PubMed Central

    Burk, Diana; Ingram, James N.; Franklin, David W.; Shadlen, Michael N.; Wolpert, Daniel M.

    2014-01-01

    After committing to an action, a decision-maker can change their mind to revise the action. Such changes of mind can even occur when the stream of information that led to the action is curtailed at movement onset. This is explained by the time delays in sensory processing and motor planning which lead to a component at the end of the sensory stream that can only be processed after initiation. Such post-initiation processing can explain the pattern of changes of mind by asserting an accumulation of additional evidence to a criterion level, termed change-of-mind bound. Here we test the hypothesis that physical effort associated with the movement required to change one's mind affects the level of the change-of-mind bound and the time for post-initiation deliberation. We varied the effort required to change from one choice target to another in a reaching movement by varying the geometry of the choice targets or by applying a force field between the targets. We show that there is a reduction in the frequency of change of mind when the separation of the choice targets would require a larger excursion of the hand from the initial to the opposite choice. The reduction is best explained by an increase in the evidence required for changes of mind and a reduced time period of integration after the initial decision. Thus the criteria to revise an initial choice is sensitive to energetic costs. PMID:24651615

  2. Informing HIV prevention efforts targeting Liberian youth: a study using the PLACE method in Liberia.

    PubMed

    McCarraher, Donna R; Chen, Mario; Wambugu, Sam; Sortijas, Steve; Succop, Stacey; Aiyengba, Bolatito; Okigbo, Chinelo C; Pack, Allison

    2013-10-09

    Preventing HIV infection among young people is a priority for the Liberian government. Data on the young people in Liberia are scarce but needed to guide HIV programming efforts. We used the Priorities for Local AIDS Control Efforts (PLACE) method to gather information on risk behaviors that young people (ages 14 to 24) engage in or are exposed to that increase their vulnerability for HIV infection. Community informants identified 240 unique venues of which 150 were visited and verified by research staff. 89 of the 150 venues comprised our sampling frame and 571 females and 548 males were interviewed in 50 venues using a behavioral survey. Ninety-one percent of females and 86% of males reported being sexually active. 56% of females and 47% of males reported they initiated sexual activity before the age of 15. Among the sexually active females, 71% reported they had received money or a gift for sex and 56% of males reported they had given money or goods for sex. 20% of females and 6% males reported that their first sexual encounter was forced and 15% of females and 6% of males reported they had been forced to have sex in the past year. Multiple partnerships were common among both sexes with 81% females and 76% males reporting one or more sex partners in the past four weeks. Less than 1% reported having experiences with injecting drugs and only 1% of males reporting have sex with men. While knowledge of HIV/AIDS was high, prevention behaviors including HIV testing and condom use were low. Youth-focused HIV efforts in Liberia need to address transactional sex and multiple and concurrent partnerships. HIV prevention interventions should include efforts to meet the economic needs of youth.

  3. Informing HIV prevention efforts targeting Liberian youth: a study using the PLACE method in Liberia

    PubMed Central

    2013-01-01

    Background Preventing HIV infection among young people is a priority for the Liberian government. Data on the young people in Liberia are scarce but needed to guide HIV programming efforts. Methods We used the Priorities for Local AIDS Control Efforts (PLACE) method to gather information on risk behaviors that young people (ages 14 to 24) engage in or are exposed to that increase their vulnerability for HIV infection. Community informants identified 240 unique venues of which 150 were visited and verified by research staff. 89 of the 150 venues comprised our sampling frame and 571 females and 548 males were interviewed in 50 venues using a behavioral survey. Results Ninety-one percent of females and 86% of males reported being sexually active. 56% of females and 47% of males reported they initiated sexual activity before the age of 15. Among the sexually active females, 71% reported they had received money or a gift for sex and 56% of males reported they had given money or goods for sex. 20% of females and 6% males reported that their first sexual encounter was forced and 15% of females and 6% of males reported they had been forced to have sex in the past year. Multiple partnerships were common among both sexes with 81% females and 76% males reporting one or more sex partners in the past four weeks. Less than 1% reported having experiences with injecting drugs and only 1% of males reporting have sex with men. While knowledge of HIV/AIDS was high, prevention behaviors including HIV testing and condom use were low. Conclusion Youth-focused HIV efforts in Liberia need to address transactional sex and multiple and concurrent partnerships. HIV prevention interventions should include efforts to meet the economic needs of youth. PMID:24107301

  4. Emotionally conditioning the target-speech voice enhances recognition of the target speech under "cocktail-party" listening conditions.

    PubMed

    Lu, Lingxi; Bao, Xiaohan; Chen, Jing; Qu, Tianshu; Wu, Xihong; Li, Liang

    2018-05-01

    Under a noisy "cocktail-party" listening condition with multiple people talking, listeners can use various perceptual/cognitive unmasking cues to improve recognition of the target speech against informational speech-on-speech masking. One potential unmasking cue is the emotion expressed in a speech voice, by means of certain acoustical features. However, it was unclear whether emotionally conditioning a target-speech voice that has none of the typical acoustical features of emotions (i.e., an emotionally neutral voice) can be used by listeners for enhancing target-speech recognition under speech-on-speech masking conditions. In this study we examined the recognition of target speech against a two-talker speech masker both before and after the emotionally neutral target voice was paired with a loud female screaming sound that has a marked negative emotional valence. The results showed that recognition of the target speech (especially the first keyword in a target sentence) was significantly improved by emotionally conditioning the target speaker's voice. Moreover, the emotional unmasking effect was independent of the unmasking effect of the perceived spatial separation between the target speech and the masker. Also, (skin conductance) electrodermal responses became stronger after emotional learning when the target speech and masker were perceptually co-located, suggesting an increase of listening efforts when the target speech was informationally masked. These results indicate that emotionally conditioning the target speaker's voice does not change the acoustical parameters of the target-speech stimuli, but the emotionally conditioned vocal features can be used as cues for unmasking target speech.

  5. Targeting Adults Who Provide Alcohol to Underage Youth: Results from a National Survey of Local Law Enforcement Agencies

    PubMed Central

    Jones-Webb, Rhonda; Toomey, Traci L.; Lenk, Kathleen M.; Nelson, Toben F.; Erickson, Darin J.

    2014-01-01

    Objective We investigated what local enforcement agencies are doing to target adults who provide alcohol to underage youth; what types of enforcement activities are being conducted to target adult providers; and factors that encourage enforcement activities that target adult providers. Method We surveyed 1056 local law enforcement agencies in the U.S. and measured whether or not the agency conducted enforcement activities that target adults who provide alcohol to underage youth. We also measured whether certain agency and jurisdiction characteristics were associated with enforcement activities that target adults who provide alcohol to underage youth. Results Less than half (42%) of local enforcement agencies conducted enforcement efforts targeting adults who provide alcohol to underage youth. Agencies that conducted the enforcement activities targeting adult providers were significantly more likely to have a full time officer specific to alcohol enforcement, a division specific to alcohol enforcement, a social host law, and to perceive underage drinking was very common. Conclusions Results suggest that targeting social providers (i.e., adults over 21 years of age) will require greater law enforcement resources, implementation of underage drinking laws (e.g., social host policies), and changing perceptions among law enforcement regarding underage drinking. Future studies are needed to identify the most effective enforcement efforts and to examine how enforcement efforts are prospectively linked to alcohol consumption. PMID:25466432

  6. Communication Efforts against AIDS in Latin America: An Updated Report.

    ERIC Educational Resources Information Center

    Simmons, Robert E.; And Others

    This paper presents recent information on the use of mass communication to combat the acquired immunodeficiency syndrome (AIDS) epidemic in Latin America. The paper takes up the following topics: (1) communication as anti-AIDS weapon; (2) the information effort lag; (3) targeting AIDS information; (4) delivering the message to health…

  7. Association between health worker motivation and healthcare quality efforts in Ghana

    PubMed Central

    2013-01-01

    Background Ghana is one of the sub-Saharan African countries making significant progress towards universal access to quality healthcare. However, it remains a challenge to attain the 2015 targets for the health related Millennium Development Goals (MDGs) partly due to health sector human resource challenges including low staff motivation. Purpose This paper addresses indicators of health worker motivation and assesses associations with quality care and patient safety in Ghana. The aim is to identify interventions at the health worker level that contribute to quality improvement in healthcare facilities. Methods The study is a baseline survey of health workers (n = 324) in 64 primary healthcare facilities in two regions in Ghana. Data collection involved quality care assessment using the SafeCare Essentials tool, the National Health Insurance Authority (NHIA) accreditation data and structured staff interviews on workplace motivating factors. The Spearman correlation test was conducted to test the hypothesis that the level of health worker motivation is associated with level of effort by primary healthcare facilities to improve quality care and patient safety. Results The quality care situation in health facilities was generally low, as determined by the SafeCare Essentials tool and NHIA data. The majority of facilities assessed did not have documented evidence of processes for continuous quality improvement and patient safety. Overall, staff motivation appeared low although workers in private facilities perceived better working conditions than workers in public facilities (P <0.05). Significant positive associations were found between staff satisfaction levels with working conditions and the clinic’s effort towards quality improvement and patient safety (P <0.05). Conclusion As part of efforts towards attainment of the health related MDGs in Ghana, more comprehensive staff motivation interventions should be integrated into quality improvement strategies especially

  8. Association between health worker motivation and healthcare quality efforts in Ghana.

    PubMed

    Alhassan, Robert Kaba; Spieker, Nicole; van Ostenberg, Paul; Ogink, Alice; Nketiah-Amponsah, Edward; de Wit, Tobias F Rinke

    2013-08-14

    Ghana is one of the sub-Saharan African countries making significant progress towards universal access to quality healthcare. However, it remains a challenge to attain the 2015 targets for the health related Millennium Development Goals (MDGs) partly due to health sector human resource challenges including low staff motivation. This paper addresses indicators of health worker motivation and assesses associations with quality care and patient safety in Ghana. The aim is to identify interventions at the health worker level that contribute to quality improvement in healthcare facilities. The study is a baseline survey of health workers (n = 324) in 64 primary healthcare facilities in two regions in Ghana. Data collection involved quality care assessment using the SafeCare Essentials tool, the National Health Insurance Authority (NHIA) accreditation data and structured staff interviews on workplace motivating factors. The Spearman correlation test was conducted to test the hypothesis that the level of health worker motivation is associated with level of effort by primary healthcare facilities to improve quality care and patient safety. The quality care situation in health facilities was generally low, as determined by the SafeCare Essentials tool and NHIA data. The majority of facilities assessed did not have documented evidence of processes for continuous quality improvement and patient safety. Overall, staff motivation appeared low although workers in private facilities perceived better working conditions than workers in public facilities (P <0.05). Significant positive associations were found between staff satisfaction levels with working conditions and the clinic's effort towards quality improvement and patient safety (P <0.05). As part of efforts towards attainment of the health related MDGs in Ghana, more comprehensive staff motivation interventions should be integrated into quality improvement strategies especially in government-owned healthcare facilities where

  9. Visual cues and listening effort: individual variability.

    PubMed

    Picou, Erin M; Ricketts, Todd A; Hornsby, Benjamin W Y

    2011-10-01

    To investigate the effect of visual cues on listening effort as well as whether predictive variables such as working memory capacity (WMC) and lipreading ability affect the magnitude of listening effort. Twenty participants with normal hearing were tested using a paired-associates recall task in 2 conditions (quiet and noise) and 2 presentation modalities (audio only [AO] and auditory-visual [AV]). Signal-to-noise ratios were adjusted to provide matched speech recognition across audio-only and AV noise conditions. Also measured were subjective perceptions of listening effort and 2 predictive variables: (a) lipreading ability and (b) WMC. Objective and subjective results indicated that listening effort increased in the presence of noise, but on average the addition of visual cues did not significantly affect the magnitude of listening effort. Although there was substantial individual variability, on average participants who were better lipreaders or had larger WMCs demonstrated reduced listening effort in noise in AV conditions. Overall, the results support the hypothesis that integrating auditory and visual cues requires cognitive resources in some participants. The data indicate that low lipreading ability or low WMC is associated with relatively effortful integration of auditory and visual information in noise.

  10. [Relationship Between Child Behavior and Emotional Problems and School Based Effort Avoidance].

    PubMed

    Weber, Hanna Maria; Büttner, Peter; Rücker, Stefan; Petermann, Franz

    2015-01-01

    The present study has examined the relationship between school based effort avoidance tendencies and problem behavior in children aged 9 to 16 years. Effort avoidance tendencies were assessed in 367 children with and without child care. Teachers and social workers rated children on behavioral and emotional problems with the Strengths and Difficulties Questionnaire (SDQ). Results confirmed significant but low correlations between teacher ratings of behavior and emotional problems in children and selected subscales of self-reported effort avoidance in school, especially for children in child care institutions. For them "conduct problems" were significantly correlated with three of the four subscales and the total sum score of effort avoidance whereas "hyperactivity" was the only scale which was significantly associated with the fourth subscale. In the school sample only "hyperactivity" and "peer problems" were significantly correlated with one subscale of school-based effort avoidance. The findings suggest that more problem behavior is in relation to more school based effort avoidance tendencies.

  11. Structural change as a key component for agricultural non-CO2 mitigation efforts.

    PubMed

    Frank, Stefan; Beach, Robert; Havlík, Petr; Valin, Hugo; Herrero, Mario; Mosnier, Aline; Hasegawa, Tomoko; Creason, Jared; Ragnauth, Shaun; Obersteiner, Michael

    2018-03-13

    Agriculture is the single largest source of anthropogenic non-carbon dioxide (non-CO 2 ) emissions. Reaching the climate target of the Paris Agreement will require significant emission reductions across sectors by 2030 and continued efforts thereafter. Here we show that the economic potential of non-CO 2 emissions reductions from agriculture is up to four times as high as previously estimated. In fact, we find that agriculture could achieve already at a carbon price of 25 $/tCO 2 eq non-CO 2 reductions of around 1 GtCO 2 eq/year by 2030 mainly through the adoption of technical and structural mitigation options. At 100 $/tCO 2 eq agriculture could even provide non-CO 2 reductions of 2.6 GtCO 2 eq/year in 2050 including demand side efforts. Immediate action to favor the widespread adoption of technical options in developed countries together with productivity increases through structural changes in developing countries is needed to move agriculture on track with a 2 °C climate stabilization pathway.

  12. From Effort to Value: Preschool Children's Alternative to Effort Justification.

    PubMed

    Benozio, Avi; Diesendruck, Gil

    2015-09-01

    In the current studies, we addressed the development of effort-based object valuation. Four- and 6-year-olds invested either great or little effort in order to obtain attractive or unattractive rewards. Children were allowed to allocate these rewards to an unfamiliar recipient (dictator game). Investing great effort to obtain attractive rewards (a consonant situation) led 6-year-olds, but not 4-year-olds, to enhance the value of the rewards and thus distribute fewer of them to others. After investing effort to attain unattractive rewards (a dissonant situation), 6-year-olds cognitively reduced the dissonance between effort and reward quality by reappraising the value of the rewards and thus distributing fewer of them. In contrast, 4-year-olds reduced the dissonance behaviorally by discarding the rewards. These findings provide evidence for the emergence of an effort-value link and underline possible mechanisms underlying the primacy of cognitive versus behavioral solutions to dissonance reduction. © The Author(s) 2015.

  13. PNC27 anticancer peptide as targeting ligand significantly improved antitumor efficacy of Doxil in HDM2-expressing cells.

    PubMed

    Darban, Shahrzad Amiri; Badiee, Ali; Jaafari, Mahmoud Reza

    2017-06-01

    To investigate the potential of PNC27 peptide, 12-26 of p53 with high affinity for HDM2 protein, as targeting ligand for Doxil to improve its antitumor activity. Doxil postinserted with 25, 50, 100 and 200 PNC27 peptides per liposome. Flow cytometry and confocal analysis were performed on C26 colon carcinoma (HDM2 positive) and B16F0 melanoma (HDM2 negative) cells. In vivo studies were performed on BALB/c mice bearing C26 and C57BL/6 mice bearing B16F0 tumor models. PNC27-Doxil showed significant cellular uptake and cytotoxicity in C26 cells compared with Doxil. PNC27-Doxil (100 PNC27 peptide) significantly improved therapeutic efficacy of Doxil without compromising its biodistribution in C26 tumor. However, these results were not observed in B16F0 cells. PNC27 is a promising targeting ligand for Doxil against HDM2-positive cancers.

  14. Effects of Effortful Swallow on Cardiac Autonomic Regulation.

    PubMed

    Gomes, Lívia M S; Silva, Roberta G; Melo, Monique; Silva, Nayra N; Vanderlei, Franciele M; Garner, David M; de Abreu, Luiz Carlos; Valenti, Vitor E

    2016-04-01

    Swallowing-induced changes in heart rate have been recently reported. However, it is not apparent the responses of heart rate variability (HRV) elicited by effortful swallow maneuver. We investigated the acute effects of effortful swallowing maneuver on HRV. This study was performed on 34 healthy women between 18 and 35 years old. We assessed heart rate variability in the time (SDNN, RMSSD, and pNN50) and frequency (HF, LF, and LF/HF ratio) domains and, visual analysis through the Poincaré plot. The subjects remained at rest for 5 min during spontaneous swallowing and then performed effortful swallowing for 5 min. HRV was analyzed during spontaneous and effortful swallowing. We found no significant differences for SDNN, pNN50, RMSSD, HF in absolute units (ms(2)). There is a trend for increase of LF in absolute (p = 0.05) and normalized (p = 0.08) units during effortful swallowing. HF in normalized units reduced (p = 0.02) during effortful swallowing and LF/HF ratio (p = 0.03) increased during effortful swallowing. In conclusion effortful swallow maneuver in healthy women increased sympathetic cardiac modulation, indicating a cardiac overload.

  15. Targeting legume loci: A comparison of three methods for target enrichment bait design in Leguminosae phylogenomics.

    PubMed

    Vatanparast, Mohammad; Powell, Adrian; Doyle, Jeff J; Egan, Ashley N

    2018-03-01

    The development of pipelines for locus discovery has spurred the use of target enrichment for plant phylogenomics. However, few studies have compared pipelines from locus discovery and bait design, through validation, to tree inference. We compared three methods within Leguminosae (Fabaceae) and present a workflow for future efforts. Using 30 transcriptomes, we compared Hyb-Seq, MarkerMiner, and the Yang and Smith (Y&S) pipelines for locus discovery, validated 7501 baits targeting 507 loci across 25 genera via Illumina sequencing, and inferred gene and species trees via concatenation- and coalescent-based methods. Hyb-Seq discovered loci with the longest mean length. MarkerMiner discovered the most conserved loci with the least flagged as paralogous. Y&S offered the most parsimony-informative sites and putative orthologs. Target recovery averaged 93% across taxa. We optimized our targeted locus set based on a workflow designed to minimize paralog/ortholog conflation and thus present 423 loci for legume phylogenomics. Methods differed across criteria important for phylogenetic marker development. We recommend Hyb-Seq as a method that may be useful for most phylogenomic projects. Our targeted locus set is a resource for future, community-driven efforts to reconstruct the legume tree of life.

  16. Directed Energy HPM, PP, & PPS Efforts: Magnetized Target Fusion - Field Reversed Configuration

    DTIC Science & Technology

    2006-08-04

    interior. 15. SUBJECT TERMS Magnetized Target Fusion (MTF), Field-Reversed Configuration (FRC), Alternative Confinement Concepts, Fusion Energy 16...research, the Department of Energy’s Office of Fusion Energy Studies (DOE OFES). Sections 2 through 4, which follow, describe in detail SAIC’s, FabTek’s...the plasma physics areas (FRCs and fusion energy ) in which we are working. The conference paper was submitted at this time, as well, and will

  17. Modulation of ventral striatal activity by cognitive effort

    PubMed Central

    Dobryakova, Ekaterina; Jessup, Ryan K; Tricomi, Elizabeth

    2016-01-01

    Effort discounting theory suggests that the value of a reward should be lower if it was effortful to obtain, whereas contrast theory suggests that the contrast between the costly effort and the reward makes the reward seem more valuable. To test these alternative hypotheses, we used functional magnetic resonance imaging (fMRI) as participants engaged in feedback-based learning that required low or high cognitive effort to obtain positive feedback, while the objective amount of information provided by feedback remained constant. In the low effort condition, a single image was presented with four response options. In the high effort condition, two images were presented, each with two response options, and correct feedback was presented only when participants responded correctly to both of the images. Accuracy was significantly lower for the high effort condition, and all participants reported that the high effort condition was more difficult. A region of the ventral striatum selected for sensitivity to feedback value also showed increased activation to feedback presentation associated with the high effort condition relative to the low effort condition, when controlling for activation from corresponding control conditions where feedback was random. These results suggest that increased cognitive effort produces corresponding increases in positive feedback-related ventral striatum activity, in line with the predictions made by contrast theory. The accomplishment of obtaining a hard-earned intrinsic reward, such as positive feedback, may be particularly likely to promote reward-related brain activity. PMID:27989778

  18. Type 2 diabetes exaggerates exercise effort and impairs exercise performance in older women.

    PubMed

    Huebschmann, A G; Kohrt, W M; Herlache, L; Wolfe, P; Daugherty, S; Reusch, J Eb; Bauer, T A; Regensteiner, J G

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is associated with high levels of disability and mortality. Regular exercise prevents premature disability and mortality, but people with T2DM are generally sedentary for reasons that are not fully established. We previously observed that premenopausal women with T2DM report greater effort during exercise than their counterparts without diabetes, as measured by the Rating of Perceived Exertion (RPE) scale. We hypothesized that RPE is greater in older women with T2DM versus no T2DM. We enrolled overweight, sedentary women aged 50-75 years with (n=26) or without T2DM (n=28). Participants performed submaximal cycle ergometer exercise at 30 W and 35% of individually-measured peak oxygen consumption (35% VO2peak). We assessed exercise effort by RPE (self-report) and plasma lactate concentration. VO2peak was lower in T2DM versus controls (p=0.003). RPE was not significantly greater in T2DM versus controls (30 W: Control, 10.4±3.2, T2DM, 11.7±2.3, p=0.08; 35% VO2peak: Control, 11.1±0.5, T2DM, 12.1±0.5, p=0.21). However, lactate was greater in T2DM versus controls (p=0.004 at 30 W; p<0.05 at 35% VO2peak). Greater RPE was associated with higher lactate, higher heart rate, and a hypertension diagnosis (p<0.05 at 30 W and 35% VO2peak). Taken together, physiological measures of exercise effort were greater in older women with T2DM than controls. Exercise effort is a modifiable and thereby targetable end point. In order to facilitate regular exercise, methods to reduce exercise effort in T2DM should be sought. NCT00785005.

  19. Leveraging the Family Influence of Women in Prostate Cancer Efforts Targeting African American Men.

    PubMed

    Okoro, O N; Rutherford, C A; Witherspoon, S F

    2017-08-25

    Incidence rate of prostate cancer among African American (AA) men is 1.6 times that in White men. Prevention efforts in this population have typically been through faith-based organizations and barber shops, with a few including significant others. Culturally, women are known to have a strong influence in the AA family. The current study assessed prostate cancer knowledge and explored perceptions on the roles of women in prostate cancer prevention. To assess prostate cancer knowledge, a 25-item questionnaire was administered to convenience samples of AA women (n = 297) and men (n = 199). Four focus groups were conducted to explore perceptions on the role of women in prostate cancer prevention. Men had a higher mean score (13.2; max of 25) than women (11.4) for knowledge of prostate cancer. For the men, higher knowledge scores were associated with having a family member diagnosed with prostate cancer and likelihood to engage healthcare providers about prostate cancer (p < 0.05). Themes from the focus groups included education/information resource, support and encouragement, instituting a "culture" of regular primary care, modeling healthcare-seeking behavior, surveillance and monitoring, motivation, and influencing diet. The major barrier to women engaging in the roles identified was limited knowledge. Including women in educational interventions may yield added benefits particularly in encouraging AA men to seek regular primary care. This affords men opportunities for dialog with healthcare providers about prostate cancer and informed decision making regarding screening.

  20. Neurocomputational mechanisms underlying subjective valuation of effort costs

    PubMed Central

    Giehl, Kathrin; Sillence, Annie

    2017-01-01

    In everyday life, we have to decide whether it is worth exerting effort to obtain rewards. Effort can be experienced in different domains, with some tasks requiring significant cognitive demand and others being more physically effortful. The motivation to exert effort for reward is highly subjective and varies considerably across the different domains of behaviour. However, very little is known about the computational or neural basis of how different effort costs are subjectively weighed against rewards. Is there a common, domain-general system of brain areas that evaluates all costs and benefits? Here, we used computational modelling and functional magnetic resonance imaging (fMRI) to examine the mechanisms underlying value processing in both the cognitive and physical domains. Participants were trained on two novel tasks that parametrically varied either cognitive or physical effort. During fMRI, participants indicated their preferences between a fixed low-effort/low-reward option and a variable higher-effort/higher-reward offer for each effort domain. Critically, reward devaluation by both cognitive and physical effort was subserved by a common network of areas, including the dorsomedial and dorsolateral prefrontal cortex, the intraparietal sulcus, and the anterior insula. Activity within these domain-general areas also covaried negatively with reward and positively with effort, suggesting an integration of these parameters within these areas. Additionally, the amygdala appeared to play a unique, domain-specific role in processing the value of rewards associated with cognitive effort. These results are the first to reveal the neurocomputational mechanisms underlying subjective cost–benefit valuation across different domains of effort and provide insight into the multidimensional nature of motivation. PMID:28234892

  1. Drug target identification in protozoan parasites.

    PubMed

    Müller, Joachim; Hemphill, Andrew

    2016-08-01

    Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses.

  2. Drug target identification in protozoan parasites

    PubMed Central

    Müller, Joachim; Hemphill, Andrew

    2016-01-01

    Introduction Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Areas covered Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Expert opinion Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses. PMID:27238605

  3. Emerging therapeutic targets in metastatic progression: a focus on breast cancer

    PubMed Central

    Li, Zhuo; Kang, Yibin

    2016-01-01

    Metastasis is the underlying cause of death for the majority of breast cancer patients. Despite significant advances in recent years in basic research and clinical development, therapies that specifically target metastatic breast cancer remain inadequate, and represents the single greatest obstacle to reducing mortality of late-stage breast cancer. Recent efforts have leveraged genomic analysis of breast cancer and molecular dissection of tumor-stromal cross-talk to uncover a number of promising candidates for targeted treatment of metastatic breast cancer. Rational combinations of therapeutic agents targeting tumor-intrinsic properties and microenvironmental components provide a promising strategy to develop precision treatments with higher specificity and less toxicity. In this review, we discuss the emerging therapeutic targets in breast cancer metastasis, from tumor-intrinsic pathways to those that involve the host tissue components, including the immune system. PMID:27000769

  4. Measuring listening effort: driving simulator vs. simple dual-task paradigm

    PubMed Central

    Wu, Yu-Hsiang; Aksan, Nazan; Rizzo, Matthew; Stangl, Elizabeth; Zhang, Xuyang; Bentler, Ruth

    2014-01-01

    Objectives The dual-task paradigm has been widely used to measure listening effort. The primary objectives of the study were to (1) investigate the effect of hearing aid amplification and a hearing aid directional technology on listening effort measured by a complicated, more real world dual-task paradigm, and (2) compare the results obtained with this paradigm to a simpler laboratory-style dual-task paradigm. Design The listening effort of adults with hearing impairment was measured using two dual-task paradigms, wherein participants performed a speech recognition task simultaneously with either a driving task in a simulator or a visual reaction-time task in a sound-treated booth. The speech materials and road noises for the speech recognition task were recorded in a van traveling on the highway in three hearing aid conditions: unaided, aided with omni directional processing (OMNI), and aided with directional processing (DIR). The change in the driving task or the visual reaction-time task performance across the conditions quantified the change in listening effort. Results Compared to the driving-only condition, driving performance declined significantly with the addition of the speech recognition task. Although the speech recognition score was higher in the OMNI and DIR conditions than in the unaided condition, driving performance was similar across these three conditions, suggesting that listening effort was not affected by amplification and directional processing. Results from the simple dual-task paradigm showed a similar trend: hearing aid technologies improved speech recognition performance, but did not affect performance in the visual reaction-time task (i.e., reduce listening effort). The correlation between listening effort measured using the driving paradigm and the visual reaction-time task paradigm was significant. The finding showing that our older (56 to 85 years old) participants’ better speech recognition performance did not result in reduced

  5. Trust and Reciprocity: Are Effort and Money Equivalent?

    PubMed Central

    Vilares, Iris; Dam, Gregory; Kording, Konrad

    2011-01-01

    Trust and reciprocity facilitate cooperation and are relevant to virtually all human interactions. They are typically studied using trust games: one subject gives (entrusts) money to another subject, which may return some of the proceeds (reciprocate). Currently, however, it is unclear whether trust and reciprocity in monetary transactions are similar in other settings, such as physical effort. Trust and reciprocity of physical effort are important as many everyday decisions imply an exchange of physical effort, and such exchange is central to labor relations. Here we studied a trust game based on physical effort and compared the results with those of a computationally equivalent monetary trust game. We found no significant difference between effort and money conditions in both the amount trusted and the quantity reciprocated. Moreover, there is a high positive correlation in subjects' behavior across conditions. This suggests that trust and reciprocity may be character traits: subjects that are trustful/trustworthy in monetary settings behave similarly during exchanges of physical effort. Our results validate the use of trust games to study exchanges in physical effort and to characterize inter-subject differences in trust and reciprocity, and also suggest a new behavioral paradigm to study these differences. PMID:21364931

  6. Effect of visual distraction and auditory feedback on patient effort during robot-assisted movement training after stroke

    PubMed Central

    2011-01-01

    Background Practicing arm and gait movements with robotic assistance after neurologic injury can help patients improve their movement ability, but patients sometimes reduce their effort during training in response to the assistance. Reduced effort has been hypothesized to diminish clinical outcomes of robotic training. To better understand patient slacking, we studied the role of visual distraction and auditory feedback in modulating patient effort during a common robot-assisted tracking task. Methods Fourteen participants with chronic left hemiparesis from stroke, five control participants with chronic right hemiparesis and fourteen non-impaired healthy control participants, tracked a visual target with their arms while receiving adaptive assistance from a robotic arm exoskeleton. We compared four practice conditions: the baseline tracking task alone; tracking while also performing a visual distracter task; tracking with the visual distracter and sound feedback; and tracking with sound feedback. For the distracter task, symbols were randomly displayed in the corners of the computer screen, and the participants were instructed to click a mouse button when a target symbol appeared. The sound feedback consisted of a repeating beep, with the frequency of repetition made to increase with increasing tracking error. Results Participants with stroke halved their effort and doubled their tracking error when performing the visual distracter task with their left hemiparetic arm. With sound feedback, however, these participants increased their effort and decreased their tracking error close to their baseline levels, while also performing the distracter task successfully. These effects were significantly smaller for the participants who used their non-paretic arm and for the participants without stroke. Conclusions Visual distraction decreased participants effort during a standard robot-assisted movement training task. This effect was greater for the hemiparetic arm

  7. The RBANS Effort Index: Base rates in geriatric samples

    PubMed Central

    Duff, Kevin; Spering, Cynthia C.; O’Bryant, Sid E.; Beglinger, Leigh J.; Moser, David J.; Bayless, John D.; Culp, Kennith R.; Mold, James W.; Adams, Russell L.; Scott, James G.

    2011-01-01

    The Effort Index (EI) of the RBANS was developed to assist clinicians in discriminating patients who demonstrate good effort from those with poor effort. However, there are concerns that older adults might be unfairly penalized by this index, which uses uncorrected raw scores. Using five independent samples of geriatric patients with a broad range of cognitive functioning (e.g., cognitively intact, nursing home residents, probable Alzheimer’s disease), base rates of failure on the EI were calculated. In cognitively intact and mildly impaired samples, few older individuals were classified as demonstrating poor effort (e.g., 3% in cognitively intact). However, in the more severely impaired geriatric patients, over one third had EI scores that fell above suggested cut-off scores (e.g., 37% in nursing home residents, 33% in probable Alzheimer’s disease). In the cognitively intact sample, older and less educated patients were more likely to have scores suggestive of poor effort. Education effects were observed in 3 of the 4 clinical samples. Overall cognitive functioning was significantly correlated with EI scores, with poorer cognition being associated with greater suspicion of low effort. The current results suggest that age, education, and level of cognitive functioning should be taken into consideration when interpreting EI results and that significant caution is warranted when examining EI scores in elders suspected of having dementia. PMID:21390895

  8. The RBANS Effort Index: base rates in geriatric samples.

    PubMed

    Duff, Kevin; Spering, Cynthia C; O'Bryant, Sid E; Beglinger, Leigh J; Moser, David J; Bayless, John D; Culp, Kennith R; Mold, James W; Adams, Russell L; Scott, James G

    2011-01-01

    The Effort Index (EI) of the RBANS was developed to assist clinicians in discriminating patients who demonstrate good effort from those with poor effort. However, there are concerns that older adults might be unfairly penalized by this index, which uses uncorrected raw scores. Using five independent samples of geriatric patients with a broad range of cognitive functioning (e.g., cognitively intact, nursing home residents, probable Alzheimer's disease), base rates of failure on the EI were calculated. In cognitively intact and mildly impaired samples, few older individuals were classified as demonstrating poor effort (e.g., 3% in cognitively intact). However, in the more severely impaired geriatric patients, over one third had EI scores that fell above suggested cutoff scores (e.g., 37% in nursing home residents, 33% in probable Alzheimer's disease). In the cognitively intact sample, older and less educated patients were more likely to have scores suggestive of poor effort. Education effects were observed in three of the four clinical samples. Overall cognitive functioning was significantly correlated with EI scores, with poorer cognition being associated with greater suspicion of low effort. The current results suggest that age, education, and level of cognitive functioning should be taken into consideration when interpreting EI results and that significant caution is warranted when examining EI scores in elders suspected of having dementia.

  9. Analyzing and Predicting Effort Associated with Finding and Fixing Software Faults

    NASA Technical Reports Server (NTRS)

    Hamill, Maggie; Goseva-Popstojanova, Katerina

    2016-01-01

    Context: Software developers spend a significant amount of time fixing faults. However, not many papers have addressed the actual effort needed to fix software faults. Objective: The objective of this paper is twofold: (1) analysis of the effort needed to fix software faults and how it was affected by several factors and (2) prediction of the level of fix implementation effort based on the information provided in software change requests. Method: The work is based on data related to 1200 failures, extracted from the change tracking system of a large NASA mission. The analysis includes descriptive and inferential statistics. Predictions are made using three supervised machine learning algorithms and three sampling techniques aimed at addressing the imbalanced data problem. Results: Our results show that (1) 83% of the total fix implementation effort was associated with only 20% of failures. (2) Both safety critical failures and post-release failures required three times more effort to fix compared to non-critical and pre-release counterparts, respectively. (3) Failures with fixes spread across multiple components or across multiple types of software artifacts required more effort. The spread across artifacts was more costly than spread across components. (4) Surprisingly, some types of faults associated with later life-cycle activities did not require significant effort. (5) The level of fix implementation effort was predicted with 73% overall accuracy using the original, imbalanced data. Using oversampling techniques improved the overall accuracy up to 77%. More importantly, oversampling significantly improved the prediction of the high level effort, from 31% to around 85%. Conclusions: This paper shows the importance of tying software failures to changes made to fix all associated faults, in one or more software components and/or in one or more software artifacts, and the benefit of studying how the spread of faults and other factors affect the fix implementation

  10. Thioredoxin and Thioredoxin Target Proteins: From Molecular Mechanisms to Functional Significance

    PubMed Central

    Lee, Samuel; Kim, Soo Min

    2013-01-01

    Abstract The thioredoxin (Trx) system is one of the central antioxidant systems in mammalian cells, maintaining a reducing environment by catalyzing electron flux from nicotinamide adenine dinucleotide phosphate through Trx reductase to Trx, which reduces its target proteins using highly conserved thiol groups. While the importance of protecting cells from the detrimental effects of reactive oxygen species is clear, decades of research in this field revealed that there is a network of redox-sensitive proteins forming redox-dependent signaling pathways that are crucial for fundamental cellular processes, including metabolism, proliferation, differentiation, migration, and apoptosis. Trx participates in signaling pathways interacting with different proteins to control their dynamic regulation of structure and function. In this review, we focus on Trx target proteins that are involved in redox-dependent signaling pathways. Specifically, Trx-dependent reductive enzymes that participate in classical redox reactions and redox-sensitive signaling molecules are discussed in greater detail. The latter are extensively discussed, as ongoing research unveils more and more details about the complex signaling networks of Trx-sensitive signaling molecules such as apoptosis signal-regulating kinase 1, Trx interacting protein, and phosphatase and tensin homolog, thus highlighting the potential direct and indirect impact of their redox-dependent interaction with Trx. Overall, the findings that are described here illustrate the importance and complexity of Trx-dependent, redox-sensitive signaling in the cell. Our increasing understanding of the components and mechanisms of these signaling pathways could lead to the identification of new potential targets for the treatment of diseases, including cancer and diabetes. Antioxid. Redox Signal. 18, 1165–1207. PMID:22607099

  11. The Effects of Hearing Aid Directional Microphone and Noise Reduction Processing on Listening Effort in Older Adults with Hearing Loss.

    PubMed

    Desjardins, Jamie L

    2016-01-01

    Older listeners with hearing loss may exert more cognitive resources to maintain a level of listening performance similar to that of younger listeners with normal hearing. Unfortunately, this increase in cognitive load, which is often conceptualized as increased listening effort, may come at the cost of cognitive processing resources that might otherwise be available for other tasks. The purpose of this study was to evaluate the independent and combined effects of a hearing aid directional microphone and a noise reduction (NR) algorithm on reducing the listening effort older listeners with hearing loss expend on a speech-in-noise task. Participants were fitted with study worn commercially available behind-the-ear hearing aids. Listening effort on a sentence recognition in noise task was measured using an objective auditory-visual dual-task paradigm. The primary task required participants to repeat sentences presented in quiet and in a four-talker babble. The secondary task was a digital visual pursuit rotor-tracking test, for which participants were instructed to use a computer mouse to track a moving target around an ellipse that was displayed on a computer screen. Each of the two tasks was presented separately and concurrently at a fixed overall speech recognition performance level of 50% correct with and without the directional microphone and/or the NR algorithm activated in the hearing aids. In addition, participants reported how effortful it was to listen to the sentences in quiet and in background noise in the different hearing aid listening conditions. Fifteen older listeners with mild sloping to severe sensorineural hearing loss participated in this study. Listening effort in background noise was significantly reduced with the directional microphones activated in the hearing aids. However, there was no significant change in listening effort with the hearing aid NR algorithm compared to no noise processing. Correlation analysis between objective and self

  12. Results of a Regional Effort to Improve Warfarin Management.

    PubMed

    Rose, Adam J; Park, Angela; Gillespie, Christopher; Van Deusen Lukas, Carol; Ozonoff, Al; Petrakis, Beth Ann; Reisman, Joel I; Borzecki, Ann M; Benedict, Ashley J; Lukesh, William N; Schmoke, Timothy J; Jones, Ellen A; Morreale, Anthony P; Ourth, Heather L; Schlosser, James E; Mayo-Smith, Michael F; Allen, Arthur L; Witt, Daniel M; Helfrich, Christian D; McCullough, Megan B

    2017-05-01

    Improved anticoagulation control with warfarin reduces adverse events and represents a target for quality improvement. No previous study has described an effort to improve anticoagulation control across a health system. To describe the results of an effort to improve anticoagulation control in the New England region of the Veterans Health Administration (VA). Our intervention encompassed 8 VA sites managing warfarin for more than 5000 patients in New England (Veterans Integrated Service Network 1 [VISN 1]). We provided sites with a system to measure processes of care, along with targeted audit and feedback. We focused on processes of care associated with site-level anticoagulation control, including prompt follow-up after out-of-range international normalized ratio (INR) values, minimizing loss to follow-up, and use of guideline-concordant INR target ranges. We used a difference-in-differences (DID) model to examine changes in anticoagulation control, measured as percentage time in therapeutic range (TTR), as well as process measures and compared VISN 1 sites with 116 VA sites located outside VISN 1. VISN 1 sites improved on TTR, our main indicator of quality, from 66.4% to 69.2%, whereas sites outside VISN 1 improved from 65.9% to 66.4% (DID 2.3%, P < 0.001). Improvement in TTR correlated strongly with the extent of improvement on process-of-care measures, which varied widely across VISN 1 sites. A regional quality improvement initiative, using performance measurement with audit and feedback, improved TTR by 2.3% more than control sites, which is a clinically important difference. Improving relevant processes of care can improve outcomes for patients receiving warfarin.

  13. Central and Peripheral Molecular Targets for Anti-Obesity Pharmacotherapy

    PubMed Central

    Valentino, Michael A.; Lin, Jieru E.; Waldman, Scott A.

    2011-01-01

    Obesity has emerged as one of the principle worldwide health concerns of the modern era, and there exists a tremendous unmet clinical need for safe and effective therapies to combat this global pandemic. The prevalence of obesity and its associated co-morbidities, including cardiovascular and metabolic diseases, has focused drug discovery and development on generating effective modalities for the treatment and prevention of obesity. Early efforts in the field of obesity pharmacotherapy centered on agents with indeterminate mechanisms of action producing treatment paradigms characterized by significant off-target effects. During the past two decades, new insights have been made into the physiologic regulation of energy balance and the subordinate central and peripheral circuits coordinating appetite, metabolism, and lipogenesis. These studies have revealed previously unrecognized molecular targets for controlling appetite and managing weight from which has emerged a new wave of targeted pharmacotherapies to prevent and control obesity. PMID:20445536

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

    PubMed

    Kalunian, K C

    2016-09-01

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

  15. Targeted gene disruption of glycerol-3-phosphate dehydrogenase in Colletotrichum gloeosporioides reveals evidence that glycerol is a significant transferred nutrient from host plant to fungal pathogen.

    PubMed

    Wei, Yangdou; Shen, Wenyun; Dauk, Melanie; Wang, Feng; Selvaraj, Gopalan; Zou, Jitao

    2004-01-02

    Unidirectional transfer of nutrients from plant host to pathogen represents a most revealing aspect of the parasitic lifestyle of plant pathogens. Whereas much effort has been focused on sugars and amino acids, the identification of other significant metabolites is equally important for comprehensive characterization of metabolic interactions between plants and biotrophic fungal pathogens. Employing a strategy of targeted gene disruption, we generated a mutant strain (gpdhDelta) defective in glycerol-3-phosphate dehydrogenase in a hemibiotrophic plant pathogen, Colletotrichum gloeosporioides f.sp. malvae. The gpdhDelta strain had severe defects in carbon utilization as it could use neither glucose nor amino acids for sustained growth. Although the mutant mycelia were able to grow on potato dextrose agar medium, they displayed arrhythmicity in growth and failure to conidiate. The metabolic defect of gpdhDelta could be entirely ameliorated by glycerol in chemically defined minimal medium. Furthermore, glycerol was the one and only metabolite that could restore rhythmic growth and conidiation of gpdhDelta. Despite the profound defects in carbon source utilization, in planta the gpdhDelta strain exhibited normal pathogenicity, proceeded normally in its life cycle, and produced abundant conidia. Analysis of plant tissues at the peripheral zone of fungal infection sites revealed a time-dependent reduction in glycerol content. This study provides strong evidence for a role of glycerol as a significant transferred metabolite from plant to fungal pathogen.

  16. Hearing Handicap and Speech Recognition Correlate With Self-Reported Listening Effort and Fatigue.

    PubMed

    Alhanbali, Sara; Dawes, Piers; Lloyd, Simon; Munro, Kevin J

    To investigate the correlations between hearing handicap, speech recognition, listening effort, and fatigue. Eighty-four adults with hearing loss (65 to 85 years) completed three self-report questionnaires: the Fatigue Assessment Scale, the Effort Assessment Scale, and the Hearing Handicap Inventory for Elderly. Audiometric assessment included pure-tone audiometry and speech recognition in noise. There was a significant positive correlation between handicap and fatigue (r = 0.39, p < 0.05) and handicap and effort (r = 0.73, p < 0.05). There were significant (but lower) correlations between speech recognition and fatigue (r = 0.22, p < 0.05) or effort (r = 0.32, p< 0.05). There was no significant correlation between hearing level and fatigue or effort. Hearing handicap and speech recognition both correlate with self-reported listening effort and fatigue, which is consistent with a model of listening effort and fatigue where perceived difficulty is related to sustained effort and fatigue for unrewarding tasks over which the listener has low control. A clinical implication is that encouraging clients to recognize and focus on the pleasure and positive experiences of listening may result in greater satisfaction and benefit from hearing aid use.

  17. Airway smooth muscle: a potential target for asthma therapy.

    PubMed

    Dowell, Maria L; Lavoie, Tera L; Solway, Julian; Krishnan, Ramaswamy

    2014-01-01

    Asthma is a major public health problem that afflicts nearly one in 20 people worldwide. Despite available treatments, asthma symptoms remain poorly controlled in a significant minority of asthma patients, especially those with severe disease. Accordingly, much ongoing effort has been directed at developing new therapeutic strategies; these efforts are described in detail below. Although mucus hypersecretion is an important component of asthma pathobiology, the primary mechanism of morbidity and mortality in asthma is excessive narrowing of the airway. The key end- effector of excessive airway narrowing is airway smooth muscle (ASM) contraction; overcoming ASM contraction is therefore a prominent therapeutic strategy. Here, we review exciting new advances aimed at ASM relaxation. Exciting advances in ASM biology have identified new therapeutic targets for the prevention or reversal of bronchoconstriction in asthma.

  18. 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.

  19. Enhancing emotional-based target prediction

    NASA Astrophysics Data System (ADS)

    Gosnell, Michael; Woodley, Robert

    2008-04-01

    This work extends existing agent-based target movement prediction to include key ideas of behavioral inertia, steady states, and catastrophic change from existing psychological, sociological, and mathematical work. Existing target prediction work inherently assumes a single steady state for target behavior, and attempts to classify behavior based on a single emotional state set. The enhanced, emotional-based target prediction maintains up to three distinct steady states, or typical behaviors, based on a target's operating conditions and observed behaviors. Each steady state has an associated behavioral inertia, similar to the standard deviation of behaviors within that state. The enhanced prediction framework also allows steady state transitions through catastrophic change and individual steady states could be used in an offline analysis with additional modeling efforts to better predict anticipated target reactions.

  20. Student Effort, Consistency, and Online Performance

    ERIC Educational Resources Information Center

    Patron, Hilde; Lopez, Salvador

    2011-01-01

    This paper examines how student effort, consistency, motivation, and marginal learning, influence student grades in an online course. We use data from eleven Microeconomics courses taught online for a total of 212 students. Our findings show that consistency, or less time variation, is a statistically significant explanatory variable, whereas…

  1. Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles.

    PubMed

    Sugo, Tsukasa; Terada, Michiko; Oikawa, Tatsuo; Miyata, Kenichi; Nishimura, Satoshi; Kenjo, Eriya; Ogasawara-Shimizu, Mari; Makita, Yukimasa; Imaichi, Sachiko; Murata, Shumpei; Otake, Kentaro; Kikuchi, Kuniko; Teratani, Mika; Masuda, Yasushi; Kamei, Takayuki; Takagahara, Shuichi; Ikeda, Shota; Ohtaki, Tetsuya; Matsumoto, Hirokazu

    2016-09-10

    Despite considerable efforts to develop efficient carriers, the major target organ of short-interfering RNAs (siRNAs) remains limited to the liver. Expanding the application outside the liver is required to increase the value of siRNAs. Here we report on a novel platform targeted to muscular organs by conjugation of siRNAs with anti-CD71 Fab' fragment. This conjugate showed durable gene-silencing in the heart and skeletal muscle for one month after intravenous administration in normal mice. In particular, 1μg siRNA conjugate showed significant gene-silencing in the gastrocnemius when injected intramuscularly. In a mouse model of peripheral artery disease, the treatment with myostatin-targeting siRNA conjugate by intramuscular injection resulted in significant silencing of myostatin and hypertrophy of the gastrocnemius, which was translated into the recovery of running performance. These data demonstrate the utility of antibody conjugation for siRNA delivery and the therapeutic potential for muscular diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Evolution of State Outreach Efforts Under SCHIP

    PubMed Central

    Williams, Susan R.; Rosenbach, Margo L.

    2007-01-01

    States have shown creativity and adaptability in developing outreach strategies to promote State Children's Health Insurance Program (SCHIP) enrollment. As the program has matured and the fiscal environment has tightened, States have learned what efforts are successful and have tailored their approaches accordingly This article reviews the evolution of State outreach strategies under SCHIP, using qualitative information from all 50 States and the District of Columbia. Early campaigns were aimed at building broad awareness of SCHIP. Over time, States have adapted their outreach campaigns to close the gaps in enrolling hard-to-reach populations, by modifying their target populations, messages, methods, organizational strategies, and emphasis. PMID:17722754

  3. The Effect of Effort and Feedback on the Formation of Student Attitudes.

    ERIC Educational Resources Information Center

    McMillan, James H.

    Students in four university classes in educational psychology were used as the target population to study the effect of two factors, degree of effort exerted studying a subject, and written feedback from the instructor, on the cognitive and affective attitudes these students formed toward the subject and their assignments. The students, unaware…

  4. The road to heaven is paved with effort: Perceived effort amplifies moral judgment.

    PubMed

    Bigman, Yochanan E; Tamir, Maya

    2016-12-01

    If good intentions pave the road to hell, what paves the road to heaven? We propose that moral judgments are based, in part, on the degree of effort exerted in performing the immoral or moral act. Because effort can serve as an index of goal importance, greater effort in performing immoral acts would lead to more negative judgments, whereas greater effort in performing moral acts would lead to more positive judgments. In support of these ideas, we found that perceived effort intensified judgments of both immoral (Studies 1-2) and moral (Studies 2-7) agents. The effect of effort on judgment was independent of the outcome (Study 3) and of perceptions of the outcome extremity (Study 6). Furthermore, the effect of effort on judgment was mediated by perceived goal importance (Studies 4-6), even when controlling for perceived intentions (Studies 5-6). Finally, we demonstrate that perceived effort can influence actual behavior, such as the assignment of monetary rewards (Study 7). We discuss the possible implications of effort as a causal motivational factor in moral judgment and social retribution. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  5. Real time target allocation in cooperative unmanned aerial vehicles

    NASA Astrophysics Data System (ADS)

    Kudleppanavar, Ganesh

    The prolific development of Unmanned Aerial Vehicles (UAV's) in recent years has the potential to provide tremendous advantages in military, commercial and law enforcement applications. While safety and performance take precedence in the development lifecycle, autonomous operations and, in particular, cooperative missions have the ability to significantly enhance the usability of these vehicles. The success of cooperative missions relies on the optimal allocation of targets while taking into consideration the resource limitation of each vehicle. The task allocation process can be centralized or decentralized. This effort presents the development of a real time target allocation algorithm that considers available stored energy in each vehicle while minimizing the communication between each UAV. The algorithm utilizes a nearest neighbor search algorithm to locate new targets with respect to existing targets. Simulations show that this novel algorithm compares favorably to the mixed integer linear programming method, which is computationally more expensive. The implementation of this algorithm on Arduino and Xbee wireless modules shows the capability of the algorithm to execute efficiently on hardware with minimum computation complexity.

  6. Rational design of chemical genetic probes of RNA function and lead therapeutics targeting repeating transcripts.

    PubMed

    Disney, Matthew D

    2013-12-01

    RNA is an important yet vastly underexploited target for small molecule chemical probes or lead therapeutics. Small molecules have been used successfully to modulate the function of the bacterial ribosome, viral RNAs and riboswitches. These RNAs are either highly expressed or can be targeted using substrate mimicry, a mainstay in the design of enzyme inhibitors. However, most cellular RNAs are neither highly expressed nor have a lead small molecule inhibitor, a significant challenge for drug discovery efforts. Herein, I describe the design of small molecules targeting expanded repeating transcripts that cause myotonic muscular dystrophy (DM). These test cases illustrate the challenges of designing small molecules that target RNA and the advantages of targeting repeating transcripts. Lastly, I discuss how small molecules might be more advantageous than oligonucleotides for targeting RNA. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Effort in Multitasking: Local and Global Assessment of Effort.

    PubMed

    Kiesel, Andrea; Dignath, David

    2017-01-01

    When performing multiple tasks in succession, self-organization of task order might be superior compared to external-controlled task schedules, because self-organization allows optimizing processing modes and thus reduces switch costs, and it increases commitment to task goals. However, self-organization is an additional executive control process that is not required if task order is externally specified and as such it is considered as time-consuming and effortful. To compare self-organized and externally controlled task scheduling, we suggest assessing global subjective and objectives measures of effort in addition to local performance measures. In our new experimental approach, we combined characteristics of dual tasking settings and task switching settings and compared local and global measures of effort in a condition with free choice of task sequence and a condition with cued task sequence. In a multi-tasking environment, participants chose the task order while the task requirement of the not-yet-performed task remained the same. This task preview allowed participants to work on the previously non-chosen items in parallel and resulted in faster responses and fewer errors in task switch trials than in task repetition trials. The free-choice group profited more from this task preview than the cued group when considering local performance measures. Nevertheless, the free-choice group invested more effort than the cued group when considering global measures. Thus, self-organization in task scheduling seems to be effortful even in conditions in which it is beneficiary for task processing. In a second experiment, we reduced the possibility of task preview for the not-yet-performed tasks in order to hinder efficient self-organization. Here neither local nor global measures revealed substantial differences between the free-choice and a cued task sequence condition. Based on the results of both experiments, we suggest that global assessment of effort in addition to

  8. Using GIS and secondary data to target diabetes-related public health efforts.

    PubMed

    Curtis, Amy B; Kothari, Catherine; Paul, Rajib; Connors, Elyse

    2013-01-01

    To efficiently help communities prevent and manage diabetes, health departments need to be able to target populations with high risk but low resources. To aid in this process, we mapped county-level diabetes-related rates and resources/use using publicly available secondary data to identify Michigan counties with high diabetes prevalence and low or no medical and/or community resources. We collected county-level diabetes-related rates and resources from Web-based sources and mapped them using geographic information systems (GIS) software. Data included age-adjusted county diabetes rates, diabetes-related medical resource and resource use (i.e., the number of endocrinologists and percentage of Medicare patients with diabetes who received hemoglobin A1c testing in the past year), community resources (i.e., the number of certified diabetes self-management education and diabetes support groups), as well as population estimates and demographics (e.g., rural residence, education, poverty, and race/ethnicity). We created GIS maps highlighting areas that had higher-than-median rates of disease and lower-than-median resources. We also conducted linear, logistic, and Poisson regression analyses to confirm GIS findings. There were clear regional trends in resource distribution across Michigan. The 15 counties in the Upper Peninsula were lacking in medical resources but higher in community resources compared with the 68 counties in the Lower Peninsula. There was little apparent association between need (diabetes prevalence) and diabetes-related resources/use. Specific counties with high diabetes prevalence and low resources were easily identified using GIS mapping. Using public data and mapping tools identified diabetes health-service shortage areas for targeted public health programming.

  9. A network-based drug repositioning infrastructure for precision cancer medicine through targeting significantly mutated genes in the human cancer genomes.

    PubMed

    Cheng, Feixiong; Zhao, Junfei; Fooksa, Michaela; Zhao, Zhongming

    2016-07-01

    Development of computational approaches and tools to effectively integrate multidomain data is urgently needed for the development of newly targeted cancer therapeutics. We proposed an integrative network-based infrastructure to identify new druggable targets and anticancer indications for existing drugs through targeting significantly mutated genes (SMGs) discovered in the human cancer genomes. The underlying assumption is that a drug would have a high potential for anticancer indication if its up-/down-regulated genes from the Connectivity Map tended to be SMGs or their neighbors in the human protein interaction network. We assembled and curated 693 SMGs in 29 cancer types and found 121 proteins currently targeted by known anticancer or noncancer (repurposed) drugs. We found that the approved or experimental cancer drugs could potentially target these SMGs in 33.3% of the mutated cancer samples, and this number increased to 68.0% by drug repositioning through surveying exome-sequencing data in approximately 5000 normal-tumor pairs from The Cancer Genome Atlas. Furthermore, we identified 284 potential new indications connecting 28 cancer types and 48 existing drugs (adjusted P < .05), with a 66.7% success rate validated by literature data. Several existing drugs (e.g., niclosamide, valproic acid, captopril, and resveratrol) were predicted to have potential indications for multiple cancer types. Finally, we used integrative analysis to showcase a potential mechanism-of-action for resveratrol in breast and lung cancer treatment whereby it targets several SMGs (ARNTL, ASPM, CTTN, EIF4G1, FOXP1, and STIP1). In summary, we demonstrated that our integrative network-based infrastructure is a promising strategy to identify potential druggable targets and uncover new indications for existing drugs to speed up molecularly targeted cancer therapeutics. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All

  10. Rabies Vaccination Targets for Stray Dog Populations

    PubMed Central

    Leung, Tiffany; Davis, Stephen A.

    2017-01-01

    The role of stray dogs in the persistence of domestic dog rabies, and whether removal of such dogs is beneficial, remains contentious issues for control programs seeking to eliminate rabies. While a community might reach the WHO vaccination target of 70% for dogs that can be handled, the stray or neighborhood dogs that are too wary of humans to be held are a more problematic population to vaccinate. Here, we present a method to estimate vaccination targets for stray dogs when the dog population is made up of stray, free-roaming, and confined dogs, where the latter two types are considered to have an identifiable owner. The control effort required for stray dogs is determined by the type-reproduction number, T1, the number of stray dogs infected by one rabid stray dog either directly or via any chain of infection involving owned dogs. Like the basic reproduction number R0 for single host populations, T1 determines the vaccination effort required to control the spread of disease when control is targeted at one host type, and there is a mix of host types. The application of T1 to rabies in mixed populations of stray and owned dogs is novel. We show that the outcome is sensitive to the vaccination coverage in the owned dog population, such that if vaccination rates of owned dogs were too low then no control effort targeting stray dogs is able to control or eliminate rabies. The required vaccination level also depends on the composition of the dog population, where a high proportion of either stray or free-roaming dogs implies unrealistically high vaccination levels are required to prevent rabies. We find that the required control effort is less sensitive to continuous culling that increases the death rate of stray dogs than to changes in the carrying capacity of the stray dog population. PMID:28451589

  11. Educational Effectiveness, Target, and Content for Prudent Antibiotic Use

    PubMed Central

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

    2015-01-01

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

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

    USGS Publications Warehouse

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

    2016-01-01

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

  13. Marine Targets Classification in PolInSAR Data

    NASA Astrophysics Data System (ADS)

    Chen, Peng; Yang, Jingsong; Ren, Lin

    2014-11-01

    In this paper, marine stationary targets and moving targets are studied by Pol-In-SAR data of Radarsat-2. A new method of stationary targets detection is proposed. The method get the correlation coefficient image of the In-SAR data, and using the histogram of correlation coefficient image. Then, A Constant False Alarm Rate (CFAR) algorithm and The Probabilistic Neural Network model are imported to detect stationary targets. To find the moving targets, Azimuth Ambiguity is show as an important feature. We use the length of azimuth ambiguity to get the target's moving direction and speed. Make further efforts, Targets classification is studied by rebuild the surface elevation of marine targets.

  14. Marine Targets Classification in PolInSAR Data

    NASA Astrophysics Data System (ADS)

    Chen, Peng; Yang, Jingsong; Ren, Lin

    2014-11-01

    In this paper, marine stationary targets and moving targets are studied by Pol-In-SAR data of Radarsat-2. A new method of stationary targets detection is proposed. The method get the correlation coefficient image of the In-SAR data, and using the histogram of correlation coefficient image. Then , A Constant False Alarm Rate (CFAR) algorithm and The Probabilistic Neural Network model are imported to detect stationary targets. To find the moving targets, Azimuth Ambiguity is show as an important feature. We use the length of azimuth ambiguity to get the target's moving direction and speed. Make further efforts, Targets classification is studied by rebuild the surface elevation of marine targets.

  15. Significant reduction in energy for plant-growth lighting in space using targeted LED lighting and spectral manipulation

    NASA Astrophysics Data System (ADS)

    Poulet, L.; Massa, G. D.; Morrow, R. C.; Bourget, C. M.; Wheeler, R. M.; Mitchell, C. A.

    2014-07-01

    Bioregenerative life-support systems involving photoautotrophic organisms will be necessary to sustain long-duration crewed missions at distant space destinations. Since sufficient sunlight will not always be available for plant growth at many space destinations, efficient electric-lighting solutions are greatly needed. The present study demonstrated that targeted plant lighting with light-emitting diodes (LEDs) and optimizing spectral parameters for close-canopy overhead LED lighting allowed the model crop leaf lettuce (Lactuca sativa L. cv. 'Waldmann's Green') to be grown using significantly less electrical energy than using traditional electric-lighting sources. Lettuce stands were grown hydroponically in a growth chamber controlling temperature, relative humidity, and CO2 level. Several red:blue ratios were tested for growth rate during the lag phase of lettuce growth. In addition, start of the exponential growth phase was evaluated. Following establishment of a 95% red + 5% blue spectral balance giving the best growth response, the energy efficiency of a targeted lighting system was compared with that of two total coverage (untargeted) LED lighting systems throughout a crop-production cycle, one using the same proportion of red and blue LEDs and the other using white LEDs. At the end of each cropping cycle, whole-plant fresh and dry mass and leaf area were measured and correlated with the amount of electrical energy (kWh) consumed for crop lighting. Lettuce crops grown with targeted red + blue LED lighting used 50% less energy per unit dry biomass accumulated, and the total coverage white LEDs used 32% less energy per unit dry biomass accumulated than did the total coverage red + blue LEDs. An energy-conversion efficiency of less than 1 kWh/g dry biomass is possible using targeted close-canopy LED lighting with spectral optimization. This project was supported by NASA grant NNX09AL99G.

  16. 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

  17. 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

  18. Effort-reward imbalance and burnout among nurses.

    PubMed

    Bakker, A B; Killmer, C H; Siegrist, J; Schaufeli, W B

    2000-04-01

    This study among a sample of 204 German nurses tested the hypothesis that an imbalance of high extrinsic efforts spent (i.e. job demands) and low extrinsic rewards obtained (e.g. poor promotion prospects) are associated with the burnout syndrome: the depletion of nurses' emotional resources. The results of a series of analyses of variances confirmed this hypothesis, by showing that those nurses who experienced an effort-reward imbalance (ERI) reported higher levels on two of the three core dimensions of burnout (i.e. emotional exhaustion and depersonalization) than those who did not experience such an imbalance. Moreover - as additionally hypothesized - significant interaction effects indicated that burnout (i.e. emotional exhaustion and reduced personal accomplishment) was particularly prevalent among those nurses who experienced ERI and put relatively high intrinsic effort into their jobs, as reflected by their strong tendency to be personally in control over job conditions.

  19. Effortful Control, Social Information Processing, and the Prevention of Aggression in Elementary Schools

    ERIC Educational Resources Information Center

    Ellis, Alan Reid

    2012-01-01

    Early aggression is a problem in its own right and a risk factor for further developmental problems. Although both effortful control and social information processing (SIP) skills are negatively associated with aggression and are targeted by aggression prevention programs, little is known about the relation between them or about their joint…

  20. KRAS as a Therapeutic Target.

    PubMed

    McCormick, Frank

    2015-04-15

    KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF-MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus. ©2015 American Association for Cancer Research.

  1. Effortful echolalia.

    PubMed

    Hadano, K; Nakamura, H; Hamanaka, T

    1998-02-01

    We report three cases of effortful echolalia in patients with cerebral infarction. The clinical picture of speech disturbance is associated with Type 1 Transcortical Motor Aphasia (TCMA, Goldstein, 1915). The patients always spoke nonfluently with loss of speech initiative, dysarthria, dysprosody, agrammatism, and increased effort and were unable to repeat sentences longer than those containing four or six words. In conversation, they first repeated a few words spoken to them, and then produced self initiated speech. The initial repetition as well as the subsequent self initiated speech, which were realized equally laboriously, can be regarded as mitigated echolalia (Pick, 1924). They were always aware of their own echolalia and tried to control it without effect. These cases demonstrate that neither the ability to repeat nor fluent speech are always necessary for echolalia. The possibility that a lesion in the left medial frontal lobe, including the supplementary motor area, plays an important role in effortful echolalia is discussed.

  2. Discovery of novel drugs for promising targets.

    PubMed

    Martell, Robert E; Brooks, David G; Wang, Yan; Wilcoxen, Keith

    2013-09-01

    Once a promising drug target is identified, the steps to actually discover and optimize a drug are diverse and challenging. The goal of this study was to provide a road map to navigate drug discovery. Review general steps for drug discovery and provide illustrating references. A number of approaches are available to enhance and accelerate target identification and validation. Consideration of a variety of potential mechanisms of action of potential drugs can guide discovery efforts. The hit to lead stage may involve techniques such as high-throughput screening, fragment-based screening, and structure-based design, with informatics playing an ever-increasing role. Biologically relevant screening models are discussed, including cell lines, 3-dimensional culture, and in vivo screening. The process of enabling human studies for an investigational drug is also discussed. Drug discovery is a complex process that has significantly evolved in recent years. © 2013 Elsevier HS Journals, Inc. All rights reserved.

  3. Effort testing in children: can cognitive and symptom validity measures differentiate malingered performances?

    PubMed

    Rambo, Philip L; Callahan, Jennifer L; Hogan, Lindsey R; Hullmann, Stephanie; Wrape, Elizabeth

    2015-01-01

    Recent efforts have contributed to significant advances in the detection of malingered performances in adults during cognitive assessment. However, children's ability to purposefully underperform has received relatively little attention. The purpose of the present investigation was to examine children's performances on common intellectual measures, as well as two symptom validity measures: the Test of Memory Malingering and the Dot-Counting Test. This was accomplished through the administration of measures to children ages 6 to 12 years old in randomly assigned full-effort (control) and poor-effort (treatment) conditions. Prior to randomization, children's general intellectual functioning (i.e., IQ) was estimated via administration of the Kaufman Brief Intellectual Battery-Second Edition (KBIT-2). Multivariate analyses revealed that the conditions significantly differed on some but not all administered measures. Specifically, children's estimated IQ in the treatment condition significantly differed from the full-effort IQ initially obtained from the same children on the KBIT-2, as well as from the IQs obtained in the full-effort control condition. These findings suggest that children are fully capable of willfully underperforming during cognitive testing; however, consistent with prior investigations, some measures evidence greater sensitivity than others in evaluating effort.

  4. Cryogenic target system for hydrogen layering

    DOE PAGES

    Parham, T.; Kozioziemski, B.; Atkinson, D.; ...

    2015-11-24

    Here, a cryogenic target positioning system was designed and installed on the National Ignition Facility (NIF) target chamber. This instrument incorporates the ability to fill, form, and characterize the NIF targets with hydrogen isotopes needed for ignition experiments inside the NIF target bay then transport and position them in the target chamber. This effort brought to fruition years of research in growing and metrologizing high-quality hydrogen fuel layers and landed it in an especially demanding operations environment in the NIF facility. D-T (deuterium-tritium) layers for NIF ignition experiments have extremely tight specifications and must be grown in a very highlymore » constrained environment: a NIF ignition target inside a cryogenic target positioner inside the NIF target bay. Exquisite control of temperature, pressure, contaminant level, and thermal uniformity are necessary throughout seed formation and layer growth to create an essentially-groove-free single crystal layer.« less

  5. The Effect of Tinnitus on Listening Effort in Normal-Hearing Young Adults: A Preliminary Study.

    PubMed

    Degeest, Sofie; Keppler, Hannah; Corthals, Paul

    2017-04-14

    The objective of this study was to investigate the effect of chronic tinnitus on listening effort. Thirteen normal-hearing young adults with chronic tinnitus were matched with a control group for age, gender, hearing thresholds, and educational level. A dual-task paradigm was used to evaluate listening effort in different listening conditions. A primary speech-recognition task and a secondary memory task were performed both separately and simultaneously. Furthermore, subjective listening effort was questioned for various listening situations. The Tinnitus Handicap Inventory was used to control for tinnitus handicap. Listening effort significantly increased in the tinnitus group across listening conditions. There was no significant difference in listening effort between listening conditions, nor was there an interaction between groups and listening conditions. Subjective listening effort did not significantly differ between both groups. This study is a first exploration of listening effort in normal-hearing participants with chronic tinnitus showing that listening effort is increased as compared with a control group. There is a need to further investigate the cognitive functions important for speech understanding and their possible relation with the presence of tinnitus and listening effort.

  6. Spectral analysis of sinus arrhythmia - A measure of mental effort

    NASA Technical Reports Server (NTRS)

    Vicente, Kim J.; Craig Thornton, D.; Moray, Neville

    1987-01-01

    The validity of the spectral analysis of sinus arrhythmia as a measure of mental effort was investigated using a computer simulation of a hovercraft piloted along a river as the experimental task. Strong correlation was observed between the subjective effort-ratings and the heart-rate variability (HRV) power spectrum between 0.06 and 0.14 Hz. Significant correlations were observed not only between subjects but, more importantly, within subjects as well, indicating that the spectral analysis of HRV is an accurate measure of the amount of effort being invested by a subject. Results also indicate that the intensity of effort invested by subjects cannot be inferred from the objective ratings of task difficulty or from performance.

  7. Methane mitigation shows significant benefits towards achieving the 1.5 degree target.

    NASA Astrophysics Data System (ADS)

    Collins, W.; Webber, C.; Cox, P. M.; Huntingford, C.; Lowe, J. A.; Sitch, S.

    2017-12-01

    Most analyses of allowable carbon emissions to achieve the 1.5 degree target implicitly assume that the ratio of CO2 to non-CO2 greenhouse gases remains near constant, and that all radiative forcing factors have similar impacts on land and ocean carbon storage. Here we determine how plausible reductions in methane emissions will make the carbon targets more feasible. We account for the latest estimates of the methane radiative effect as well as the indirect effects of methane on ozone. We particularly address the differing effects of methane and CO2 mitigation on the land carbon storage including via reduced concentrations of surface ozone. The methodology uses an intermediate complexity climate model (IMOGEN) coupled to a land surface model (JULES) which represents the details of the terrestrial carbon cycle. The carbon emissions inputs to IMOGEN are varied to find allowable pathways consistent with the Paris 1.5 K or 2.0 K targets. The IMOGEN physical parameters are altered to represent the climate characteristics of 38 CMIP5 models (such as climate sensitivity) to provide bounds on the range of allowable CO2 emissions. We examine the effects of three different methane mitigation options that are broadly consistent with the ranges in the SSP scenarios: little mitigation, cost-optimal mitigation, and maximal mitigation. The land and ocean carbon storage increases with methane mitigation, allowing more flexibility in CO2 emission reduction. This is mostly since CO2 fertilisation is reduced less with high methane mitigation, with a small contribution from reduced plant damage with lower surface ozone levels.

  8. Direct-to-Consumer Marketing: A Complementary Approach to Traditional Dissemination and implementation Efforts for Mental Health and Substance Abuse Interventions

    PubMed Central

    Becker, Sara J.

    2014-01-01

    The overall chasm between those who need treatment for mental health and substance abuse (M/SU) and those who receive effective treatment consists of two, interrelated gaps: the research-to-practice gap and the treatment gap. Prior efforts to disseminate evidence-based practice (EBP) for M/SU have predominantly targeted the research-to-practice gap, by focusing efforts toward treatment providers. This article introduces direct-to-consumer (DTC) marketing that targets patients and caregivers as a complementary approach to existing dissemination efforts. Specific issues discussed include: rationale for DTC marketing based on the concept of push versus pull marketing; overview of key stakeholders involved in DTC marketing; and description of the Marketing Mix planning framework. The applicability of these issues to the dissemination of EBP for M/SU is discussed. PMID:25937710

  9. Direct-to-Consumer Marketing: A Complementary Approach to Traditional Dissemination and implementation Efforts for Mental Health and Substance Abuse Interventions.

    PubMed

    Becker, Sara J

    2015-03-01

    The overall chasm between those who need treatment for mental health and substance abuse (M/SU) and those who receive effective treatment consists of two, interrelated gaps: the research-to-practice gap and the treatment gap. Prior efforts to disseminate evidence-based practice (EBP) for M/SU have predominantly targeted the research-to-practice gap, by focusing efforts toward treatment providers. This article introduces direct-to-consumer (DTC) marketing that targets patients and caregivers as a complementary approach to existing dissemination efforts. Specific issues discussed include: rationale for DTC marketing based on the concept of push versus pull marketing; overview of key stakeholders involved in DTC marketing; and description of the Marketing Mix planning framework. The applicability of these issues to the dissemination of EBP for M/SU is discussed.

  10. Topics in LIFE Target Survival: 11-SI-004 Final Report

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

    Miles, Robin; Benett, Bill; Bond, Tiziana

    The LIFE target design incorporates many considerations to generate the desired fusion gain including the physics design, the cost of manufacturing of the target, the injectability of the target, the aerodynamic flight characteristics of the target, the ability to track and engage the target and to maintain the structural and thermal integrity of the target. This document describes the effort that was made in support of issues of survivability of the target during injection which included issues massmanufactural materials and processes which could be used in the target.

  11. TARGET: Rapid Capture of Process Knowledge

    NASA Technical Reports Server (NTRS)

    Ortiz, C. J.; Ly, H. V.; Saito, T.; Loftin, R. B.

    1993-01-01

    TARGET (Task Analysis/Rule Generation Tool) represents a new breed of tool that blends graphical process flow modeling capabilities with the function of a top-down reporting facility. Since NASA personnel frequently perform tasks that are primarily procedural in nature, TARGET models mission or task procedures and generates hierarchical reports as part of the process capture and analysis effort. Historically, capturing knowledge has proven to be one of the greatest barriers to the development of intelligent systems. Current practice generally requires lengthy interactions between the expert whose knowledge is to be captured and the knowledge engineer whose responsibility is to acquire and represent the expert's knowledge in a useful form. Although much research has been devoted to the development of methodologies and computer software to aid in the capture and representation of some types of knowledge, procedural knowledge has received relatively little attention. In essence, TARGET is one of the first tools of its kind, commercial or institutional, that is designed to support this type of knowledge capture undertaking. This paper will describe the design and development of TARGET for the acquisition and representation of procedural knowledge. The strategies employed by TARGET to support use by knowledge engineers, subject matter experts, programmers and managers will be discussed. This discussion includes the method by which the tool employs its graphical user interface to generate a task hierarchy report. Next, the approach to generate production rules for incorporation in and development of a CLIPS based expert system will be elaborated. TARGET also permits experts to visually describe procedural tasks as a common medium for knowledge refinement by the expert community and knowledge engineer making knowledge consensus possible. The paper briefly touches on the verification and validation issues facing the CLIPS rule generation aspects of TARGET. A description of

  12. Dynamic FLIR Target Acquisition. Phase I.

    DTIC Science & Technology

    1978-08-02

    The execution of the experimental plan developed and outlined in this report will make up the bulk of our second year effort. The third year will be...outlined in this report will make up the bulk of our second year effort. The third year will be devoted to further experimentation and analysis of...established. 2.1 TARGET SELECTION In an analysis of the success or failure of past air strike campaigns from WW II through the Six Day War (see Figure 2

  13. Propagation of Significant Figures.

    ERIC Educational Resources Information Center

    Schwartz, Lowell M.

    1985-01-01

    Shows that the rules of thumb for propagating significant figures through arithmetic calculations frequently yield misleading results. Also describes two procedures for performing this propagation more reliably than the rules of thumb. However, both require considerably more calculational effort than do the rules. (JN)

  14. Autonomous target recognition using remotely sensed surface vibration measurements

    NASA Astrophysics Data System (ADS)

    Geurts, James; Ruck, Dennis W.; Rogers, Steven K.; Oxley, Mark E.; Barr, Dallas N.

    1993-09-01

    The remotely measured surface vibration signatures of tactical military ground vehicles are investigated for use in target classification and identification friend or foe (IFF) systems. The use of remote surface vibration sensing by a laser radar reduces the effects of partial occlusion, concealment, and camouflage experienced by automatic target recognition systems using traditional imagery in a tactical battlefield environment. Linear Predictive Coding (LPC) efficiently represents the vibration signatures and nearest neighbor classifiers exploit the LPC feature set using a variety of distortion metrics. Nearest neighbor classifiers achieve an 88 percent classification rate in an eight class problem, representing a classification performance increase of thirty percent from previous efforts. A novel confidence figure of merit is implemented to attain a 100 percent classification rate with less than 60 percent rejection. The high classification rates are achieved on a target set which would pose significant problems to traditional image-based recognition systems. The targets are presented to the sensor in a variety of aspects and engine speeds at a range of 1 kilometer. The classification rates achieved demonstrate the benefits of using remote vibration measurement in a ground IFF system. The signature modeling and classification system can also be used to identify rotary and fixed-wing targets.

  15. Effort reward imbalance, and salivary cortisol in the morning.

    PubMed

    Eller, Nanna Hurwitz; Nielsen, Søren Feodor; Blønd, Morten; Nielsen, Martin Lindhardt; Hansen, Åse Marie; Netterstrøm, Bo

    2012-02-01

    Effort reward imbalance (ERI) is suggested to increase risk for stress and is hypothesized to increase cortisol levels, especially the awakening cortisol response, ACR. In 2006 and 2008, 480 individuals collected saliva samples at awakening and 30 min post-awakening. Mixed effects models with subject as a random effect and appropriate covariates were used to evaluate associations between the Effort Reward Model, and salivary cortisol at awakening (S0), and ACR. ERI was negatively and significantly associated with S0 for women and positively associated with ACR. S0 and ACR increased significantly from 2006 to 2008. ERI was significantly associated with cortisol levels at awakening (inverse association) for women, and positively associated with ACR. The population experienced a significant increase in morning cortisol levels and ACR from 2006 to 2008, which may originate in a re-organization of the included work places. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Separate and overlapping brain areas encode subjective value during delay and effort discounting.

    PubMed

    Massar, Stijn A A; Libedinsky, Camilo; Weiyan, Chee; Huettel, Scott A; Chee, Michael W L

    2015-10-15

    Making decisions about rewards that involve delay or effort requires the integration of value and cost information. The brain areas recruited in this integration have been well characterized for delay discounting. However only a few studies have investigated how effort costs are integrated into value signals to eventually determine choice. In contrast to previous studies that have evaluated fMRI signals related to physical effort, we used a task that focused on cognitive effort. Participants discounted the value of delayed and effortful rewards. The value of cognitively effortful rewards was represented in the anterior portion of the inferior frontal gyrus and dorsolateral prefrontal cortex. Additionally, the value of the chosen option was encoded in the anterior cingulate cortex, caudate, and cerebellum. While most brain regions showed no significant dissociation between effort discounting and delay discounting, the ACC was significantly more activated in effort compared to delay discounting tasks. Finally, overlapping regions within the right orbitofrontal cortex and lateral temporal and parietal cortices encoded the value of the chosen option during both delay and effort discounting tasks. These results indicate that encoding of rewards discounted by cognitive effort and delay involves partially dissociable brain areas, but a common representation of chosen value is present in the orbitofrontal, temporal and parietal cortices. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. MUC4 mucin- a therapeutic target for pancreatic ductal adenocarcinoma.

    PubMed

    Gautam, Shailendra K; Kumar, Sushil; Cannon, Andrew; Hall, Bradley; Bhatia, Rakesh; Nasser, Mohd Wasim; Mahapatra, Sidharth; Batra, Surinder K; Jain, Maneesh

    2017-07-01

    Pancreatic cancer (PC) is characterized by mucin overexpression. MUC4 is the most differentially overexpressed membrane-bound mucin that plays a functional role in disease progression and therapy resistance. Area covered: We describe the clinicopathological significance of MUC4, summarize mechanisms contributing to its deregulated expression, review preclinical studies aimed at inhibiting MUC4, and discuss how MUC4 overexpression provides opportunities for developing targeted therapies. Finally, we discuss the challenges for developing MUC4-based therapeutics, and identify areas where efforts should be directed to effectively exploit MUC4 as a therapeutic target for PC. Expert opinion: Studies demonstrating that abrogation of MUC4 expression reduces proliferation and metastasis of PC cells and enhances sensitivity to therapeutic agents affirm its utility as a therapeutic target. Emerging evidence also supports the suitability of MUC4 as a potential immunotherapy target. However, these studies have been limited to in vitro, ex vivo or in vivo approaches using xenograft tumors in immunodeficient murine models. For translational relevance, MUC4-targeted therapies should be evaluated in murine models with intact immune system and accurate tumor microenvironment. Additionally, future studies evaluating MUC4 as a target for immunotherapy must entail characterization of immune response in PC patients and investigate its association with immunosuppression and survival.

  18. Inequity responses of monkeys modified by effort.

    PubMed

    van Wolkenten, Megan; Brosnan, Sarah F; de Waal, Frans B M

    2007-11-20

    Without joint benefits, joint actions could never have evolved. Cooperative animals need to monitor closely how large a share they receive relative to their investment toward collective goals. This work documents the sensitivity to reward division in brown, or tufted, capuchin monkeys (Cebus apella). In addition to confirming previous results with a larger subject pool, this work rules out several alternative explanations and adds data on effort sensitivity. Thirteen adult monkeys exchanged tokens for rewards, showing negative reactions to receiving a less-favored reward than their partner. Because their negative reaction could not be attributed to the mere visibility of better rewards (greed hypothesis) nor to having received such rewards in the immediate past (frustration hypothesis), it must have been caused by seeing their partner obtain the better reward. Effort had a major effect in that by far the lowest level of performance in the entire study occurred in subjects required to expend a large effort while at the same time seeing their partner receive a better reward. It is unclear whether this effort-effect was based on comparisons with the partner, but it added significantly to the intensity of the inequity response. These effects are as expected if the inequity response evolved in the context of cooperative survival strategies.

  19. A clip-based protocol for breast boost radiotherapy provides clear target visualisation and demonstrates significant volume reduction over time

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

    Lewis, Lorraine; Cox, Jennifer; Faculty of Health Sciences, University of Sydney, Sydney, New South Wales

    2015-09-15

    The clinical target volume (CTV) for early stage breast cancer is difficult to clearly identify on planning computed tomography (CT) scans. Surgical clips inserted around the tumour bed should help to identify the CTV, particularly if the seroma has been reabsorbed, and enable tracking of CTV changes over time. A surgical clip-based CTV delineation protocol was introduced. CTV visibility and its post-operative shrinkage pattern were assessed. The subjects were 27 early stage breast cancer patients receiving post-operative radiotherapy alone and 15 receiving post-operative chemotherapy followed by radiotherapy. The radiotherapy alone (RT/alone) group received a CT scan at median 25 daysmore » post-operatively (CT1rt) and another at 40 Gy, median 68 days (CT2rt). The chemotherapy/RT group (chemo/RT) received a CT scan at median 18 days post-operatively (CT1ch), a planning CT scan at median 126 days (CT2ch), and another at 40 Gy (CT3ch). There was no significant difference (P = 0.08) between the initial mean CTV for each cohort. The RT/alone cohort showed significant CTV volume reduction of 38.4% (P = 0.01) at 40 Gy. The Chemo/RT cohort had significantly reduced volumes between CT1ch: median 54 cm{sup 3} (4–118) and CT2ch: median 16 cm{sup 3}, (2–99), (P = 0.01), but no significant volume reduction thereafter. Surgical clips enable localisation of the post-surgical seroma for radiotherapy targeting. Most seroma shrinkage occurs early, enabling CT treatment planning to take place at 7 weeks, which is within the 9 weeks recommended to limit disease recurrence.« less

  20. Thermal targets for satellite calibration

    NASA Astrophysics Data System (ADS)

    Villa-Aleman, Eliel; Garrett, Alfred J.; Kurzeja, Robert J.; O'Steen, Byron L.; Pendergast, Malcolm M.

    2001-03-01

    The Savannah River Technology Center (SRTC) is currently calibrating the Multispectral Thermal Imager (MTI) satellite sponsored by the Department of Energy. The MTI imager is a research and development project with 15 wavebands in the visible, near-infrared, short-wave infrared, mid-wave infrared and long-wave infrared spectral regions. A plethora of targets with known temperatures such as power plant heated lakes, volcano lava vents, desert playas and aluminized Mylar tarps are being used in the validation of the five thermal bands of the MTI satellite. SRTC efforts in the production of cold targets with aluminized Mylar tarps will be described. Visible and thermal imagery and wavelength dependent radiance measurements of the calibration targets will be presented.

  1. Are there benefits or harm from pressure targeting during lung-protective ventilation?

    PubMed

    MacIntyre, Neil R; Sessler, Curtis N

    2010-02-01

    Mechanically, breath design is usually either flow/volume-targeted or pressure-targeted. Both approaches can effectively provide lung-protective ventilation, but they prioritize different ventilation parameters, so their responses to changing respiratory-system mechanics and patient effort are different. These different response behaviors have advantages and disadvantages that can be important in specific circumstances. Flow/volume targeting guarantees a set minute ventilation but sometimes may be difficult to synchronize with patient effort, and it will not limit inspiratory pressure. In contrast, pressure targeting, with its variable flow, may be easier to synchronize and will limit inspiratory pressure, but it provides no control over delivered volume. Skilled clinicians can maximize benefits and minimize problems with either flow/volume targeting or pressure targeting. Indeed, as is often the case in managing complex life-support devices, it is operator expertise rather than the device design features that most impacts patient outcomes.

  2. Commuter Chronicle: An Effort to Enhance Commuter Communication in a Traditional Residential Campus Environment.

    ERIC Educational Resources Information Center

    Henckler, Joyce D.

    1982-01-01

    In an effort to inform commuter students of services and programs on a regular basis, the University of Maine at Orono launched a campaign consisting of a newsletter and orientation sessions targeted directly at commuter students. The newsletter included topics of special interest to commuter students such as housing services, ridesharing, child…

  3. Predicting Pilot Error in Nextgen: Pilot Performance Modeling and Validation Efforts

    NASA Technical Reports Server (NTRS)

    Wickens, Christopher; Sebok, Angelia; Gore, Brian; Hooey, Becky

    2012-01-01

    We review 25 articles presenting 5 general classes of computational models to predict pilot error. This more targeted review is placed within the context of the broader review of computational models of pilot cognition and performance, including such aspects as models of situation awareness or pilot-automation interaction. Particular emphasis is placed on the degree of validation of such models against empirical pilot data, and the relevance of the modeling and validation efforts to Next Gen technology and procedures.

  4. Why are U.S. nuclear weapon modernization efforts controversial?

    NASA Astrophysics Data System (ADS)

    Acton, James

    2016-03-01

    U.S. nuclear weapon modernization programs are focused on extending the lives of existing warheads and developing new delivery vehicles to replace ageing bombers, intercontinental ballistic missiles, and ballistic missile submarines. These efforts are contested and controversial. Some critics argue that they are largely unnecessary, financially wasteful and potentially destabilizing. Other critics posit that they do not go far enough and that nuclear weapons with new military capabilities are required. At its core, this debate centers on three strategic questions. First, what roles should nuclear weapons be assigned? Second, what military capabilities do nuclear weapons need to fulfill these roles? Third, how severe are the unintended escalation risks associated with particular systems? Proponents of scaled-down modernization efforts generally argue for reducing the role of nuclear weapons but also that, even under existing policy, new military capabilities are not required. They also tend to stress the escalation risks of new--and even some existing--capabilities. Proponents of enhanced modernization efforts tend to advocate for a more expansive role for nuclear weapons in national security strategy. They also often argue that nuclear deterrence would be enhanced by lower yield weapons and/or so called bunker busters able to destroy more deeply buried targets. The debate is further fueled by technical disagreements over many aspects of ongoing and proposed modernization efforts. Some of these disagreements--such as the need for warhead life extension programs and their necessary scope--are essentially impossible to resolve at the unclassified level. By contrast, unclassified analysis can help elucidate--though not answer--other questions, such as the potential value of bunker busters.

  5. NASA Efforts on Nanotechnology

    NASA Technical Reports Server (NTRS)

    Miranda, Felix A.

    2003-01-01

    An overview of the field of nanotechnology within the theme of "New efforts in Nanotechnology Research," will be presented. NASA's interest, requirements and current efforts in this emerging field will be discussed. In particular, NASA efforts to develop nanoelectronic devices, fuel cells, and other applications of interest using this novel technology by collaborating with academia will be addressed. Progress on current collaborations in this area with the University of Puerto Rico will be highlighted.

  6. Design of ligand-targeted nanoparticles for enhanced cancer targeting

    NASA Astrophysics Data System (ADS)

    Stefanick, Jared F.

    Ligand-targeted nanoparticles are increasingly used as drug delivery vehicles for cancer therapy, yet have not consistently produced successful clinical outcomes. Although these inconsistencies may arise from differences in disease models and target receptors, nanoparticle design parameters can significantly influence therapeutic efficacy. By employing a multifaceted synthetic strategy to prepare peptide-targeted nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities, this work evaluates the roles of polyethylene glycol (PEG) coating, ethylene glycol (EG) peptide-linker length, peptide hydrophilicity, peptide density, and nanoparticle size on tumor targeting in a systematic manner. These parameters were analyzed in multiple disease models by targeting human epidermal growth factor receptor 2 (HER2) in breast cancer and very late antigen-4 (VLA-4) in multiple myeloma to demonstrate the widespread applicability of this approach. By increasing the hydrophilicity of the targeting peptide sequence and simultaneously optimizing the EG peptide-linker length, the in vitro cellular uptake of targeted liposomes was significantly enhanced. Specifically, including a short oligolysine chain adjacent to the targeting peptide sequence effectively increased cellular uptake ~80-fold using an EG6 peptide-linker compared to ~10-fold using an EG45 linker. In vivo, targeted liposomes prepared in a traditional manner lacking the oligolysine chain demonstrated similar biodistribution and tumor uptake to non-targeted liposomes. However, by including the oligolysine chain, targeted liposomes using an EG45 linker significantly improved tumor uptake ~8-fold over non-targeted liposomes, while the use of an EG6 linker decreased tumor accumulation and uptake, owing to differences in cellular uptake kinetics, clearance mechanisms, and binding site barrier effects. To further improve tumor targeting and enhance the selectivity of targeted

  7. Multi-Organization Multi-Discipline Effort Developing a Mitigation Concept for Planetary Defense

    NASA Technical Reports Server (NTRS)

    Leung, Ronald Y.; Barbee, Brent W.; Seery, Bernard D.; Bambacus, Myra; Finewood, Lee; Greenaugh, Kevin C.; Lewis, Anthony; Dearborn, David; Miller, Paul L.; Weaver, Robert P.; hide

    2017-01-01

    There have been significant recent efforts in addressing mitigation approaches to neutralize Potentially Hazardous Asteroids (PHA). One such research effort was performed in 2015 by an integrated, inter-disciplinary team of asteroid scientists, energy deposition modeling scientists, payload engineers, orbital dynamist engineers, spacecraft discipline engineers, and systems architecture engineer from NASAs Goddard Space Flight Center (GSFC) and the Department of Energy (DoE) National Nuclear Security Administration (NNSA) laboratories (Los Alamos National Laboratory (LANL), Lawrence Livermore National Laboratories (LLNL) and Sandia National Laboratories). The study team collaborated with GSFCs Integrated Design Centers Mission Design Lab (MDL) which engaged a team of GSFC flight hardware discipline engineers to work with GSFC, LANL, and LLNL NEA-related subject matter experts during a one-week intensive concept formulation study in an integrated concurrent engineering environment. This team has analyzed the first of several distinct study cases for a multi-year NASA research grant. This Case 1 study references the Near-Earth Asteroid (NEA) named Bennu as the notional target due to the availability of a very detailed Design Reference Asteroid (DRA) model for its orbit and physical characteristics (courtesy of the Spectral Interpretation, Resource Identification, Security-Regolith Explorer (OSIRIS-REx) mission team). The research involved the formulation and optimization of spacecraft trajectories to intercept Bennu, overall mission and architecture concepts, and high-fidelity modeling of both kinetic impact (spacecraft collision to change a NEAs momentum and orbit) and nuclear detonation effects on Bennu, for purposes of deflecting Bennu.

  8. Monitoring and evaluation of disaster response efforts undertaken by local health departments: a rapid realist review.

    PubMed

    Gossip, Kate; Gouda, Hebe; Lee, Yong Yi; Firth, Sonja; Bermejo, Raoul; Zeck, Willibald; Jimenez Soto, Eliana

    2017-06-29

    Local health departments are often at the forefront of a disaster response, attending to the immediate trauma inflicted by the disaster and also the long term health consequences. As the frequency and severity of disasters are projected to rise, monitoring and evaluation (M&E) efforts are critical to help local health departments consolidate past experiences and improve future response efforts. Local health departments often conduct M&E work post disaster, however, many of these efforts fail to improve response procedures. We undertook a rapid realist review (RRR) to examine why M&E efforts undertaken by local health departments do not always result in improved disaster response efforts. We aimed to complement existing frameworks by focusing on the most basic and pragmatic steps of a M&E cycle targeted towards continuous system improvements. For these purposes, we developed a theoretical framework that draws on the quality improvement literature to 'frame' the steps in the M&E cycle. This framework encompassed a M&E cycle involving three stages (i.e., document and assess, disseminate and implement) that must be sequentially completed to learn from past experiences and improve future disaster response efforts. We used this framework to guide our examination of the literature and to identify any context-mechanism-outcome (CMO) configurations which describe how M&E may be constrained or enabled at each stage of the M&E cycle. This RRR found a number of explanatory CMO configurations that provide valuable insights into some of the considerations that should be made when using M&E to improve future disaster response efforts. Firstly, to support the accurate documentation and assessment of a disaster response, local health departments should consider how they can: establish a culture of learning within health departments; use embedded training methods; or facilitate external partnerships. Secondly, to enhance the widespread dissemination of lessons learned and facilitate

  9. Electroplating targets for production of unique PET radionuclides

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

    Bui, V.; Sheh, Y.; Finn, R.

    1994-12-31

    The past decade has witnessed the applications of Positron Emission Tomography (PET) evolving from a purely research endeavour to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules i.e. monoclonal antibodies and pepetides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing themore » Memorial Sloan-Kettering Cancer Center cyclotron are examples of target design and development applicable to many medical accelerators.« less

  10. Electroplated targets for production of unique PET radionuclides

    NASA Astrophysics Data System (ADS)

    Bui, V.; Sheh, Y.; Finn, R.; Francesconi, L.; Cai, S.; Schlyer, D.; Wieland, B.

    1995-12-01

    The past decade has witnessed the applications of positron emission tomography (PET) evolving from a purely research endeavor to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in both medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules, i.e. monoclonal antibodies and peptides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing the Memorial Sloan-Kettering Cancer Center (MSKCC) cyclotron are examples of target design and development applicable to many medical accelerators.

  11. A mid-term analysis of progress toward international biodiversity targets.

    PubMed

    Tittensor, Derek P; Walpole, Matt; Hill, Samantha L L; Boyce, Daniel G; Britten, Gregory L; Burgess, Neil D; Butchart, Stuart H M; Leadley, Paul W; Regan, Eugenie C; Alkemade, Rob; Baumung, Roswitha; Bellard, Céline; Bouwman, Lex; Bowles-Newark, Nadine J; Chenery, Anna M; Cheung, William W L; Christensen, Villy; Cooper, H David; Crowther, Annabel R; Dixon, Matthew J R; Galli, Alessandro; Gaveau, Valérie; Gregory, Richard D; Gutierrez, Nicolas L; Hirsch, Tim L; Höft, Robert; Januchowski-Hartley, Stephanie R; Karmann, Marion; Krug, Cornelia B; Leverington, Fiona J; Loh, Jonathan; Lojenga, Rik Kutsch; Malsch, Kelly; Marques, Alexandra; Morgan, David H W; Mumby, Peter J; Newbold, Tim; Noonan-Mooney, Kieran; Pagad, Shyama N; Parks, Bradley C; Pereira, Henrique M; Robertson, Tim; Rondinini, Carlo; Santini, Luca; Scharlemann, Jörn P W; Schindler, Stefan; Sumaila, U Rashid; Teh, Louise S L; van Kolck, Jennifer; Visconti, Piero; Ye, Yimin

    2014-10-10

    In 2010, the international community, under the auspices of the Convention on Biological Diversity, agreed on 20 biodiversity-related "Aichi Targets" to be achieved within a decade. We provide a comprehensive mid-term assessment of progress toward these global targets using 55 indicator data sets. We projected indicator trends to 2020 using an adaptive statistical framework that incorporated the specific properties of individual time series. On current trajectories, results suggest that despite accelerating policy and management responses to the biodiversity crisis, the impacts of these efforts are unlikely to be reflected in improved trends in the state of biodiversity by 2020. We highlight areas of societal endeavor requiring additional efforts to achieve the Aichi Targets, and provide a baseline against which to assess future progress. Copyright © 2014, American Association for the Advancement of Science.

  12. Arterial cord blood lactate at birth correlates with duration of pushing efforts.

    PubMed

    Dessolle, Lionel; Lebrec, Jeremie; Daraï, Emile

    2010-01-01

    To evaluate the impact of the duration of pushing efforts on arterial cord blood lactate values. This was a prospective observational study of 124 consecutive normal vaginal deliveries in a tertiary teaching hospital. Arterial cord blood lactate was determined immediately at birth with a test strip method. Univariate and multivariate analyses were performed to check for clinical determinants of lactate levels. The main measure was lactate according to the duration of pushing efforts. Arterial cord lactates increased significantly and were strongly correlated with the duration of pushing efforts, independent of gestational age and birthweight. Women pushing for more than 20 min had higher arterial cord blood lactates (4.9 +/- 1.4 vs. 3.3 +/- 1.16 mM, respectively) and a higher rate of lactates >6 mM (18 vs. 3%) than those pushing for less than 20 min. At normal delivery, arterial cord blood lactates increase significantly with the duration of pushing efforts. Pushing for more than 20 min is associated with an increased risk of metabolic acidosis in the neonate. Further studies are required to evaluate the clinical significance of these observations. 2009 S. Karger AG, Basel.

  13. Examining the target levels of state renewable portfolio standards

    NASA Astrophysics Data System (ADS)

    Helwig, Laurence Douglas

    At present 37 U.S. states have passed Renewable Portfolio Standards (RPS) or have a legislative driven goal that supports investment in renewable energy (RE) technologies. Previous research has identified economic, governmental, ideological and infrastructural characteristics as key predictors of policy adoption and renewable energy deployment efforts (Carley, 2009; Davis & Davis, 2009; Bohn & Lant, 2009; Lyon & Yin, 2010). To date, only a few studies have investigated the target levels of renewable portfolio standards. Carley & Miller (2012) found that policies of differing stringencies were motivated by systematically different factors that included governmental ideology. The purpose of this dissertation is to replicate and expand upon earlier models that predicted RPS adoption and RE deployment efforts by adding regulatory, infrastructural and spatial characteristics to predict RPS target levels. Hypotheses were tested using three alternative measurements of RPS target level strength to determine to what extent a combination of explanatory variables explain variation in policy target levels. Multivariate linear regression and global spatial autocorrelation results indicated that multiple state internal determinants influenced RPS target level including average electricity price, state government ideology and to a lesser extent actual RE potential capacity. In addition, some diffusion effects were found to exist that indicated that states are setting their RPS target levels lower than their neighboring states and a local geo-spatial clustering effect was observed in the target levels for a grouping of northeastern states.

  14. Cognitive effort: A neuroeconomic approach

    PubMed Central

    Braver, Todd S.

    2015-01-01

    Cognitive effort has been implicated in numerous theories regarding normal and aberrant behavior and the physiological response to engagement with demanding tasks. Yet, despite broad interest, no unifying, operational definition of cognitive effort itself has been proposed. Here, we argue that the most intuitive and epistemologically valuable treatment is in terms of effort-based decision-making, and advocate a neuroeconomics-focused research strategy. We first outline psychological and neuroscientific theories of cognitive effort. Then we describe the benefits of a neuroeconomic research strategy, highlighting how it affords greater inferential traction than do traditional markers of cognitive effort, including self-reports and physiologic markers of autonomic arousal. Finally, we sketch a future series of studies that can leverage the full potential of the neuroeconomic approach toward understanding the cognitive and neural mechanisms that give rise to phenomenal, subjective cognitive effort. PMID:25673005

  15. The impact of effort-reward imbalance on quality of life among Japanese working men.

    PubMed

    Watanabe, Mayumi; Tanaka, Katsutoshi; Aratake, Yutaka; Kato, Noritada; Sakata, Yumi

    2008-07-01

    Health-related quality of life (HRQL) is an important measure of health outcome in working and healthy populations. Here, we investigated the impact of effort-reward imbalance (ERI), a representative work-stress model, on HRQL of Japanese working men. The study targeted 1,096 employees from a manufacturing plant in Japan. To assess HRQL and ERI, participants were surveyed using the Japanese version of the Short-Form 8 Health Survey (SF-8) and effort-reward imbalance model. Of the 1,096 employees, 1,057 provided valid responses to the questionnaire. For physical summary scores, the adjusted effort-reward imbalance odds ratios of middle vs. bottom and top vs. bottom tertiles were 0.24 (95% confidence interval, 0.08-0.70) and 0.09 (95% confidence interval, 0.03-0.28), respectively. For mental summary scores, ratios were 0.21 (95% confidence interval, 0.07-0.63) and 0.07 (95% confidence interval, 0.02-0.25), respectively. These findings demonstrate that effort-reward imbalance is independently associated with HRQL among Japanese employees.

  16. Joint Force Cyberspace Component Command: Establishing Cyberspace Operations Unity of Effort for the Joint Force Commander

    DTIC Science & Technology

    2015-05-01

    say/. According to the article, “the hackers targeted big-name makers of nuclear and solar technology, stealing confidential business information...As JTF-GNO synchronized efforts to disinfect and protect over 2.5 million computers in 3,500 DoD organizations spanning 99 countries, Defense

  17. The Significance of MMP-1 in EGFR-TKI-Resistant Lung Adenocarcinoma: Potential for Therapeutic Targeting.

    PubMed

    Saito, Ryoko; Miki, Yasuhiro; Ishida, Naoya; Inoue, Chihiro; Kobayashi, Masayuki; Hata, Shuko; Yamada-Okabe, Hisafumi; Okada, Yoshinori; Sasano, Hironobu

    2018-02-18

    Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance is one of the most important problems in lung cancer therapy. Lung adenocarcinoma with EGFR-TKI resistance was reported to have higher abilities of invasion and migration than cancers sensitive to EGFR-TKI, but the function of matrix metalloproteinases (MMPs) has not been explored in EGFR-TKI-resistant lung adenocarcinoma. This study aims to clarify the significance of MMP-1 in EGFR-TKI-resistant lung adenocarcinoma. From the results of in vitro studies of migration and invasion assays using EGFR-TKI-sensitive and -resistant cell lines and phosphorylation antibody arrays using EGF and rapamycin, we first demonstrate that overexpression of MMP-1, which might follow activation of a mammalian target of rapamycin (mTOR) pathway, plays an important role in the migration and invasion abilities of EGFR-TKI-resistant lung adenocarcinoma. Additionally, immunohistochemical studies using 89 cases of lung adenocarcinoma demonstrate that high expression of MMP-1 is significantly correlated with poor prognosis and factors such as smoking history and the subtype of invasive mucinous adenocarcinoma. These are consistent with the results of this in vitro study. To conclude, this study provides insights into the development of a possible alternative therapy manipulating MMP-1 and the mTOR signaling pathway in EGFR-TKI-resistant lung adenocarcinoma.

  18. The association of perceived organizational justice and organizational expectations with nurses' efforts.

    PubMed

    Motlagh, Farhad Shafiepour; Yarmohammadian, Mohammad Hossein; Yaghoubi, Maryam

    2012-03-01

    One important factor in growth, progress, and increase in work efficiency of employees of any enterprise is to make considerable effort. Supreme leader of the Islamic Republic of Iran also addressed the issue of need for more efforts. The goal of this study was to determine the association of perceived organizational justice and organizational expectations with efforts of nurses to provide a suitable model. The current study was a descriptive study. The study group consists of all nurses who worked in hospitals of Isfahan. Due to some limitations all nurses of the special unit, surgery wards and operating room were questioned. The data collection tools were the Organizational Justice Questionnaire, organizational expectations questionnaire, and double effort questionnaire. Content validity of the mentioned questionnaires was confirmed after considering the experts' comments. The reliability of these questionnaires, using the Cronbach's alpha, were 0.79, 0.83 and 0.92, respectively. The Pearson correlation and the structural equation model were used for the analysis of data. There was a significant correlation between the perceived organizational justice and the double effort of nurses during the surgery of patients. Correlation of the expectation from job, usefulness of job, and its attractiveness with double effort of nurses before the surgery was also statistically significant. Moreover, it was shown that the root of the mean square error of estimation (RMSEA) was 0.087, the fitted goodness index (GFI) was 0.953, the value of chi-square was 268.5, and the model was statistically significant (p < 0.001). Today Justice is an essential need for human life and its importance in organizations and social life of individuals is evident.

  19. Productive and Ineffective Efforts: How Student Effort in High School Mathematics Relates to College Calculus Success

    ERIC Educational Resources Information Center

    Barnett, M.D.; Sonnert, G.; Sadler, P.M.

    2014-01-01

    Relativizing the popular belief that student effort is the key to success, this article finds that effort in the most advanced mathematics course in US high schools is not consistently associated with college calculus performance. We distinguish two types of student effort: productive and ineffective efforts. Whereas the former carries the…

  20. Creative motivation: creative achievement predicts cardiac autonomic markers of effort during divergent thinking.

    PubMed

    Silvia, Paul J; Beaty, Roger E; Nusbaum, Emily C; Eddington, Kari M; Kwapil, Thomas R

    2014-10-01

    Executive approaches to creativity emphasize that generating creative ideas can be hard and requires mental effort. Few studies, however, have examined effort-related physiological activity during creativity tasks. Using motivational intensity theory as a framework, we examined predictors of effort-related cardiac activity during a creative challenge. A sample of 111 adults completed a divergent thinking task. Sympathetic (PEP and RZ) and parasympathetic (RSA and RMSSD) outcomes were assessed using impedance cardiography. As predicted, people with high creative achievement (measured with the Creative Achievement Questionnaire) showed significantly greater increases in sympathetic activity from baseline to task, reflecting higher effort. People with more creative achievements generated ideas that were significantly more creative, and creative performance correlated marginally with PEP and RZ. The results support the view that creative thought can be a mental challenge. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Effect of effort-reward imbalance and burnout on infection control among Ecuadorian nurses.

    PubMed

    Colindres, C V; Bryce, E; Coral-Rosero, P; Ramos-Soto, R M; Bonilla, F; Yassi, A

    2018-06-01

    Nurses are frequently exposed to transmissible infections, yet adherence to infection control measures is suboptimal. There has been inadequate research into how the psychosocial work environment affects compliance with infection control measures, especially in low- and middle-income countries. To examine the association between effort-reward imbalance, burnout and adherence to infection control measures among nurses in Ecuador. A cross-sectional study linking psychosocial work environment indicators to infection control adherence. The study was conducted among 333 nurses in four Ecuadorian hospitals. Self-administered questionnaires assessed demographic variables, perceived infection risk, effort-reward imbalance, burnout and infection control adherence. Increased effort-reward imbalance was found to be a unique incremental predictor of exposure to burnout, and burnout was a negative unique incremental predictor of nurses' self-reported adherence with infection control measures. Results suggest an effort-reward imbalance-burnout continuum, which, at higher levels, contributes to reduce adherence to infection control. The Ecuadorean government has made large efforts to improve universal access to health care, yet this study suggests that workplace demands on nurses remain problematic. This study highlights the contribution of effort-reward-imbalance-burnout continuum to the chain of infection by decreased adherence to infection control of nurses. Health authorities should closely monitor the effect of new policies on psychosocial work environment, especially when expanding services and increasing public accessibility with limited resources. Additionally, organizational and psychosocial interventions targeting effort-reward imbalance and burnout in nurses should be considered part of a complete infection prevention and control strategy. Further study is warranted to identify interventions that best ameliorate effort-reward imbalance and burnout in low- and middle

  2. Effort test failure: toward a predictive model.

    PubMed

    Webb, James W; Batchelor, Jennifer; Meares, Susanne; Taylor, Alan; Marsh, Nigel V

    2012-01-01

    Predictors of effort test failure were examined in an archival sample of 555 traumatically brain-injured (TBI) adults. Logistic regression models were used to examine whether compensation-seeking, injury-related, psychological, demographic, and cultural factors predicted effort test failure (ETF). ETF was significantly associated with compensation-seeking (OR = 3.51, 95% CI [1.25, 9.79]), low education (OR:. 83 [.74, . 94]), self-reported mood disorder (OR: 5.53 [3.10, 9.85]), exaggerated displays of behavior (OR: 5.84 [2.15, 15.84]), psychotic illness (OR: 12.86 [3.21, 51.44]), being foreign-born (OR: 5.10 [2.35, 11.06]), having sustained a workplace accident (OR: 4.60 [2.40, 8.81]), and mild traumatic brain injury severity compared with very severe traumatic brain injury severity (OR: 0.37 [0.13, 0.995]). ETF was associated with a broader range of statistical predictors than has previously been identified and the relative importance of psychological and behavioral predictors of ETF was evident in the logistic regression model. Variables that might potentially extend the model of ETF are identified for future research efforts.

  3. Druggable orthosteric and allosteric hot spots to target protein-protein interactions.

    PubMed

    Ma, Buyong; Nussinov, Ruth

    2014-01-01

    Drug designing targeting protein-protein interactions is challenging. Because structural elucidation and computational analysis have revealed the importance of hot spot residues in stabilizing these interactions, there have been on-going efforts to develop drugs which bind the hot spots and out-compete the native protein partners. The question arises as to what are the key 'druggable' properties of hot spots in protein-protein interactions and whether these mimic the general hot spot definition. Identification of orthosteric (at the protein- protein interaction site) and allosteric (elsewhere) druggable hot spots is expected to help in discovering compounds that can more effectively modulate protein-protein interactions. For example, are there any other significant features beyond their location in pockets in the interface? The interactions of protein-protein hot spots are coupled with conformational dynamics of protein complexes. Currently increasing efforts focus on the allosteric drug discovery. Allosteric drugs bind away from the native binding site and can modulate the native interactions. We propose that identification of allosteric hot spots could similarly help in more effective allosteric drug discovery. While detection of allosteric hot spots is challenging, targeting drugs to these residues has the potential of greatly increasing the hot spot and protein druggability.

  4. Targeted Nanoparticles for Image-guided Treatment of Triple Negative Breast Cancer: Clinical Significance and Technological Advances

    PubMed Central

    Miller-Kleinhenz, Jasmine M.; Bozeman, Erica N.

    2015-01-01

    Effective treatment of triple negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and non-invasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise towards the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug-resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention (EPR) effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor associated endothelial cells, stromal fibroblasts and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as others and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. PMID:25966677

  5. Anticipation of a mentally effortful task recruits Dorsolateral Prefrontal Cortex: An fNIRS validation study.

    PubMed

    Vassena, Eliana; Gerrits, Robin; Demanet, Jelle; Verguts, Tom; Siugzdaite, Roma

    2018-04-26

    Preparing for a mentally demanding task calls upon cognitive and motivational resources. The underlying neural implementation of these mechanisms is receiving growing attention because of its implications for professional, social, and medical contexts. While several fMRI studies converge in assigning a crucial role to a cortico-subcortical network including Anterior Cigulate Cortex (ACC) and striatum, the involvement of Dorsolateral Prefrontal Cortex (DLPFC) during mental effort anticipation has yet to be replicated. This study was designed to target DLPFC contribution to anticipation of a difficult task using functional Near Infrared Spectroscopy (fNIRS), as a more cost-effective tool measuring cortical hemodynamics. We adapted a validated mental effort task, where participants performed easy and difficult mental calculation, and measured DLPFC activity during the anticipation phase. As hypothesized, DLPFC activity increased during anticipation of a hard task as compared to an easy task. Besides replicating previous fMRI work, these results establish fNIRS as an effective tool to investigate cortical contributions to anticipation of effortful behavior. This is especially useful if one requires testing large samples (e.g., to target individual differences), populations with contraindication for functional MRI (e.g., infants or patients with metal implants), or subjects in more naturalistic environments (e.g., work or sport). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Vena Cava Responsiveness to Controlled Isovolumetric Respiratory Efforts.

    PubMed

    Folino, Anna; Benzo, Marco; Pasquero, Paolo; Laguzzi, Andrea; Mesin, Luca; Messere, Alessandro; Porta, Massimo; Roatta, Silvestro

    2017-10-01

    Respirophasic variation of inferior vena cava (IVC) size is affected by large variability with spontaneous breathing. This study aims at characterizing the dependence of IVC size on controlled changes in intrathoracic pressure. Ten healthy subjects, in supine position, performed controlled isovolumetric respiratory efforts at functional residual capacity, attaining positive (5, 10, and 15 mmHg) and negative (-5, -10, and -15 mmHg) alveolar pressure levels. The isovolumetric constraint implies that equivalent changes are exhibited by alveolar and intrathoracic pressures during respiratory tasks. The IVC cross-sectional area equal to 2.88 ± 0.43 cm 2 at baseline (alveolar pressure = 0 mmHg) was progressively decreased by both expiratory and inspiratory efforts of increasing strength, with diaphragmatic efforts producing larger effects than thoracic ones: -55 ± 15% decrease, at +15 mmHg of alveolar pressure (P < .01), -80 ± 33 ± 12% at -15 mmHg diaphragmatic (P < .01), -33 ± 12% at -15 mmHg thoracic. Significant IVC changes in size (P < .01) and pulsatility (P < .05), along with non significant reduction in the response to respiratory efforts, were also observed during the first 30 minutes of supine rest, detecting an increase in vascular filling, and taking place after switching from the standing to the supine position. This study quantified the dependence of the IVC cross-sectional area on controlled intrathoracic pressure changes and evidenced the stronger influence of diaphragmatic over thoracic activity. Individual variability in thoracic/diaphragmatic respiratory pattern should be considered in the interpretation of the respirophasic modulations of IVC size. © 2017 by the American Institute of Ultrasound in Medicine.

  7. The quest for significance model of radicalization: implications for the management of terrorist detainees.

    PubMed

    Dugas, Michelle; Kruglanski, Arie W

    2014-01-01

    Radicalization and its culmination in terrorism represent a grave threat to the security and stability of the world. A related challenge is effective management of extremists who are detained in prison facilities. The major aim of this article is to review the significance quest model of radicalization and its implications for management of terrorist detainees. First, we review the significance quest model, which elaborates on the roles of motivation, ideology, and social processes in radicalization. Secondly, we explore the implications of the model in relation to the risks of prison radicalization. Finally, we analyze the model's implications for deradicalization strategies and review preliminary evidence for the effectiveness of a rehabilitation program targeting components of the significance quest. Based on this evidence, we argue that the psychology of radicalization provides compelling reason for the inclusion of deradicalization efforts as an essential component of the management of terrorist detainees. Copyright © 2014 John Wiley & Sons, Ltd.

  8. HIV-1 Gag as an Antiviral Target: Development of Assembly and Maturation Inhibitors.

    PubMed

    Spearman, Paul

    2016-01-01

    HIV-1 Gag is the master orchestrator of particle assembly. The central role of Gag at multiple stages of the HIV lifecycle has led to efforts to develop drugs that directly target Gag and prevent the formation and release of infectious particles. Until recently, however, only the catalytic site protease inhibitors have been available to inhibit late stages of HIV replication. This review summarizes the current state of development of antivirals that target Gag or disrupt late events in the retrovirus lifecycle such as maturation of the viral capsid. Maturation inhibitors represent an exciting new series of antiviral compounds, including those that specifically target CA-SP1 cleavage and the allosteric integrase inhibitors that inhibit maturation by a completely different mechanism. Numerous small molecules and peptides targeting CA have been studied in attempts to disrupt steps in assembly. Efforts to target CA have recently gained considerable momentum from the development of small molecules that bind CA and alter capsid stability at the post-entry stage of the lifecycle. Efforts to develop antivirals that inhibit incorporation of genomic RNA or to inhibit late budding events remain in preliminary stages of development. Overall, the development of novel antivirals targeting Gag and the late stages in HIV replication appears much closer to success than ever, with the new maturation inhibitors leading the way.

  9. ANITA (Advanced Network for Isotope and TArget laboratories) - The urgent need for a European target preparation network

    NASA Astrophysics Data System (ADS)

    Schumann, Dorothea; Sibbens, Goedele; Stolarz, Anna; Eberhardt, Klaus; Lommel, Bettina; Stodel, Christelle

    2018-05-01

    A wide number of research fields in the nuclear sector requires high-quality and well-characterized samples and targets. Currently, only a few laboratories own or have access to the equipment allowing fulfilling such demands. Coordination of activities and sharing resources is therefore mandatory to meet the increasing needs. This very urgent issue has now been addressed by six European target laboratories with an initiative called ANITA (Advanced Network for Isotope and TArget laboratories). The global aim of ANITA is to establish an overarching research infrastructure service for isotope and target production and develop a tight cooperation between the target laboratories in Europe in order to transfer the knowledge and improve the production techniques of well-characterized samples and targets. Moreover, the interaction of the target producers with the users shall be encouraged and intensified to deliver tailor-made targets best-suited to the envisaged experiments. For the realization of this ambitious goal, efforts within the European Commission and strong support by the target-using communities will be necessary. In particular, an appropriate funding instrument has to be found and applied, enabling ANITA to develop from an initiative employed by the interested parties to a real coordination platform.

  10. Synergies and trade-offs in achieving global biodiversity targets.

    PubMed

    Di Marco, Moreno; Butchart, Stuart H M; Visconti, Piero; Buchanan, Graeme M; Ficetola, Gentile F; Rondinini, Carlo

    2016-02-01

    After their failure to achieve a significant reduction in the global rate of biodiversity loss by 2010, world governments adopted 20 new ambitious Aichi biodiversity targets to be met by 2020. Efforts to achieve one particular target can contribute to achieving others, but different targets may sometimes require conflicting solutions. Consequently, lack of strategic thinking might result, once again, in a failure to achieve global commitments to biodiversity conservation. We illustrate this dilemma by focusing on Aichi Target 11. This target requires an expansion of terrestrial protected area coverage, which could also contribute to reducing the loss of natural habitats (Target 5), reducing human-induced species decline and extinction (Target 12), and maintaining global carbon stocks (Target 15). We considered the potential impact of expanding protected areas to mitigate global deforestation and the consequences for the distribution of suitable habitat for >10,000 species of forest vertebrates (amphibians, birds, and mammals). We first identified places where deforestation might have the highest impact on remaining forests and then identified places where deforestation might have the highest impact on forest vertebrates (considering aggregate suitable habitat for species). Expanding protected areas toward locations with the highest deforestation rates (Target 5) or the highest potential loss of aggregate species' suitable habitat (Target 12) resulted in partially different protected area network configurations (overlapping with each other by about 73%). Moreover, the latter approach contributed to safeguarding about 30% more global carbon stocks than the former. Further investigation of synergies and trade-offs between targets would shed light on these and other complex interactions, such as the interaction between reducing overexploitation of natural resources (Targets 6, 7), controlling invasive alien species (Target 9), and preventing extinctions of native

  11. Value-focused framework for defining landscape-scale conservation targets

    USGS Publications Warehouse

    Romañach, Stephanie; Benscoter, Allison M.; Brandt, Laura A.

    2016-01-01

    Conservation of natural resources can be challenging in a rapidly changing world and require collaborative efforts for success. Conservation planning is the process of deciding how to protect, conserve, and enhance or minimize loss of natural and cultural resources. Establishing conservation targets (also called indicators or endpoints), the measurable expressions of desired resource conditions, can help with site-specific up to landscape-scale conservation planning. Using conservation targets and tracking them through time can deliver benefits such as insight into ecosystem health and providing early warnings about undesirable trends. We describe an approach using value-focused thinking to develop statewide conservation targets for Florida. Using such an approach allowed us to first identify stakeholder objectives and then define conservation targets to meet those objectives. Stakeholders were able to see how their shared efforts fit into the broader conservation context, and also anticipate the benefits of multi-agency and -organization collaboration. We developed an iterative process for large-scale conservation planning that included defining a shared framework for the process, defining the conservation targets themselves, as well as developing management and monitoring strategies for evaluation of their effectiveness. The process we describe is applicable to other geographies where multiple parties are seeking to implement collaborative, large-scale biological planning.

  12. Assessing the success of invasive species prevention efforts at changing the behaviors of recreational boaters.

    PubMed

    Cole, Ellen; Keller, Reuben P; Garbach, Kelly

    2016-12-15

    Aquatic invasive species (AIS) pose major conservation challenges in freshwater ecosystems. In response, conservation organizations invest considerable resources in outreach to encourage AIS prevention behaviors among recreational boaters. Despite this, remarkably little is known about whether these efforts catalyze significant changes in boaters' perceptions, or whether they cause changes in behaviors that reduce AIS risk. We interviewed managers at the 14 Illinois organizations active in AIS outreach to determine regional priorities for, and investment in, AIS outreach. The results show a network of collaboration that reinforces a limited set of conservation messages. Next, we surveyed 515 recreational boaters to evaluate access to outreach, knowledge of AIS, and consistency of prevention behavior. Boater recognition of prevention slogans and knowledge of AIS and AIS prevention behavior was similar across Illinois regions despite large regional differences in investment in outreach. Most boaters (94%) report never intentionally moving organisms among waterbodies. Fewer reported that they Always perform recommended actions to reduce risk of AIS spread on their boat interior (68%), boat exterior (63%), or fishing tackle (47%). Recognition of prevention slogans and the number of AIS recognized were significantly, positively, associated with Always performing AIS prevention behavior on the vectors of the boat exterior, and fishing tackle, respectively. Our results suggest that increasing knowledge may be a necessary condition for higher adoption of AIS prevention behaviors, but that this alone may not be sufficient. Instead, efforts targeted at boaters who do not currently practice the recommended actions are likely to be necessary. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Anti-tumour strategies aiming to target tumour-associated macrophages

    PubMed Central

    Tang, Xiaoqiang; Mo, Chunfen; Wang, Yongsheng; Wei, Dandan; Xiao, Hengyi

    2013-01-01

    Tumour-associated macrophages (TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2-like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAM-targeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAM-targeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM-targeted tumour therapy. PMID:23113570

  14. Targeted inhibition of EG-1 blocks breast tumor growth.

    PubMed

    Lu, Ming; Sartippour, Maryam R; Zhang, Liping; Norris, Andrew J; Brooks, Mai N

    2007-06-01

    EG-1 is a gene product that is significantly elevated in human breast cancer tissues. Previously, we have shown that EG-1 overexpression stimulates cellular proliferation both in vitro and in vivo. Here, we ask whether this molecule can be targeted for experimental therapeutic purpose. siRNA lentivirus and polyclonal antibodies were designed to suppress EG-1 expression. These agents were then used in cell culture proliferation assays and breast tumor xenograft models. Serum and urine from breast cancer patients were also analyzed for the presence of EG-1 peptide. We report here for the first time that endogenous EG-1 can be targeted to inhibit breast tumor growth. This inhibition, whether delivered via siRNA lentivirus or polyclonal antibody, resulted in decreased cellular proliferation in culture and smaller xenografts in mice. The effects were shown in both ER (estrogen receptor)-positive human breast cancer MCF-7 cells, as well as in ER-negative MDA-MB-231 cells. Furthermore, we detected soluble EG-1 in serum and urine of breast cancer patients. These observations demonstrate that EG-1 is relevant to human breast cancer, and is a molecular target worthy of translational efforts into effective breast cancer therapy.

  15. Targeting cysteine proteases in trypanosomatid disease drug discovery.

    PubMed

    Ferreira, Leonardo G; Andricopulo, Adriano D

    2017-12-01

    Chagas disease and human African trypanosomiasis are endemic conditions in Latin America and Africa, respectively, for which no effective and safe therapy is available. Efforts in drug discovery have focused on several enzymes from these protozoans, among which cysteine proteases have been validated as molecular targets for pharmacological intervention. These enzymes are expressed during the entire life cycle of trypanosomatid parasites and are essential to many biological processes, including infectivity to the human host. As a result of advances in the knowledge of the structural aspects of cysteine proteases and their role in disease physiopathology, inhibition of these enzymes by small molecules has been demonstrated to be a worthwhile approach to trypanosomatid drug research. This review provides an update on drug discovery strategies targeting the cysteine peptidases cruzain from Trypanosoma cruzi and rhodesain and cathepsin B from Trypanosoma brucei. Given that current chemotherapy for Chagas disease and human African trypanosomiasis has several drawbacks, cysteine proteases will continue to be actively pursued as valuable molecular targets in trypanosomatid disease drug discovery efforts. Copyright © 2017. Published by Elsevier Inc.

  16. Targeted nanoparticles for image-guided treatment of triple-negative breast cancer: clinical significance and technological advances.

    PubMed

    Miller-Kleinhenz, Jasmine M; Bozeman, Erica N; Yang, Lily

    2015-01-01

    Effective treatment of triple-negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and noninvasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise toward the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle-based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor-associated endothelial cells, stromal fibroblasts, and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in-depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as by others, and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. © 2015 Wiley Periodicals, Inc.

  17. Detection of suboptimal effort with symbol span: development of a new embedded index.

    PubMed

    Young, J Christopher; Caron, Joshua E; Baughman, Brandon C; Sawyer, R John

    2012-03-01

    Developing embedded indicators of suboptimal effort on objective neurocognitive testing is essential for detecting increasingly sophisticated forms of symptom feigning. The current study explored whether Symbol Span, a novel Wechsler Memory Scale-fourth edition measure of supraspan visual attention, could be used to discriminate adequate effort from suboptimal effort. Archival data were collected from 136 veterans classified into Poor Effort (n = 42) and Good Effort (n = 94) groups based on symptom validity test (SVT) performance. The Poor Effort group had significantly lower raw scores (p < .001) and age-corrected scaled scores (p < .001) than the Good Effort group on the Symbol Span test. A raw score cutoff of <14 produced 83% specificity and 50% sensitivity for detection of Poor Effort. Similarly, sensitivity was 52% and specificity was 84% when employing a cutoff of <7 for Age-Corrected Scale Score. Collectively, present results suggest that Symbol Span can effectively differentiate veterans with multiple failures on established free-standing and embedded SVTs.

  18. Systems genetics for drug target discovery

    PubMed Central

    Penrod, Nadia M.; Cowper-Sal_lari, Richard; Moore, Jason H.

    2011-01-01

    The collection and analysis of genomic data has the potential to reveal novel druggable targets by providing insight into the genetic basis of disease. However, the number of drugs, targeting new molecular entities, approved by the US Food and Drug Administration (FDA) has not increased in the years since the collection of genomic data has become commonplace. The paucity of translatable results can be partly attributed to conventional analysis methods that test one gene at a time in an effort to identify disease-associated factors as candidate drug targets. By disengaging genetic factors from their position within the genetic regulatory system, much of the information stored within the genomic data set is lost. Here we discuss how genomic data is used to identify disease-associated genes or genomic regions, how disease-associated regions are validated as functional targets, and the role network analysis can play in bridging the gap between data generation and effective drug target identification. PMID:21862141

  19. Effort-reward imbalance and organisational injustice among aged nurses: a moderated mediation model.

    PubMed

    Topa, Gabriela; Guglielmi, Dina; Depolo, Marco

    2016-09-01

    To test the effort-reward imbalance model among older nurses, expanding it to include the moderation of overcommitment and age in the stress-health complaints relationship, mediated by organisational injustice. The theoretical framework included the effort-reward imbalance, the uncertainty management and the socio-emotional selectivity models. Employing a two-wave design, the participants were 255 nurses aged 45 years and over, recruited from four large hospitals in Spain (Madrid and Basque Country). The direct effect of imbalance on health complaints was supported: it was significant when overcommitment was low but not when it was high. Organisational injustice mediated the influence of effort-reward imbalance on health complaints. The conditional effect of the mediation of organisational injustice was significant in three of the overcommitment/age conditions but it weakened, becoming non-significant, when the level of overcommitment was low and age was high. The study tested the model in nursing populations and expanded it to the settings of occupational health and safety at work. The results of this study highlight the importance of effort-reward imbalance and organisational justice for creating healthy work environments. © 2016 John Wiley & Sons Ltd.

  20. Would You Recommend Your Institution's Effort-Reporting Process to Others? Determining Best Practices in Effort-Reporting Compliance

    ERIC Educational Resources Information Center

    Whitaker, Ashley E.

    2015-01-01

    Effort-reporting compliance at higher education institutions was examined to discern best practices from those that would recommend their effort-reporting process. Data were derived from a survey of effort administrators--the research administrators responsible for the effort-reporting compliance program at their respective higher education…

  1. Effort-reward imbalance at school and depressive symptoms in Chinese adolescents: the role of family socioeconomic status.

    PubMed

    Guo, Hongxiang; Yang, Wenjie; Cao, Ying; Li, Jian; Siegrist, Johannes

    2014-06-10

    Depression is a major mental health problem during adolescence. This study, using a sample of Chinese adolescents, examined the separate and combined effects of perceived school-related stress and of family socioeconomic status (SES) on the prevalence of depressive symptoms. A total of 1774 Chinese students from Grades 7-12 were recruited into our questionnaire survey. School-related stress was measured by the Effort-Reward Imbalance Questionnaire-School Version, family SES was assessed by a standardized question, and depressive symptoms were evaluated by the Center for Epidemiological Studies Depression Scale for Children. Multivariate logistic regression was applied, adjusting for age, gender, grade, smoking, alcohol drinking and physical activity. It was found that high school-related stress and low family SES were associated with elevated odds of depressive symptoms, respectively. The effect of school-related stress was particularly strong in low SES group. In adolescents with both high stress at school and low SES, the odds ratio was 9.18 (95% confidence interval = 6.53-12.89) compared to the reference group (low stress at school and high SES). A significant synergistic interaction effect was observed (synergy index = 2.28, 95% confidence interval = 1.56-3.32). The findings indicated that perceived school-related stress, in terms of effort-reward imbalance, was related to depressive symptoms in this sample of Chinese adolescents. The strong interaction with family SES suggests that health promoting efforts in school settings should be targeted specifically at these socially deprived groups.

  2. [Effort-Reward Imbalance and psychophysical health of teachers].

    PubMed

    Zurlo, Maria Clelia; Pes, Daniela

    2012-01-01

    The present study referred to the Effort-Reward Imbalance Model applied to the evaluation of teacher stress and, by means of the italian version of the ERI test, explored the connections between the dimensions of the model and the specific effects of occupational stress on teacher's psychophysical diseases and leaving intentions. METHODS. The: subjects were 476 teachers working in Campania (region in southern Italy), belonging to all levels of teaching, who completed a questionnaire containing measures of Effort-Reward Imbalance, psychophysical health and intention to leave the teaching profession. RESULTS. Results showed the relevant: perception, among teachers, of Effort-reward Imbalance and of different physical and psychological diseases. All the dimensions of the ERI model emerged to be significantly related, in the direction stated by the model, to the different forms of psychological and physical disease considered, highlighting specific influences on them. The ERI-test and model provide a useful measure and a significative interpretative frame to explore the dimensions of teacher's stress and to arrange interventions for the prevention of psychophysical diseases.

  3. Gains to Language Learners from Viewing Target Language Closed-Captioned Films

    ERIC Educational Resources Information Center

    Stewart, Melissa A.; Pertusa, Inmaculada

    2004-01-01

    In an effort to facilitate students' understanding of films in the target language, many instructors turn to films with English subtitles. Viewing films subtitled in English does not encourage learners to use their previously acquired listening skills, but rather allows them to rely on reading English instead of making the extra effort required to…

  4. Efficacy and non-target impact of midstory injection in bottomland hardwoods

    Treesearch

    Derek K. Alkire; Andrew W. Ezell; Andrew B. Self; Stephen Demarais; Bronson K. Strickland

    2012-01-01

    The need for midstory control in bottomland hardwood regeneration work has been well documented. However, only a few research efforts have documented the efficacy of such efforts and the potential negative effects on non-target stems. This potential negative impact is extremely important in these stands where individual stem values are characteristically high. As part...

  5. Productive and ineffective efforts: how student effort in high school mathematics relates to college calculus success

    NASA Astrophysics Data System (ADS)

    Barnett, M. D.; Sonnert, G.; Sadler, P. M.

    2014-10-01

    Relativizing the popular belief that student effort is the key to success, this article finds that effort in the most advanced mathematics course in US high schools is not consistently associated with college calculus performance. We distinguish two types of student effort: productive and ineffective efforts. Whereas the former carries the commonly expected benefits, the latter is associated with negative consequences. Time spent reading the course text in US high schools was negatively related to college calculus performance. Daily study time, however, was found to be either a productive or an ineffective effort, depending on the level of high school mathematics course and the student's performance in it.

  6. Linking customisation of ERP systems to support effort: an empirical study

    NASA Astrophysics Data System (ADS)

    Koch, Stefan; Mitteregger, Kurt

    2016-01-01

    The amount of customisation to an enterprise resource planning (ERP) system has always been a major concern in the context of the implementation. This article focuses on the phase of maintenance and presents an empirical study about the relationship between the amount of customising and the resulting support effort. We establish a structural equation modelling model that explains support effort using customisation effort, organisational characteristics and scope of implementation. The findings using data from an ERP provider show that there is a statistically significant effect: with an increasing amount of customisation, the quantity of telephone calls to support increases, as well as the duration of each call.

  7. Respiratory effort correction strategies to improve the reproducibility of lung expansion measurements

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

    Du, Kaifang; Reinhardt, Joseph M.; Christensen, Gary E.

    2013-12-15

    correlated with respiratory effort difference (R = 0.744 for ELV in the cohort with tidal volume difference greater than 100 cc). In general for all subjects, global normalization, ETV and ELV significantly improved reproducibility compared to no effort correction (p = 0.009, 0.002, 0.005 respectively). When tidal volume difference was small (less than 100 cc), none of the three effort correction strategies improved reproducibility significantly (p = 0.52, 0.46, 0.46 respectively). For the cohort (N = 13) with tidal volume difference greater than 100 cc, the average gamma pass rate improves from 57.3% before correction to 66.3% after global normalization, and 76.3% after ELV. ELV was found to be significantly better than global normalization (p = 0.04 for all subjects, and p = 0.003 for the cohort with tidal volume difference greater than 100 cc).Conclusions: All effort correction strategies improve the reproducibility of the authors' pulmonary ventilation measures, and the improvement of reproducibility is highly correlated with the changes in respiratory effort. ELV gives better results as effort difference increase, followed by ETV, then global. However, based on the spatial and temporal heterogeneity in the lung expansion rate, a single scaling factor (e.g., global normalization) appears to be less accurate to correct the ventilation map when changes in respiratory effort are large.« less

  8. Targeting key proximal drivers of type 2 inflammation in disease.

    PubMed

    Gandhi, Namita A; Bennett, Brandy L; Graham, Neil M H; Pirozzi, Gianluca; Stahl, Neil; Yancopoulos, George D

    2016-01-01

    Systemic type 2 inflammation encompassing T helper 2 (TH2)-type responses is emerging as a unifying feature of both classically defined allergic diseases, such as asthma, and a range of other inflammatory diseases. Rather than reducing inflammation with broad-acting immunosuppressants or narrowly targeting downstream products of the TH2 pathway, such as immunoglobulin E (IgE), efforts to target the key proximal type 2 cytokines - interleukin-4 (IL-4), IL-5 and IL-13 - represent a promising strategy to achieve therapeutic benefit across multiple diseases. After several initial disappointing clinical results with therapies targeting IL-4, IL-5 or IL-13 in asthma, applying a personalized approach achieved therapeutic benefit in an asthma subtype exhibiting an 'allergic' phenotype. More recently, efficacy was extended into a broad population of people with asthma. This argues that the Type 2 inflammation is broadly relevant across the severe asthma population if the key upstream drivers are properly blocked. Moreover, the simultaneous inhibition of IL-4 and IL-13 has shown significant clinical activity in diseases that are often co-morbid with asthma - atopic dermatitis and chronic sinusitis with nasal polyps - supporting the hypothesis that targeting a central 'driver pathway' could benefit multiple allergic diseases.

  9. Target validation: linking target and chemical properties to desired product profile.

    PubMed

    Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D; Fairlamb, Alan H

    2011-01-01

    The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under-funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.

  10. Inequity responses of monkeys modified by effort

    PubMed Central

    van Wolkenten, Megan; Brosnan, Sarah F.; de Waal, Frans B. M.

    2007-01-01

    Without joint benefits, joint actions could never have evolved. Cooperative animals need to monitor closely how large a share they receive relative to their investment toward collective goals. This work documents the sensitivity to reward division in brown, or tufted, capuchin monkeys (Cebus apella). In addition to confirming previous results with a larger subject pool, this work rules out several alternative explanations and adds data on effort sensitivity. Thirteen adult monkeys exchanged tokens for rewards, showing negative reactions to receiving a less-favored reward than their partner. Because their negative reaction could not be attributed to the mere visibility of better rewards (greed hypothesis) nor to having received such rewards in the immediate past (frustration hypothesis), it must have been caused by seeing their partner obtain the better reward. Effort had a major effect in that by far the lowest level of performance in the entire study occurred in subjects required to expend a large effort while at the same time seeing their partner receive a better reward. It is unclear whether this effort–effect was based on comparisons with the partner, but it added significantly to the intensity of the inequity response. These effects are as expected if the inequity response evolved in the context of cooperative survival strategies. PMID:18000045

  11. Sampling effort affects multivariate comparisons of stream assemblages

    USGS Publications Warehouse

    Cao, Y.; Larsen, D.P.; Hughes, R.M.; Angermeier, P.L.; Patton, T.M.

    2002-01-01

    Multivariate analyses are used widely for determining patterns of assemblage structure, inferring species-environment relationships and assessing human impacts on ecosystems. The estimation of ecological patterns often depends on sampling effort, so the degree to which sampling effort affects the outcome of multivariate analyses is a concern. We examined the effect of sampling effort on site and group separation, which was measured using a mean similarity method. Two similarity measures, the Jaccard Coefficient and Bray-Curtis Index were investigated with 1 benthic macroinvertebrate and 2 fish data sets. Site separation was significantly improved with increased sampling effort because the similarity between replicate samples of a site increased more rapidly than between sites. Similarly, the faster increase in similarity between sites of the same group than between sites of different groups caused clearer separation between groups. The strength of site and group separation completely stabilized only when the mean similarity between replicates reached 1. These results are applicable to commonly used multivariate techniques such as cluster analysis and ordination because these multivariate techniques start with a similarity matrix. Completely stable outcomes of multivariate analyses are not feasible. Instead, we suggest 2 criteria for estimating the stability of multivariate analyses of assemblage data: 1) mean within-site similarity across all sites compared, indicating sample representativeness, and 2) the SD of within-site similarity across sites, measuring sample comparability.

  12. Using task effort and pupil size to track covert shifts of visual attention independently of a pupillary light reflex.

    PubMed

    Brocher, Andreas; Harbecke, Raphael; Graf, Tim; Memmert, Daniel; Hüttermann, Stefanie

    2018-03-07

    We tested the link between pupil size and the task effort involved in covert shifts of visual attention. The goal of this study was to establish pupil size as a marker of attentional shifting in the absence of luminance manipulations. In three experiments, participants evaluated two stimuli that were presented peripherally, appearing equidistant from and on opposite sides of eye fixation. The angle between eye fixation and the peripherally presented target stimuli varied from 12.5° to 42.5°. The evaluation of more distant stimuli led to poorer performance than did the evaluation of more proximal stimuli throughout our study, confirming that the former required more effort than the latter. In addition, in Experiment 1 we found that pupil size increased with increasing angle and that this effect could not be reduced to the operation of low-level visual processes in the task. In Experiment 2 the pupil dilated more strongly overall when participants evaluated the target stimuli, which required shifts of attention, than when they merely reported on the target's presence versus absence. Both conditions yielded larger pupils for more distant than for more proximal stimuli, however. In Experiment 3, we manipulated task difficulty more directly, by changing the contrast at which the target stimuli were presented. We replicated the results from Experiment 1 only with the high-contrast stimuli. With stimuli of low contrast, ceiling effects in pupil size were observed. Our data show that the link between task effort and pupil size can be used to track the degree to which an observer covertly shifts attention to or detects stimuli in peripheral vision.

  13. Generating Electricity during Walking with a Lower Limb-Driven Energy Harvester: Targeting a Minimum User Effort.

    PubMed

    Shepertycky, Michael; Li, Qingguo

    2015-01-01

    Much research in the field of energy harvesting has sought to develop devices capable of generating electricity during daily activities with minimum user effort. No previous study has considered the metabolic cost of carrying the harvester when determining the energetic effects it has on the user. When considering device carrying costs, no energy harvester to date has demonstrated the ability to generate a substantial amount of electricity (> 5W) while maintaining a user effort at the same level or lower than conventional power generation methods (e.g. hand crank generator). We developed a lower limb-driven energy harvester that is able to generate approximately 9W of electricity. To quantify the performance of the harvester, we introduced a new performance measure, total cost of harvesting (TCOH), which evaluates a harvester's overall efficiency in generating electricity including the device carrying cost. The new harvester captured the motion from both lower limbs and operated in the generative braking mode to assist the knee flexor muscles in slowing the lower limbs. From a testing on 10 participants under different walking conditions, the harvester achieved an average TCOH of 6.1, which is comparable to the estimated TCOH for a conventional power generation method of 6.2. When generating 5.2W of electricity, the TCOH of the lower limb-driven energy harvester (4.0) is lower than that of conventional power generation methods. These results demonstrated that the lower limb-driven energy harvester is an energetically effective option for generating electricity during daily activities.

  14. APS Education and Diversity Efforts

    NASA Astrophysics Data System (ADS)

    Prestridge, Katherine; Hodapp, Theodore

    2015-11-01

    American Physical Society (APS) has a wide range of education and diversity programs and activities, including programs that improve physics education, increase diversity, provide outreach to the public, and impact public policy. We present the latest programs spearheaded by the Committee on the Status of Women in Physics (CSWP), with highlights from other diversity and education efforts. The CSWP is working to increase the fraction of women in physics, understand and implement solutions for gender-specific issues, enhance professional development opportunities for women in physics, and remedy issues that impact gender inequality in physics. The Conferences for Undergraduate Women in Physics, Professional Skills Development Workshops, and our new Professional Skills program for students and postdocs are all working towards meeting these goals. The CSWP also has site visit and conversation visit programs, where department chairs request that the APS assess the climate for women in their departments or facilitate climate discussions. APS also has two significant programs to increase participation by underrepresented minorities (URM). The newest program, the APS National Mentoring Community, is working to provide mentoring to URM undergraduates, and the APS Bridge Program is an established effort that is dramatically increasing the number of URM PhDs in physics.

  15. Identifying vaccine targets for anti-leishmanial vaccine development

    PubMed Central

    Sundar, Shyam; Singh, Bhawana

    2014-01-01

    Leishmaniasis is a neglected tropical disease spread by an arthropod vector. It remains a significant health problem with an incidence of 0.2–0.4 million VL and 0.7–1.2 million CL cases each year. There are limitations associated with the current therapeutic regimens for leishmaniasis and the fact that after recovery from infection the host becomes immune to subsequent infection therefore, these factors forces the feasibility of a vaccine for leishmaniasis. Publication of the genome sequence of Leishmania has paved a new way to understand the pathogenesis and host immunological status therefore providing a deep insight in the field of vaccine research. This review is an effort to study the antigenic targets in Leishmania to develop anti-leishmanial vaccine. PMID:24606556

  16. Effort-reward imbalance and self-rated health among Gambian healthcare professionals.

    PubMed

    Darboe, Amadou; Lin, I-Feng; Kuo, Hsien-Wen

    2016-04-11

    The effort-reward imbalance (ERI) model of work stress has been widely applied in investigating association between psychosocial factors at work and health. This study examined associations between perceived psychosocial work stress as measured by the ERI model and self-rated health (SRH) among nurses and environmental health officers (EHOs) working in secondary public healthcare facilities in the Gambia. A cross-sectional study on a random sample of 287 health care professionals (201 nurses and 86 EHOs). A 22-item ERI questionnaire was used to collect data on the psychosocial factors defined by the ERI model. SRH was assessed using a single item measure. The distribution of subjective health was not statistically different between nurses and EHOs. However, our study uncovered significant associations between perceived psychosocial work stress and subjective health. Specifically, we found that a perceived high effort-reward imbalance (ER-ratio > 1) is a significant risk factor for poor SRH, in both occupational groups. However, over-commitment was not significantly associated with poor SRH in the two groups. When efforts and rewards were considered as separate variables in the analysis, rewards were inversely associated with poor SRH in both groups. Because of the high perceived Effort-Reward Imbalance among healthcare professionals at secondary public healthcare facilities, it is necessary to modify working conditions through improvement of psychosocial work environment, such as reasonable allocation of resources to increase pay, incentives or other forms of rewards from government. Interventions that could mitigate and prevent stress at work are worth considering in future healthcare policies.

  17. Student Teachers' Attitudes and Beliefs about Using the Target Language in the Classroom

    ERIC Educational Resources Information Center

    Bateman, Blair E.

    2008-01-01

    Although the language teaching profession has long emphasized the use of the target language in the classroom, student teachers face various challenges in their efforts to conduct class in their target language. This case study focused on 10 student teachers with respect to (1) their initial attitudes and beliefs about using the target language,…

  18. Efforts to Prevent Concussions Target Schools

    ERIC Educational Resources Information Center

    Samuels, Christina A.

    2010-01-01

    The number of sports-related concussions reported by young athletes is on the rise, prompting awareness campaigns from athletic and medical groups, as well as proposed federal legislation to set minimum standards for concussion management in public schools. Concussions are caused by a jolt to the body or a blow to the head that causes the head to…

  19. Neural substrates of the impaired effort expenditure decision making in schizophrenia.

    PubMed

    Huang, Jia; Yang, Xin-Hua; Lan, Yong; Zhu, Cui-Ying; Liu, Xiao-Qun; Wang, Ye-Fei; Cheung, Eric F C; Xie, Guang-Rong; Chan, Raymond C K

    2016-09-01

    Unwillingness to expend more effort to pursue high value rewards has been associated with motivational anhedonia in schizophrenia (SCZ) and abnormal dopamine activity in the nucleus accumbens (NAcc). The authors hypothesized that dysfunction of the NAcc and the associated forebrain regions are involved in the impaired effort expenditure decision-making of SCZ. A 2 (reward magnitude: low vs. high) × 3 (probability: 20% vs. 50% vs. 80%) event-related fMRI design in the effort-expenditure for reward task (EEfRT) was used to examine the neural response of 23 SCZ patients and 23 demographically matched control participants when the participants made effort expenditure decisions to pursue uncertain rewards. SCZ patients were significantly less likely to expend high level of effort in the medium (50%) and high (80%) probability conditions than healthy controls. The neural response in the NAcc, the posterior cingulate gyrus and the left medial frontal gyrus in SCZ patients were weaker than healthy controls and did not linearly increase with an increase in reward magnitude and probability. Moreover, NAcc activity was positively correlated with the willingness to expend high-level effort and concrete consummatory pleasure experience. NAcc and posterior cingulate dysfunctions in SCZ patients may be involved in their impaired effort expenditure decision-making. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  20. [Maternal effects of prolonged expulsive efforts].

    PubMed

    Korb, D; Merazka, R; Théau, A; Goffinet, F; Le Ray, C

    2016-02-01

    Some studies found an association between duration of expulsive efforts (DEE) and risk of postpartum haemorrhage (PPH). But none demonstrated an association between DEE and severe perineal lacerations. Our aim was to evaluate the impact of prolonged expulsive efforts (EE) beyond 45min on the risk of maternal complication, especially risk of severe perineal laceration. We performed a retrospective study comparing 2 groups, 1: women with an instrumental vaginal delivery performed before 45min for non-fetal progression without FHR abnormalities (VBI for NP<45min) and 2: women with a DEE longer than 45min (DEE≥45min). We compared maternal issues (3rd and 4th degrees perineal lacerations and PPH), using uni- and multivariate analysis. We compared 85 women in group VBI for NP<45min with 124 women in group EE≥45min. In the group EE≥45min, 39% of women had an instrumental vaginal delivery versus 100% in the group VBI for NP<45min (P<0.001). The rate of severe perineal lacerations was significantly higher in the group VBI for NP<45min (8.2% versus 1.7%, P=0.027) and its risk remained significant after adjustment (adjusted OR=6.5 [1.1-40.1]). The rate of PPH was higher in the group EE≥45min (12.9% versus 3.5%, P=0.016), however this association was not significant after adjustment (adjusted OR=3.4 [0.9-12.4]). There was no difference about neonatal issues between the two studied groups. In comparison with a limitation of EE, to prolong EE beyond 45min allows a spontaneous vaginal delivery for more than half of women, if FHR is normal. Such strategy should also decrease the risk of severe perineal laceration. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Mercury target R&D for the Oak Ridge spallation neutron source

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

    Haines, J.R.; DiStefano, J.; Farrell, K.

    1996-06-01

    The conceptual design for the Oak Ridge Spallation Neutron Source (ORSNS) incorporates liquid mercury as its reference target material. A flowing liquid target was selected mainly because of the increased power handling capability possible with the convective transport process. The major reasons for choosing mercury as the liquid target material are because it: (1) is a liquid at room temperature, (2) has good heat transport properties, and (3) has a high atomic number and mass density resulting in high neutron yield and source brightness. Since liquid targets are not widely utilized in presently operating accelerator targets and because of themore » challenges posed by the intense, pulsed thermal energy deposition ({approximately}20-100 kJ deposited during each 1-10 {mu}s pulse), considerable R&D is planned for the mercury target concept. The key feasibility issue that will be addressed in early R&D efforts are the effects of the thermal shock environment, which will include development and testing of approaches to mitigate these effects. Materials compatiblity and ES&H issues associated with the use of liquid mercury are also of major importance in early R&D efforts. A brief description of the mercury target design concept, results of initial evaluations of its performance characteristics, identification of its critical issues, and an outline of the R&D program aimed at addressing these issues will be presented.« less

  2. Effect of Active Videogames on Underserved Children's Classroom Behaviors, Effort, and Fitness.

    PubMed

    Gao, Zan; Lee, Jung Eun; Pope, Zachary; Zhang, Dachao

    2016-09-30

    The purpose of this study was to examine the effect of active videogames (AVGs) on underserved minority children's on-task classroom behavior, academic effort, and fitness. A one group pre- and posttest repeated measures design was used. In Fall 2013, 95 fourth grade children (57 boys, 38 girls; 96% of minority) from three classes at an underserved urban elementary school participated in teacher-supervised AVG activities (e.g., Wii Sports, Xbox Just Dance). Specifically, students participated in a 50-minute weekly AVG program at school for 6 weeks. Children's academic effort was evaluated by classroom teachers using a validated scale that assessed activity, attention, conduct, and social/emotional behavior. Moreover, children's classroom behavior was observed immediately before and after each AVG session by trained researchers. Finally, cardiovascular fitness was also measured. A paired t-test was used to assess teacher-rated student effort, while one-way (gender) analysis of variance (ANOVA) with repeated measures was performed to analyze children's on-task classroom behavior. There was a significant effect on children's effort between the first (mean = 3.24, SD = 0.75) and last week (mean = 3.41, SD = 0.73) assessments, t = 2.42, P = 0.02. In addition, there was a significant effect on classroom behavior, F = 33.103, P < 0.01. In detail, children scored significantly higher on on-task behavior during the post-AVG observation (mean = 81.4, SD = 12.3) than seen during the pre-AVG observation (mean = 69.8, SD = 14.9). However, no main effect was indicated for gender, F = 0.39, P = 0.54. No significant improvement in cardiovascular fitness was observed, although slight improvements were seen. Offering an AVG program at school could improve underserved minority children's classroom on-task behavior and academic effort. Future studies may include a control group to further confirm the effectiveness of AVG

  3. Materials characterization on efforts for ablative materials

    NASA Technical Reports Server (NTRS)

    Tytula, Thomas P.; Schad, Kristin C.; Swann, Myles H.

    1992-01-01

    Experimental efforts to develop a new procedure to measure char depth in carbon phenolic nozzle material are described. Using a Shor Type D Durometer, hardness profiles were mapped across post fired sample blocks and specimens from a fired rocket nozzle. Linear regression was used to estimate the char depth. Results are compared to those obtained from computed tomography in a comparative experiment. There was no significant difference in the depth estimates obtained by the two methods.

  4. Deep-sea crustacean trawling fisheries in Portugal: quantification of effort and assessment of landings per unit effort using a Vessel Monitoring System (VMS)

    NASA Astrophysics Data System (ADS)

    Bueno-Pardo, Juan; Ramalho, Sofia P.; García-Alegre, Ana; Morgado, Mariana; Vieira, Rui P.; Cunha, Marina R.; Queiroga, Henrique

    2017-01-01

    Mapping and quantifying bottom trawling fishing pressure on the seafloor is pivotal to understand its effects on deep-sea benthic habitats. Using data from the Vessel Monitoring System of crustacean trawlers along the Portuguese margin, we have identified the most exploited areas and characterized the most targeted habitats and water depths. We estimated a total trawling effort of 69596, 66766, and 63427 h y-1 for the years 2012, 2013, and 2014 respectively which, considering the total landings estimated for this gear, yield values of 20.76, 21.06, and 19.11 kg of landed fish per trawled hour. The main trawling pressure is exerted in the South and Southwest Portuguese margins, on muddy and muddy-sand bottoms between 200 and 700 m water depths, while in the North and Central-West coasts a minor effort, at shallower waters and across a wider range of habitats, is also applied. The most landed species are crustaceans such as rose shrimp and Norway lobster, although this varies importantly between the different regions of Portugal, being fish and cephalopods the main captures in the Northern ports. We discuss the consequences of trawling for the impacted communities as well as the characteristics of the commercialization of these captures in Portugal.

  5. Deep-sea crustacean trawling fisheries in Portugal: quantification of effort and assessment of landings per unit effort using a Vessel Monitoring System (VMS)

    PubMed Central

    Bueno-Pardo, Juan; Ramalho, Sofia P.; García-Alegre, Ana; Morgado, Mariana; Vieira, Rui P.; Cunha, Marina R.; Queiroga, Henrique

    2017-01-01

    Mapping and quantifying bottom trawling fishing pressure on the seafloor is pivotal to understand its effects on deep-sea benthic habitats. Using data from the Vessel Monitoring System of crustacean trawlers along the Portuguese margin, we have identified the most exploited areas and characterized the most targeted habitats and water depths. We estimated a total trawling effort of 69596, 66766, and 63427 h y−1 for the years 2012, 2013, and 2014 respectively which, considering the total landings estimated for this gear, yield values of 20.76, 21.06, and 19.11 kg of landed fish per trawled hour. The main trawling pressure is exerted in the South and Southwest Portuguese margins, on muddy and muddy-sand bottoms between 200 and 700 m water depths, while in the North and Central-West coasts a minor effort, at shallower waters and across a wider range of habitats, is also applied. The most landed species are crustaceans such as rose shrimp and Norway lobster, although this varies importantly between the different regions of Portugal, being fish and cephalopods the main captures in the Northern ports. We discuss the consequences of trawling for the impacted communities as well as the characteristics of the commercialization of these captures in Portugal. PMID:28098211

  6. Aided target recognition processing of MUDSS sonar data

    NASA Astrophysics Data System (ADS)

    Lau, Brian; Chao, Tien-Hsin

    1998-09-01

    The Mobile Underwater Debris Survey System (MUDSS) is a collaborative effort by the Navy and the Jet Propulsion Lab to demonstrate multi-sensor, real-time, survey of underwater sites for ordnance and explosive waste (OEW). We describe the sonar processing algorithm, a novel target recognition algorithm incorporating wavelets, morphological image processing, expansion by Hermite polynomials, and neural networks. This algorithm has found all planted targets in MUDSS tests and has achieved spectacular success upon another Coastal Systems Station (CSS) sonar image database.

  7. Target Deconvolution Efforts on Wnt Pathway Screen Reveal Dual Modulation of Oxidative Phosphorylation and SERCA2.

    PubMed

    Casás-Selves, Matias; Zhang, Andrew X; Dowling, James E; Hallén, Stefan; Kawatkar, Aarti; Pace, Nicholas J; Denz, Christopher R; Pontz, Timothy; Garahdaghi, Farzin; Cao, Qing; Sabirsh, Alan; Thakur, Kumar; O'Connell, Nichole; Hu, Jun; Cornella-Taracido, Iván; Weerapana, Eranthie; Zinda, Michael; Goodnow, Robert A; Castaldi, M Paola

    2017-06-21

    Wnt signaling is critical for development, cell proliferation and differentiation, and mutations in this pathway resulting in constitutive signaling have been implicated in various cancers. A pathway screen using a Wnt-dependent reporter identified a chemical series based on a 1,2,3-thiadiazole-5-carboxamide (TDZ) core with sub-micromolar potency. Herein we report a comprehensive mechanism-of-action deconvolution study toward identifying the efficacy target(s) and biological implication of this chemical series involving bottom-up quantitative chemoproteomics, cell biology, and biochemical methods. Through observing the effects of our probes on metabolism and performing confirmatory cellular and biochemical assays, we found that this chemical series inhibits ATP synthesis by uncoupling the mitochondrial potential. Affinity chemoproteomics experiments identified sarco(endo)plasmic reticulum Ca 2+ -dependent ATPase (SERCA2) as a binding partner of the TDZ series, and subsequent validation studies suggest that the TDZ series can act as ionophores through SERCA2 toward Wnt pathway inhibition. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Compensatory Effort Parallels Midbrain Deactivation during Mental Fatigue: An fMRI Study

    PubMed Central

    Nakagawa, Seishu; Sugiura, Motoaki; Akitsuki, Yuko; Hosseini, S. M. Hadi; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Yomogida, Yukihito; Yokoyama, Ryoichi; Takeuchi, Hikaru; Kawashima, Ryuta

    2013-01-01

    Fatigue reflects the functioning of our physiological negative feedback system, which prevents us from overworking. When fatigued, however, we often try to suppress this system in an effort to compensate for the resulting deterioration in performance. Previous studies have suggested that the effect of fatigue on neurovascular demand may be influenced by this compensatory effort. The primary goal of the present study was to isolate the effect of compensatory effort on neurovascular demand. Healthy male volunteers participated in a series of visual and auditory divided attention tasks that steadily increased fatigue levels for 2 hours. Functional magnetic resonance imaging scans were performed during the first and last quarter of the study (Pre and Post sessions, respectively). Tasks with low and high attentional load (Low and High conditions, respectively) were administrated in alternating blocks. We assumed that compensatory effort would be greater under the High-attentional-load condition compared with the Low-load condition. The difference was assessed during the two sessions. The effect of compensatory effort on neurovascular demand was evaluated by examining the interaction between load (High vs. Low) and time (Pre vs. Post). Significant fatigue-induced deactivation (i.e., Pre>Post) was observed in the frontal, temporal, occipital, and parietal cortices, in the cerebellum, and in the midbrain in both the High and Low conditions. The interaction was significantly greater in the High than in the Low condition in the midbrain. Neither significant fatigue-induced activation (i.e., Pre[PreE– PostE]) may reflect suppression of the negative feedback system that normally triggers recuperative rest to maintain homeostasis. PMID:23457592

  9. Contrast and the justification of effort.

    PubMed

    Klein, Emily D; Bhatt, Ramesh S; Zentall, Thomas R

    2005-04-01

    When humans are asked to evaluate rewards or outcomes that follow unpleasant (e.g., high-effort) events, they often assign higher value to that reward. This phenomenon has been referred to as cognitive dissonance or justification of effort. There is now evidence that a similar phenomenon can be found in nonhuman animals. When demonstrated in animals, however, it has been attributed to contrast between the unpleasant high effort and the conditioned stimulus for food. In the present experiment, we asked whether an analogous effect could be found in humans under conditions similar to those found in animals. Adult humans were trained to discriminate between shapes that followed a high-effort versus a low-effort response. In test, participants were found to prefer shapes that followed the high-effort response in training. These results suggest the possibility that contrast effects of the sort extensively studied in animals may play a role in cognitive dissonance and other related phenomena in humans.

  10. Understanding text-based persuasion and support tactics of concerned significant others

    PubMed Central

    van Stolk-Cooke, Katherine; Hayes, Marie; Baumel, Amit

    2015-01-01

    The behavior of concerned significant others (CSOs) can have a measurable impact on the health and wellness of individuals attempting to meet behavioral and health goals, and research is needed to better understand the attributes of text-based CSO language when encouraging target significant others (TSOs) to achieve those goals. In an effort to inform the development of interventions for CSOs, this study examined the language content of brief text-based messages generated by CSOs to motivate TSOs to achieve a behavioral goal. CSOs generated brief text-based messages for TSOs for three scenarios: (1) to help TSOs achieve the goal, (2) in the event that the TSO is struggling to meet the goal, and (3) in the event that the TSO has given up on meeting the goal. Results indicate that there was a significant relationship between the tone and compassion of messages generated by CSOs, the CSOs’ perceptions of TSO motivation, and their expectation of a grateful or annoyed reaction by the TSO to their feedback or support. Results underscore the importance of attending to patterns in language when CSOs communicate with TSOs about goal achievement or failure, and how certain variables in the CSOs’ perceptions of their TSOs affect these characteristics. PMID:26312172

  11. Understanding text-based persuasion and support tactics of concerned significant others.

    PubMed

    van Stolk-Cooke, Katherine; Hayes, Marie; Baumel, Amit; Muench, Frederick

    2015-01-01

    The behavior of concerned significant others (CSOs) can have a measurable impact on the health and wellness of individuals attempting to meet behavioral and health goals, and research is needed to better understand the attributes of text-based CSO language when encouraging target significant others (TSOs) to achieve those goals. In an effort to inform the development of interventions for CSOs, this study examined the language content of brief text-based messages generated by CSOs to motivate TSOs to achieve a behavioral goal. CSOs generated brief text-based messages for TSOs for three scenarios: (1) to help TSOs achieve the goal, (2) in the event that the TSO is struggling to meet the goal, and (3) in the event that the TSO has given up on meeting the goal. Results indicate that there was a significant relationship between the tone and compassion of messages generated by CSOs, the CSOs' perceptions of TSO motivation, and their expectation of a grateful or annoyed reaction by the TSO to their feedback or support. Results underscore the importance of attending to patterns in language when CSOs communicate with TSOs about goal achievement or failure, and how certain variables in the CSOs' perceptions of their TSOs affect these characteristics.

  12. Volitional chewing with a conscious effort alters and facilitates swallowing during feeding sequence.

    PubMed

    Furuya, J; Hara, A; Nomura, T; Kondo, H

    2014-03-01

    The key objective of mastication is to form a food bolus suitable for smooth swallowing. However, chewing is usually performed without a conscious effort. Poor bolus formation can cause pharyngeal residue and suffocation in elderly individuals with reduced swallowing function. Therefore, chewing with a conscious effort may help the bolus to more easily pass the pharynx. This study aimed to clarify the impact of mastication with a conscious effort on the feeding sequence. Subjects included 25 dentulous volunteers who were informed and provided written consent. Lateral videofluoroscopy was performed during the feeding of solid agar jelly under two conditions: chewing naturally in their usual manner (without volition) and chewing with a conscious effort (with volition). Temporal evaluation was performed for mastication, stage II transport (STII), swallow onset and oropharyngeal transit time. Moreover, bolus volume at swallow onset and subjective evaluation of swallowing easiness were measured. Volitional chewing with a conscious effort lengthened the duration of the chewing sequence before and after STII and delayed the swallow onset despite the fact that the bolus volume in the vallecula and hypopharynx (HYP) had significantly increased. Furthermore, with volition, the bolus transit time from swallow onset in the oral cavity, upper oropharynx and HYP was reduced, and subjective evaluation of swallowing easiness demonstrated significant improvement. These results suggest that volitional chewing with a conscious effort can alter bolus transport and swallowing, resulting in easier swallowing. © 2014 John Wiley & Sons Ltd.

  13. Children's Effort/Ability Reasoning: Individual Differences and Motivational Consequences.

    ERIC Educational Resources Information Center

    Leggett, Ellen L.; Dweck, Carol S.

    Individual differences in same-aged children's reasoning about effort and ability, as well as the consequences of different forms of reasoning in actual achievement situations, were investigated. It was hypothesized that different forms of children's reasoning would be related to different (helpless versus mastery-oriented) motivational patterns.…

  14. Increasing motivation changes subjective reports of listening effort and choice of coping strategy.

    PubMed

    Picou, Erin M; Ricketts, Todd A

    2014-06-01

    The purpose of this project was to examine the effect of changing motivation on subjective ratings of listening effort and on the likelihood that a listener chooses either a controlling or an avoidance coping strategy. Two experiments were conducted, one with auditory-only (AO) and one with auditory-visual (AV) stimuli, both using the same speech recognition in noise materials. Four signal-to-noise ratios (SNRs) were used, two in each experiment. The two SNRs targeted 80% and 50% correct performance. Motivation was manipulated by either having participants listen carefully to the speech (low motivation), or listen carefully to the speech and then answer quiz questions about the speech (high motivation). Sixteen participants with normal hearing participated in each experiment. Eight randomly selected participants participated in both. Using AO and AV stimuli, motivation generally increased subjective ratings of listening effort and tiredness. In addition, using auditory-visual stimuli, motivation generally increased listeners' willingness to do something to improve the situation, and decreased their willingness to avoid the situation. These results suggest a listener's mental state may influence listening effort and choice of coping strategy.

  15. Common pitfalls in preclinical cancer target validation.

    PubMed

    Kaelin, William G

    2017-07-01

    An alarming number of papers from laboratories nominating new cancer drug targets contain findings that cannot be reproduced by others or are simply not robust enough to justify drug discovery efforts. This problem probably has many causes, including an underappreciation of the danger of being misled by off-target effects when using pharmacological or genetic perturbants in complex biological assays. This danger is particularly acute when, as is often the case in cancer pharmacology, the biological phenotype being measured is a 'down' readout (such as decreased proliferation, decreased viability or decreased tumour growth) that could simply reflect a nonspecific loss of cellular fitness. These problems are compounded by multiple hypothesis testing, such as when candidate targets emerge from high-throughput screens that interrogate multiple targets in parallel, and by a publication and promotion system that preferentially rewards positive findings. In this Perspective, I outline some of the common pitfalls in preclinical cancer target identification and some potential approaches to mitigate them.

  16. Using habitat suitability models to target invasive plant species surveys.

    PubMed

    Crall, Alycia W; Jarnevich, Catherine S; Panke, Brendon; Young, Nick; Renz, Mark; Morisette, Jeffrey

    2013-01-01

    Managers need new tools for detecting the movement and spread of nonnative, invasive species. Habitat suitability models are a popular tool for mapping the potential distribution of current invaders, but the ability of these models to prioritize monitoring efforts has not been tested in the field. We tested the utility of an iterative sampling design (i.e., models based on field observations used to guide subsequent field data collection to improve the model), hypothesizing that model performance would increase when new data were gathered from targeted sampling using criteria based on the initial model results. We also tested the ability of habitat suitability models to predict the spread of invasive species, hypothesizing that models would accurately predict occurrences in the field, and that the use of targeted sampling would detect more species with less sampling effort than a nontargeted approach. We tested these hypotheses on two species at the state scale (Centaurea stoebe and Pastinaca sativa) in Wisconsin (USA), and one genus at the regional scale (Tamarix) in the western United States. These initial data were merged with environmental data at 30-m2 resolution for Wisconsin and 1-km2 resolution for the western United States to produce our first iteration models. We stratified these initial models to target field sampling and compared our models and success at detecting our species of interest to other surveys being conducted during the same field season (i.e., nontargeted sampling). Although more data did not always improve our models based on correct classification rate (CCR), sensitivity, specificity, kappa, or area under the curve (AUC), our models generated from targeted sampling data always performed better than models generated from nontargeted data. For Wisconsin species, the model described actual locations in the field fairly well (kappa = 0.51, 0.19, P < 0.01), and targeted sampling did detect more species than nontargeted sampling with less

  17. Alterations to Swallowing Physiology as the Result of Effortful Swallowing in Healthy Seniors.

    PubMed

    Molfenter, Sonja M; Hsu, Chuan-Ya; Lu, Ying; Lazarus, Cathy L

    2018-06-01

    A significant proportion of healthy seniors report difficulty swallowing, thought to result from age-related decline in muscle bulk/function. Effortful Swallowing (ES) is used both as a compensatory maneuver to improve pharyngeal propulsion/clearance and has been proposed as an exercise to improve pharyngeal strength. This study sought to quantify the immediate kinematic, temporal, and functional changes during an ES maneuver to quantify its exercise potential to combat age-related changes in swallowing. Videofluoroscopy data were collected from 44 healthy seniors (21 male) over 65 years old (mean = 76.9, SD = 7.1). Each participant swallowed six 5 ml boluses of Varibar nectar-thick liquids: three with regular effort and three using ES. Individual swallows (n = 260) were measured on pharyngeal constriction, pharyngeal shortening, laryngeal closure duration, hyoid movement duration, UES opening duration, stage transition duration, pharyngeal transit time, pharyngeal response duration, Normalized Residue Ratio Scale (NRRS), and the Penetration-Aspiration Scale (PAS). Non-parametric Wilcoxon Rank Sum for repeated measures tested the effect of ES on each outcome. Exact p-values were calculated based on permutation methods, individual p values < 0.008 was deemed to be significant. The ES maneuver significantly prolonged all temporal variables. While we found no significant differences for pharyngeal constriction, significantly less (i.e., worse) pharyngeal shortening was observed in ES condition compared with regular effort swallows. Further, significantly worse pyriform sinus residue (NRRSv) was observed in the ES condition. No differences between ES and regular effort swallows were noted for pharyngeal constriction, NRRSv or PAS. We speculate that these negative manifestations of worse kinematics (less pharyngeal shortening) and function (increase in NRRSp) may be the result of forced volitional manipulation of swallowing in the ES condition in an otherwise

  18. Effort-Reward Imbalance at School and Depressive Symptoms in Chinese Adolescents: The Role of Family Socioeconomic Status

    PubMed Central

    Guo, Hongxiang; Yang, Wenjie; Cao, Ying; Li, Jian; Siegrist, Johannes

    2014-01-01

    Depression is a major mental health problem during adolescence. This study, using a sample of Chinese adolescents, examined the separate and combined effects of perceived school-related stress and of family socioeconomic status (SES) on the prevalence of depressive symptoms. A total of 1774 Chinese students from Grades 7–12 were recruited into our questionnaire survey. School-related stress was measured by the Effort-Reward Imbalance Questionnaire-School Version, family SES was assessed by a standardized question, and depressive symptoms were evaluated by the Center for Epidemiological Studies Depression Scale for Children. Multivariate logistic regression was applied, adjusting for age, gender, grade, smoking, alcohol drinking and physical activity. It was found that high school-related stress and low family SES were associated with elevated odds of depressive symptoms, respectively. The effect of school-related stress was particularly strong in low SES group. In adolescents with both high stress at school and low SES, the odds ratio was 9.18 (95% confidence interval = 6.53–12.89) compared to the reference group (low stress at school and high SES). A significant synergistic interaction effect was observed (synergy index = 2.28, 95% confidence interval = 1.56–3.32). The findings indicated that perceived school-related stress, in terms of effort-reward imbalance, was related to depressive symptoms in this sample of Chinese adolescents. The strong interaction with family SES suggests that health promoting efforts in school settings should be targeted specifically at these socially deprived groups. PMID:24919130

  19. Multisensor fusion for the detection of mines and minelike targets

    NASA Astrophysics Data System (ADS)

    Hanshaw, Terilee

    1995-06-01

    The US Army's Communications and Electronics Command through the auspices of its Night Vision and Electronics Sensors Directorate (CECOM-NVESD) is actively applying multisensor techniques to the detection of mine targets. This multisensor research results from the 'detection activity' with its broad range of operational conditions and targets. Multisensor operation justifies significant attention by yielding high target detection and low false alarm statistics. Furthermore, recent advances in sensor and computing technologies make its practical application realistic and affordable. The mine detection field-of-endeavor has since its WWI baptismal investigated the known spectra for applicable mine observation phenomena. Countless sensors, algorithms, processors, networks, and other techniques have been investigated to determine candidacy for mine detection. CECOM-NVESD efforts have addressed a wide range of sensors spanning the spectrum from gravity field perturbations, magentic field disturbances, seismic sounding, electromagnetic fields, earth penetrating radar imagery, and infrared/visible/ultraviolet surface imaging technologies. Supplementary analysis has considered sensor candidate applicability by testing under field conditions (versus laboratory), in determination of fieldability. As these field conditions directly effect the probability of detection and false alarms, sensor employment and design must be considered. Consequently, as a given sensor's performance is influenced directly by the operational conditions, tradeoffs are necessary. At present, mass produced and fielded mine detection techniques are limited to those incorporating a single sensor/processor methodology such as, pulse induction and megnetometry, as found in hand held detectors. The most sensitive fielded systems can detect minute metal components in small mine targets but result in very high false alarm rates reducing velocity in operation environments. Furthermore, the actual speed of

  20. Targeting Virus-host Interactions of HIV Replication.

    PubMed

    Weydert, Caroline; De Rijck, Jan; Christ, Frauke; Debyser, Zeger

    2016-01-01

    Cellular proteins that are hijacked by HIV in order to complete its replication cycle, form attractive new targets for antiretroviral therapy. In particular, the protein-protein interactions between these cellular proteins (cofactors) and viral proteins are of great interest to develop new therapies. Research efforts have led to the validation of different cofactors and some successes in therapeutic applications. Maraviroc, the first cofactor inhibitor approved for human medicinal use, provided a proof of concept. Furthermore, compounds developed as Integrase-LEDGF/p75 interaction inhibitors (LEDGINs) have advanced to early clinical trials. Other compounds targeting cofactors and cofactor-viral protein interactions are currently under development. Likewise, interactions between cellular restriction factors and their counteracting HIV protein might serve as interesting targets in order to impair HIV replication. In this respect, compounds targeting the Vif-APOBEC3G interaction have been described. In this review, we focus on compounds targeting the Integrase- LEDGF/p75 interaction, the Tat-P-TEFb interaction and the Vif-APOBEC3G interaction. Additionally we give an overview of currently discovered compounds presumably targeting cellular cofactor-HIV protein interactions.

  1. A method of determining where to target surveillance efforts in heterogeneous epidemiological systems

    PubMed Central

    van den Bosch, Frank; Gottwald, Timothy R.; Alonso Chavez, Vasthi

    2017-01-01

    The spread of pathogens into new environments poses a considerable threat to human, animal, and plant health, and by extension, human and animal wellbeing, ecosystem function, and agricultural productivity, worldwide. Early detection through effective surveillance is a key strategy to reduce the risk of their establishment. Whilst it is well established that statistical and economic considerations are of vital importance when planning surveillance efforts, it is also important to consider epidemiological characteristics of the pathogen in question—including heterogeneities within the epidemiological system itself. One of the most pronounced realisations of this heterogeneity is seen in the case of vector-borne pathogens, which spread between ‘hosts’ and ‘vectors’—with each group possessing distinct epidemiological characteristics. As a result, an important question when planning surveillance for emerging vector-borne pathogens is where to place sampling resources in order to detect the pathogen as early as possible. We answer this question by developing a statistical function which describes the probability distributions of the prevalences of infection at first detection in both hosts and vectors. We also show how this method can be adapted in order to maximise the probability of early detection of an emerging pathogen within imposed sample size and/or cost constraints, and demonstrate its application using two simple models of vector-borne citrus pathogens. Under the assumption of a linear cost function, we find that sampling costs are generally minimised when either hosts or vectors, but not both, are sampled. PMID:28846676

  2. Targeting Mitogen-activated Protein Kinase-activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts to Lead Small Molecule Inhibitors to Clinical Trials

    PubMed Central

    Fiore, Mario; Forli, Stefano; Manetti, Fabrizio

    2015-01-01

    The p38/MAPK-activated kinase 2 (MK2) pathway is involved in a series of pathological conditions (inflammation diseases and metastasis) and in the resistance mechanism to antitumor agents. None of the p38 inhibitors entered advanced clinical trials because of their unwanted systemic side effects. For this reason, MK2 was identified as an alternative target to block the pathway, but avoiding the side effects of p38 inhibition. However, ATP-competitive MK2 inhibitors suffered from low solubility, poor cell permeability, and scarce kinase selectivity. Fortunately, non-ATP-competitive inhibitors of MK2 have been already discovered that allowed circumventing the selectivity issue. These compounds showed the additional advantage to be effective at lower concentrations in comparison to the ATP-competitive inhibitors. Therefore, although the significant difficulties encountered during the development of these inhibitors, MK2 is still considered as an attractive target to treat inflammation and related diseases, to prevent tumor metastasis, and to increase tumor sensitivity to chemotherapeutics. PMID:26502061

  3. Targeting RSV with Vaccines and Small Molecule Drugs

    PubMed Central

    Costello, Heather M.; Ray, William C.; Chaiwatpongsakorn, Supranee; Peeples, Mark E.

    2012-01-01

    Respiratory syncytial virus (RSV) is the most significant cause of pediatric respiratory infections. Palivizumab (Synagis®), a humanized monoclonal antibody, has been used successfully for a number of years to prevent severe RSV disease in at-risk infants. However, despite intense efforts, there is no approved vaccine or small molecule drug for RSV. As an enveloped virus, RSV must fuse its envelope with the host cell membrane, which is accomplished through the actions of the fusion (F) glycoprotein, with attachment help from the G glycoprotein. Because of their integral role in initiation of infection and their accessibility outside the lipid bilayer, these proteins have been popular targets in the discovery and development of antiviral compounds and vaccines against RSV. This review examines advances in the development of antiviral compounds and vaccine candidates. PMID:22335496

  4. Perceived distributed effort in team ball sports.

    PubMed

    Beniscelli, Violeta; Tenenbaum, Gershon; Schinke, Robert Joel; Torregrosa, Miquel

    2014-01-01

    In this study, we explored the multifaceted concept of perceived mental and physical effort in team sport contexts where athletes must invest individual and shared efforts to reach a common goal. Semi-structured interviews were conducted with a convenience sample of 15 Catalan professional coaches (3 women and 12 men, 3 each from the following sports: volleyball, basketball, handball, soccer, and water polo) to gain their views of three perceived effort-related dimensions: physical, psychological, and tactical. From a theoretical thematic analysis, it was found that the perception of effort is closely related to how effort is distributed within the team. Moreover, coaches viewed physical effort in relation to the frequency and intensity of the players' involvement in the game. They identified psychological effort in situations where players pay attention to proper cues, and manage emotions under difficult circumstances. Tactical effort addressed the decision-making process of players and how they fulfilled their roles while taking into account the actions of their teammates and opponents. Based on these findings, a model of perceived distributed effort was developed, which delineates the elements that compose each of the aforementioned dimensions. Implications of perceived distributed effort in team coordination and shared mental models are discussed.

  5. Pupillary Responses as a Biomarker of Diminished Effort Associated With Defeatist Attitudes and Negative Symptoms in Schizophrenia.

    PubMed

    Granholm, Eric; Ruiz, Ivan; Gallegos-Rodriguez, Yuliana; Holden, Jason; Link, Peter C

    2016-10-15

    The hypothesis that defeatist performance attitudes are associated with decreased goal-directed task effort and negative symptoms in consumers with schizophrenia was investigated by using pupillary responses as a biomarker of task effort. Pupillary dilation during cognitive tasks provides a biomarker of effort devoted to the task, with greater dilation indicating greater effort. Defeatist attitudes were assessed in 149 consumers with schizophrenia or schizoaffective disorder and 50 healthy control subjects, and consumers were divided into three groups (tertile split) with respect to severity of defeatist attitudes. Pupillary dilation responses were recorded during a digit-span task with three-, six-, and nine-digit spans. Effort allocation (pupillary responses) to the task increased as the processing load increased from low (three-digit) to moderate (six-digit) demands in healthy control subjects and consumers with schizophrenia with mild and moderate severity of defeatist attitudes. In contrast, consumers with severe defeatist attitudes did not increase their effort when processing demands increased from low to moderate loads. These consumers showed significantly less effort in the six-digit condition relative to consumers with mild defeatist attitudes. Moreover, consumers with severe defeatist attitudes showed significantly greater severity of negative symptoms relative to consumers with mild defeatist attitudes and negative symptoms were significantly correlated with defeatist attitudes. These results suggest a relationship between defeatist performance attitudes, goal-directed task effort indexed by pupillary responses, and negative symptoms in schizophrenia. The findings have implications for using cognitive therapy to reduce defeatist attitudes that may contribute to diminished effort and negative symptoms in schizophrenia. Published by Elsevier Inc.

  6. Low-effort thought promotes political conservatism.

    PubMed

    Eidelman, Scott; Crandall, Christian S; Goodman, Jeffrey A; Blanchar, John C

    2012-06-01

    The authors test the hypothesis that low-effort thought promotes political conservatism. In Study 1, alcohol intoxication was measured among bar patrons; as blood alcohol level increased, so did political conservatism (controlling for sex, education, and political identification). In Study 2, participants under cognitive load reported more conservative attitudes than their no-load counterparts. In Study 3, time pressure increased participants' endorsement of conservative terms. In Study 4, participants considering political terms in a cursory manner endorsed conservative terms more than those asked to cogitate; an indicator of effortful thought (recognition memory) partially mediated the relationship between processing effort and conservatism. Together these data suggest that political conservatism may be a process consequence of low-effort thought; when effortful, deliberate thought is disengaged, endorsement of conservative ideology increases.

  7. Concerted Efforts to Control or Eliminate Neglected Tropical Diseases: How Much Health Will Be Gained?

    PubMed Central

    Hontelez, Jan A. C.; Bakker, Roel; Blok, David J.; Cai, Rui; Houweling, Tanja A. J.; Kulik, Margarete C.; Lenk, Edeltraud J.; Luyendijk, Marianne; Matthijsse, Suzette M.; Redekop, William K.; Wagenaar, Inge; Jacobson, Julie; Nagelkerke, Nico J. D.; Richardus, Jan H.

    2016-01-01

    Background The London Declaration (2012) was formulated to support and focus the control and elimination of ten neglected tropical diseases (NTDs), with targets for 2020 as formulated by the WHO Roadmap. Five NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths and trachoma) are to be controlled by preventive chemotherapy (PCT), and four (Chagas’ disease, human African trypanosomiasis, leprosy and visceral leishmaniasis) by innovative and intensified disease management (IDM). Guinea worm, virtually eradicated, is not considered here. We aim to estimate the global health impact of meeting these targets in terms of averted morbidity, mortality, and disability adjusted life years (DALYs). Methods The Global Burden of Disease (GBD) 2010 study provides prevalence and burden estimates for all nine NTDs in 1990 and 2010, by country, age and sex, which were taken as the basis for our calculations. Estimates for other years were obtained by interpolating between 1990 (or the start-year of large-scale control efforts) and 2010, and further extrapolating until 2030, such that the 2020 targets were met. The NTD disease manifestations considered in the GBD study were analyzed as either reversible or irreversible. Health impacts were assessed by comparing the results of achieving the targets with the counterfactual, construed as the health burden had the 1990 (or 2010 if higher) situation continued unabated. Principle Findings/Conclusions Our calculations show that meeting the targets will lead to about 600 million averted DALYs in the period 2011–2030, nearly equally distributed between PCT and IDM-NTDs, with the health gain amongst PCT-NTDs mostly (96%) due to averted disability and amongst IDM-NTDs largely (95%) from averted mortality. These health gains include about 150 million averted irreversible disease manifestations (e.g. blindness) and 5 million averted deaths. Control of soil-transmitted helminths accounts for one third of all

  8. Goal striving strategies and effort mobilization: When implementation intentions reduce effort-related cardiac activity during task performance.

    PubMed

    Freydefont, Laure; Gollwitzer, Peter M; Oettingen, Gabriele

    2016-09-01

    Two experiments investigate the influence of goal and implementation intentions on effort mobilization during task performance. Although numerous studies have demonstrated the beneficial effects of setting goals and making plans on performance, the effects of goals and plans on effort-related cardiac activity and especially the cardiac preejection period (PEP) during goal striving have not yet been addressed. According to the Motivational Intensity Theory, participants should increase effort mobilization proportionally to task difficulty as long as success is possible and justified. Forming goals and making plans should allow for reduced effort mobilization when participants perform an easy task. However, when the task is difficult, goals and plans should differ in their effect on effort mobilization. Participants who set goals should disengage, whereas participants who made if-then plans should stay in the field showing high effort mobilization during task performance. As expected, using an easy task in Experiment 1, we observed a lower cardiac PEP in both the implementation intention and the goal intention condition than in the control condition. In Experiment 2, we varied task difficulty and demonstrated that while participants with a mere goal intention disengaged from difficult tasks, participants with an implementation intention increased effort mobilization proportionally with task difficulty. These findings demonstrate the influence of goal striving strategies (i.e., mere goals vs. if-then plans) on effort mobilization during task performance. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. The influence of music on mental effort and driving performance.

    PubMed

    Ünal, Ayça Berfu; Steg, Linda; Epstude, Kai

    2012-09-01

    The current research examined the influence of loud music on driving performance, and whether mental effort mediated this effect. Participants (N=69) drove in a driving simulator either with or without listening to music. In order to test whether music would have similar effects on driving performance in different situations, we manipulated the simulated traffic environment such that the driving context consisted of both complex and monotonous driving situations. In addition, we systematically kept track of drivers' mental load by making the participants verbally report their mental effort at certain moments while driving. We found that listening to music increased mental effort while driving, irrespective of the driving situation being complex or monotonous, providing support to the general assumption that music can be a distracting auditory stimulus while driving. However, drivers who listened to music performed as well as the drivers who did not listen to music, indicating that music did not impair their driving performance. Importantly, the increases in mental effort while listening to music pointed out that drivers try to regulate their mental effort as a cognitive compensatory strategy to deal with task demands. Interestingly, we observed significant improvements in driving performance in two of the driving situations. It seems like mental effort might mediate the effect of music on driving performance in situations requiring sustained attention. Other process variables, such as arousal and boredom, should also be incorporated to study designs in order to reveal more on the nature of how music affects driving. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. International aerospaceplane efforts

    NASA Technical Reports Server (NTRS)

    Lindley, Charles A.

    1992-01-01

    Although the U.S. began the first reusable space booster effort in the late 1950's, it is no longer an exclusive field. All of the technologically advanced nations, and several groups of nations, have one or more reusable booster efforts in progress. A listing of the entries in the field is presented. The list is somewhat misleading, because it includes both fully reusable and partially reusable boosters, both manned and unmanned, and both flight test and operational proposals. Additionally, not all of the projects are funded, and only a few of the projects will survive. The most likely candidates are the following: France/ESA, Germany/ESA, Great Britain/ESA/(USSR), USSR(past), and Japan. A discussion of the preceding projects is provided.

  11. Design and Fabrication of Opacity Targets for the National Ignition Facility

    DOE PAGES

    Cardenas, Tana; Schmidt, Derek William; Dodd, Evan S.; ...

    2017-12-22

    Accurate models for opacity of partially ionized atoms are important for modeling and understanding stellar interiors and other high-energy-density phenomena such as inertial confinement fusion. Lawrence Livermore National Laboratory is leading a multilaboratory effort to conduct experiments on the National Ignition Facility (NIF) to try to reproduce recent opacity tests at the Sandia National Laboratory Z-facility. Since 2015, the NIF effort has evolved several hohlraum designs that consist of multiple pieces joined together. The target also has three components attached to the main stalk over a long distance with high tolerances that have resulted in several design iterations. The targetmore » has made use of rapid prototyped features to attach a capsule and collimator under the hohlraum while avoiding interference with the beams. Furthermore, this paper discusses the evolution of the hohlraum and overall target design and the challenges involved with fabricating and assembling these targets.« less

  12. Design and Fabrication of Opacity Targets for the National Ignition Facility

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

    Cardenas, Tana; Schmidt, Derek William; Dodd, Evan S.

    Accurate models for opacity of partially ionized atoms are important for modeling and understanding stellar interiors and other high-energy-density phenomena such as inertial confinement fusion. Lawrence Livermore National Laboratory is leading a multilaboratory effort to conduct experiments on the National Ignition Facility (NIF) to try to reproduce recent opacity tests at the Sandia National Laboratory Z-facility. Since 2015, the NIF effort has evolved several hohlraum designs that consist of multiple pieces joined together. The target also has three components attached to the main stalk over a long distance with high tolerances that have resulted in several design iterations. The targetmore » has made use of rapid prototyped features to attach a capsule and collimator under the hohlraum while avoiding interference with the beams. Furthermore, this paper discusses the evolution of the hohlraum and overall target design and the challenges involved with fabricating and assembling these targets.« less

  13. Effort, anhedonia, and function in schizophrenia: reduced effort allocation predicts amotivation and functional impairment.

    PubMed

    Barch, Deanna M; Treadway, Michael T; Schoen, Nathan

    2014-05-01

    One of the most debilitating aspects of schizophrenia is an apparent interest in or ability to exert effort for rewards. Such "negative symptoms" may prevent individuals from obtaining potentially beneficial outcomes in educational, occupational, or social domains. In animal models, dopamine abnormalities decrease willingness to work for rewards, implicating dopamine (DA) function as a candidate substrate for negative symptoms given that schizophrenia involves dysregulation of the dopamine system. We used the effort-expenditure for rewards task (EEfRT) to assess the degree to which individuals with schizophrenia were wiling to exert increased effort for either larger magnitude rewards or for rewards that were more probable. Fifty-nine individuals with schizophrenia and 39 demographically similar controls performed the EEfRT task, which involves making choices between "easy" and "hard" tasks to earn potential rewards. Individuals with schizophrenia showed less of an increase in effort allocation as either reward magnitude or probability increased. In controls, the frequency of choosing the hard task in high reward magnitude and probability conditions was negatively correlated with depression severity and anhedonia. In schizophrenia, fewer hard task choices were associated with more severe negative symptoms and worse community and work function as assessed by a caretaker. Consistent with patterns of disrupted dopamine functioning observed in animal models of schizophrenia, these results suggest that 1 mechanism contributing to impaired function and motivational drive in schizophrenia may be a reduced allocation of greater effort for higher magnitude or higher probability rewards.

  14. Relationship between effort-reward imbalance and hair cortisol concentration in female kindergarten teachers.

    PubMed

    Qi, Xingliang; Zhang, Jing; Liu, Yapeng; Ji, Shuang; Chen, Zheng; Sluiter, Judith K; Deng, Huihua

    2014-04-01

    The present study aims to investigate the relationship between effort-reward imbalance and hair cortisol concentration among teachers to examine whether hair cortisol can be a biomarker of chronic work stress. Hair samples were collected from 39 female teachers from three kindergartens. Cortisol was extracted from the hair samples with methanol, and cortisol concentrations were measured with high performance liquid chromatography-tandem mass spectrometry. Work stress was measured using the effort-reward imbalance scale. The ratio of effort to reward showed significantly positive association with hair cortisol concentration. The cortisol concentration in the system increases with the effort-reward imbalance. Measurement of hair cortisol can become a useful biomarker of chronic work stress. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Current trends in the use of liposomes for tumor targeting

    PubMed Central

    Deshpande, Pranali P; Biswas, Swati; Torchilin, Vladimir P

    2013-01-01

    The use of liposomes for drug delivery began early in the history of pharmaceutical nanocarriers. These nanosized, lipid bilayered vesicles have become popular as drug delivery systems owing to their efficiency, biocompatibility, nonimmunogenicity, enhanced solubility of chemotherapeutic agents and their ability to encapsulate a wide array of drugs. Passive and ligand-mediated active targeting promote tumor specificity with diminished adverse off-target effects. The current field of liposomes focuses on both clinical and diagnostic applications. Recent efforts have concentrated on the development of multifunctional liposomes that target cells and cellular organelles with a single delivery system. This review discusses the recent advances in liposome research in tumor targeting. PMID:23914966

  16. Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer

    PubMed Central

    UMENE, KIYOKO; YANOKURA, MEGUMI; BANNO, KOUJI; IRIE, HARUKO; ADACHI, MASATAKA; IIDA, MIHO; NAKAMURA, KANAKO; NOGAMI, YUYA; MASUDA, KENTA; KOBAYASHI, YUSUKE; TOMINAGA, EIICHIRO; AOKI, DAISUKE

    2015-01-01

    Aurora kinase A (AURKA) regulates the cell cycle checkpoint and maintains genomic integrity. AURKA is overexpressed in various malignant tumors and its upregulation induces chromosomal instability, which leads to aneuploidy and cell transformation. To investigate the role of AURKA in endometrial cancer, we evaluated the association of immunohistochemical expression of AURKA with clinicopathological factors. Furthermore, we examined the effects of AURKA inhibition by transfected siRNA in HEC-1B cells on colony-forming ability, invasion and migration capacity, and chemosensitivity. Immunohistochemical staining showed that overexpression of AURKA was significantly associated with tumor grade (P<0.05) and poor histologic differentiation (P<0.05). The recurrence rate also tended to be high in cases with overexpression of AURKA (P<0.1) and these cases also had a tendency for shorter disease-free survival (DFS) (P<0.1). AURKA inhibition in endometrial cancer cell lines significantly decreased cell growth, invasion and migration (P<0.05), and increased chemosensitivity to paclitaxel. We also evaluated the efficacy of a combination of AURKA siRNA and paclitaxel against subcutaneous tumors formed in a nude mouse. After treatment, the tumor volume shrank significantly compared to treatment with paclitaxel only (P<0.05). To our knowledge, this is the first study in endometrial carcinoma to show a correlation between overexpression of AURKA and tumor grade, histological type and sensitivity to paclitaxel. AURKA is a promising therapeutic target in endometrial cancer and the combination therapy with AURKA inhibitors and paclitaxel could be effective for endometrial cancer that is resistant to conventional treatment and has a poor prognosis. PMID:25625960

  17. Social facilitation in virtual reality-enhanced exercise: competitiveness moderates exercise effort of older adults.

    PubMed

    Anderson-Hanley, Cay; Snyder, Amanda L; Nimon, Joseph P; Arciero, Paul J

    2011-01-01

    This study examined the effect of virtual social facilitation and competitiveness on exercise effort in exergaming older adults. Fourteen exergaming older adults participated. Competitiveness was assessed prior to the start of exercise. Participants were trained to ride a "cybercycle;" a virtual reality-enhanced stationary bike with interactive competition. After establishing a cybercycling baseline, competitive avatars were introduced. Pedaling effort (watts) was assessed. Repeated measures ANOVA revealed a significant group (high vs low competitiveness) × time (pre- to post-avatar) interaction (F[1,12] = 13.1, P = 0.003). Virtual social facilitation increased exercise effort among more competitive exercisers. Exercise programs that match competitiveness may maximize exercise effort.

  18. Social facilitation in virtual reality-enhanced exercise: competitiveness moderates exercise effort of older adults

    PubMed Central

    Anderson-Hanley, Cay; Snyder, Amanda L; Nimon, Joseph P; Arciero, Paul J

    2011-01-01

    This study examined the effect of virtual social facilitation and competitiveness on exercise effort in exergaming older adults. Fourteen exergaming older adults participated. Competitiveness was assessed prior to the start of exercise. Participants were trained to ride a “cybercycle;” a virtual reality-enhanced stationary bike with interactive competition. After establishing a cybercycling baseline, competitive avatars were introduced. Pedaling effort (watts) was assessed. Repeated measures ANOVA revealed a significant group (high vs low competitiveness) × time (pre- to post-avatar) interaction (F[1,12] = 13.1, P = 0.003). Virtual social facilitation increased exercise effort among more competitive exercisers. Exercise programs that match competitiveness may maximize exercise effort. PMID:22087067

  19. Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

    PubMed

    Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

    2014-11-21

    In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

  20. Results of efforts by the Convention on Biological Diversity to describe ecologically or biologically significant marine areas.

    PubMed

    Bax, Nicholas J; Cleary, Jesse; Donnelly, Ben; Dunn, Daniel C; Dunstan, Piers K; Fuller, Mike; Halpin, Patrick N

    2016-06-01

    In 2004, Parties to the Convention on Biological Diversity (CBD) addressed a United Nations (UN) call for area-based planning, including for marine-protected areas that resulted in a global effort to describe ecologically or biologically significant marine areas (EBSAs). We summarized the results, assessed their consistency, and evaluated the process developed by the Secretariat of the CBD to engage countries and experts in 9 regional workshops held from 2011 to 2014. Experts from 92 countries and 79 regional or international bodies participated. They considered 250 million km(2) of the world's ocean area (two-thirds of the total). The 204 areas they examined in detail differed widely in area (from 5.5 km(2) to 11.1 million km(2) ). Despite the initial focus of the CBD process on areas outside national jurisdiction, only 31 of the areas examined were solely outside national jurisdiction. Thirty-five extended into national jurisdictions, 137 were solely within national jurisdictions, and 28 included the jurisdictions of more than 1 country (1 area lacked precise boundaries). Data were sufficient to rank 88-99% of the areas relative to each of the 7 criteria for EBSAs agreed to previously by Parties to the CBD. The naturalness criterion ranked high for a smaller percentage of the EBSAs (31%) than other criteria (51-70%), indicating the difficulty in finding relatively undisturbed areas in the ocean. The highly participatory nature of the workshops, including easy and consistent access to the relevant information facilitated by 2 technical teams, contributed to the workshop participants success in identifying areas that could be ranked relative to most criteria and areas that extend across jurisdictional boundaries. The formal recognition of workshop results by the Conference of Parties to the CBD resulted in these 204 areas being identified as EBSAs by the 196 Parties. They represent the only suite of marine areas recognized by the international community for their

  1. The impact of effort-reward imbalance and learning motivation on teachers' sickness absence.

    PubMed

    Derycke, Hanne; Vlerick, Peter; Van de Ven, Bart; Rots, Isabel; Clays, Els

    2013-02-01

    The aim of this study was to analyse the impact of the effort-reward imbalance and learning motivation on sickness absence duration and sickness absence frequency among beginning teachers in Flanders (Belgium). A total of 603 teachers, who recently graduated, participated in this study. Effort-reward imbalance and learning motivation were assessed by means of self-administered questionnaires. Prospective data of registered sickness absence during 12 months follow-up were collected. Multivariate logistic regression analyses were performed. An imbalance between high efforts and low rewards (extrinsic hypothesis) was associated with longer sickness absence duration and more frequent absences. A low level of learning motivation (intrinsic hypothesis) was not associated with longer sickness absence duration but was significantly positively associated with sickness absence frequency. No significant results were obtained for the interaction hypothesis between imbalance and learning motivation. Further research is needed to deepen our understanding of the impact of psychosocial work conditions and personal resources on both sickness absence duration and frequency. Specifically, attention could be given to optimizing or reducing efforts spent at work, increasing rewards and stimulating learning motivation to influence sickness absence. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Mental health among Norwegian priests: associations with effort-reward imbalance and overcommitment.

    PubMed

    Lau, Bjørn

    2018-01-01

    The aim of the study was to determine the prevalence of anxiety and depression symptoms among Norwegian priests and to examine their associations with effort-reward imbalance (ERI) and overcommitment. Eight hundred four priests in the Norwegian Church completed the Hospital Anxiety and Depression Scale (HADS), the Effort-Reward Imbalance Questionnaire (ERI-Q), and the Intrinsic Effort Scale, measuring overcommitment. A significant proportion of the priests (23.4%) had HADS scores indicating a possible anxiety problem. Somewhat fewer had depression problems (9.3%). Both anxiety and depression difficulties were associated with an imbalance between effort given and rewards received at work. Priests characterized by a combination of this imbalance and high scores on overcommitment had more anxiety and depression symptoms. There is a higher occurrence of mental health challenges among priests than among the regular population. This applies in particular to anxiety symptoms measured by the HADS. These findings also indicate that it may be fruitful to explore mental health conditions among priests who report different combinations of effort-reward and overcommitment.

  3. Learning Environment and Student Effort

    ERIC Educational Resources Information Center

    Hopland, Arnt O.; Nyhus, Ole Henning

    2016-01-01

    Purpose: The purpose of this paper is to explore the relationship between satisfaction with learning environment and student effort, both in class and with homework assignments. Design/methodology/approach: The authors use data from a nationwide and compulsory survey to analyze the relationship between learning environment and student effort. The…

  4. Burglar Target Selection

    PubMed Central

    Townsley, Michael; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

  5. Sediment contribution from coastal-cliff erosion into the Nile's littoral cell and its significance to cliff-retreat mitigation efforts

    NASA Astrophysics Data System (ADS)

    Katz, Oded; Mushkin, Amit; Crouvi, Onn; Alter, Samuel; Shemesh, Ran

    2017-04-01

    In 2013 the government of Israel initiated a national mitigation program aimed to prevent further collapse and retreat of the country's coastal cliffs, which occur along the northern termination of the Niles's littoral cell (NLC) in the eastern Mediterranean. The goals of this large-scale program are to protect infrastructure and property proximal to the cliff and to conduct long-term maintenance and monitoring of this highly dynamic and sensitive land-sea interface that spans 40 km of Israel's coast line. Here, we examine the possible impact of proposed cliff retreat mitigation efforts on long-shore sediment transport (LST) and coastal dynamics in the region. We used airborne LiDAR spanning a 9-year period between 2006 and 2015 to quantify the annual contribution of sediment eroded from a 20-km-long segment of Israel's coastal cliffs into the NLC. Our measurements reveal 282±85*103 m3 of sediment eroded from the cliff and delivered into the NLC during the studied period. Considering our study area comprises 50% of Israel's sea cliffs we infer an average contribution rate of 30,000-60,000 m^3/yr of cliff-derived sediment into the NLC prior to the planned broad-scale implementation of cliff-retreat mitigation measures. Previous studies report an average net LST flux of 80,000 - 90,000 m3 that reaches the northern termination of the NLC at Haifa Bay annually. Thus, our results suggest that Israel's actively eroding coastal cliffs are primary contributors (40-80%) to the LST budget along the northern termination of the NLC. It therefore appears that successful implementation of the coastal-cliff protection program along Israel's coastline will result in a significant sand deficit, which may drive LST in this part of the NLC out of its 'background' state. In the likely case that the energy/currents driving LST do not change, a possible outcome of this sediment deficit could be increased beach erosion along Israel's coast line to make up for the lost volumes of cliff

  6. Sediment contribution from coastal-cliff erosion into the Nile's littoral cell and its significance to cliff-retreat mitigation efforts

    NASA Astrophysics Data System (ADS)

    Katz, O.; Mushkin, A.; Crouvi, O.; Alter, S.; Shemesh, R.

    2016-12-01

    In 2013 the government of Israel initiated a national mitigation program aimed to prevent further collapse and retreat of the country's coastal cliffs, which occur along the northern termination of the Niles's littoral cell (NLC) in the eastern Mediterranean. The goals of this large-scale program are to protect infrastructure and property proximal to the cliff and to conduct long-term maintenance and monitoring of this highly dynamic and sensitive land-sea interface that spans 40 km of Israel's coast line. Here, we examine the possible impact of proposed cliff retreat mitigation efforts on long-shore sediment transport (LST) and coastal dynamics in the region. We used airborne LiDAR spanning a 9-year period between 2006 and 2015 to quantify the annual contribution of sediment eroded from a 20-km-long segment of Israel's coastal cliffs into the NLC. Our measurements reveal 282±85*103 m3 of sediment eroded from the cliff and delivered into the NLC during the studied period. Considering our study area comprises 50% of Israel's sea cliffs we infer an average contribution rate of 30,000-60,000 m3/yr of cliff-derived sediment into the NLC prior to the planned broad-scale implementation of cliff-retreat mitigation measures. Previous studies report an average net LST flux of 80,000 - 90,000 m3 that reaches the northern termination of the NLC at Haifa Bay annually. Thus, our results suggest that Israel's actively eroding coastal cliffs are primary contributors (40-80%) to the LST budget along the northern termination of the NLC. It therefore appears that successful implementation of the coastal-cliff protection program along Israel's coastline will result in a significant sand deficit, which may drive LST in this part of the NLC out of its `background' state. In the likely case that the energy/currents driving LST do not change, a possible outcome of this sediment deficit could be increased beach erosion along Israel's coast line to make up for the lost volumes of cliff

  7. Test of memory malingering (TOMM) trial 1 as a screening measure for insufficient effort.

    PubMed

    O'Bryant, Sid E; Engel, Lisa R; Kleiner, Jennifer S; Vasterling, Jennifer J; Black, F William

    2007-05-01

    The identification of insufficient effort is critical to neuropsychological evaluation, and several existing instruments assess effort on neuropsychological tasks. Yet instruments designed to detect insufficient effort are underutilized in standard neuropsychological assessments, perhaps in part because they typically require significant administration time and are, therefore, not ideally suited to screening contexts. The Test of Memory Malingering (TOMM) is a commonly administered, well-validated symptom validity test. This study evaluates the utility of TOMM Trial 1 as a relatively brief screening measure of insufficient effort. Results suggest that TOMM Trial 1 demonstrates high diagnostic accuracy and is a viable option for screening insufficient effort. Diagnostic accuracy estimates are presented for a range of base rates. The need for more comprehensive SVT assessment in most clinical and forensic situation is discussed.

  8. Grading System and Student Effort

    ERIC Educational Resources Information Center

    Paredes, Valentina

    2017-01-01

    Several papers have proposed that the grading system affects students' incentives to exert effort. In particular, the previous literature has compared student effort under relative and absolute grading systems, but the results are mixed and the implications of the models have not been empirically tested. In this paper, I build a model where…

  9. The cigarette manufacturers' efforts to promote tobacco to the U.S. military.

    PubMed

    Joseph, Anne M; Muggli, Monique; Pearson, Kathryn C; Lando, Harry

    2005-10-01

    This article describes findings from review of tobacco industry documents regarding promotion of tobacco to the military, and efforts to influence Department of Defense policies regarding the use and sale of tobacco products. The documents reveal that the industry has targeted the military for decades for reasons including: (1) the volume of worldwide military personnel; (2) the opportunity to attract young men who fit a specific socioeconomic and cultural profile; (3) potential carryover of profits to civilian markets; and (4) the unusual price structure of commissaries and exchanges. The industry used distinctive promotion methods such as in-store merchandising, sponsorships, and even brand development to target the military, both in the United States and abroad during times of conflict. Legislative activity to protect tobacco promotion to this vulnerable population was carried out in response to smoking policy changes proposed by the Department of Defense. The tobacco industry has contributed to the high prevalence of smoking in the military and among veterans.

  10. [Psychometric properties of the French version of the Effort-Reward Imbalance model].

    PubMed

    Niedhammer, I; Siegrist, J; Landre, M F; Goldberg, M; Leclerc, A

    2000-10-01

    Two main models are currently used to evaluate psychosocial factors at work: the Job Strain model developed by Karasek and the Effort-Reward Imbalance model. A French version of the first model has been validated for the dimensions of psychological demands and decision latitude. As regards the second one evaluating three dimensions (extrinsic effort, reward, and intrinsic effort), there are several versions in different languages, but until recently there was no validated French version. The objective of this study was to explore the psychometric properties of the French version of the Effort-Reward Imbalance model in terms of internal consistency, factorial validity, and discriminant validity. The present study was based on the GAZEL cohort and included the 10 174 subjects who were working at the French national electric and gas company (EDF-GDF) and answered the questionnaire in 1998. A French version of Effort-Reward Imbalance was included in this questionnaire. This version was obtained by a standard forward/backward translation procedure. Internal consistency was satisfactory for the three scales of extrinsic effort, reward, and intrinsic effort: Cronbach's Alpha coefficients higher than 0.7 were observed. A one-factor solution was retained for the factor analysis of the scale of extrinsic effort. A three-factor solution was retained for the factor analysis of reward, and these dimensions were interpreted as the factor analysis of intrinsic effort did not support the expected four-dimension structure. The analysis of discriminant validity displayed significant associations between measures of Effort-Reward Imbalance and the variables of sex, age, education level, and occupational grade. This study is the first one supporting satisfactory psychometric properties of the French version of the Effort-Reward Imbalance model. However, the factorial validity of intrinsic effort could be questioned. Furthermore, as most previous studies were based on male samples

  11. Burnout and effort-reward-imbalance in a sample of 949 German teachers.

    PubMed

    Unterbrink, Thomas; Hack, Anna; Pfeifer, Ruth; Buhl-Griesshaber, Veronika; Müller, Udo; Wesche, Helmut; Frommhold, Markus; Scheuch, Klaus; Seibt, Reingard; Wirsching, Michael; Bauer, Joachim

    2007-04-01

    High rates of teachers' premature retirement initiated a research investigating their occupational burden. The aim of this study was to elaborate on and extend previous investigations exploring (1) teacher burnout and (2) the relationship between teachers' efforts and their rewards. A sample of 949 German teachers in 10 Gymnasien (grammar schools) and 79 Hauptschulen (secondary modern schools) was investigated applying the Maslach Burnout Inventory (MBI-D) and the Effort Reward Imbalance Inventory (ERI). Compared with other studies investigating burnout in employees, we found high rates of burnout symptoms such as emotional exhaustion, depersonalisation, and low personal accomplishment. Male teachers showed significantly lower personal accomplishment and more depersonalization than female teachers. With respect to school types, teachers in Hauptschulen were more often affected by emotional exhaustion and showed more depersonalization. Part-time teachers felt less personal accomplishment than full-time teachers. The ERI cut off was exceeded by 21.6% of all teachers indicating that this subgroup is affected by an imbalance between too much effort and too little reward. With respect to the ERI, significant differences were found for school types, with a higher proportion of Hauptschulen teachers being above this cut off. At present, the working situation of teachers appears to be characterized by a perceived imbalance of effort and reward and is associated with a high risk of developing burnout symptoms.

  12. Divided attention and mental effort after severe traumatic brain injury.

    PubMed

    Azouvi, Philippe; Couillet, Josette; Leclercq, Michel; Martin, Yves; Asloun, Sybille; Rousseaux, Marc

    2004-01-01

    The aim of this study was to assess dual-task performance in TBI patients, under different experimental conditions, with or without explicit emphasis on one of two tasks. Results were compared with measurement of the subjective mental effort required to perform each task. Forty-three severe TBI patients at the subacute or chronic phase performed two tasks under single- and dual-task conditions: (a) random generation; (b) visual go-no go reaction time task. Three dual-task conditions were given, requiring either to consider both tasks as equally important or to focus preferentially on one of them. Patients were compared to matched controls. Subjective mental effort was rated on a visual analogic scale. TBI patients showed a disproportionate increase in reaction time in the go-no go task under the dual-task condition. However, they were just as able as controls to adapt performance to the specific instructions about the task to be emphasised. Patients reported significantly higher subjective mental effort, but the variation of mental effort according to task condition was similar to that of controls. These results suggest that the divided attention deficit of TBI patients is related to a reduction in available processing resources rather than an impairment of strategic processes responsible for attentional allocation and switching. The higher level of subjective mental effort may explain why TBI patients frequently complain of mental fatigue, although this subjective complaint seems to be relatively independent of cognitive impairment.

  13. Effort-Based Decision-Making in Schizophrenia.

    PubMed

    Culbreth, Adam J; Moran, Erin K; Barch, Deanna M

    2018-08-01

    Motivational impairment has long been associated with schizophrenia but the underlying mechanisms are not clearly understood. Recently, a small but growing literature has suggested that aberrant effort-based decision-making may be a potential contributory mechanism for motivational impairments in psychosis. Specifically, multiple reports have consistently demonstrated that individuals with schizophrenia are less willing than healthy controls to expend effort to obtain rewards. Further, this effort-based decision-making deficit has been shown to correlate with severity of negative symptoms and level of functioning, in many but not all studies. In the current review, we summarize this literature and discuss several factors that may underlie aberrant effort-based decision-making in schizophrenia.

  14. The Relationship among Rank, Experience, and Accounting Faculty Effort Allocations.

    ERIC Educational Resources Information Center

    Cox, Clifford T.

    1991-01-01

    Analysis of questionnaires returned by 16 of 450 accounting faculty found that (1) experience is inversely related to the amount of effort allocated to research alone and to the aggregate of teaching, research, and service; and (2) a significant positive relationship was found between rank and administrative activity. (SK)

  15. The effort-reward imbalance work-stress model and daytime salivary cortisol and dehydroepiandrosterone (DHEA) among Japanese women.

    PubMed

    Ota, Atsuhiko; Mase, Junji; Howteerakul, Nopporn; Rajatanun, Thitipat; Suwannapong, Nawarat; Yatsuya, Hiroshi; Ono, Yuichiro

    2014-09-17

    We examined the influence of work-related effort-reward imbalance and overcommitment to work (OC), as derived from Siegrist's Effort-Reward Imbalance (ERI) model, on the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that, among healthy workers, both cortisol and dehydroepiandrosterone (DHEA) secretion would be increased by effort-reward imbalance and OC and, as a result, cortisol-to-DHEA ratio (C/D ratio) would not differ by effort-reward imbalance or OC. The subjects were 115 healthy female nursery school teachers. Salivary cortisol, DHEA, and C/D ratio were used as indexes of HPA activity. Mixed-model analyses of variance revealed that neither the interaction between the ERI model indicators (i.e., effort, reward, effort-to-reward ratio, and OC) and the series of measurement times (9:00, 12:00, and 15:00) nor the main effect of the ERI model indicators was significant for daytime salivary cortisol, DHEA, or C/D ratio. Multiple linear regression analyses indicated that none of the ERI model indicators was significantly associated with area under the curve of daytime salivary cortisol, DHEA, or C/D ratio. We found that effort, reward, effort-reward imbalance, and OC had little influence on daytime variation patterns, levels, or amounts of salivary HPA-axis-related hormones. Thus, our hypotheses were not supported.

  16. Focus on flaviviruses: current and future drug targets.

    PubMed

    Geiss, Brian J; Stahla, Hillary; Hannah, Amanda M; Gari, Amanda M; Keenan, Susan M

    2009-05-01

    Infection by mosquito-borne flaviviruses (family Flaviviridae) is increasing in prevalence worldwide. The vast global, social and economic impact due to the morbidity and mortality associated with the diseases caused by these viruses necessitates therapeutic intervention. There is currently no effective clinical treatment for any flaviviral infection. Therefore, there is a great need for the identification of novel inhibitors to target the virus life cycle. In this article, we discuss structural and nonstructural viral proteins that are the focus of current target validation and drug discovery efforts. Both inhibition of essential enzymatic activities and disruption of necessary protein–protein interactions are considered. In addition, we address promising new targets for future research. As our molecular and biochemical understanding of the flavivirus life cycle increases, the number of targets for antiviral therapeutic discovery grows and the possibility for novel drug discovery continues to strengthen.

  17. What makes a reach movement effortful? Physical effort discounting supports common minimization principles in decision making and motor control

    PubMed Central

    Ulbrich, Philipp; Gail, Alexander

    2017-01-01

    When deciding between alternative options, a rational agent chooses on the basis of the desirability of each outcome, including associated costs. As different options typically result in different actions, the effort associated with each action is an essential cost parameter. How do humans discount physical effort when deciding between movements? We used an action-selection task to characterize how subjective effort depends on the parameters of arm transport movements and controlled for potential confounding factors such as delay discounting and performance. First, by repeatedly asking subjects to choose between 2 arm movements of different amplitudes or durations, performed against different levels of force, we identified parameter combinations that subjects experienced as identical in effort (isoeffort curves). Movements with a long duration were judged more effortful than short-duration movements against the same force, while movement amplitudes did not influence effort. Biomechanics of the movements also affected effort, as movements towards the body midline were preferred to movements away from it. Second, by introducing movement repetitions, we further determined that the cost function for choosing between effortful movements had a quadratic relationship with force, while choices were made on the basis of the logarithm of these costs. Our results show that effort-based action selection during reaching cannot easily be explained by metabolic costs. Instead, force-loaded reaches, a widely occurring natural behavior, imposed an effort cost for decision making similar to cost functions in motor control. Our results thereby support the idea that motor control and economic choice are governed by partly overlapping optimization principles. PMID:28586347

  18. Targeting Political Communications: A Problem in Market Segmentation.

    ERIC Educational Resources Information Center

    Markwart, Richard I.

    Political campaigns are major, high-budget marketing efforts, but because they are usually managed by people with little training in either marketing or communications, they fail to persuade voters to vote in the desired way. Political targeting can be treated as a segmentation problem, one of identifying and responding to the specific qualities…

  19. Targeted drug delivery for cancer therapy: the other side of antibodies

    PubMed Central

    2012-01-01

    Therapeutic monoclonal antibody (TMA) based therapies for cancer have advanced significantly over the past two decades both in their molecular sophistication and clinical efficacy. Initial development efforts focused mainly on humanizing the antibody protein to overcome problems of immunogenicity and on expanding of the target antigen repertoire. In parallel to naked TMAs, antibody-drug conjugates (ADCs) have been developed for targeted delivery of potent anti-cancer drugs with the aim of bypassing the morbidity common to conventional chemotherapy. This paper first presents a review of TMAs and ADCs approved for clinical use by the FDA and those in development, focusing on hematological malignancies. Despite advances in these areas, both TMAs and ADCs still carry limitations and we highlight the more important ones including cancer cell specificity, conjugation chemistry, tumor penetration, product heterogeneity and manufacturing issues. In view of the recognized importance of targeted drug delivery strategies for cancer therapy, we discuss the advantages of alternative drug carriers and where these should be applied, focusing on peptide-drug conjugates (PDCs), particularly those discovered through combinatorial peptide libraries. By defining the advantages and disadvantages of naked TMAs, ADCs and PDCs it should be possible to develop a more rational approach to the application of targeted drug delivery strategies in different situations and ultimately, to a broader basket of more effective therapies for cancer patients. PMID:23140144

  20. Documentary effort.

    PubMed

    2006-01-01

    This spring, Virtua Health, the largest health system in Southern New Jersey, launched an innovative campaign aimed at raising overall awareness of its facilities by documenting real-life patients undergoing a variety of experiences (e.g., breast cancer, high-risk pregnancy, spine surgery, and minimally-invasive knee replacement surgery). The effort, called "The Virtua Experience" became a 30-minute hospital documentary that aired on Philadelphia's NBC affiliate this summer.

  1. The Interaction Between Punishment Sensitivity and Effortful Control for Emerging Adults' Substance Use Behaviors.

    PubMed

    Kahn, Rachel E; Chiu, Pearl H; Deater-Deckard, Kirby; Hochgraf, Anna K; King-Casas, Brooks; Kim-Spoon, Jungmeen

    2018-01-08

    Within the dual systems perspective, high reward sensitivity and low punishment sensitivity in conjunction with deficits in cognitive control may contribute to high levels of risk taking, such as substance use. The current study examined whether the individual components of effortful control (inhibitory control, attentional control, and activation control) serve as regulators and moderate the association between reward or punishment sensitivity and substance use behaviors. A total of 1,808 emerging adults from a university setting (Mean age = 19.48; 72% female) completed self-report measures of reward and punishment sensitivity, effortful control, and substance use. Findings indicated significant two-way interactions for punishment sensitivity and inhibitory control for alcohol and marijuana use. The form of these interactions revealed a significant negative association between punishment sensitivity and alcohol and marijuana use at low levels of inhibitory control. No significant interactions emerged for reward sensitivity or other components of effortful control. The current findings provide preliminary evidence suggesting the dual systems theorized to influence risk taking behavior interact to make joint contributions to health risk behaviors such as substance use in emerging adults.

  2. Animal Companions: Fostering Children's Effort-Making by Nurturing Virtual Pets

    ERIC Educational Resources Information Center

    Chen, Zhi-Hong; Liao, Calvin; Chien, Tzu-Chao; Chan, Tak-Wai

    2011-01-01

    Virtual character is a significant application in the research field of technology-enhanced learning. In this study, the concept of animal companions, "non-smart" virtual characters, is proposed as a way to encourage students to promote effort-making learning behaviours. The two underpinning design rationales are first discussed followed by the…

  3. Development efforts to improve curved-channel microchannel plates

    NASA Technical Reports Server (NTRS)

    Corbett, M. B.; Feller, W. B.; Laprade, B. N.; Cochran, R.; Bybee, R.; Danks, A.; Joseph, C.

    1993-01-01

    Curved-channel microchannel plate (C-plate) improvements resulting from an ongoing NASA STIS microchannel plate (MCP) development program are described. Performance limitations of previous C-plates led to a development program in support of the STIS MAMA UV photon counter, a second generation instrument on the Hubble Space Telescope. C-plate gain, quantum detection efficiency, dark noise, and imaging distortion, which are influenced by channel curvature non-uniformities, have all been improved through use of a new centrifuge fabrication technique. This technique will be described, along with efforts to improve older, more conventional shearing methods. Process optimization methods used to attain targeted C-plate performance goals will be briefly characterized. Newly developed diagnostic measurement techniques to study image distortion, gain uniformity, input bias angle, channel curvature, and ion feedback, will be described. Performance characteristics and initial test results of the improved C-plates will be reported. Future work and applications will also be discussed.

  4. Small molecules targeting viral RNA.

    PubMed

    Hermann, Thomas

    2016-11-01

    Highly conserved noncoding RNA (ncRNA) elements in viral genomes and transcripts offer new opportunities to expand the repertoire of drug targets for the development of antiinfective therapy. Ligands binding to ncRNA architectures are able to affect interactions, structural stability or conformational changes and thereby block processes essential for viral replication. Proof of concept for targeting functional RNA by small molecule inhibitors has been demonstrated for multiple viruses with RNA genomes. Strategies to identify antiviral compounds as inhibitors of ncRNA are increasingly emphasizing consideration of drug-like properties of candidate molecules emerging from screening and ligand design. Recent efforts of antiviral lead discovery for RNA targets have provided drug-like small molecules that inhibit viral replication and include inhibitors of human immunodeficiency virus (HIV), hepatitis C virus (HCV), severe respiratory syndrome coronavirus (SARS CoV), and influenza A virus. While target selectivity remains a challenge for the discovery of useful RNA-binding compounds, a better understanding is emerging of properties that define RNA targets amenable for inhibition by small molecule ligands. Insight from successful approaches of targeting viral ncRNA in HIV, HCV, SARS CoV, and influenza A will provide a basis for the future exploration of RNA targets for therapeutic intervention in other viral pathogens which create urgent, unmet medical needs. Viruses for which targeting ncRNA components in the genome or transcripts may be promising include insect-borne flaviviruses (Dengue, Zika, and West Nile) and filoviruses (Ebola and Marburg). WIREs RNA 2016, 7:726-743. doi: 10.1002/wrna.1373 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  5. Leveraging the Educational Outreach Efforts of Low-Cost Missions

    NASA Technical Reports Server (NTRS)

    Fisher, Diane K.; Leon, Nancy J.

    2000-01-01

    A small portion of the budget for every NASA mission must be devoted to education and public outreach. The question is, how can projects best leverage these funds to create a high-quality message and get it disseminated to the largest and most appropriate audience? This paper describes the approach taken by a small educational outreach team for NASA's New Millennium Program (NMP). The team's approach has been twofold: develop a highly desirable suite of products designed to appeal to, as well as enlighten, the target audience; then negotiate relationships with existing, often under-utilized channels for dissemination of these products. Starting with NMP missions as the base of support for these efforts, the team has invited participation by other missions. This approach has resulted in a richer and broader message, and has allowed the continuing development of the audience base.

  6. Changing strategies for target therapy in gastric cancer.

    PubMed

    Lee, Suk-Young; Oh, Sang Cheul

    2016-01-21

    In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer.

  7. Different effort constructs and effort-reward imbalance: effects on employee well-being in ancillary health care workers.

    PubMed

    van Vegchel, N; de Jonge, J; Meijer, T; Hamers, J P

    2001-04-01

    The present study investigates the relationship between Effort-Reward Imbalance (ERI) and employee well-being, using three different concepts of efforts (i.e. psychological demands, physical demands and emotional demands). The ERI model had been used as a theoretical framework, indicating that work stress is related to high efforts (i.e. job demands) and low occupational rewards (e.g. money, esteem and security/career opportunities). The ERI model also predicts that, in overcommitted workers, effects of ERI on employee well-being are stronger compared with their less committed counterparts. A cross-sectional survey among 167 ancillary health care workers of two nursing homes was conducted. Multiple univariate logistic regression analyses were used to test the relationship between ERI and employee well-being. Results of the logistic regression analyses showed that employees with both high (psychological, physical and emotional) efforts and low rewards had higher risks of psychosomatic health complaints, physical health symptoms and job dissatisfaction (odds ratios (ORs) ranged from 5.09 to 18.55). Moreover, employees who reported both high efforts and high rewards had elevated risks of physical symptoms and exhaustion (ORs ranged from 6.17 to 9.39). No support was found for the hypothesis on the moderating effect of overcommitment. Results show some support for the ERI model; ancillary health care workers with high effort/low reward imbalance had elevated risks of poor employee well-being. In addition, results show that the combination of high efforts and high rewards is important for employee well-being. Finally, some practical implications are discussed to combat work stress in health care work.

  8. What Are the Targets of Inflammatory Bowel Disease Management.

    PubMed

    Lega, Sara; Dubinsky, Marla C

    2018-04-25

    With recent evidence suggesting that keeping the inflammatory process under tight control prevents long-term disability, the aim of treatments in inflammatory bowel disease (IBD) has shifted from symptom control toward the resolution of bowel inflammation. Mucosal healing is currently recognized as the principal treatment target to be used in a "treat to target" paradigm, whereas histologic healing and normalization of biomarkers are being evaluated as potential future targets. Although symptom relief is no longer a sufficient target, patient experience with the disease is of unquestionable importance and should be assessed in the form of patient-reported outcomes, to be used as a co-primary target with an objective measure of disease activity. IBD in is a heterogeneous disease; thus besides defining common treatment targets, every effort should be made to deliver a personalized treatment plan based on the risk factors for disease progression and individual drug metabolism to improve treatment success.

  9. MRI Fusion-Targeted Transrectal Prostate Biopsy and the Role of Prostate-Specific Antigen Density and Prostate Health Index for the Detection of Clinically Significant Prostate Cancer in Southeast Asian Men.

    PubMed

    Tan, Teck Wei; Png, Keng Siang; Lee, Chau Hung; Yuwono, Arianto; Yeow, Yuyi; Chong, Kian Tai; Lee, Yee Mun; Tan, Cher Heng; Tan, Yung Khan

    2017-11-01

    To test the hypothesis that targeted biopsy has a higher detection rate for clinically significant prostate cancer (csPCa) than systematic biopsy. We defined csPCa as any Gleason sum ≥7 cancer. In patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, to determine if factors, such as prostate-specific antigen density (PSAD) and prostate health index (PHI), can predict csPCa and help select patients for biopsy. We report the first series of targeted biopsies in Southeast Asian men, with comparison against systematic biopsy. Consecutive patients were registered into a prospective institutional review board-approved database in our institution. We reviewed patients who underwent biopsy from May 2016 to June 2017. Inclusion criteria for our study were patients with at least one PI-RADS ≥3, and who underwent both targeted and systematic biopsies in the same sitting. There were 115 patients in the study, of whom 74 (64.3%) had a previous negative systematic biopsy. Targeted biopsies detected significantly less Gleason 6 cancers than systematic biopsies (p < 0.01), and demonstrated significantly higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for the detection of csPCa. For patients with PI-RADS 3 lesions, PHI and PSAD were found to be the best predictors for csPCa. PSAD <0.10 ng/mL/mL had an NPV of 93% and sensitivity of 92%, while allowing 20% of patients to avoid biopsy. PHI cutoff of <27 would allow 34% of patients to avoid biopsy, with both sensitivity and NPV of 100%. Targeted prostate biopsies were found to be significantly superior to systematic biopsies for the detection of csPCa, while detecting less Gleason 6 cancer. Usage of PSAD and PHI cutoff levels in patients with PI-RADS 3 lesions may enable a number of patients to avoid unnecessary biopsy.

  10. Effort levels of the partners in networked manufacturing

    NASA Astrophysics Data System (ADS)

    Chai, G. R.; Cai, Z.; Su, Y. N.; Zong, S. L.; Zhai, G. Y.; Jia, J. H.

    2017-08-01

    Compared with traditional manufacturing mode, could networked manufacturing improve effort levels of the partners? What factors will affect effort level of the partners? How to encourage the partners to improve their effort levels? To answer these questions, we introduce network effect coefficient to build effort level model of the partners in networked manufacturing. The results show that (1) with the increase of the network effect in networked manufacturing, the actual effort level can go beyond the ideal level of traditional manufacturing. (2) Profit allocation based on marginal contribution rate would help improve effort levels of the partners in networked manufacturing. (3) The partners in networked manufacturing who wishes to have a larger distribution ratio must make a higher effort level, and enterprises with insufficient effort should be terminated in networked manufacturing.

  11. Effort-Reward Imbalance and Burnout Among ICU Nursing Staff: A Cross-Sectional Study.

    PubMed

    Padilla Fortunatti, Cristobal; Palmeiro-Silva, Yasna K

    Occupational stress is commonly observed among staff in intensive care units (ICUs). Sociodemographic, organizational, and job-related factors may lead to burnout among ICU health workers. In addition, these factors could modify the balance between efforts done and rewards perceived by workers; consequently, this imbalance could increase levels of emotional exhaustion and depersonalization and decrease a sense of personal accomplishment. The purpose of this study was to analyze the relationship between effort-reward imbalance and burnout dimensions (emotional exhaustion, depersonalization, and personal accomplishment) among ICU nursing staff in a university hospital in Santiago, Chile. A convenience sample of 36 registered nurses and 46 nurse aides answered the Maslach Burnout Inventory and Effort-Reward Imbalance Questionnaire and provided sociodemographic and work-related data. Age and effort-reward imbalance were significantly associated with emotional exhaustion in both registered nurses and nurse aides; age was negatively correlated with emotional exhaustion, whereas effort-reward imbalance was positively correlated. Age was negatively associated with depersonalization. None of the predictors were associated with personal accomplishment. This study adds valuable information about relationships of sociodemographic factors and effort-reward imbalance and their impact on dimensions of burnout, particularly on emotional exhaustion.

  12. Molecular targets for flavivirus drug discovery

    PubMed Central

    Sampath, Aruna; Padmanabhan, R.

    2009-01-01

    Flaviviruses are a major cause of infectious disease in humans. Dengue virus causes an estimated 50 million cases of febrile illness each year, including an increasing number of cases of hemorrhagic fever. West Nile virus, which recently spread from the Mediterranean basin to the Western Hemisphere, now causes thousands of sporadic cases of encephalitis annually. Despite the existence of licensed vaccines, yellow fever, Japanese encephalitis and tick-borne encephalitis also claim many thousands of victims each year across their vast endemic areas. Antiviral therapy could potentially reduce morbidity and mortality from flavivirus infections, but no effective drugs are currently available. This article introduces a collection of papers in Antiviral Research on molecular targets for flavivirus antiviral drug design and murine models of dengue virus disease that aims to encourage drug development efforts. After reviewing the flavivirus replication cycle, we discuss the envelope glycoprotein, NS3 protease, NS3 helicase, NS5 methyltransferase and NS5 RNA-dependent RNA polymerase as potential drug targets, with special attention being given to the viral protease. The other viral proteins are the subject of individual articles in the journal. Together, these papers highlight current status of drug discovery efforts for flavivirus diseases and suggest promising areas for further research. PMID:18796313

  13. Trying to remember: Effort mediates the relationship between frequency of cannabis use and memory performance.

    PubMed

    Hirst, Rayna B; Young, Kaitlyn R; Sodos, Louise M; Wickham, Robert E; Earleywine, Mitch

    2017-06-01

    While many studies suggest that regular cannabis use leads to deficits in cognitive functioning, particularly in memory, few have measured effort put forth during testing, and none have examined this as a potential mediator. Both age of onset of regular cannabis use and frequency of use have been linked to increased risk of memory deficits. The present study sought to determine whether effort mediated the relationship between frequency or age of onset of cannabis use and learning and memory performance. Sixty-two participants (74% male, mean age = 19.25 years) who met criteria for chronic cannabis use (four or more days per week for at least 12 months) completed a neuropsychological battery including the California Verbal Learning Test-II (CVLT-II) and the Rey Complex Figure (RCF) as measures of learning and memory, and the Word Memory Test (WMT) as a measure of effort put forth during neuropsychological assessment. Participants who more frequently used cannabis exhibited poorer effort (as measured by WMT performance; p < .01). Bootstrapping yielded 95% confidence intervals for indirect effects and revealed that effort significantly mediated the relationship between frequency of cannabis use and CVLT-II Learning (Sum of Trials 1-5), CVLT-II Delayed Recall, and RCF Delayed Recall, but not RCF Immediate Recall. Age of onset of cannabis use was not significantly related to effort. Findings indicate that effort mediates the relationship between frequency of cannabis use and performance on learning and memory measures, suggesting that effort performance should be measured and controlled for in future studies assessing cognition in frequent cannabis users.

  14. Networking grassroots efforts to improve safety and health in informal economy workplaces in Asia.

    PubMed

    Kawakami, Tsuyoshi

    2006-01-01

    Many workers in Asia are in the informal economy. They often work in substandard conditions, exposed to hazards in the workplace. Learning from the recent successes of participatory training programmes to improve safety and health in Asia, the ILO has strengthened its partnership efforts with local people to improve safety and health of informal economy workplaces. The target groups were: (1) home workplaces in Cambodia and Thailand, (2) salt fields and fishing villages in Cambodia where many young workers are working, and (3) small construction sites in Cambodia, Laos, Mongolia, Thailand and Vietnam. The walk-through survey results showed that the workers and owners in the target informal economy workplaces had the strong will to improve safety and health at their own initiatives and needed practical support. In the participatory, action-oriented training workshops carried out, the participated workers and owners were able to identify their priority safety and health actions. Commonly identified were clear and safe transport ways, safer handling of hazardous substances, basic welfare needs such as drinking water and sanitary toilets, and work posture. The follow-up visits confirmed that many of the proposed actions were actually taken by using low-cost available materials. These positive changes were possible by applying the participatory training tools such as illustrated checklists and extensive use of photographs showing local good examples and placing emphasis on facilitator roles of trainers. In conclusion, the target informal economy workplaces in Asia made positive changes in safety and health through the participatory, action-oriented training focusing on local initiative and low-cost improvement measures. Local network support mechanisms to share lessons from good practices played essential roles in encouraging the voluntary implementation of practical improvement actions. It is important to increase our joint efforts to reach more informal economy

  15. Non-conscious visual cues related to affect and action alter perception of effort and endurance performance

    PubMed Central

    Blanchfield, Anthony; Hardy, James; Marcora, Samuele

    2014-01-01

    The psychobiological model of endurance performance proposes that endurance performance is determined by a decision-making process based on perception of effort and potential motivation. Recent research has reported that effort-based decision-making during cognitive tasks can be altered by non-conscious visual cues relating to affect and action. The effects of these non-conscious visual cues on effort and performance during physical tasks are however unknown. We report two experiments investigating the effects of subliminal priming with visual cues related to affect and action on perception of effort and endurance performance. In Experiment 1 thirteen individuals were subliminally primed with happy or sad faces as they cycled to exhaustion in a counterbalanced and randomized crossover design. A paired t-test (happy vs. sad faces) revealed that individuals cycled significantly longer (178 s, p = 0.04) when subliminally primed with happy faces. A 2 × 5 (condition × iso-time) ANOVA also revealed a significant main effect of condition on rating of perceived exertion (RPE) during the time to exhaustion (TTE) test with lower RPE when subjects were subliminally primed with happy faces (p = 0.04). In Experiment 2, a single-subject randomization tests design found that subliminal priming with action words facilitated a significantly longer TTE (399 s, p = 0.04) in comparison to inaction words. Like Experiment 1, this greater TTE was accompanied by a significantly lower RPE (p = 0.03). These experiments are the first to show that subliminal visual cues relating to affect and action can alter perception of effort and endurance performance. Non-conscious visual cues may therefore influence the effort-based decision-making process that is proposed to determine endurance performance. Accordingly, the findings raise notable implications for individuals who may encounter such visual cues during endurance competitions, training, or health related exercise. PMID:25566014

  16. Measuring collections effort improves cash performance.

    PubMed

    Shutts, Joe

    2009-09-01

    Having a satisfied work force can lead to an improved collections effort. Hiring the right people and training them ensures employee engagement. Measuring collections effort and offering incentives is key to revenue cycle success.

  17. Reproductive effort affects oxidative status and stress in an Antarctic penguin species: An experimental study.

    PubMed

    Colominas-Ciuró, Roger; Santos, Mercedes; Coria, Néstor; Barbosa, Andrés

    2017-01-01

    The oxidative cost of reproduction has been a matter of debate in recent years presumably because of the lack of proper experimental studies. Based on the hypothesis that different brood sizes produce differential reproductive costs, an experimental manipulation during breeding of Adélie penguins was conducted at Hope Bay, Antarctica, to study oxidative status and stress. We predict that a lower reproductive effort should be positively related to low oxidative and physiological stress. We randomly assigned nests with two chicks to a control reproductive effort group (CRE), and by removing one chick from some nests with two chicks, formed a second, low reproductive effort group (LRE). We examined how oxidative status in blood plasma (reactive oxygen metabolites, ROMs, and total antioxidant capacity, OXY) and stress (heterophil/lymphocyte ratio, H/L) responded to a lower production of offspring total biomass. Our nest manipulation showed significant differences in offspring total biomass, which was lower in the LRE group. As predicted, the LRE group had higher antioxidant capacity than individuals in the CRE group. We have also found, although marginally significant, interactions between sex and treatment in the three variables analysed. Females had higher OXY, lower ROMs and lower H/L ratio when rearing one chick, whereas males did so when rearing two except for OXY which was high regardless of treatment. Moreover, there was a significant negative correlation between the H/L ratio and OXY in females. Finally, we have found a negative and significant relationship between the duration of the experiment and OXY and ROMs and positive with H/L ratio which suggests that indeed breeding penguins are paying an effort in physiological terms in relation to the duration of the chick rearing. In conclusion, a reduction of the reproductive effort decreased oxidative stress in this long-lived bird meaning that a link exists between breeding effort and oxidative stress. However

  18. Real-time multisensor data fusion for target detection, classification, tracking, counting, and range estimates

    NASA Astrophysics Data System (ADS)

    Tsui, Eddy K.; Thomas, Russell L.

    2004-09-01

    As part of the Commanding General of Army Material Command's Research, Development & Engineering Command (RDECOM), the U.S. Army Research Development and Engineering Center (ARDEC), Picatinny funded a joint development effort with McQ Associates, Inc. to develop an Advanced Minefield Sensor (AMS) as a technology evaluation prototype for the Anti-Personnel Landmine Alternatives (APLA) Track III program. This effort laid the fundamental groundwork of smart sensors for detection and classification of targets, identification of combatant or noncombatant, target location and tracking at and between sensors, fusion of information across targets and sensors, and automatic situation awareness to the 1st responder. The efforts have culminated in developing a performance oriented architecture meeting the requirements of size, weight, and power (SWAP). The integrated digital signal processor (DSP) paradigm is capable of computing signals from sensor modalities to extract needed information within either a 360° or fixed field of view with acceptable false alarm rate. This paper discusses the challenges in the developments of such a sensor, focusing on achieving reasonable operating ranges, achieving low power, small size and low cost, and applications for extensions of this technology.

  19. Distinct effects of apathy and dopamine on effort-based decision-making in Parkinson's disease.

    PubMed

    Le Heron, Campbell; Plant, Olivia; Manohar, Sanjay; Ang, Yuen-Siang; Jackson, Matthew; Lennox, Graham; Hu, Michele T; Husain, Masud

    2018-05-01

    high effort, high reward offers, irrespective of underlying motivational state. Dopamine also exerted a main effect on motor vigour, increasing force production independently of reward offered, while apathy did not affect this measure. The findings demonstrate that disrupted effort-based decision-making underlies Parkinson's disease apathy, but in a manner distinct to that caused by dopamine depletion. Apathy is associated with reduced incentivization by the rewarding outcomes of actions. In contrast, dopamine has a general effect in motivating behaviour for high effort, high reward options without altering the response pattern that characterizes the apathetic state. Thus, the motivational deficit observed in Parkinson's disease appears not to be simply secondary to dopaminergic depletion of mesocorticolimbic pathways, suggesting non-dopaminergic therapeutic strategies for apathy may be important future targets.

  20. Parenting and the development of effortful control from early childhood to early adolescence: A transactional developmental model.

    PubMed

    Tiberio, Stacey S; Capaldi, Deborah M; Kerr, David C R; Bertrand, Maria; Pears, Katherine C; Owen, Lee

    2016-08-01

    Poor effortful control is a key temperamental factor underlying behavioral problems. The bidirectional association of child effortful control with both positive parenting and negative discipline was examined from ages approximately 3 to 13-14 years, involving five time points, and using data from parents and children in the Oregon Youth Study-Three Generational Study (N = 318 children from 150 families). Based on a dynamic developmental systems approach, it was hypothesized that there would be concurrent associations between parenting and child effortful control and bidirectional effects across time from each aspect of parenting to effortful control and from effortful control to each aspect of parenting. It was also hypothesized that associations would be more robust in early childhood, from ages 3 to 7 years, and would diminish as indicated by significantly weaker effects at the older ages, 11-12 to 13-14 years. Longitudinal feedback or mediated effects were also tested. The findings supported (a) stability in each construct over multiple developmental periods; (b) concurrent associations, which were significantly weaker at the older ages; (c) bidirectional effects, consistent with the interpretation that at younger ages children's effortful control influenced parenting, whereas at older child ages, parenting influenced effortful control; and (d) a transactional effect, such that maternal parenting in late childhood was a mechanism explaining children's development of effortful control from middle childhood to early adolescence.

  1. Parenting and the Development of Effortful Control from Early Childhood to Early Adolescence: A Transactional Developmental Model

    PubMed Central

    Capaldi, Deborah M.; Kerr, David C. R.; Bertrand, Maria; Pears, Katherine C.; Owen, Lee

    2016-01-01

    Poor effortful control is a key temperamental factor underlying behavioral problems. The bidirectional association of child effortful control with both positive parenting and negative discipline was examined from ages approximately 3 to 13–14 years, involving 5 time points, and using data from parents and children in the Oregon Youth Study-Three Generational Study (N = 318 children from 150 families). Based on a dynamic developmental systems approach, it was hypothesized that there would be concurrent associations between parenting and child effortful control and bidirectional effects across time from each aspect of parenting to effortful control and from effortful control to each aspect of parenting. It was also hypothesized that associations would be more robust in early childhood, from ages 3 to 7 years, and would diminish as indicated by significantly weaker effects at the older ages, 11–12 to 13–14 years. Longitudinal feedback or mediated effects were also tested. Findings supported (a) stability in each construct over multiple developmental periods; (b) concurrent associations, which were significantly weaker at the older ages; (c) bidirectional effects, consistent with the interpretation that at younger ages children’s effortful control influenced parenting, whereas at older child ages, parenting influenced effortful control; and (d) a transactional effect, such that maternal parenting in late childhood was a mechanism explaining children’s development of effortful control from midchildhood to early adolescence. PMID:27427809

  2. Patterns in artisanal coral reef fisheries revealed through local monitoring efforts

    PubMed Central

    Teneva, Lida T.; Ogawa, Tom; Friedlander, Alan M.

    2017-01-01

    Sustainable fisheries management is key to restoring and maintaining ecological function and benefits to people, but it requires accurate information about patterns of resource use, particularly fishing pressure. In most coral reef fisheries and other data-poor contexts, obtaining such information is challenging and remains an impediment to effective management. We developed the most comprehensive regional view of shore-based fishing effort and catch published to date, to show detailed fishing patterns from across the main Hawaiian Islands (MHI). We reveal these regional patterns through fisher “creel” surveys conducted by local communities, state agencies, academics, and/or environmental organizations, at 18 sites, comprising >10,000 h of monitoring across a range of habitats and human influences throughout the MHI. All creel surveys included in this study except for one were previously published in some form (peer-reviewed articles or gray literature reports). Here, we synthesize these studies to document spatial patterns in nearshore fisheries catch, effort, catch rates (i.e., catch-per-unit-effort (CPUE)), and catch disposition (i.e., use of fish after catch is landed). This effort provides for a description of general regional patterns based on these location-specific studies. Line fishing was by far the dominant gear type employed. The most efficient gear (i.e., highest CPUE) was spear (0.64 kg h−1), followed closely by net (0.61 kg h−1), with CPUE for line (0.16 kg h−1) substantially lower than the other two methods. Creel surveys also documented illegal fishing activity across the studied locations, although these activities were not consistent across sites. Overall, most of the catch was not sold, but rather retained for home consumption or given away to extended family, which suggests that cultural practices and food security may be stronger drivers of fishing effort than commercial exploitation for coral reef fisheries in Hawai‘i. Increased

  3. Target materials for exotic ISOL beams

    NASA Astrophysics Data System (ADS)

    Gottberg, A.

    2016-06-01

    The demand for intensity, purity, reliability and availability of short-lived isotopes far from stability is steadily high, and considerably exceeding the supply. In many cases the ISOL (Isotope Separation On-Line) method can provide beams of high intensity and purity. Limitations in terms of accessible chemical species and minimum half-life are driven mainly by chemical reactions and physical processes inside of the thick target. A wide range of materials are in use, ranging from thin metallic foils and liquids to refractory ceramics, while poly-phasic mixed uranium carbides have become the reference target material for most ISOL facilities world-wide. Target material research and development is often complex and especially important post-irradiation analyses are hindered by the high intrinsic radiotoxicity of these materials. However, recent achievements have proven that these investigations are possible if the effort of different facilities is combined, leading to the development of new material matrices that can supply new beams of unprecedented intensity and beam current stability.

  4. Workplace violence against nurses--prevalence and association with hospital organizational characteristics and health-promotion efforts: Cross-sectional study.

    PubMed

    Wei, Ching-Yao; Chiou, Shu-Ti; Chien, Li-Yin; Huang, Nicole

    2016-04-01

    To determine the prevalence of workplace violence and explore the role of hospital organizational characteristics and health promotion efforts in reducing hospital violence among nurses in Taiwan. Cross-sectional survey. One hundred hospitals across Taiwan. The final sample in our study comprised responses from 26,979 nurses. The data were obtained from a nationwide hospital survey, Physical and Mental Health and Safety Needs in Full-Time Health Care Staff, which was developed and conducted by the Bureau of Health Promotion, Taiwan, in 2011. The main dependent variable was whether nurses had experienced violence within the past year. Physical violence, threatened or intimidated personal safety, verbal violence or sexual harassment were all included. Of the 26,979 nurses, 13,392 nurses (49.6%) had experienced at least one episode of any type of violence in the past year; 5150 nurses (19.1%) had been exposed to physical violence, and 12,491 nurses (46.3%) had been exposed to non-physical violence. The prevalence of having experienced any violence varied widely and ranged from the highest (55.5%) in an emergency room or intensive care unit to the lowest (28.3%) among those aged 55-65 years. After adjusting for other characteristics, younger nurses were significantly more likely to be exposed to any violent threat. Nurses working in public hospitals had a significantly higher risk of workplace violence than those working in private hospitals. Significant variations were also observed among work units. Although nurses working in a certified health promoting hospital (HPH) did not have a lower risk of workplace violence, those working in an outstanding HPH had a significantly lower risk of workplace violence. A similar pattern was observed for non-physical violence. Workplace violence is a major challenge to workplace safety for nurses in hospitals. This large scale nurse survey identified individual, work and hospital characteristics associated with workplace violence

  5. Greater effort increases perceived value in an invertebrate.

    PubMed

    Czaczkes, Tomer J; Brandstetter, Birgit; di Stefano, Isabella; Heinze, Jürgen

    2018-05-01

    Expending effort is generally considered to be undesirable. However, both humans and vertebrates will work for a reward they could also get for free. Moreover, cues associated with high-effort rewards are preferred to low-effort associated cues. Many explanations for these counterintuitive findings have been suggested, including cognitive dissonance (self-justification) or a greater contrast in state (e.g., energy or frustration level) before and after an effort-linked reward. Here, we test whether effort expenditure also increases perceived value in ants, using both classical cue-association methods and pheromone deposition, which correlates with perceived value. In 2 separate experimental setups, we show that pheromone deposition is higher toward the reward that requires more effort: 47% more pheromone deposition was performed for rewards reached via a vertical runway (high effort) compared with ones reached via a horizontal runway (low effort), and deposition rates were 28% higher on rough (high effort) versus smooth (low effort) runways. Using traditional cue-association methods, 63% of ants trained on different surface roughness, and 70% of ants trained on different runway elevations, preferred the high-effort related cues on a Y maze. Finally, pheromone deposition to feeders requiring memorization of one path bifurcation was up to 29% higher than to an identical feeder requiring no learning. Our results suggest that effort affects value perception in ants. This effect may stem from a cognitive process, which monitors the change in a generalized hedonic state before and after reward. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  6. 7 CFR 622.31 - Basic planning efforts.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Basic planning efforts. 622.31 Section 622.31..., DEPARTMENT OF AGRICULTURE WATER RESOURCES WATERSHED PROJECTS Planning § 622.31 Basic planning efforts. Upon... the need for planning effort. Once planning is authorized by the Chief of NRCS, a watershed plan...

  7. Targeting blood–brain barrier changes during inflammatory pain: an opportunity for optimizing CNS drug delivery

    PubMed Central

    Ronaldson, Patrick T; Davis, Thomas P

    2012-01-01

    The blood–brain barrier (BBB) is the most significant obstacle to effective CNS drug delivery. It possesses structural and biochemical features (i.e., tight-junction protein complexes and, influx and efflux transporters) that restrict xenobiotic permeation. Pathophysiological stressors (i.e., peripheral inflammatory pain) can alter BBB tight junctions and transporters, which leads to drug-permeation changes. This is especially critical for opioids, which require precise CNS concentrations to be safe and effective analgesics. Recent studies have identified molecular targets (i.e., endogenous transporters and intracellular signaling systems) that can be exploited for optimization of CNS drug delivery. This article summarizes current knowledge in this area and emphasizes those targets that present the greatest opportunity for controlling drug permeation and/or drug transport across the BBB in an effort to achieve optimal CNS opioid delivery. PMID:22468221

  8. Assessment of fertility control efforts in a selected area of Karachi, Pakistan.

    PubMed

    Shirmeen, Amra; Khan, Muhammad F H; Khan, Khizer H; Khan, Khurum H

    2007-09-01

    To investigate the impact of fertility control efforts on reducing fertility and to study the contributory role of fertility inhibiting factors viz, age of the marriage, breast feeding and post-partum amenorrhea, abortion and use of contraceptives in selected area in Karachi, Pakistan. The aim was to estimate the gap between knowledge of contraceptives and its practice i.e. KAP-GAP as well as to determine the level of unmet need in the PIB colony in Karachi. A sample survey was conducted in PIB colony in Karachi from October 2005 to November 2005 by interviewing 340 married women in reproductive ages. The data was tabulated and John Bongaarts technique was used to analyse the success of fertility control efforts in the selected area. Of the total of 340 respondents, 38% were currently using contraceptive methods with 26% using OCP's and 12% were condom users. A slight reduction in total fertility (TFR) was noticed. The population policy of Pakistan envisages achieving population stabilization in 2020 by reducing the annual rate of population growth from 1.9% to 1.3% and TFR at 2.1. This target requires strenuous efforts to make the concept of small family an accepted milieu through an eagerly designed communication and education campaign. Concentration on proximate determinants of fertility particularly breast feeding and prolonging birth interval will not generate opposition from the community because these concepts are in accordance with Islamic injunctions and teachings.

  9. Applying the Policy Ecology Framework to Philadelphia’s Behavioral Health Transformation Efforts

    PubMed Central

    Powell, Byron J.; Beidas, Rinad S.; Rubin, Ronnie M.; Stewart, Rebecca E.; Wolk, Courtney Benjamin; Matlin, Samantha L.; Weaver, Shawna; Hurford, Matthew O.; Evans, Arthur C.; Hadley, Trevor R.; Mandell, David S.

    2016-01-01

    Raghavan et al. (2008) proposed that effective implementation of evidence-based practices requires implementation strategies deployed at multiple levels of the “policy ecology,” including the organizational, regulatory or purchaser agency, political, and social levels. However, much of implementation research and practice targets providers without accounting for contextual factors that may influence provider behavior. This paper examines Philadelphia’s efforts to work toward an evidence-based and recovery-oriented behavioral health system, and uses the policy ecology framework to illustrate how multifaceted, multilevel implementation strategies can facilitate the widespread implementation of evidence-based practices. Ongoing challenges and implications for research and practice are discussed. PMID:27032411

  10. Neural Mechanisms for Adaptive Learned Avoidance of Mental Effort.

    PubMed

    Mitsuto Nagase, Asako; Onoda, Keiichi; Clifford Foo, Jerome; Haji, Tomoki; Akaishi, Rei; Yamaguchi, Shuhei; Sakai, Katsuyuki; Morita, Kenji

    2018-02-05

    Humans tend to avoid mental effort. Previous studies have demonstrated this tendency using various demand-selection tasks; participants generally avoid options associated with higher cognitive demand. However, it remains unclear whether humans avoid mental effort adaptively in uncertain and non-stationary environments, and if so, what neural mechanisms underlie this learned avoidance and whether they remain the same irrespective of cognitive-demand types. We addressed these issues by developing novel demand-selection tasks where associations between choice options and cognitive-demand levels change over time, with two variations using mental arithmetic and spatial reasoning problems (29:4 and 18:2 males:females). Most participants showed avoidance, and their choices depended on the demand experienced on multiple preceding trials. We assumed that participants updated the expected cost of mental effort through experience, and fitted their choices by reinforcement learning models, comparing several possibilities. Model-based fMRI analyses revealed that activity in the dorsomedial and lateral frontal cortices was positively correlated with the trial-by-trial expected cost for the chosen option commonly across the different types of cognitive demand, and also revealed a trend of negative correlation in the ventromedial prefrontal cortex. We further identified correlates of cost-prediction-error at time of problem-presentation or answering the problem, the latter of which partially overlapped with or were proximal to the correlates of expected cost at time of choice-cue in the dorsomedial frontal cortex. These results suggest that humans adaptively learn to avoid mental effort, having neural mechanisms to represent expected cost and cost-prediction-error, and the same mechanisms operate for various types of cognitive demand. SIGNIFICANCE STATEMENT In daily life, humans encounter various cognitive demands, and tend to avoid high-demand options. However, it remains unclear

  11. ALCOHOLIC HEPATITIS: TRANSLATIONAL APPROACHES TO DEVELOP TARGETED THERAPIES

    PubMed Central

    Mandrekar, Pranoti; Bataller, Ramon; Tsukamoto, Hidekazu; Gao, Bin

    2016-01-01

    Alcoholic liver disease (ALD) is a leading cause of liver related mortality worldwide. In contrast to recent advances in therapeutic strategies for patients with viral hepatitis, there is a significant lack of novel therapeutic options for patients with ALD. In particular, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of ALD. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with AH is very high (20–50% at 3 months). Available therapies are not effective in many patients and targeted approaches are imminently needed. The development of such therapies requires translational studies in human samples and suitable animal models that reproduce clinical and histological features of AH. In recent years, new animal models that simulate some of the features of human AH have been developed, and translational studies using human samples have identified potential pathogenic factors and histological parameters that predict survival. This review article summarizes the unmet needs for translational studies on the pathogenesis of AH, pre-clinical translational tools, and emerging drug targets to benefit the AH patient. PMID:26940353

  12. cGMP signaling as a target for the prevention and treatment of breast cancer.

    PubMed

    Windham, Perrin F; Tinsley, Heather N

    2015-04-01

    One in eight women in the United States will be diagnosed with invasive breast cancer in her lifetime. Advances in therapeutic strategies, diagnosis, and improved awareness have resulted in a significant reduction in breast cancer related mortality. However, there is a continued need for more effective and less toxic drugs for both the prevention and the treatment of breast cancer in order to see a continued decline in the morbidity and mortality associated with this disease. Recent studies suggest that the cGMP signaling pathway may be aberrantly regulated in breast cancer. As such, this pathway may serve as a source of novel targets for future breast cancer drug discovery efforts. This review provides an overview of cGMP signaling in normal physiology and in breast cancer as well as current strategies being investigated for targeting this pathway in breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Addressing the Immunogenicity of the Cargo and of the Targeting Antibodies with a Focus on Deimmunized Bacterial Toxins and on Antibody-Targeted Human Effector Proteins

    PubMed Central

    Grinberg, Yehudit; Benhar, Itai

    2017-01-01

    Third-generation immunotoxins are composed of a human, or humanized, targeting moiety, usually a monoclonal antibody or an antibody fragment, and a non-human effector molecule. Due to the non-human origin of the cytotoxic domain, these molecules stimulate potent anti-drug immune responses, which limit treatment options. Efforts are made to deimmunize such immunotoxins or to combine treatment with immunosuppression. An alternative approach is using the so-called “human cytotoxic fusion proteins”, in which antibodies are used to target human effector proteins. Here, we present three relevant approaches for reducing the immunogenicity of antibody-targeted protein therapeutics: (1) reducing the immunogenicity of the bacterial toxin, (2) fusing human cytokines to antibodies to generate immunocytokines and (3) addressing the immunogenicity of the targeting antibodies. PMID:28574434

  14. Increase in Jumping Height Associated with Maximal Effort Vertical Depth Jumps.

    ERIC Educational Resources Information Center

    Bedi, John F.; And Others

    1987-01-01

    In order to assess if there existed a statistically significant increase in jumping performance when dropping from different heights, 32 males, aged 19 to 26, performed a series of maximal effort vertical jumps after dropping from eight heights onto a force plate. Results are analyzed. (Author/MT)

  15. HER2-family signalling mechanisms, clinical implications and targeting in breast cancer.

    PubMed

    Elster, N; Collins, D M; Toomey, S; Crown, J; Eustace, A J; Hennessy, B T

    2015-01-01

    Approximately 20 % of human breast cancers (BC) overexpress HER2 protein, and HER2-positivity is associated with a worse prognosis. Although HER2-targeted therapies have significantly improved outcomes for HER2-positive BC patients, resistance to trastuzumab-based therapy remains a clinical problem. In order to better understand resistance to HER2-targeted therapies in HER2-positive BC, it is necessary to examine HER family signalling as a whole. An extensive literature search was carried out to critically assess the current knowledge of HER family signalling in HER2-positive BC and response to HER2-targeted therapy. Known mechanisms of trastuzumab resistance include reduced receptor-antibody binding (MUC4, p95HER2), increased signalling through alternative HER family receptor tyrosine kinases (RTK), altered intracellular signalling involving loss of PTEN, reduced p27kip1, or increased PI3K/AKT activity and altered signalling via non-HER family RTKs such as IGF1R. Emerging strategies to circumvent resistance to HER2-targeted therapies in HER2-positive BC include co-targeting HER2/PI3K, pan-HER family inhibition, and novel therapies such as T-DM1. There is evidence that immunity plays a key role in the efficacy of HER-targeted therapy, and efforts are being made to exploit the immune system in order to improve the efficacy of current anti-HER therapies. With our rapidly expanding understanding of HER2 signalling mechanisms along with the repertoire of HER family and other targeted therapies, it is likely that the near future holds further dramatic improvements to the prognosis of women with HER2-positive BC.

  16. Safety behaviors and sleep effort predict sleep disturbance and fatigue in an outpatient sample with anxiety and depressive disorders.

    PubMed

    Fairholme, Christopher P; Manber, Rachel

    2014-03-01

    Theoretical and empirical support for the role of dysfunctional beliefs, safety behaviors, and increased sleep effort in the maintenance of insomnia has begun to accumulate. It is not yet known how these factors predict sleep disturbance and fatigue occurring in the context of anxiety and mood disorders. It was hypothesized that these three insomnia-specific cognitive-behavioral factors would be uniquely associated with insomnia and fatigue among patients with emotional disorders after adjusting for current symptoms of anxiety and depression and trait levels of neuroticism and extraversion. Outpatients with a current anxiety or mood disorder (N = 63) completed self-report measures including the Dysfunctional Beliefs About Sleep Scale (DBAS), Sleep-Related Safety Behaviors Questionnaire (SRBQ), Glasgow Sleep Effort Scale (GSES), Pittsburgh Sleep Quality Index (PSQI), NEO Five-Factor Inventory (FFI), and the 21-item Depression Anxiety and Stress Scale (DASS). Multivariate path analysis was used to evaluate study hypotheses. SRBQ (B = .60, p < .001, 95% CI [.34, .86]) and GSES (B = .31, p < .01, 95% CI [.07, .55]) were both significantly associated with PSQI. There was a significant interaction between SRBQ and DBAS (B = .25, p < .05, 95% CI [.04, .47]) such that the relationship between safety behaviors and fatigue was strongest among individuals with greater levels of dysfunctional beliefs. Findings are consistent with cognitive behavioral models of insomnia and suggest that sleep-specific factors might be important treatment targets among patients with anxiety and depressive disorders with disturbed sleep. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Relationship between mid-water trawling effort and catch composition uncertainty in two large lakes (Huron and Michigan) dominated by alosines, osmerids, and coregonines

    USGS Publications Warehouse

    Warner, David M.; Claramunt, Randall M.; Schaeffer, Jeffrey S.; Yule, Daniel L.; Hrabik, Tom R.; Peintka, Bernie; Rudstam, Lars G.; Holuszko, Jeffrey D.; O'Brien, Timothy P.

    2012-01-01

    Because it is not possible to identify species with echosounders alone, trawling is widely used as a method for collecting species and size composition data for allocating acoustic fish density estimates to species or size groups. In the Laurentian Great Lakes, data from midwater trawls are commonly used for such allocations. However, there are no rules for how much midwater trawling effort is required to adequately describe species and size composition of the pelagic fish communities in these lakes, so the balance between acoustic sampling effort and trawling effort has been unguided. We used midwater trawl data collected between 1986 and 2008 in lakes Michigan and Huron and a variety of analytical techniques to develop guidance for appropriate levels of trawl effort. We used multivariate regression trees and re-sampling techniques to i. identify factors that influence species and size composition of the pelagic fish communities in these lakes, ii. identify stratification schemes for the two lakes, iii. determine if there was a relationship between uncertainty in catch composition and the number of tows made, and iv. predict the number of tows required to reach desired uncertainty targets. We found that depth occupied by fish below the surface was the most influential explanatory variable. Catch composition varied between lakes at depths <38.5 m below the surface, but not at depths ≥38.5 m below the surface. Year, latitude, and bottom depth influenced catch composition in the near-surface waters of Lake Michigan, while only year was important for Lake Huron surface waters. There was an inverse relationship between RSE [relative standard error = 100 × (SE/mean)] and the number of tows made for the proportions of the different size and species groups. We found for the fifth (Lake Huron) and sixth (Lake Michigan) largest lakes in the world, 15–35 tows were adequate to achieve target RSEs (15% and 30%) for ubiquitous species, but rarer species required much

  18. Bilateral asymmetries in max effort single-leg vertical jumps.

    PubMed

    Stephens, Thomas M; Lawson, Brooke R; Reiser, Raoul F

    2005-01-01

    While asymmetries in the lower extremity during jumping may have implications during rehabilitation, it is not clear if healthy subjects should be expected to jump equivalently on each leg. Therefore, the goal of this study was to determine if asymmetries exist in maximal effort single-leg vertical jumps. After obtaining university-approved informed consent, 13 men and 12 women with competitive volleyball playing experience and no injuries of the lower-extremity that would predispose them to asymmetries participated. After thorough warm-up, five maximal effort vertical jumps with countermovement were performed on each leg (random order) with ground reaction forces and lower extremity kinematics recorded. The best three jumps from each leg were analyzed, assigning the leg with the highest jump height average as the dominant side. Asymmetry was assessed by determining statistical significance in the dominant versus non-dominant sides (p < 0.05). A significant interaction existed between side and gender for thigh length and peak vertical ground reaction force. Women had a significantly shorter thigh and men a greater peak vertical ground reaction force on their dominant side. All other parameters were assessed as whole group. Jumps were significantly greater off the dominant leg (2.8 cm on average). No other differences between sides were observed. Significant differences in magnitude (p < 0.05) existed between the men and women in jump height, several anthropometric parameters, minimum ankle and hip angles, and vertical ground reaction forces (peak and average). In conclusion, though a person may jump slightly higher on one leg relative to the other, and women may jump slightly differently than men, the magnitude of the difference should be relatively small and due to the multi-factorial nature of jump performance, individual parameters related to performance may not be consistently different.

  19. Landscape connectivity promotes plant biodiversity spillover into non-target habitats.

    PubMed

    Brudvig, Lars A; Damschen, Ellen I; Tewksbury, Joshua J; Haddad, Nick M; Levey, Douglas J

    2009-06-09

    Conservation efforts typically focus on maximizing biodiversity in protected areas. The space available for reserves is limited, however, and conservation efforts must increasingly consider how management of protected areas can promote biodiversity beyond reserve borders. Habitat corridors are considered an important feature of reserves because they facilitate movement of organisms between patches, thereby increasing species richness in those patches. Here we demonstrate that by increasing species richness inside target patches, corridors additionally benefit biodiversity in surrounding non-target habitat, a biodiversity "spillover" effect. Working in the world's largest corridor experiment, we show that increased richness extends for approximately 30% of the width of the 1-ha connected patches, resulting in 10-18% more vascular plant species around patches of target habitat connected by corridors than around unconnected but otherwise equivalent patches of habitat. Furthermore, corridor-enhanced spillover into non-target habitat can be predicted by a simple plant life-history trait: seed dispersal mode. Species richness of animal-dispersed plants in non-target habitat increased in response to connectivity provided by corridors, whereas species richness of wind-dispersed plants was unaffected by connectivity and increased in response to changes in patch shape--higher edge-to-interior ratio--created by corridors. Corridors promoted biodiversity spillover for native species of the threatened longleaf pine ecosystem being restored in our experiment, but not for exotic species. By extending economically driven spillover concepts from marine fisheries and crop pollination systems, we show how reconnecting landscapes amplifies biodiversity conservation both within and beyond reserve borders.

  20. The role of low cognitive effort and negative symptoms in neuropsychological impairment in schizophrenia.

    PubMed

    Strauss, Gregory P; Morra, Lindsay F; Sullivan, Sara K; Gold, James M

    2015-03-01

    Two experiments were conducted to examine whether insufficient effort, negative symptoms (e.g., avolition, anhedonia), and psychological variables (e.g., anhedonia and perception of low cognitive resources) predict generalized neurocognitive impairment in individuals with schizophrenia (SZ). In Experiment 1, participants included 97 individuals with SZ and 63 healthy controls (CN) who completed the Victoria Symptom Validity Test (VSVT), the MATRICS Consensus Cognitive Battery (MCCB), and self-report anhedonia questionnaires. In Experiment 2, participants included 46 individuals with SZ and 33 CN who completed Green's Word Memory Test (WMT), the MCCB, and self-reports of anhedonia, defeatist performance beliefs, and negative expectancy appraisals. RESULTS indicated that a low proportion of individuals with SZ failed effort testing (1.0% Experiment 1; 15.2% Experiment 2); however, global neurocognitive impairment was significantly predicted by low effort and negative symptoms. Findings indicate that low effort does not threaten the validity of neuropsychological test results in the majority of individuals with schizophrenia; however, effort testing may be useful in SZ patients with severe negative symptoms who may be more likely to put forth insufficient effort due to motivational problems. Although the base rate of failure is relatively low, it may be beneficial to screen for insufficient effort in SZ and exclude individuals who fail effort testing from pharmacological or cognitive remediation trials. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  1. Identifying relationships between unrelated pharmaceutical target proteins on the basis of shared active compounds.

    PubMed

    Miljković, Filip; Kunimoto, Ryo; Bajorath, Jürgen

    2017-08-01

    Computational exploration of small-molecule-based relationships between target proteins from different families. Target annotations of drugs and other bioactive compounds were systematically analyzed on the basis of high-confidence activity data. A total of 286 novel chemical links were established between distantly related or unrelated target proteins. These relationships involved a total of 1859 bioactive compounds including 147 drugs and 141 targets. Computational analysis of large amounts of compounds and activity data has revealed unexpected relationships between diverse target proteins on the basis of compounds they share. These relationships are relevant for drug discovery efforts. Target pairs that we have identified and associated compound information are made freely available.

  2. Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma

    PubMed Central

    Wachsmann, Jason; Peng, Fangyu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC. PMID:26755872

  3. Interests, Effort, Achievement and Vocational Preference.

    ERIC Educational Resources Information Center

    Sjoberg, L.

    1984-01-01

    Relationships between interest in natural sciences and technology and perceived ability, success, and invested effort were studied in Swedish secondary school students. Interests were accounted for by logical orientation and practical value. Interests and grades were strongly correlated, but correlations between interests and effort and vocational…

  4. Targeted Nanotechnology for Cancer Imaging

    PubMed Central

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

    2014-01-01

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

  5. Has Malaysia's antidrug effort been effective?

    PubMed

    Scorzelli, J F

    1992-01-01

    It is a common belief that a massive effort in law enforcement, preventive education and rehabilitation will result in the elimination of a country's drug problem. Based on this premise. Malaysia in 1983 implemented such a multifaceted anti-drug strategy, and the results of a 1987 study by the author suggested that Malaysia's effort had begun to contribute to a steady decrease in the number of identified drug abusers. Although the number of drug-addicted individuals declined, the country's recidivism rates were still high. Because of this high relapse rate, Malaysia expanded their rehabilitation effort and developed a community transition program. In order to determine the impact of these changes on the country's battle against drug abuse, a follow-up study was conducted in 1990. The results of this study did not clearly demonstrate that the Malaysian effort had been successful in eliminating the problem of drug abuse, and raised some questions concerning the effectiveness of the country's drug treatment programs.

  6. LBNF 1.2 MW Target: Conceptual Design & Fabrication

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

    Crowley, C.; Ammigan, K.; Anderson, K.

    2015-06-01

    Fermilab’s Long-Baseline Neutrino Facility (LBNF) will utilize a modified design based on the NuMI low energy target that is reconfigured to accommodate beam operation at 1.2 MW. Achieving this power with a graphite target material and ancillary systems originally rated for 400 kW requires several design changes and R&D efforts related to material bonding and electrical isolation. Target cooling, structural design, and fabrication techniques must address higher stresses and heat loads that will be present during 1.2 MW operation, as the assembly will be subject to cyclic loads and thermal expansion. Mitigations must be balanced against compromises in neutrino yield.more » Beam monitoring and subsystem instrumentation will be updated and added to ensure confidence in target positioning and monitoring. Remote connection to the target hall support structure must provide for the eventual upgrade to a 2.4 MW target design, without producing excessive radioactive waste or unreasonable exposure to technicians during reconfiguration. Current designs and assembly layouts will be presented, in addition to current findings on processes and possibilities for prototype and final assembly fabrication.« less

  7. LBNF 1.2 MW TARGET: CONCEPTUAL DESIGN & FABRICATION

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

    Crowley, Cory F.; Ammigan, K.; Anderson, K.

    2015-06-29

    Fermilab’s Long-Baseline Neutrino Facility (LBNF) will utilize a modified design based on the NuMI low energy target that is reconfigured to accommodate beam operation at 1.2 MW. Achieving this power with a graphite target material and ancillary systems originally rated for 400 kW requires several design changes and R&D efforts related to material bonding and electrical isolation. Target cooling, structural design, and fabrication techniques must address higher stresses and heat loads that will be present during 1.2 MW operation, as the assembly will be subject to cyclic loads and thermal expansion. Mitigations must be balanced against compromises in neutrino yield.more » Beam monitoring and subsystem instrumentation will be updated and added to ensure confidence in target positioning and monitoring. Remote connection to the target hall support structure must provide for the eventual upgrade to a 2.4 MW target design, without producing excessive radioactive waste or unreasonable exposure to technicians during reconfiguration. Current designs and assembly layouts will be presented, in addition to current findings on processes and possibilities for prototype and final assembly fabrication.« less

  8. MicroRNA-targeted therapeutics for lung cancer treatment.

    PubMed

    Xue, Jing; Yang, Jiali; Luo, Meihui; Cho, William C; Liu, Xiaoming

    2017-02-01

    Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists. Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease. Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.

  9. Listening Effort and Speech Recognition with Frequency Compression Amplification for Children and Adults with Hearing Loss.

    PubMed

    Brennan, Marc A; Lewis, Dawna; McCreery, Ryan; Kopun, Judy; Alexander, Joshua M

    2017-10-01

    Nonlinear frequency compression (NFC) can improve the audibility of high-frequency sounds by lowering them to a frequency where audibility is better; however, this lowering results in spectral distortion. Consequently, performance is a combination of the effects of increased access to high-frequency sounds and the detrimental effects of spectral distortion. Previous work has demonstrated positive benefits of NFC on speech recognition when NFC is set to improve audibility while minimizing distortion. However, the extent to which NFC impacts listening effort is not well understood, especially for children with sensorineural hearing loss (SNHL). To examine the impact of NFC on recognition and listening effort for speech in adults and children with SNHL. Within-subject, quasi-experimental study. Participants listened to amplified nonsense words that were (1) frequency-lowered using NFC, (2) low-pass filtered at 5 kHz to simulate the restricted bandwidth (RBW) of conventional hearing aid processing, or (3) low-pass filtered at 10 kHz to simulate extended bandwidth (EBW) amplification. Fourteen children (8-16 yr) and 14 adults (19-65 yr) with mild-to-severe SNHL. Participants listened to speech processed by a hearing aid simulator that amplified input signals to fit a prescriptive target fitting procedure. Participants were blinded to the type of processing. Participants' responses to each nonsense word were analyzed for accuracy and verbal-response time (VRT; listening effort). A multivariate analysis of variance and linear mixed model were used to determine the effect of hearing-aid signal processing on nonsense word recognition and VRT. Both children and adults identified the nonsense words and initial consonants better with EBW and NFC than with RBW. The type of processing did not affect the identification of the vowels or final consonants. There was no effect of age on recognition of the nonsense words, initial consonants, medial vowels, or final consonants. VRT did

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

    PubMed

    Siliciano, Janet D; Siliciano, Robert F

    2016-02-01

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

  11. Pilots' Attention Distributions Between Chasing a Moving Target and a Stationary Target.

    PubMed

    Li, Wen-Chin; Yu, Chung-San; Braithwaite, Graham; Greaves, Matthew

    2016-12-01

    Attention plays a central role in cognitive processing; ineffective attention may induce accidents in flight operations. The objective of the current research was to examine military pilots' attention distributions between chasing a moving target and a stationary target. In the current research, 37 mission-ready F-16 pilots participated. Subjects' eye movements were collected by a portable head-mounted eye-tracker during tactical training in a flight simulator. The scenarios of chasing a moving target (air-to-air) and a stationary target (air-to-surface) consist of three operational phases: searching, aiming, and lock-on to the targets. The findings demonstrated significant differences in pilots' percentage of fixation during the searching phase between air-to-air (M = 37.57, SD = 5.72) and air-to-surface (M = 33.54, SD = 4.68). Fixation duration can indicate pilots' sustained attention to the trajectory of a dynamic target during air combat maneuvers. Aiming at the stationary target resulted in larger pupil size (M = 27,105, SD = 6565), reflecting higher cognitive loading than aiming at the dynamic target (M = 23,864, SD = 8762). Pilots' visual behavior is not only closely related to attention distribution, but also significantly associated with task characteristics. Military pilots demonstrated various visual scan patterns for searching and aiming at different types of targets based on the research settings of a flight simulator. The findings will facilitate system designers' understanding of military pilots' cognitive processes during tactical operations. They will assist human-centered interface design to improve pilots' situational awareness. The application of an eye-tracking device integrated with a flight simulator is a feasible and cost-effective intervention to improve the efficiency and safety of tactical training.Li W-C, Yu C-S, Braithwaite G, Greaves M. Pilots' attention distributions between chasing a moving target and a stationary target. Aerosp Med

  12. Reward circuitry activation reflects social preferences in the face of cognitive effort.

    PubMed

    Sullivan-Toole, Holly; Dobryakova, Ekaterina; DePasque, Samantha; Tricomi, Elizabeth

    2018-06-12

    Research at the intersection of social neuroscience and cognitive effort is an interesting new area for exploration. There is great potential to broaden our understanding of how social context and cognitive effort processes, currently addressed in disparate literatures, interact with one another. In this paper, we briefly review the literature on cognitive effort, focusing on effort-linked valuation and the gap in the literature regarding cognitive effort in the social domain. Next, we present a study designed to explore valuation processes linked to cognitive effort within the social context of an inequality manipulation. More specifically, we created monetary inequality among the participant (SELF, endowed with $50) and two confederates: one also endowed with $50 (OTHER HIGH) and another with only $5 (OTHER LOW). We then scanned participants using fMRI as they attempted to earn bonus payments for themselves and others through a cognitively effortful feedback-based learning task. Positive feedback produced significantly greater activation than negative feedback in key valuation regions, the ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC), both when participants were performing the task on their own behalf and when earning rewards for others. While reward-related activity in the VS was exaggerated for SELF compared to OTHER HIGH for both positive and negative feedback, activity in the vmPFC did not distinguish between recipients in the group-level results. Furthermore, participants naturally fell into two groups: those most engaged when playing for themselves and those who reported engagement for others. While Self-Engaged participants showed differences between the SELF and both OTHER conditions in the VS and vmPFC, Other-Engaged participants only showed an attenuated response to negative feedback for OTHER HIGH compared to SELF in the VS and no differences between recipient conditions in the vmPFC. Together, this work shows the importance of

  13. Enhancing and targeting nucleic acid delivery by magnetic force.

    PubMed

    Plank, Christian; Anton, Martina; Rudolph, Carsten; Rosenecker, Joseph; Krötz, Florian

    2003-08-01

    Insufficient contact of inherently highly active nucleic acid delivery systems with target cells is a primary reason for their often observed limited efficacy. Physical methods of targeting can overcome this limitation and reduce the risk of undesired side effects due to non-target site delivery. The authors and others have developed a novel means of physical targeting, exploiting magnetic force acting on nucleic acid vectors associated with magnetic particles in order to mediate the rapid contact of vectors with target cells. Here, the principles of magnetic drug and nucleic acid delivery are reviewed, and the facts and potentials of the technique for research and therapeutic applications are discussed. Magnetically enhanced nucleic acid delivery - magnetofection - is universally applicable to viral and non-viral vectors, is extraordinarily rapid, simple and yields saturation level transfection at low dose in vitro. The method is useful for site-specific vector targeting in vivo. Exploiting the full potential of the technique requires an interdisciplinary research effort in magnetic field physics, magnetic particle chemistry, pharmaceutical formulation and medical application.

  14. Defining Team Effort Involved in Patient Care from the Primary Care Physician's Perspective.

    PubMed

    Hwang, Andrew S; Atlas, Steven J; Hong, Johan; Ashburner, Jeffrey M; Zai, Adrian H; Grant, Richard W; Hong, Clemens S

    2017-03-01

    A better understanding of the attributes of patients who require more effort to manage may improve risk adjustment approaches and lead to more efficient resource allocation, improved patient care and health outcomes, and reduced burnout in primary care clinicians. To identify and characterize high-effort patients from the physician's perspective. Cohort study. Ninety-nine primary care physicians in an academic primary care network. From a list of 100 randomly selected patients in their panels, PCPs identified patients who required a high level of team-based effort and patients they considered complex. For high-effort patients, PCPs indicated which factors influenced their decision: medical/care coordination, behavioral health, and/or socioeconomic factors. We examined differences in patient characteristics based on PCP-defined effort and complexity. Among 9594 eligible patients, PCPs classified 2277 (23.7 %) as high-effort and 2676 (27.9 %) as complex. Behavioral health issues were the major driver of effort in younger patients, while medical/care coordination issues predominated in older patients. Compared to low-effort patients, high-effort patients were significantly (P < 0.01 for all) more likely to have higher rates of medical (e.g. 23.2 % vs. 6.3 % for diabetes) and behavioral health problems (e.g. 9.8 % vs. 2.9 % for substance use disorder), more frequent primary care visits (10.9 vs. 6.0 visits), and higher acute care utilization rates (25.8 % vs. 7.7 % for emergency department [ED] visits and 15.0 % vs. 3.9 % for hospitalization). Almost one in five (18 %) patients who were considered high-effort were not deemed complex by the same PCPs. Patients defined as high-effort by their primary care physicians, not all of whom were medically complex, appear to have a high burden of psychosocial issues that may not be accounted for in current chronic disease-focused risk adjustment approaches.

  15. Natural selection and the evolution of reproductive effort.

    PubMed

    Hirshfield, M F; Tinkle, D W

    1975-06-01

    Reproductive effort is defined as that proportion of the total energy budget of an organism that is devoted to reproductive processes. Reproductive effort at a given age within a species will be selected to maximize reproductive value at that age. Reproductive effort is not directly affected by changes in juvenile survivorship, nor necessarily reduced by an increase in adult survivorship. Selection for high levels of reproductive effort should occur when extrinsic adult mortality is high, in environments with constant juvenile survivorship, and in good years for juvenile survivorship in a variable environment, provided that the quality of the year is predictable by adults. Data necessary to measure reproductive effort and to understand how selection results in different levels of effort between individuals and species are discussed. We make several predictions about the effect of increased resource availability on reproductive effort. The empirical bases for testing these predictions are presently inadequate, and we consider data on energy budgets of organisms in nature to be essential for such test. We also conclude that variance in life table parameters must be known in detail to understand the selective bases of levels of reproductive effort.

  16. ASME Code Efforts Supporting HTGRs

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

    D.K. Morton

    2010-09-01

    In 1999, an international collaborative initiative for the development of advanced (Generation IV) reactors was started. The idea behind this effort was to bring nuclear energy closer to the needs of sustainability, to increase proliferation resistance, and to support concepts able to produce energy (both electricity and process heat) at competitive costs. The U.S. Department of Energy has supported this effort by pursuing the development of the Next Generation Nuclear Plant, a high temperature gas-cooled reactor. This support has included research and development of pertinent data, initial regulatory discussions, and engineering support of various codes and standards development. This reportmore » discusses the various applicable American Society of Mechanical Engineers (ASME) codes and standards that are being developed to support these high temperature gascooled reactors during construction and operation. ASME is aggressively pursuing these codes and standards to support an international effort to build the next generation of advanced reactors so that all can benefit.« less

  17. ASME Code Efforts Supporting HTGRs

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

    D.K. Morton

    2011-09-01

    In 1999, an international collaborative initiative for the development of advanced (Generation IV) reactors was started. The idea behind this effort was to bring nuclear energy closer to the needs of sustainability, to increase proliferation resistance, and to support concepts able to produce energy (both electricity and process heat) at competitive costs. The U.S. Department of Energy has supported this effort by pursuing the development of the Next Generation Nuclear Plant, a high temperature gas-cooled reactor. This support has included research and development of pertinent data, initial regulatory discussions, and engineering support of various codes and standards development. This reportmore » discusses the various applicable American Society of Mechanical Engineers (ASME) codes and standards that are being developed to support these high temperature gascooled reactors during construction and operation. ASME is aggressively pursuing these codes and standards to support an international effort to build the next generation of advanced reactors so that all can benefit.« less

  18. ASME Code Efforts Supporting HTGRs

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

    D.K. Morton

    2012-09-01

    In 1999, an international collaborative initiative for the development of advanced (Generation IV) reactors was started. The idea behind this effort was to bring nuclear energy closer to the needs of sustainability, to increase proliferation resistance, and to support concepts able to produce energy (both electricity and process heat) at competitive costs. The U.S. Department of Energy has supported this effort by pursuing the development of the Next Generation Nuclear Plant, a high temperature gas-cooled reactor. This support has included research and development of pertinent data, initial regulatory discussions, and engineering support of various codes and standards development. This reportmore » discusses the various applicable American Society of Mechanical Engineers (ASME) codes and standards that are being developed to support these high temperature gascooled reactors during construction and operation. ASME is aggressively pursuing these codes and standards to support an international effort to build the next generation of advanced reactors so that all can benefit.« less

  19. Responding to a significant recruitment challenge within three nationwide psychoeducational trials for cancer patients.

    PubMed

    Stanton, Annette L; Morra, Marion E; Diefenbach, Michael A; Miller, Suzanne M; Slevin Perocchia, Rosemarie; Raich, Peter C; Fleisher, Linda; Wen, Kuang-Yi; Tran, Zung Vu; Mohamed, Nihal E; George, Roshini; Bright, Mary Anne; Marcus, Alfred C

    2013-09-01

    When faced with a significant recruitment challenge for three nationwide psychoeducational trials targeting prostate and breast cancer patients, the Cancer Information Service Research Consortium initiated outreach efforts to increase accrual. Recruitment is reported by major outreach strategy to inform the use of similar campaigns, either as primary recruitment efforts or to supplement "in-reach" recruitment within oncology settings. During a 33-month period, recruitment was tracked from the National Cancer Institute's Cancer Information Service (CIS), the American Cancer Society (ACS), Dr. Susan Love Research Foundation's Love/Avon Army of Women (AOW), Internet advertising, press releases, radio/television interviews, recruitment materials in community venues, and outreach to churches and cancer support organizations. Across projects, the majority (89 %) of recruited participants (N = 2,134) was obtained from the CIS (n = 901, 19 months of recruitment), AOW (n = 869, 18 months), and ACS (n = 123, 12 months). Other efforts showed minimal gain in recruitment. Cancer information programs (e.g., CIS and ACS) and registries of individuals willing to participate in cancer-related research (e.g., AOW) can represent exceptional resources for outreach recruitment of cancer patients, especially when the eligibility criteria are highly restrictive. However, these resources do not yield samples representative of the larger population of adults diagnosed with cancer, and conclusions from such trials must be tempered accordingly. Inadequate recruitment to randomized controlled trials limits the creation of useful interventions for cancer survivors. By enrolling in cancer registries and taking part in research, cancer survivors can contribute to the development of effective resources for the survivor population.

  20. Musculoskeletal pain and effort-reward imbalance--a systematic review.

    PubMed

    Koch, Peter; Schablon, Anja; Latza, Ute; Nienhaus, Albert

    2014-01-15

    Musculoskeletal pain may be triggered by physical strains and psychosocial risk factors. The effort-reward imbalance model (ERI model) is a stress model which measures psychosocial factors in the working world. The question is whether workers with an effort-reward imbalance report musculoskeletal pain more frequently than those with no effort-reward imbalance. A systematic review using a best evidence synthesis approach was conducted to answer this question. A literature search was conducted for the period from 1996 to 2012, using three databases (Pubmed, Embase and PsycINFO). The research criteria related to psychosocial, work-related stress as per the ERI model and to musculoskeletal pain. A quality score was developed using various quality criteria to assess the standard of the studies. The level of evidence was graded as in (Am J Ind Med 39:180-193, 2001). After applying the inclusion criteria, a total of 19 studies were included in the review: 15 cross-sectional studies, three prospective studies and one case-control study. 74% of all studies exhibited good methodological quality, 53% collected data using the original ERI questionnaire, and in 42% of the studies, there was adequate control for physical working conditions. Furthermore, different cut-off points were used to classify exposed and non-exposed individuals. On the basis of 13 studies with a positive, statistically significant association, a moderate level of evidence was inferred for the association between effort-reward imbalance and musculoskeletal pain. The evidence for a role of over-commitment and for its interaction with effort-reward imbalance was rated as inconclusive - on the basis of eight and five studies, respectively. On the basis of the available evidence, no reliable conclusion may be drawn about any association between the psychosocial factors ascertained using the ERI model and musculoskeletal pain. Before a reliable statement can be made on the association between ERI and

  1. Functional-anatomic study of episodic retrieval using fMRI. I. Retrieval effort versus retrieval success.

    PubMed

    Buckner, R L; Koutstaal, W; Schacter, D L; Wagner, A D; Rosen, B R

    1998-04-01

    A number of recent functional imaging studies have identified brain areas activated during tasks involving episodic memory retrieval. The identification of such areas provides a foundation for targeted hypotheses regarding the more specific contributions that these areas make to episodic retrieval. As a beginning effort toward such an endeavor, whole-brain functional magnetic resonance imaging (fMRI) was used to examine 14 subjects during episodic word recognition in a block-designed fMRI experiment. Study conditions were manipulated by presenting either shallow or deep encoding tasks. This manipulation yielded two recognition conditions that differed with regard to retrieval effort and retrieval success: shallow encoding yielded low levels of recognition success with high levels of retrieval effort, and deep encoding yielded high levels of recognition success with low levels of effort. Many brain areas were activated in common by these two recognition conditions compared to a low-level fixation condition, including left and right prefrontal regions often detected during PET episodic retrieval paradigms (e.g., R. L. Buckner et al., 1996, J. Neurosci. 16, 6219-6235) thereby generalizing these findings to fMRI. Characterization of the activated regions in relation to the separate recognition conditions showed (1) bilateral anterior insular regions and a left dorsal prefrontal region were more active after shallow encoding, when retrieval demanded greatest effort, and (2) right anterior prefrontal cortex, which has been implicated in episodic retrieval, was most active during successful retrieval after deep encoding. We discuss these findings in relation to component processes involved in episodic retrieval and in the context of a companion study using event-related fMRI.

  2. Consumption‐Based Conservation Targeting: Linking Biodiversity Loss to Upstream Demand through a Global Wildlife Footprint

    PubMed Central

    Berlow, Eric; Conlisk, Erin; Erb, Karlheinz; Iha, Katsunori; Martinez, Neo; Newman, Erica A.; Plutzar, Christoph; Smith, Adam B.; Harte, John

    2016-01-01

    Abstract Although most conservation efforts address the direct, local causes of biodiversity loss, effective long‐term conservation will require complementary efforts to reduce the upstream economic pressures, such as demands for food and forest products, which ultimately drive these downstream losses. Here, we present a wildlife footprint analysis that links global losses of wild birds to consumer purchases across 57 economic sectors in 129 regions. The United States, India, China, and Brazil have the largest regional wildlife footprints, while per‐person footprints are highest in Mongolia, Australia, Botswana, and the United Arab Emirates. A US$100 purchase of bovine meat or rice products occupies approximately 0.1 km2 of wild bird ranges, displacing 1–2 individual birds, for 1 year. Globally significant importer regions, including Japan, the United Kingdom, Germany, Italy, and France, have large footprints that drive wildlife losses elsewhere in the world and represent important targets for consumption‐focused conservation attention. PMID:29104616

  3. Overview of NASA's Propulsion 21 Effort

    NASA Technical Reports Server (NTRS)

    Long-Davis, Mary Jo

    2006-01-01

    Propulsion 21 technologies contribute to reducing CO2 and NO(x) emissions and noise. Integrated Government/Industry/University research efforts have produced promising initial technical results. Graduate students from 5 partnering universities will benefit from this collaborative research--> educating the future engineering workforce. Phase 2 Efforts scheduled to be completed 3QFY06.

  4. Self-generated persuasion: effects of the target and direction of arguments.

    PubMed

    Briñol, Pablo; McCaslin, Michael J; Petty, Richard E

    2012-05-01

    Previous research has revealed that self-persuasion can occur either through role-playing (i.e., when arguments are generated to convince another person) or, more directly, through trying to convince oneself (i.e., when arguments are generated with oneself as the target). Combining these 2 traditions in the domain of attitude change, the present research investigated the impact on self-persuasion of the specific target of one's own persuasive attempt (i.e., others vs. oneself). We found that the efficacy of self-persuasion depended on whether people believed that they would have to put more or less effort in convincing the self or others. Specifically, we found opposite effects for self-generated arguments depending on whether the topic of persuasion was proattitudinal or counterattitudinal. Across 4 studies, it was shown that when the topic of the message was counterattitudinal, people were more effective in convincing themselves when the intended target of the arguments was themselves versus another person. However, the opposite was the case when the topic was proattitudinal. These effects were shown to stem from the differential effort perceived as necessary and actually exerted in trying to produce persuasion under these conditions.

  5. Spontaneous Effort During Mechanical Ventilation: Maximal Injury With Less Positive End-Expiratory Pressure.

    PubMed

    Yoshida, Takeshi; Roldan, Rollin; Beraldo, Marcelo A; Torsani, Vinicius; Gomes, Susimeire; De Santis, Roberta R; Costa, Eduardo L V; Tucci, Mauro R; Lima, Raul G; Kavanagh, Brian P; Amato, Marcelo B P

    2016-08-01

    We recently described how spontaneous effort during mechanical ventilation can cause "pendelluft," that is, displacement of gas from nondependent (more recruited) lung to dependent (less recruited) lung during early inspiration. Such transfer depends on the coexistence of more recruited (source) liquid-like lung regions together with less recruited (target) solid-like lung regions. Pendelluft may improve gas exchange, but because of tidal recruitment, it may also contribute to injury. We hypothesize that higher positive end-expiratory pressure levels decrease the propensity to pendelluft and that with lower positive end-expiratory pressure levels, pendelluft is associated with improved gas exchange but increased tidal recruitment. Crossover design. University animal research laboratory. Anesthetized landrace pigs. Surfactant depletion was achieved by saline lavage in anesthetized pigs, and ventilator-induced lung injury was produced by ventilation with high tidal volume and low positive end-expiratory pressure. Ventilation was continued in each of four conditions: positive end-expiratory pressure (low or optimized positive end-expiratory pressure after recruitment) and spontaneous breathing (present or absent). Tidal recruitment was assessed using dynamic CT and regional ventilation/perfusion using electric impedance tomography. Esophageal pressure was measured using an esophageal balloon manometer. Among the four conditions, spontaneous breathing at low positive end-expiratory pressure not only caused the largest degree of pendelluft, which was associated with improved ventilation/perfusion matching and oxygenation, but also generated the greatest tidal recruitment. At low positive end-expiratory pressure, paralysis worsened oxygenation but reduced tidal recruitment. Optimized positive end-expiratory pressure decreased the magnitude of spontaneous efforts (measured by esophageal pressure) despite using less sedation, from -5.6 ± 1.3 to -2.0 ± 0.7 cm H2

  6. A model to estimate cost-savings in diabetic foot ulcer prevention efforts.

    PubMed

    Barshes, Neal R; Saedi, Samira; Wrobel, James; Kougias, Panos; Kundakcioglu, O Erhun; Armstrong, David G

    2017-04-01

    Sustained efforts at preventing diabetic foot ulcers (DFUs) and subsequent leg amputations are sporadic in most health care systems despite the high costs associated with such complications. We sought to estimate effectiveness targets at which cost-savings (i.e. improved health outcomes at decreased total costs) might occur. A Markov model with probabilistic sensitivity analyses was used to simulate the five-year survival, incidence of foot complications, and total health care costs in a hypothetical population of 100,000 people with diabetes. Clinical event and cost estimates were obtained from previously-published trials and studies. A population without previous DFU but with 17% neuropathy and 11% peripheral artery disease (PAD) prevalence was assumed. Primary prevention (PP) was defined as reducing initial DFU incidence. PP was more than 90% likely to provide cost-savings when annual prevention costs are less than $50/person and/or annual DFU incidence is reduced by at least 25%. Efforts directed at patients with diabetes who were at moderate or high risk for DFUs were very likely to provide cost-savings if DFU incidence was decreased by at least 10% and/or the cost was less than $150 per person per year. Low-cost DFU primary prevention efforts producing even small decreases in DFU incidence may provide the best opportunity for cost-savings, especially if focused on patients with neuropathy and/or PAD. Mobile phone-based reminders, self-identification of risk factors (ex. Ipswich touch test), and written brochures may be among such low-cost interventions that should be investigated for cost-savings potential. Published by Elsevier Inc.

  7. Partnering against cancer today: a blueprint for coordinating efforts through communication science.

    PubMed

    Hesse, Bradford W; Cole, Galen E; Powe, Barbara D

    2013-12-01

    One of the hallmarks of the communication revolution over the past decade has been its support for participation, whether that be in the active engagement of patients searching the Web for answers to vital health questions, or in the collective energies of self-organizing communities through social media. At the same time, some of the major obstacles to achieving a full and equitable reach of evidence-based cancer control knowledge have been traced back to discontinuities in communication either within clinical care or the broader public awareness system. Communication scientists from the National Cancer Institute, the Centers for Disease Control and Prevention, and the American Cancer Society joined forces in 2010 to investigate ways in which communication science can be used to improve coordination and enhance participation in cancer control for the nation. From 2010 to 2013, the three organizations worked together in 1) convening two meetings designed to assess the status of funded research in communication science, 2) completing a systematic review of literature published over the previous 10 years, and 3) authoring a blueprint for coordinated efforts using the implications of communication science. The blueprint consists of three major goals: first, to identify high-yield targets of opportunity using the health impact pyramid articulated by Centers for Disease Control and Prevention Director, Thomas Frieden; second, to leverage opportunities within the new communication environment, including the opportunities catalyzed by national efforts to create an infrastructure for evidence implementation through health information technology; and third, to assist in coordinating efforts across collaborative entities through participative media.

  8. Partnering Against Cancer Today: A Blueprint for Coordinating Efforts Through Communication Science

    PubMed Central

    2013-01-01

    One of the hallmarks of the communication revolution over the past decade has been its support for participation, whether that be in the active engagement of patients searching the Web for answers to vital health questions, or in the collective energies of self-organizing communities through social media. At the same time, some of the major obstacles to achieving a full and equitable reach of evidence-based cancer control knowledge have been traced back to discontinuities in communication either within clinical care or the broader public awareness system. Communication scientists from the National Cancer Institute, the Centers for Disease Control and Prevention, and the American Cancer Society joined forces in 2010 to investigate ways in which communication science can be used to improve coordination and enhance participation in cancer control for the nation. From 2010 to 2013, the three organizations worked together in 1) convening two meetings designed to assess the status of funded research in communication science, 2) completing a systematic review of literature published over the previous 10 years, and 3) authoring a blueprint for coordinated efforts using the implications of communication science. The blueprint consists of three major goals: first, to identify high-yield targets of opportunity using the health impact pyramid articulated by Centers for Disease Control and Prevention Director, Thomas Frieden; second, to leverage opportunities within the new communication environment, including the opportunities catalyzed by national efforts to create an infrastructure for evidence implementation through health information technology; and third, to assist in coordinating efforts across collaborative entities through participative media. PMID:24395998

  9. Strategic targeting of advance care planning interventions: the Goldilocks phenomenon.

    PubMed

    Billings, J Andrew; Bernacki, Rachelle

    2014-04-01

    Strategically selecting patients for discussions and documentation about limiting life-sustaining treatments-choosing the right time along the end-of-life trajectory for such an intervention and identifying patients at high risk of facing end-of-life decisions-can have a profound impact on the value of advance care planning (ACP) efforts. Timing is important because the completion of an advance directive (AD) too far from or too close to the time of death can lead to end-of-life decisions that do not optimally reflect the patient's values, goals, and preferences: a poorly chosen target patient population that is unlikely to need an AD in the near future may lead to patients making unrealistic, hypothetical choices, while assessing preferences in the emergency department or hospital in the face of a calamity is notoriously inadequate. Because much of the currently studied ACP efforts have led to a disappointingly small proportion of patients eventually benefitting from an AD, careful targeting of the intervention should also improve the efficacy of such projects. A key to optimal timing and strategic selection of target patients for an ACP program is prognostication, and we briefly highlight prognostication tools and studies that may point us toward high-value AD interventions.

  10. Disease mapping for informing targeted health interventions: childhood pneumonia in Bohol, Philippines.

    PubMed

    Thomas, Deborah S K; Anthamatten, Peter; Root, Elisabeth Dowling; Lucero, Marilla; Nohynek, Hanna; Tallo, Veronica; Williams, Gail M; Simões, Eric A F

    2015-11-01

    Acute lower respiratory tract infections (ALRI) are the leading cause of childhood mortality worldwide. Currently, most developing countries assign resources at a district level, and yet District Medical Officers have few tools for directing targeted interventions to high mortality or morbidity areas. Mapping of ALRI at the local level can guide more efficient allocation of resources, coordination of efforts and targeted interventions, which are particularly relevant for health management in resource-scarce settings. An efficacy study of 11-valent pneumococcal vaccine was conducted in six municipalities in the Bohol Province of central Philippines from July 2000 to December 2004. Geocoded under-five pneumonia cases (using WHO classifications) were mapped to create spatial patterns of pneumonia at the local health unit (barangay) level. There were 2951 children with WHO-defined clinical pneumonia, of whom 1074 were severe or very severely ill, 278 were radiographic, and 219 were hypoxaemic. While most children with pneumonia were from urban barangays, there was a disproportionately higher distribution of severe/very severe pneumonia in rural barangays and the most severe hypoxaemic children were concentrated in the northern barangays most distant from the regional hospital. Mapping of ALRI at the local administrative health level can be performed relatively simply. If these principles are applied to routinely collected IMCI classification of disease at the district level in developing countries, such efforts can form the basis for directing public health and healthcare delivery efforts in a targeted manner. © 2015 John Wiley & Sons Ltd.

  11. Sodium intake reduction efforts in Lebanon

    PubMed Central

    Almedawar, Mohamad M.; Nasreddine, Lara; Olabi, Ammar; Hamade, Haya; Awad, Elie; Toufeili, Imad; Arnaout, Samir

    2015-01-01

    Sodium intake reduction efforts in Lebanon are quite recent and have just started to take effect on the national level. Starting out from an academic institution, the Lebanese Action on Sodium and Health (LASH) campaign was established to counter the increasing prevalence of hypertension and associated adverse health effects. The campaign’s strategy was based on four pillars: research, health communication, advocacy, and monitoring. The LASH group set out with determining: baseline sodium intake of the population, main sources of sodium intake, and the knowledge, attitudes, and behaviors (KAB) of the population as a situation analysis that prompts for action. This gave LASH tangible evidence of the magnitude of the problem and the need for the government, the food industry, and the consumers, to be mobilized to take part in devising a solution. Currently, Lebanon is at a stage of technically working to reduce the sodium content in the major sources of sodium, namely local bread and bread-like products. The next steps will include implementation of a plan for monitoring industry compliance, while studying other food targets, including dairy products and processed meat. Meanwhile, the health communication plan is ongoing and the Salt Awareness Week is celebrated every year with media appearances of LASH researchers to raise the issue to the public eye. PMID:26090328

  12. Impacts on terrestrial biodiversity of moving from a 2°C to a 1.5°C target

    NASA Astrophysics Data System (ADS)

    Smith, Pete; Price, Jeff; Molotoks, Amy; Warren, Rachel; Malhi, Yadvinder

    2018-05-01

    We applied a recently developed tool to examine the reduction in climate risk to biodiversity in moving from a 2°C to a 1.5°C target. We then reviewed the recent literature examining the impact of (a) land-based mitigation options and (b) land-based greenhouse gas removal options on biodiversity. We show that holding warming to 1.5°C versus 2°C can significantly reduce the number of species facing a potential loss of 50% of their climatic range. Further, there would be an increase of 5.5-14% of the globe that could potentially act as climatic refugia for plants and animals, an area equivalent to the current global protected area network. Efforts to meet the 1.5°C target through mitigation could largely be consistent with biodiversity protection/enhancement. For impacts of land-based greenhouse gas removal technologies on biodiversity, some (e.g. soil carbon sequestration) could be neutral or positive, others (e.g. bioenergy with carbon capture and storage) are likely to lead to conflicts, while still others (e.g. afforestation/reforestation) are context-specific, when applied at scales necessary for meaningful greenhouse gas removal. Additional effort to meet the 1.5°C target presents some risks, particularly if inappropriately managed, but it also presents opportunities. This article is part of the theme issue `The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.

  13. Using habitat suitability models to target invasive plant species surveys

    USGS Publications Warehouse

    Crall, Alycia W.; Jarnevich, Catherine S.; Panke, Brendon; Young, Nick; Renz, Mark; Morisette, Jeffrey

    2013-01-01

    Managers need new tools for detecting the movement and spread of nonnative, invasive species. Habitat suitability models are a popular tool for mapping the potential distribution of current invaders, but the ability of these models to prioritize monitoring efforts has not been tested in the field. We tested the utility of an iterative sampling design (i.e., models based on field observations used to guide subsequent field data collection to improve the model), hypothesizing that model performance would increase when new data were gathered from targeted sampling using criteria based on the initial model results. We also tested the ability of habitat suitability models to predict the spread of invasive species, hypothesizing that models would accurately predict occurrences in the field, and that the use of targeted sampling would detect more species with less sampling effort than a nontargeted approach. We tested these hypotheses on two species at the state scale (Centaurea stoebe and Pastinaca sativa) in Wisconsin (USA), and one genus at the regional scale (Tamarix) in the western United States. These initial data were merged with environmental data at 30-m2 resolution for Wisconsin and 1-km2 resolution for the western United States to produce our first iteration models. We stratified these initial models to target field sampling and compared our models and success at detecting our species of interest to other surveys being conducted during the same field season (i.e., nontargeted sampling). Although more data did not always improve our models based on correct classification rate (CCR), sensitivity, specificity, kappa, or area under the curve (AUC), our models generated from targeted sampling data always performed better than models generated from nontargeted data. For Wisconsin species, the model described actual locations in the field fairly well (kappa = 0.51, 0.19, P 2) = 47.42, P < 0.01). From these findings, we conclude that habitat suitability models can be

  14. Assessing the efficacy of rescue equipment in lifeguard resuscitation efforts for drowning.

    PubMed

    Barcala-Furelos, Roberto; Szpilman, David; Palacios-Aguilar, Jose; Costas-Veiga, Javier; Abelairas-Gomez, Cristian; Bores-Cerezal, Antonio; López-García, Sergio; Rodríguez-Nuñez, Antonio

    2016-03-01

    The whole drowning process usually occurs within seconds to a few minutes. An early rescue may stop and/or prevent most medical complications. Fins, rescue tube, and rescue board (RB) are the equipment most frequently used by lifeguards. Our objective was to compare, in a water rescue quasiexperimental trial, these different pieces of rescue equipment to define the safest and with the lower rescue time as well as to assess their effects on the lifeguards' physiological state and cardiopulmonary resuscitation (CPR) performance. A controlled trial was conducted to study the time effect of 4 different rescue techniques and assess CPR quality, along with the physiological effects of each rescue technique (blood lactate and subjective Borg's scale effort perception) on 35 lifeguards. Among the final sample subjects (n = 23), a total of 92 rescues were completed. Total water rescue time was longer without equipment (NE). The total rescue time was significantly lower using RB (P < .001). Similar good quality of CPR before and after water rescue was observed in all trials (P > .05), although correct ventilations represented less than 50% of total in all trials. Blood lactate increased after all rescues. The subjective effort Borg's scale showed significantly less effort using RB vs without equipment, fins, and fins and rescue tube. The use of propelling and/or floating equipment saves precious time with repercussions in the reduction of drowning mortality and morbidity. The RB offers a significant advantage. Lifeguards need more CPR training, especially considering the importance of efficient ventilations for drowning victims. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Efforts to improve international migration statistics: a historical perspective.

    PubMed

    Kraly, E P; Gnanasekaran, K S

    1987-01-01

    During the past decade, the international statistical community has made several efforts to develop standards for the definition, collection and publication of statistics on international migration. This article surveys the history of official initiatives to standardize international migration statistics by reviewing the recommendations of the International Statistical Institute, International Labor Organization, and the UN, and reports a recently proposed agenda for moving toward comparability among national statistical systems. Heightening awareness of the benefits of exchange and creating motivation to implement international standards requires a 3-pronged effort from the international statistical community. 1st, it is essential to continue discussion about the significance of improvement, specifically standardization, of international migration statistics. The move from theory to practice in this area requires ongoing focus by migration statisticians so that conformity to international standards itself becomes a criterion by which national statistical practices are examined and assessed. 2nd, the countries should be provided with technical documentation to support and facilitate the implementation of the recommended statistical systems. Documentation should be developed with an understanding that conformity to international standards for migration and travel statistics must be achieved within existing national statistical programs. 3rd, the call for statistical research in this area requires more efforts by the community of migration statisticians, beginning with the mobilization of bilateral and multilateral resources to undertake the preceding list of activities.

  16. Agency attributions of mental effort during self-regulated learning.

    PubMed

    Koriat, Asher

    2018-04-01

    Previous results suggest that the monitoring of one's own performance during self-regulated learning is mediated by self-agency attributions and that these attributions can be influenced by poststudy effort-framing instructions. These results pose a challenge to the study of issues of self-agency in metacognition when the objects of self-regulation are mental operations rather than motor actions that have observable outcomes. When participants studied items in Experiment 1 under time pressure, they invested greater study effort in the easier items in the list. However, the effects of effort framing were the same as when learners typically invest more study effort in the more difficult items: Judgments of learning (JOLs) decreased with effort when instructions biased the attribution of effort to nonagentic sources but increased when they biased attribution to agentic sources. However, the effects of effort framing were constrained by parameters of the study task: Interitem differences in difficulty constrained the attribution of effort to agentic regulation (Experiment 2) whereas interitem differences in the incentive for recall constrained the attribution of effort to nonagentic sources (Experiment 3). The results suggest that the regulation and attribution of effort during self-regulated learning occur within a module that is dissociated from the learner's superordinate agenda but is sensitive to parameters of the task. A model specifies the stage at which effort framing affects the effort-JOL relationship by biasing the attribution of effort to agentic or nonagentic sources. The potentialities that exist in metacognition for the investigation of issues of self-agency are discussed.

  17. Deorphaning the Macromolecular Targets of the Natural Anticancer Compound Doliculide.

    PubMed

    Schneider, Gisbert; Reker, Daniel; Chen, Tao; Hauenstein, Kurt; Schneider, Petra; Altmann, Karl-Heinz

    2016-09-26

    The cyclodepsipeptide doliculide is a marine natural product with strong actin-polymerizing and anticancer activities. Evidence for doliculide acting as a potent and subtype-selective antagonist of prostanoid E receptor 3 (EP3) is presented. Computational target prediction suggested that this membrane receptor is a likely macromolecular target and enabled immediate in vitro validation. This proof-of-concept study demonstrates the in silico deorphanization of phenotypic screening hits as a viable concept for future natural-product-inspired chemical biology and drug discovery efforts. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Recent Advances in Targeted Therapy for Glioma.

    PubMed

    Lin, Lin; Cai, Jinquan; Jiang, Chuanlu

    2017-01-01

    Gliomas are the most common primary malignant brain tumors, which have a universally fatal outcome. Current standard treatment for glioma patients is surgical removal followed by radiotherapy and adjuvant chemotherapy. Due to therapeutic resistance and tumor recurrence, efforts are ongoing to identify the molecules that are fundamental to regulate the tumor progression and provide additional methods for individual treatment of glioma patients. By studying the initiation and maintenance of glioma, studies focused on the targets of tyrosine kinase receptors including EGFR, PDGFR and other crucial signal pathways such as PI3K/AKT and RAS/RAF/MAPK pathway. Furthermore, recent advances in targeting immunotherapy and stem cell therapy also brought numerous strategies to glioma treatment. This article reviewed the researches focused on the advanced strategies of various target therapies for improving the glioma treatment efficacy, and discussed the challenges and future directions for glioma therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Measuring Cycling Effort.

    ERIC Educational Resources Information Center

    Jahnke, Thomas; Hamson, Mike

    1999-01-01

    Investigates the basic mechanics of cycling with a simple reckoning of how much effort is needed from the cyclist. The work done by the cyclist is quantified when the ride is on the flat and also when pedaling uphill. Proves that by making use of the available gears on a mountain bike, cycling uphill can be accomplished without pain. (Author/ASK)

  20. New Horizons Launch Contingency Effort

    NASA Astrophysics Data System (ADS)

    Chang, Yale; Lear, Matthew H.; McGrath, Brian E.; Heyler, Gene A.; Takashima, Naruhisa; Owings, W. Donald

    2007-01-01

    On 19 January 2006 at 2:00 PM EST, the NASA New Horizons spacecraft (SC) was launched from the Cape Canaveral Air Force Station (CCAFS), FL, onboard an Atlas V 551/Centaur/STAR™ 48B launch vehicle (LV) on a mission to explore the Pluto Charon planetary system and possibly other Kuiper Belt Objects. It carried a single Radioisotope Thermoelectric Generator (RTG). As part of the joint NASA/US Department of Energy (DOE) safety effort, contingency plans were prepared to address the unlikely events of launch accidents leading to a near-pad impact, a suborbital reentry, an orbital reentry, or a heliocentric orbit. As the implementing organization. The Johns Hopkins University Applied Physics Laboratory (JHU/APL) had expanded roles in the New Horizons launch contingency effort over those for the Cassini mission and Mars Exploration Rovers missions. The expanded tasks included participation in the Radiological Control Center (RADCC) at the Kennedy Space Center (KSC), preparation of contingency plans, coordination of space tracking assets, improved aerodynamics characterization of the RTG's 18 General Purpose Heat Source (GPHS) modules, and development of spacecraft and RTG reentry breakup analysis tools. Other JHU/APL tasks were prediction of the Earth impact footprints (ElFs) for the GPHS modules released during the atmospheric reentry (for purposes of notification and recovery), prediction of the time of SC reentry from a potential orbital decay, pre-launch dissemination of ballistic coefficients of various possible reentry configurations, and launch support of an Emergency Operations Center (EOC) on the JHU/APL campus. For the New Horizons launch, JHU/APL personnel at the RADCC and at the EOC were ready to implement any real-time launch contingency activities. A successful New Horizons launch and interplanetary injection precluded any further contingency actions. The New Horizons launch contingency was an interagency effort by several organizations. This paper

  1. Diagnostic Performance of Multiparametric Magnetic Resonance Imaging and Fusion Targeted Biopsy to Detect Significant Prostate Cancer.

    PubMed

    Hoffmann, Manuela A; Taymoorian, Kasra; Ruf, Christian; Gerhards, Arnd; Leyendecker, Karlheinz; Stein, Thomas; Jakobs, Frank M; Schreckenberger, Mathias

    2017-12-01

    Multiparametric magnetic resonance imaging combined with ultrasound-fusion-targeted biopsy of the prostate intends to increase diagnostic precision, which has to be clarified. We performed multiparametric magnetic resonance imaging followed by ultrasound-fusion-guided perineal biopsy in 99 male patients with elevated prostate-specific-antigen and previous negative standard biopsy-procedures. In 33/99 patients (33%) no malignancy could be confirmed by histopathology. Low-grade carcinomas (Gleason-Score 6+7a) were found in 42/66 (64%) and high-grade carcinomas (Gleason-Score ≥7b) in 24/66 (36%) men. A high-grade carcinoma corresponded to PI-RADS 4 or 5 (suspected malignancy) in 21/24 cases, which accounted for a sensitivity of 88% and negative-predictive-value of 85% (p=0.002). Differentiation between high-/low-grade carcinomas (Gleason-Score ≤7a vs. ≥7b) by means of PI-RADS related to a sensitivity of 88% and a negative-predictive-value of 70% (p=0.74). The results support the view that multiparametric magnetic resonance imaging/ultrasound-fusion-guided biopsy promotes considerably higher detection rates of clinically relevant prostate malignancies than do conventional diagnostic procedures. With regard to differentiation between high- and low-grade carcinomas, no significant difference was demonstrated. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. Targeting targeted agents: open issues for clinical trial design.

    PubMed

    Bria, Emilio; Di Maio, Massimo; Carlini, Paolo; Cuppone, Federica; Giannarelli, Diana; Cognetti, Francesco; Milella, Michele

    2009-05-22

    Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

  3. Protein tyrosine phosphatases as potential therapeutic targets

    PubMed Central

    He, Rong-jun; Yu, Zhi-hong; Zhang, Ruo-yu; Zhang, Zhong-yin

    2014-01-01

    Protein tyrosine phosphorylation is a key regulatory process in virtually all aspects of cellular functions. Dysregulation of protein tyrosine phosphorylation is a major cause of human diseases, such as cancers, diabetes, autoimmune disorders, and neurological diseases. Indeed, protein tyrosine phosphorylation-mediated signaling events offer ample therapeutic targets, and drug discovery efforts to date have brought over two dozen kinase inhibitors to the clinic. Accordingly, protein tyrosine phosphatases (PTPs) are considered next-generation drug targets. For instance, PTP1B is a well-known targets of type 2 diabetes and obesity, and recent studies indicate that it is also a promising target for breast cancer. SHP2 is a bona-fide oncoprotein, mutations of which cause juvenile myelomonocytic leukemia, acute myeloid leukemia, and solid tumors. In addition, LYP is strongly associated with type 1 diabetes and many other autoimmune diseases. This review summarizes recent findings on several highly recognized PTP family drug targets, including PTP1B, Src homology phosphotyrosyl phosphatase 2(SHP2), lymphoid-specific tyrosine phosphatase (LYP), CD45, Fas associated phosphatase-1 (FAP-1), striatal enriched tyrosine phosphatases (STEP), mitogen-activated protein kinase/dual-specificity phosphatase 1 (MKP-1), phosphatases of regenerating liver-1 (PRL), low molecular weight PTPs (LMWPTP), and CDC25. Given that there are over 100 family members, we hope this review will serve as a road map for innovative drug discovery targeting PTPs. PMID:25220640

  4. The opportunity cost of time modulates cognitive effort.

    PubMed

    Otto, A Ross; Daw, Nathaniel D

    2018-05-08

    A spate of recent work demonstrates that humans seek to avoid the expenditure of cognitive effort, much like physical effort or economic resources. Less is clear, however, about the circumstances dictating how and when people decide to expend cognitive effort. Here we adopt a popular theory of opportunity costs and response vigor and to elucidate this question. This account, grounded in Reinforcement Learning, formalizes a trade-off between two costs: the harder work assumed necessary to emit faster actions and the opportunity cost inherent in acting more slowly (i.e., the delay that results to the next reward and subsequent rewards). Recent work reveals that the opportunity cost of time-operationalized as the average reward rate per unit time, theorized to be signaled by tonic dopamine levels, modulates the speed with which a person responds in a simple discrimination tasks. We extend this framework to cognitive effort in a diverse range of cognitive tasks, for which 1) the amount of cognitive effort demanded from the task varies from trial to trial and 2) the putative expenditure of cognitive effort holds measureable consequences in terms of accuracy and response time. In the domains of cognitive control, perceptual decision-making, and task-switching, we found that subjects tuned their level of effort exertion in accordance with the experienced average reward rate: when the opportunity cost of time was high, subjects made more errors and responded more quickly, which we interpret as a withdrawal of cognitive effort. That is, expenditure of cognitive effort appeared to be modulated by the opportunity cost of time. Further, and consistent with our account, the strength of this modulation was predicted by individual differences in efficacy of cognitive control. Taken together, our results elucidate the circumstances dictating how and when people expend cognitive effort. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Characterization of reward and effort mechanisms in apathy

    PubMed Central

    Bonnelle, Valerie; Veromann, Kai-Riin; Burnett Heyes, Stephanie; Lo Sterzo, Elena; Manohar, Sanjay; Husain, Masud

    2015-01-01

    Apathy is a common but poorly understood condition with a wide societal impact observed in several brain disorders as well as, to some extent, in the normal population. Hence the need for better characterization of the underlying mechanisms. The processes by which individuals decide to attribute physical effort to obtain rewards might be particularly relevant to relate to apathy traits. Here, we designed two paradigms to assess individual differences in physical effort production and effort-based decision-making and their relation to apathy in healthy people. Apathy scores were measured using a modified version of the Lille Apathy Rating Scale, suitable for use in a non-clinical population. In the first study, apathy scores were correlated with the degree to which stake (reward on offer) and difficulty level impacts on physical effort production. Individuals with relatively high apathy traits showed an increased modulation of effort while more motivated individuals generally exerted greater force across different levels of stake. To clarify the underlying mechanisms for this behavior, we designed a second task that allows independent titration of stake and effort levels for which subjects are willing to engage in an effortful response to obtain a reward. Our results suggest that apathy traits in the normal population are related to the way reward subjectively affects the estimation of effort costs, and more particularly manifest as decreased willingness to exert effort when rewards are small, or below threshold. The tasks we introduce here may provide useful tools to further investigate apathy in clinical populations. PMID:24747776

  6. Vocal effort and voice handicap among teachers.

    PubMed

    Sampaio, Márcio Cardoso; dos Reis, Eduardo José Farias Borges; Carvalho, Fernando Martins; Porto, Lauro Antonio; Araújo, Tânia Maria

    2012-11-01

    The relationship between voice handicap and professional vocal effort was investigated among teachers in a cross-sectional study of census nature on 4496 teachers within the public elementary education network in Salvador, Bahia, Brazil. Voice handicap (the outcome of interest) was evaluated using the Voice Handicap Index 10. The main exposure, the lifetime vocal effort index, was obtained as the product of the number of years working as a teacher multiplied by the mean weekly working hours. The prevalence of voice handicap was 28.8% among teachers with high professional vocal effort and 21.3% among those with acceptable vocal effort, thus yielding a crude prevalence ratio (PR) of 1.36 (95% confidence interval [CI]=1.14-1.61). In the final logistic model, the prevalence of voice handicap was statistically associated with the professional vocal effort index (PR=1.47; 95% CI=1.19-1.82), adjusted according to sex, microphone availability in the classroom, excessive noise, pressure from the school management, heartburn, and rhinitis. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  7. Polarized Solid State Target

    NASA Astrophysics Data System (ADS)

    Dutz, Hartmut; Goertz, Stefan; Meyer, Werner

    2017-01-01

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

  8. Attention, effort, and fatigue: Neuropsychological perspectives

    NASA Technical Reports Server (NTRS)

    Cohen, Ronald A.; Odonnell, Brian F.

    1988-01-01

    Models of attention, effort, and fatigue are reviewed. Methods are discussed for measuring these phenomena from a neuropsychological and psychophysiological perspective. The following methodologies are included: (1) the autonomic measurement of cognitive effort and quality of encoding; (2) serial assessment approaches to neurophysiological assessment; and (3) the assessment of subjective reports of fatigue using multidimensional ratings and their relationship to neurobehavioral measures.

  9. Genomic profiling in a homogeneous molecular subtype of non-small cell lung cancer: An effort to explore new drug targets.

    PubMed

    Veldore, Vidya H; Patil, S; Satheesh, C T; Shashidhara, H P; Tejaswi, R; Prabhudesai, Shilpa A; Krishnamoorthy, N; Hazarika, D; Naik, R; Rao, Raghavendra M; Ajai Kumar, B S

    2015-01-01

    Patients' who are positive for kinase domain activating mutations in epidermal growth factor receptor (EGFR) gene, constitute 30-40% of non-small cell lung cancer (NSCLC), and are suitable candidates for Tyrosine Kinase Inhibitor based targeted/personalized therapy. In EGFR non-mutated subset, 8-10% that show molecular abnormalities such as EML4-ALK, ROS1-ALK, KIP4-ALK, may also derive the benefit of targeted therapy. However, 40% of NSCLC belong to a grey zone of tumours that are negative for the clinically approved biomarkers for personalized therapy. This pilot study aims to identify and classify molecular subtypes of this group to address the un-met need for new drug targets in this category. Here we screened for known/novel oncogenic driver mutations using a 46 gene Ampliseq Panel V1.0 that includes Ser/Thr/Tyr kinases, transcription factors and tumor suppressors. NSCLC with tumor burden of at least 40% on histopathology were screened for 29 somatic mutations in the EGFR kinase domain by real-time polymerase chain reaction methods. 20 cases which were EGFR non-mutated for TK domain mutations were included in this study. DNA Quality was verified from each of the 20 cases by fluorimeter, pooled and subjected to targeted re-sequencing in the Ion Torrent platform. Torrent Suite software was used for next generation sequencing raw data processing and variant calling. The clinical relevance and pathological role of all the mutations/variants that include SNPs and Indels was assessed using polyphen-2/SIFT/PROVEAN/mutation assessor structure function prediction programs. There were 10 pathogenic mutations in six different oncogenes for which annotation was available in the COSMIC database; C420R mutation in PIK3CA, Q472H mutation in vascular endothelial growth factor receptor 2 (VEGFR2) (KDR), C630W and C634R in RET, K367M mutation in fibroblast growth factor receptor 2 (FGFR2), G12C in KRAS and 4 pathogenic mutations in TP53 in the DNA binding domain (E285K, R213L, R

  10. Characteristics of physicians targeted by the pharmaceutical industry to participate in e-detailing.

    PubMed

    Alkhateeb, Fadi M; Khanfar, Nile M; Doucette, William R; Loudon, David

    2009-01-01

    Electronic detailing (e-detailing) has been introduced in the last few years by the pharmaceutical industry as a new communication channel through which to promote pharmaceutical products to physicians. E-detailing involves using digital technology, such as Internet, video conferencing, and interactive voice response, by which drug companies target their marketing efforts toward specific physicians with pinpoint accuracy. A mail survey of 671 Iowa physicians was used to gather information about the physician characteristics and practice setting characteristics of those who are usually targeted by pharmaceutical companies to participate in e-detailing. A model is developed and tested to explain firms' targeting strategy for targeting physicians for e-detailing.

  11. 48 CFR 1511.011-73 - Level of effort.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Level of effort. 1511.011... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS 1511.011-73 Level of effort. The Contracting Officer shall insert the clause at 1552.211-73, Level of Effort, in term form contracts. ...

  12. SETI target selection.

    PubMed

    Latham, D W; Soderblom, D R

    1995-01-01

    The NASA High Resolution Microwave Survey consists of two complementary elements: a Sky Survey of the entire sky to a moderate level of sensitivity; and a Targeted Search of nearby stars, one at a time, to a much deeper level of sensitivity. In this paper we propose strategies for target selection. We have two goals: to improve the chances of successful detection of signals from technical civilizations that inhabit planets around solar-type stars, and to minimize the chances of missing signals from unexpected sites. For the main Targeted Search survey of approximately 1000 nearby solar-type stars, we argue that the selection criteria should be heavily biased by what we know about the origin and evolution of life here on Earth. We propose that observations of stars with stellar companions orbiting near the habitable zone should be de-emphasized, because such companions would prevent the formation of habitable planets. We also propose that observations of stars younger than about three billion years should be de-emphasized in favor of older stars, because our own technical civilization took longer than three billion years to evolve here on Earth. To provide the information needed for the preparation of specific target lists, we have undertaken an inventory of a large sample of solar-type stars out to a distance of 60 pc, with the goal of characterizing the relevant astrophysical properties of these stars, especially their ages and companionship. To complement the main survey, we propose that a modest sample of the nearest stars should be observed without any selection biases whatsoever. Finally, we argue that efforts to identify stars with planetary systems should be expanded. If found, such systems should receive intensive scrutiny.

  13. High-efficiency-release targets for use at ISOL facilities: computational design

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Alton, G. D.

    1999-12-01

    This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat-removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated-vitreous-carbon fiber (RVCF) or carbon-bonded-carbon fiber (CBCF) to form highly permeable composite target matrices. Computational studies that simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived from diffusion release-rate simulation studies for selected targets and thermal analyses of temperature distributions within a prototype target/heat-sink system subjected to primary ion beam irradiation are presented in this report.

  14. The role of the striatum in effort-based decision-making in the absence of reward.

    PubMed

    Schouppe, Nathalie; Demanet, Jelle; Boehler, Carsten N; Ridderinkhof, K Richard; Notebaert, Wim

    2014-02-05

    Decision-making involves weighing costs against benefits, for instance, in terms of the effort it takes to obtain a reward of a given magnitude. This evaluation process has been linked to the dorsal anterior cingulate cortex (dACC) and the striatum, with activation in these brain structures reflecting the discounting effect of effort on reward. Here, we investigate how cognitive effort influences neural choice processes in the absence of an extrinsic reward. Using functional magnetic resonance imaging in humans, we used an effort-based decision-making task in which participants were required to choose between two options for a subsequent flanker task that differed in the amount of cognitive effort. Cognitive effort was manipulated by varying the proportion of incongruent trials associated with each choice option. Choice-locked activation in the striatum was higher when participants chose voluntarily for the more effortful alternative but displayed the opposite trend on forced-choice trials. The dACC revealed a similar, yet only trend-level significant, activation pattern. Our results imply that activation levels in the striatum reflect a cost-benefit analysis, in which a balance is made between effort discounting and the intrinsic motivation to choose a cognitively challenging task. Moreover, our findings indicate that it matters whether this challenge is voluntarily chosen or externally imposed. As such, the present findings contrast with classical findings on effort discounting that found reductions in striatum activation for higher effort by finding enhancements of the same neural circuits when a cognitively challenging task is voluntarily selected and does not entail the danger of losing reward.

  15. Emerging Paradigm of Intracellular Targeting of G Protein-Coupled Receptors.

    PubMed

    Chaturvedi, Madhu; Schilling, Justin; Beautrait, Alexandre; Bouvier, Michel; Benovic, Jeffrey L; Shukla, Arun K

    2018-05-04

    G protein-coupled receptors (GPCRs) recognize a diverse array of extracellular stimuli, and they mediate a broad repertoire of signaling events involved in human physiology. Although the major effort on targeting GPCRs has typically been focused on their extracellular surface, a series of recent developments now unfold the possibility of targeting them from the intracellular side as well. Allosteric modulators binding to the cytoplasmic surface of GPCRs have now been described, and their structural mechanisms are elucidated by high-resolution crystal structures. Furthermore, pepducins, aptamers, and intrabodies targeting the intracellular face of GPCRs have also been successfully utilized to modulate receptor signaling. Moreover, small molecule compounds, aptamers, and synthetic intrabodies targeting β-arrestins have also been discovered to modulate GPCR endocytosis and signaling. Here, we discuss the emerging paradigm of intracellular targeting of GPCRs, and outline the current challenges, potential opportunities, and future outlook in this particular area of GPCR biology. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Polysaccharide-based micro/nanocarriers for oral colon-targeted drug delivery.

    PubMed

    Zhang, Lin; Sang, Yuan; Feng, Jing; Li, Zhaoming; Zhao, Aili

    2016-08-01

    Oral colon-targeted drug delivery has attracted many researchers because of its distinct advantages of increasing the bioavailability of the drug at the target site and reducing the side effects. Polysaccharides that are precisely activated by the physiological environment of the colon hold greater promise for colon targeting. Considerable research efforts have been directed towards developing polysaccharide-based micro/nanocarriers. Types of polysaccharides for colon targeting and in vitro/in vivo assessments of polysaccharide-based carriers for oral colon-targeted drug delivery are summarised. Polysaccharide-based microspheres have gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon (colon cancer, inflammatory bowel disease (IBD), amoebiasis and irritable bowel syndrome (IBS)), but also for it's potential for the delivery of anti-rheumatoid arthritis and anti-chronic stable angina drugs. Besides, Polysaccharide-based micro/nanocarriers such as microbeads, microcapsules, microparticles, nanoparticles, nanogels and nanospheres are also introduced in this review.

  17. KCa 3.1-a microglial target ready for drug repurposing?

    PubMed

    Dale, Elena; Staal, Roland G W; Eder, Claudia; Möller, Thomas

    2016-10-01

    Over the past decade, glial cells have attracted attention for harboring unexploited targets for drug discovery. Several glial targets have attracted de novo drug discovery programs, as highlighted in this GLIA Special Issue. Drug repurposing, which has the objective of utilizing existing drugs as well as abandoned, failed, or not yet pursued clinical development candidates for new indications, might provide a faster opportunity to bring drugs for glial targets to patients with unmet needs. Here, we review the potential of the intermediate-conductance calcium-activated potassium channels KCa 3.1 as the target for such a repurposing effort. We discuss the data on KCa 3.1 expression on microglia in vitro and in vivo and review the relevant literature on the two KCa 3.1 inhibitors TRAM-34 and Senicapoc. Finally, we provide an outlook of what it might take to harness the potential of KCa 3.1 as a bona fide microglial drug target. GLIA 2016;64:1733-1741. © 2016 Wiley Periodicals, Inc.

  18. The AstroHDF Effort

    NASA Astrophysics Data System (ADS)

    Masters, J.; Alexov, A.; Folk, M.; Hanisch, R.; Heber, G.; Wise, M.

    2012-09-01

    Here we update the astronomy community on our effort to deal with the demands of ever-increasing astronomical data size and complexity, using the Hierarchical Data Format, version 5 (HDF5) format (Wise et al. 2011). NRAO, LOFAR and VAO have joined forces with The HDF Group to write an NSF grant, requesting funding to assist in the effort. This paper briefly summarizes our motivation for the proposed project, an outline of the project itself, and some of the material discussed at the ADASS Birds of a Feather (BoF) discussion. Topics of discussion included: community experiences with HDF5 and other file formats; toolsets which exist and/or can be adapted for HDF5; a call for development towards visualizing large (> 1 TB) image cubes; and, general lessons learned from working with large and complex data.

  19. Does increased effort compensate for performance debilitating test anxiety?

    PubMed

    Putwain, David W; Symes, Wendy

    2018-05-24

    It is well established that test anxiety is negatively related to examination performance. Based on attentional control theory, the aim of this study was to examine whether increased effort can protect against performance debilitating test anxiety. Four hundred and sixty-six participants (male = 228; 48.9%; White = 346, 74.3%; mean age = 15.7 years) completed self-report measures of test anxiety and effort that were matched to performance on a high-stakes secondary school examination. The worry and bodily symptoms components of test anxiety were negatively, and effort, positively related to examination performance. Effort moderated the negative relation between bodily symptoms and examination performance. At low effort, the negative relationship was amplified and at high effort was attenuated. Compensatory effort protects performance against bodily symptoms but not worry. It is possible that the cognitive load on working memory arising from the combination of worry and examination demands may be too high to be compensated by effort. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  20. Alcoholic hepatitis: Translational approaches to develop targeted therapies.

    PubMed

    Mandrekar, Pranoti; Bataller, Ramon; Tsukamoto, Hidekazu; Gao, Bin

    2016-10-01

    Alcoholic liver disease is a leading cause of liver-related mortality worldwide. In contrast to recent advances in therapeutic strategies for patients with viral hepatitis, there is a significant lack of novel therapeutic options for patients with alcoholic liver disease. In particular, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of alcoholic liver disease. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with AH is very high (20%-50% at 3 months). Available therapies are not effective in many patients, and targeted approaches are imminently needed. The development of such therapies requires translational studies in human samples and suitable animal models that reproduce the clinical and histological features of AH. In recent years, new animal models that simulate some of the features of human AH have been developed, and translational studies using human samples have identified potential pathogenic factors and histological parameters that predict survival. This review summarizes the unmet needs for translational studies on the pathogenesis of AH, preclinical translational tools, and emerging drug targets to benefit the AH patient. (Hepatology 2016;64:1343-1355). © 2016 by the American Association for the Study of Liver Diseases.

  1. Independent validation of the MMPI-2-RF Somatic/Cognitive and Validity scales in TBI Litigants tested for effort.

    PubMed

    Youngjohn, James R; Wershba, Rebecca; Stevenson, Matthew; Sturgeon, John; Thomas, Michael L

    2011-04-01

    The MMPI-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) is replacing the MMPI-2 as the most widely used personality test in neuropsychological assessment, but additional validation studies are needed. Our study examines MMPI-2-RF Validity scales and the newly created Somatic/Cognitive scales in a recently reported sample of 82 traumatic brain injury (TBI) litigants who either passed or failed effort tests (Thomas & Youngjohn, 2009). The restructured Validity scales FBS-r (restructured symptom validity), F-r (restructured infrequent responses), and the newly created Fs (infrequent somatic responses) were not significant predictors of TBI severity. FBS-r was significantly related to passing or failing effort tests, and Fs and F-r showed non-significant trends in the same direction. Elevations on the Somatic/Cognitive scales profile (MLS-malaise, GIC-gastrointestinal complaints, HPC-head pain complaints, NUC-neurological complaints, and COG-cognitive complaints) were significant predictors of effort test failure. Additionally, HPC had the anticipated paradoxical inverse relationship with head injury severity. The Somatic/Cognitive scales as a group were better predictors of effort test failure than the RF Validity scales, which was an unexpected finding. MLS arose as the single best predictor of effort test failure of all RF Validity and Somatic/Cognitive scales. Item overlap analysis revealed that all MLS items are included in the original MMPI-2 Hy scale, making MLS essentially a subscale of Hy. This study validates the MMPI-2-RF as an effective tool for use in neuropsychological assessment of TBI litigants.

  2. Responding to a Significant Recruitment Challenge within Three Nationwide Psycho-Educational Trials for Cancer Patients

    PubMed Central

    Stanton, Annette L.; Morra, Marion E.; Miller, Suzanne M.; Diefenbach, Michael A.; Slevin-Perocchia, Rosemarie; Raich, Peter C.; Fleisher, Linda; Wen, Kuang-Yi; Tran, Zung Vu; Mohamed, Nihal E.; George, Roshini; Bright, Mary Anne; Marcus, Alfred C.

    2013-01-01

    Purpose When faced with a significant recruitment challenge for three nationwide psycho-educational trials targeting prostate and breast cancer patients, the Cancer Information Service Research Consortium initiated outreach efforts to increase accrual. Recruitment is reported by major outreach strategy to inform the use of similar campaigns, either as primary recruitment efforts or to supplement “in-reach” recruitment within oncology settings. Methods During a 33-month period, recruitment was tracked from the National Cancer Institute’s Cancer Information Service (CIS), the American Cancer Society (ACS), Dr. Susan Love Research Foundation’s Love/Avon Army of Women (AOW), Internet advertising, press releases, radio/television interviews, recruitment materials in community venues, and outreach to churches and cancer support organizations. Results Across projects, the majority (89%) of recruited participants (N = 2,134) was obtained from the CIS (n = 901, 19 months of recruitment), AOW (n = 869, 18 months), and ACS (n = 123, 12 months). Other efforts showed minimal gain in recruitment. Conclusions Cancer information programs (e.g., CIS, ACS) and registries of individuals willing to participate in cancer-related research (e.g., AOW) can represent exceptional resources for outreach recruitment of cancer patients, especially when the eligibility criteria are highly restrictive. However, these resources do not yield samples representative of the larger population of adults diagnosed with cancer, and conclusions from such trials must be tempered accordingly. Implications for cancer survivors Inadequate recruitment to randomized controlled trials limits the creation of useful interventions for cancer survivors. By enrolling in cancer registries and taking part in research, cancer survivors can contribute to the development of effective resources for the survivor population. PMID:23595235

  3. Cognitive effort and pupil dilation in controlled and automatic processes.

    PubMed

    Querino, Emanuel; Dos Santos, Lafaiete; Ginani, Giuliano; Nicolau, Eduardo; Miranda, Débora; Romano-Silva, Marco; Malloy-Diniz, Leandro

    2015-01-01

    The Five Digits Test (FDT) is a Stroop paradigm test that aims to evaluate executive functions. It is composed of four parts, two of which are related to automatic and two of which are related to controlled processes. It is known that pupillary diameter increases as the task's cognitive demand increases. In the present study, we evaluated whether the pupillary diameter could distinguish cognitive effort between automated and controlled cognitive processing during the FDT as the task progressed. As a control task, we used a simple reading paradigm with a similar visual aspect as the FDT. We then divided each of the four parts into two blocks in order to evaluate the differences between the first and second half of the task. Results indicated that, compared to a control task, the FDT required higher cognitive effort for each consecutive part. Moreover, the first half of every part of the FDT induced dilation more than the second. The differences in pupil dilation during the first half of the four FDT parts were statistically significant between the parts 2 and 4 (p=0.023), and between the parts 3 and 4 (p=0.006). These results provide further evidence that cognitive effort and pupil diameter can distinguish controlled from automatic processes.

  4. 48 CFR 2052.216-70 - Level of effort.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Level of effort. 2052.216... Level of effort. As prescribed at 2016.307-70(a) the contracting officer shall insert the following..., time and materials, or labor hours basis. Level of Effort (JAN 1993) The NRC's estimate of the total...

  5. Is children's listening effort in background noise influenced by the speaker's voice quality?

    PubMed

    Sahlén, Birgitta; Haake, Magnus; von Lochow, Heike; Holm, Lucas; Kastberg, Tobias; Brännström, K Jonas; Lyberg-Åhlander, Viveka

    2018-07-01

    The present study aims at exploring the influence of voice quality on listening effort in children performing a language comprehension test with sentences of increasing difficulty. Listening effort is explored in relation to gender ( = cisgender). The study has a between-groups design. Ninety-three mainstreamed children aged 8;2 to 9;3 with typical language development participated. The children were randomly assigned to two groups (n = 46/47) with equal allocation of boys and girls and for the analysis to four groups depending of gender and voice condition. Working memory capacity and executive functions were tested in quiet. A digital version of a language comprehension test (the TROG-2) was used to measure the effect of voice quality on listening effort, measured as response time in a forced-choice paradigm. The groups listened to sentences through recordings of the same female voice, one group with a typical voice and one with a dysphonic voice, both in competing multi-talker babble noise. Response times were logged after a time buffer between the sentence-ending and indication of response. There was a significant increase in response times with increased task difficulty and response times between the two voice conditions differed significantly. The girls in the dysphonic condition were slower with increasing task difficulty. A dysphonic voice clearly adds to the noise burden and listening effort is greater in girls than in boys when the teacher speaks with dysphonic voice in a noisy background. These findings might mirror gender differences as for coping strategies in challenging contexts and have important implications for education.

  6. Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin

    PubMed Central

    Hauck, Nastasja C.; Kirpach, Josiane; Kiefer, Christina; Farinelle, Sophie; Morris, Stephen A.; Muller, Claude P.; Lu, I-Na

    2018-01-01

    To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA) long alpha helix (LAH). Our vaccine targeting LAH of hemagglutinin elicited significant seroconversion and protection against homologous and heterologous influenza virus strains in mice. The vaccine not only significantly reduced lung viral titers, but also induced a well-known bottleneck effect by decreasing virus diversity. In contrast to the classical bottleneck effect, here we showed a significant increase in the frequency of viruses with amino acid sequences identical to that of vaccine targeting LAH domain. No escape mutant emerged after vaccination. These results not only support the potential of a universal influenza vaccine targeting the conserved LAH domains, but also clearly demonstrate that the well-established bottleneck effect on viral quasispecies evolution does not necessarily generate escape mutants. PMID:29587397

  7. When is Deceptive Message Production More Effortful than Truth-Telling? A Baker's Dozen of Moderators.

    PubMed

    Burgoon, Judee K

    2015-01-01

    Deception is thought to be more effortful than telling the truth. Empirical evidence from many quarters supports this general proposition. However, there are many factors that qualify and even reverse this pattern. Guided by a communication perspective, I present a baker's dozen of moderators that may alter the degree of cognitive difficulty associated with producing deceptive messages. Among sender-related factors are memory processes, motivation, incentives, and consequences. Lying increases activation of a network of brain regions related to executive memory, suppression of unwanted behaviors, and task switching that is not observed with truth-telling. High motivation coupled with strong incentives or the risk of adverse consequences also prompts more cognitive exertion-for truth-tellers and deceivers alike-to appear credible, with associated effects on performance and message production effort, depending on the magnitude of effort, communicator skill, and experience. Factors related to message and communication context include discourse genre, type of prevarication, expected response length, communication medium, preparation, and recency of target event/issue. These factors can attenuate the degree of cognitive taxation on senders so that truth-telling and deceiving are similarly effortful. Factors related to the interpersonal relationship among interlocutors include whether sender and receiver are cooperative or adversarial and how well-acquainted they are with one another. A final consideration is whether the unit of analysis is the utterance, turn at talk, episode, entire interaction, or series of interactions. Taking these factors into account should produce a more nuanced answer to the question of when deception is more difficult than truth-telling.

  8. Stretch-sensitive paresis and effort perception in hemiparesis.

    PubMed

    Vinti, Maria; Bayle, Nicolas; Hutin, Emilie; Burke, David; Gracies, Jean-Michel

    2015-08-01

    In spastic paresis, stretch applied to the antagonist increases its inappropriate recruitment during agonist command (spastic co-contraction). It is unknown whether antagonist stretch: (1) also affects agonist recruitment; (2) alters effort perception. We quantified voluntary activation of ankle dorsiflexors, effort perception, and plantar flexor co-contraction during graded dorsiflexion efforts at two gastrocnemius lengths. Eighteen healthy (age 41 ± 13) and 18 hemiparetic (age 54 ± 12) subjects performed light, medium and maximal isometric dorsiflexion efforts with the knee flexed or extended. We determined dorsiflexor torque, Root Mean Square EMG and Agonist Recruitment/Co-contraction Indices (ARI/CCI) from the 500 ms peak voluntary agonist recruitment in a 5-s maximal isometric effort in tibialis anterior, soleus and medial gastrocnemius. Subjects retrospectively reported effort perception on a 10-point visual analog scale. During gastrocnemius stretch in hemiparetic subjects, we observed: (1) a 25 ± 7 % reduction of tibialis anterior voluntary activation (maximum reduction 98 %; knee extended vs knee flexed; p = 0.007, ANOVA); (2) an increase in dorsiflexion effort perception (p = 0.03, ANCOVA). Such changes did not occur in healthy subjects. Effort perception depended on tibialis anterior recruitment only (βARI(TA) = 0.61, p < 0.01) in healthy subjects (not on gastrocnemius medialis co-contraction) while it depended on both tibialis anterior agonist recruitment (βARI(TA) = 0.41, p < 0.001) and gastrocnemius medialis co-contraction (βCCI(MG) = 0.43, p < 0.001) in hemiparetic subjects. In hemiparesis, voluntary ability to recruit agonist motoneurones is impaired--sometimes abolished--by antagonist stretch, a phenomenon defined here as stretch-sensitive paresis. In addition, spastic co-contraction increases effort perception, an additional incentive to evaluate and treat this phenomenon.

  9. mA beam acceleration efforts on 100 MeV H- cyclotron at CIAE

    NASA Astrophysics Data System (ADS)

    Zhang, Tianjue; An, Shizhong; Lv, Yinlong; Ge, Tao; Jia, Xianlu; Ji, Bin; Yin, Zhiguo; Pan, Gaofeng; Cao, Lei; Guan, Fengping; Yang, Jianjun; Li, Zhenguo; Zhao, Zhenlu; Wu, Longcheng; Zhang, He; Wang, Jingfeng; Zhang, Yiwang; Liu, Jingyuan; Li, Shiqiang; Lu, Xiaotong; Liu, Zhenwei; Li, Yaoqian; Guo, Juanjuan; Cao, Xuelong; Guan, Leilei; Wang, Fei; Wang, Yang; Yang, Guang; Zhang, Suping; Hou, Shigang; Wang, Feng

    2017-09-01

    Various technologies for high current compact H- cyclotron have been developed at CIAE since 1990s. A 375 μA proton beam was extracted from a 30 MeV compact H- cyclotron CYCIAE-30 at the end of 1994. A central region model cyclotron CYCIAE-CRM was developed for the design verification of a 100 MeV high current compact H- cyclotron CYCIAE-100. It is also a 10 MeV proton machine as a prototype for PET application. A 430 μA beam was achieved in 2009. The first beam was extracted from the CYCIAE-100 cyclotron on July 4, 2014, the operation stability has been improved and beam current has been increased gradually. A 1.1 mA proton beam was measured on the internal target in July 2016. The effort for an increasing of proton beam has continued till now. In this paper, the effort on several aspects for mA beam development will be presented, including the multi-cusp source, buncher, matching from the energy of the injected beam, vertical beam line and central region, beam loading of the RF system and instrumentation for beam diagnostics etc.

  10. Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?

    PubMed

    Montella, Liliana; Palmieri, Giovannella; Addeo, Raffaele; Del Prete, Salvatore

    2016-07-21

    Cancer treatment has been revolutionized by the advent of new molecular targeted and immunotherapeutic agents. Identification of the role of tumor angiogenesis changed the understanding of many tumors. After the unsuccessful results with chemotherapy, sorafenib, by interfering with angiogenic pathways, has become pivotal in the treatment of hepatocellular carcinoma. Sorafenib is the only systemic treatment to show a modest but statistically significant survival benefit. All novel drugs and strategies for treatment of advanced hepatocellular carcinoma must be compared with the results obtained with sorafenib, but no new drug or drug combination has yet achieved better results. In our opinion, the efforts to impact the natural history of the disease will be directed not only to drug development but also to understanding the underlying liver disease (usually hepatitis B virus- or hepatitis C virus-related) and to interrupting the progression of cirrhosis. It will be important to define the role and amount of mutations in the complex pathogenesis of hepatocellular carcinoma and to better integrate locoregional and systemic therapies. It will be important also to optimize the therapeutic strategies with existing chemotherapeutic drugs and new targeted agents.

  11. Health Promotion Efforts as Predictors of Physical Activity in Schools: An Application of the Diffusion of Innovations Model.

    PubMed

    Glowacki, Elizabeth M; Centeio, Erin E; Van Dongen, Daniel J; Carson, Russell L; Castelli, Darla M

    2016-06-01

    Implementing a comprehensive school physical activity program (CSPAP) effectively addresses public health issues by providing opportunities for physical activity (PA). Grounded in the Diffusion of Innovations model, the purpose of this study was to identify how health promotion efforts facilitate opportunities for PA. Physical and health education teachers (N = 256) nationwide were surveyed using a CSPAP Index to identify teacher's efforts for providing opportunities for PA within a school setting. A hierarchical regression analysis revealed total number of PA opportunities was significantly predicted by teachers' health promotion efforts, p < .001. Sex and years of experience were not significant covariates, p = .35, in the final step of the model. Accounting for teaching environments, the model was significant, p < .001. The strongest predictors were the promotional efforts of PA for family and community, p < .001, PA for staff members, p < .01, PA during the school day, p < .05, and PA before school, p < .05. To increase PA opportunities for children in schools, emphasis should be placed on health promotion. This study confirms the importance of teachers involving family, community, and staff members as co-health promoters when trying to increase PA engagement surrounding schools. © 2016, American School Health Association.

  12. Associations between working environment and weight control efforts among workers with obesity in Korea.

    PubMed

    Hyun, Hye Sun; Kim, Yunyoung

    2018-06-01

    Objective The aim of this study was to investigate the relationship between working environment and weight control efforts among obese workers in Korea. Methods This study was based on the 2011 3rd Korean Working Conditions Survey, which was conducted on workers aged 15 years or older. A sample of 484 obese workers was included in the study. Multivariable logistic regression analysis was used to investigate the relationship between working environment and weight control efforts after controlling for individual variables. Adjusted odds ratios (ORs) and 95% confidence intervals were calculated. Results Of the participants, 63.4% reported that they made efforts to control their weight. After controlling for personal factors, the OR of weight control efforts for individuals working 40-49 hours per week was 2.4 times that for individuals working 60 hours or more per week. The OR of regular employment workers was 2.2 times that of non-regular workers. Conclusion We established that working hours and employment type were significantly related to weight control efforts. Therefore, we recommend that working conditions should be considered in designing effective workplace health promotion programs.

  13. Physician Practice Audit Targets Now Become Hospital and Health System Compliance Risks.

    PubMed

    Hirsch, Ronald L

    2015-01-01

    In 2013, 22% of the federal budget was spent on Medicare and Medicaid. The Medicare Trust Fund is forecast to be depleted in 2030. More than 12% of Medicare fee-for-service payments in 2014 were made in error. These factors have led Congress to apply more pressure to reduce improper payments. Although hospitals were the initial targets because of their higher reimbursement, recent efforts have shifted to physician billing. Hospitals and health systems continue to acquire physician practices, making them liable for the billing activities of physicians. And for physicians who remain independent, the cost and effort required to respond to audits and denials can be financially devastating, further demonstrating the importance of prevention. This article addresses some of the common audit targets and mistakes made by physicians and provides strategies for physician practices and health systems to respond to and, ultimately, avoid these denials.

  14. Musculoskeletal pain and effort-reward imbalance- a systematic review

    PubMed Central

    2014-01-01

    Background Musculoskeletal pain may be triggered by physical strains and psychosocial risk factors. The effort-reward imbalance model (ERI model) is a stress model which measures psychosocial factors in the working world. The question is whether workers with an effort-reward imbalance report musculoskeletal pain more frequently than those with no effort-reward imbalance. A systematic review using a best evidence synthesis approach was conducted to answer this question. Methods A literature search was conducted for the period from 1996 to 2012, using three databases (Pubmed, Embase and PsycINFO). The research criteria related to psychosocial, work-related stress as per the ERI model and to musculoskeletal pain. A quality score was developed using various quality criteria to assess the standard of the studies. The level of evidence was graded as in (Am J Ind Med 39:180–193, 2001). Results After applying the inclusion criteria, a total of 19 studies were included in the review: 15 cross-sectional studies, three prospective studies and one case–control study. 74% of all studies exhibited good methodological quality, 53% collected data using the original ERI questionnaire, and in 42% of the studies, there was adequate control for physical working conditions. Furthermore, different cut-off points were used to classify exposed and non-exposed individuals. On the basis of 13 studies with a positive, statistically significant association, a moderate level of evidence was inferred for the association between effort-reward imbalance and musculoskeletal pain. The evidence for a role of over-commitment and for its interaction with effort-reward imbalance was rated as inconclusive - on the basis of eight and five studies, respectively. Conclusions On the basis of the available evidence, no reliable conclusion may be drawn about any association between the psychosocial factors ascertained using the ERI model and musculoskeletal pain. Before a reliable statement can be made on

  15. Mass spectrometry-based targeted quantitative proteomics: achieving sensitive and reproducible detection of proteins.

    PubMed

    Boja, Emily S; Rodriguez, Henry

    2012-04-01

    Traditional shotgun proteomics used to detect a mixture of hundreds to thousands of proteins through mass spectrometric analysis, has been the standard approach in research to profile protein content in a biological sample which could lead to the discovery of new (and all) protein candidates with diagnostic, prognostic, and therapeutic values. In practice, this approach requires significant resources and time, and does not necessarily represent the goal of the researcher who would rather study a subset of such discovered proteins (including their variations or posttranslational modifications) under different biological conditions. In this context, targeted proteomics is playing an increasingly important role in the accurate measurement of protein targets in biological samples in the hope of elucidating the molecular mechanism of cellular function via the understanding of intricate protein networks and pathways. One such (targeted) approach, selected reaction monitoring (or multiple reaction monitoring) mass spectrometry (MRM-MS), offers the capability of measuring multiple proteins with higher sensitivity and throughput than shotgun proteomics. Developing and validating MRM-MS-based assays, however, is an extensive and iterative process, requiring a coordinated and collaborative effort by the scientific community through the sharing of publicly accessible data and datasets, bioinformatic tools, standard operating procedures, and well characterized reagents. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Stuttering Frequency, Speech Rate, Speech Naturalness, and Speech Effort During the Production of Voluntary Stuttering.

    PubMed

    Davidow, Jason H; Grossman, Heather L; Edge, Robin L

    2018-05-01

    Voluntary stuttering techniques involve persons who stutter purposefully interjecting disfluencies into their speech. Little research has been conducted on the impact of these techniques on the speech pattern of persons who stutter. The present study examined whether changes in the frequency of voluntary stuttering accompanied changes in stuttering frequency, articulation rate, speech naturalness, and speech effort. In total, 12 persons who stutter aged 16-34 years participated. Participants read four 300-syllable passages during a control condition, and three voluntary stuttering conditions that involved attempting to produce purposeful, tension-free repetitions of initial sounds or syllables of a word for two or more repetitions (i.e., bouncing). The three voluntary stuttering conditions included bouncing on 5%, 10%, and 15% of syllables read. Friedman tests and follow-up Wilcoxon signed ranks tests were conducted for the statistical analyses. Stuttering frequency, articulation rate, and speech naturalness were significantly different between the voluntary stuttering conditions. Speech effort did not differ between the voluntary stuttering conditions. Stuttering frequency was significantly lower during the three voluntary stuttering conditions compared to the control condition, and speech effort was significantly lower during two of the three voluntary stuttering conditions compared to the control condition. Due to changes in articulation rate across the voluntary stuttering conditions, it is difficult to conclude, as has been suggested previously, that voluntary stuttering is the reason for stuttering reductions found when using voluntary stuttering techniques. Additionally, future investigations should examine different types of voluntary stuttering over an extended period of time to determine their impact on stuttering frequency, speech rate, speech naturalness, and speech effort.

  17. Motivation and effort in individuals with social anhedonia

    PubMed Central

    McCarthy, Julie M.; Treadway, Michael T.; Blanchard, Jack J.

    2015-01-01

    It has been proposed that anhedonia may, in part, reflect difficulties in reward processing and effortful decision-making. The current study aimed to replicate previous findings of effortful decision-making deficits associated with elevated anhedonia and expand upon these findings by investigating whether these decision-making deficits are specific to elevated social anhedonia or are also associated with elevated positive schizotypy characteristics. The current study compared controls (n = 40) to individuals elevated on social anhedonia (n = 30), and individuals elevated on perceptual aberration/magical ideation (n = 30) on the Effort Expenditure for Rewards Task (EEfRT). Across groups, participants chose a higher proportion of hard tasks with increasing probability of reward and reward magnitude, demonstrating sensitivity to probability and reward values. Contrary to our expectations, when the probability of reward was most uncertain (50% probability), at low and medium reward values, the social anhedonia group demonstrated more effortful decision-making than either individuals high in positive schizotypy or controls. The positive schizotypy group only differed from controls (making less effortful choices than controls) when reward probability was lowest (12%) and the magnitude of reward was the smallest. Our results suggest that social anhedonia is related to intact motivation and effort for monetary rewards, but that individuals with this characteristic display a unique and perhaps inefficient pattern of effort allocation when the probability of reward is most uncertain. Future research is needed to better understand effortful decision-making and the processing of reward across a range of individual difference characteristics. PMID:25888337

  18. Motivation and effort in individuals with social anhedonia.

    PubMed

    McCarthy, Julie M; Treadway, Michael T; Blanchard, Jack J

    2015-06-01

    It has been proposed that anhedonia may, in part, reflect difficulties in reward processing and effortful decision making. The current study aimed to replicate previous findings of effortful decision making deficits associated with elevated anhedonia and expand upon these findings by investigating whether these decision making deficits are specific to elevated social anhedonia or are also associated with elevated positive schizotypy characteristics. The current study compared controls (n=40) to individuals elevated on social anhedonia (n=30), and individuals elevated on perceptual aberration/magical ideation (n=30) on the Effort Expenditure for Rewards Task (EEfRT). Across groups, participants chose a higher proportion of hard tasks with increasing probability of reward and reward magnitude, demonstrating sensitivity to probability and reward values. Contrary to our expectations, when the probability of reward was most uncertain (50% probability), at low and medium reward values, the social anhedonia group demonstrated more effortful decision making than either individuals high in positive schizotypy or controls. The positive schizotypy group only differed from controls (making less effortful choices than controls) when reward probability was lowest (12%) and the magnitude of reward was the smallest. Our results suggest that social anhedonia is related to intact motivation and effort for monetary rewards, but that individuals with this characteristic display a unique and perhaps inefficient pattern of effort allocation when the probability of reward is most uncertain. Future research is needed to better understand effortful decision making and the processing of reward across a range of individual difference characteristics. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. What predicts dissemination efforts among public health researchers in the United States?

    PubMed

    Tabak, Rachel G; Stamatakis, Katherine A; Jacobs, Julie A; Brownson, Ross C

    2014-01-01

    We identified factors related to dissemination efforts by researchers to non-research audiences to reduce the gap between research generation and uptake in public health practice. We conducted a cross-sectional study of 266 researchers at universities, the National Institutes of Health (NIH), and CDC. We identified scientists using a search of public health journals and lists from government-sponsored research. The scientists completed a 35-item online survey in 2012. Using multivariable logistic regression, we compared self-rated effort to disseminate findings to non-research audiences (excellent/good vs. poor) across predictor variables in three categories: perceptions or reasons to disseminate, perceived expectation by employer/funders, and professional training and experience. One-third of researchers rated their dissemination efforts as poor. Many factors were significantly related to whether a researcher rated him/herself as excellent/good, including obligation to disseminate findings (odds ratio [OR] = 2.7, 95% confidence interval [CI] 1.1, 6.8), dissemination important for their department (OR=2.3, 95% CI 1.2, 4.5), dissemination expected by employer (OR=2.0, 95% CI 1.2, 3.2) or by funder (OR=2.1, 95% CI 1.3, 3.2), previous work in a practice/policy setting (OR=4.4, 95% CI 2.1, 9.3), and university researchers with Prevention Research Center affiliation vs. NIH researchers (OR=4.7, 95% CI 1.4, 15.7). With all variables in the model, dissemination expected by funder (OR=2.0, 95% CI 1.2, 3.1) and previous work in a practice/policy setting (OR=3.5, OR 1.7, 7.1) remained significant. These findings support the need for structural changes to the system, including funding agency priorities and participation of researchers in practice- and policy-based experiences, which may enhance efforts to disseminate by researchers.

  20. Army and Marine Corps Active Protection System (APS) Efforts

    DTIC Science & Technology

    2016-08-30

    efforts—the Expedited, Non-Developmental Item (NDI) APS effort and the Modular Active Protection System (MAPS) effort. The Marines describe their...17 Modular Active Protection System (MAPS) Effort .......................................................... 18 The Marine Corps APS...Merkava Mark 4 tank was designed around the Trophy APS. 32 The Army’s Modular Active Protection System (MAPS) effort, described below, is intended to

  1. Review of HIV in the Caribbean: significant progress and outstanding challenges.

    PubMed

    Figueroa, J Peter

    2014-06-01

    This paper reviews the recent literature on HIV in the Caribbean and discusses the challenges faced. HIV incidence in the Caribbean has declined by 49 % in the past decade, coverage of persons living with HIV among those eligible for antiretroviral treatment as per national guidelines was 70 % in 2012, and some countries are meeting the target of virtual elimination of mother-to-child transmission. HIV prevalence in the Caribbean is 1 % with features of both a generalized and concentrated HIV epidemic. HIV prevalence among female sex workers has declined but remains unacceptably high among men who have sex with men. Social and cultural factors, gender norms, and strong stigma associated with HIV and homosexuality contribute to the continued spread of HIV. Caribbean countries and their partners have invested significant resources, creative effort and impressive research in strengthening the HIV response nationally and regionally. However, in order to control the HIV epidemic, leaders at all levels, and the people, must address fundamental structural barriers in society that deny marginalized persons their rights, undermine public health goals, and impede universal access to HIV prevention, treatment, and care.

  2. Dependence of phonatory effort on hydration level.

    PubMed

    Verdolini, K; Titze, I R; Fennell, A

    1994-10-01

    In this study, a double-blind placebo-controlled approach was used to assess the relation between hydration level and phonatory effort. Twelve adult, untrained voice users with normal voices participated as subjects. Each subject received a 4-hour hydration treatment, a 4-hour dehydration treatment, and a 4-hour placebo (control) treatment. Following each treatment, phonatory effort was measured with a physiological measure, phonation threshold pressure (PTP), and with a psychological measure, direct magnitude estimation of perceived phonatory effort (DMEPPE). Summarizing the results across these measures, the findings indicated an inverse relation between phonatory effort and hydration level, but primarily for high-pitched phonation tasks. The findings for PTPs replicated those from an earlier study conducted without double-blind experimental manipulations (Verdolini-Marston, Titze, & Druker, 1990). Theoretical discussion focuses on the possible role of vocal fold tissue viscosity for hydration and dehydration effects, although direct measures of tissue viscosity are lacking.

  3. Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology

    PubMed Central

    Yohn, Samantha E.; López-Cruz, Laura; San Miguel, Noemí; Correa, Mercè

    2016-01-01

    Abstract Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work-related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort-related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson’s disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort

  4. Sincerity of effort versus feigned movement control of the cervical spine in patients with whiplash-associated disorders and asymptomatic persons: a case-control study.

    PubMed

    Oddsdóttir, Gudny Lilja; Kristjansson, Eythor; Gislason, Magnus Kjartan

    2015-01-01

    Cross-sectional design. To investigate whether the Fly Test can be used to differentiate patients with whiplash-associated disorders (WAD) from asymptomatic persons who deliberately feign symptoms and from WAD patients exaggerating symptoms. The lack of valid clinical tests makes it difficult to detect a justifiable cause for compensation claims in traumatic neck-pain disorders. The Fly Test recorded the accuracy of neck movements in patients with WAD (n = 34) and asymptomatic persons (n = 31). The participants followed a moving "Fly" on a computer screen with a cursor from sensors mounted on the head. Two conditions were tested, sincere versus feigned efforts. In the former, the participants moved their neck as accurately as possible. In the latter, a short text was presented describing a fictitious accident (asymptomatic group) or imagining more intense pain/suffering (WAD group), and the test was performed as affected by these more serious conditions. Amplitude accuracy (AA), time on target (ToT) and jerk index (JI) were compared across patterns, conditions and groups. The sincere effort in the WAD group was significant compared to the feigned effort of the asymptomatic group (p < 0.001). For AA, correct categorization of 81.5% of the performances was made, where a mean score above 5.5 mm differentiated feigned versus sincere efforts in asymptomatic and WAD groups (sensitivity 79.4%, specificity 67.7%). For ToT, score above 11% indicated correctly categorized WAD patients (sensitivity 82.4%, specificity 64.5%). The Fly Test can provide clinicians a clue when patients with mild to moderate pain/disability are feigning or exaggerating symptoms.

  5. Incorporating discrete event simulation into quality improvement efforts in health care systems.

    PubMed

    Rutberg, Matthew Harris; Wenczel, Sharon; Devaney, John; Goldlust, Eric Jonathan; Day, Theodore Eugene

    2015-01-01

    Quality improvement (QI) efforts are an indispensable aspect of health care delivery, particularly in an environment of increasing financial and regulatory pressures. The ability to test predictions of proposed changes to flow, policy, staffing, and other process-level changes using discrete event simulation (DES) has shown significant promise and is well reported in the literature. This article describes how to incorporate DES into QI departments and programs in order to support QI efforts, develop high-fidelity simulation models, conduct experiments, make recommendations, and support adoption of results. The authors describe how DES-enabled QI teams can partner with clinical services and administration to plan, conduct, and sustain QI investigations. © 2013 by the American College of Medical Quality.

  6. An analysis of the diffusion of new antidepressants: variety, quality, and marketing efforts.

    PubMed

    Berndt, Ernst R; Bhattacharjya, Ashoke; Mishol, David N; Arcelus, Almudena; Lasky, Thomas

    2002-03-01

    those for side effects. Marketing efforts respond to science-based events, such as new FDA indication approvals, and to effectiveness and side-effect quality improvements. Total antidepressant sales are positively and significantly related to price reductions, increased marketing efforts, and the level and variety of side effect profiles involving antidepressants. The level and variety of effectiveness does not significantly affect total antidepressant sales. Order of entry effects are important in affecting product market shares, while marketing efforts and relative quality attributes (particularly a more favorable side effect profile) have positive and significant impacts on relative market shares. Since patient response to SSRIs and related products is idiosyncratic, greater product variety facilitates better matching of antidepressant with patient. Much of the growth of the SSRIs and related antidepressants since 1988 can be attributed to increased product attribute variety, to improved changes in side effect quality relative to that of the tricyclics, and to the marketing of those improvements. Marketing efforts play an important role in diffusing product information. Marketing efforts increase considerably following FDA approval for indications other than depression, and also increase with the average effectiveness and the average side effect rating of the products. Whether the relatively minor role that perceived effectiveness has in affecting sales relative to perceived side effect profile is unique to antidepressants, or generalizes to other therapeutic classes, merits further examination.

  7. Respiratory sinus arrhythmia, effortful control, and parenting as predictors of children's sympathy across early childhood.

    PubMed

    Taylor, Zoe E; Eisenberg, Nancy; Spinrad, Tracy L

    2015-01-01

    The goal of this study was to examine physiological and environmental predictors of children's sympathy (an emotional response consisting of feelings of concern or sorrow for others who are distressed or in need) and whether temperamental effortful control mediated these relations. Specifically, in a study of 192 children (23% Hispanic; 54% male), respiratory sinus arrhythmia (RSA), a measure thought to reflect physiological regulation, and observed authoritative parenting (both at 42 months) were examined as predictors of children's effortful control (at 54 months) and, in turn, children's sympathy (at 72 and 84 months). Measures of both baseline RSA and RSA suppression were examined. In a structural equation model, observed parenting was positively related to children's subsequent sympathy through its positive relation to effortful control. Furthermore, the indirect path from baseline RSA to higher sympathy through effortful control was marginally significant. Authoritative parenting and baseline RSA uniquely predicted individual differences in children's effortful control. Findings highlight the potential role of both authoritative parenting and physiological regulation in the development of children's sympathy.

  8. Target Charaterization and Follow-Up Observations in Support of the Kepler Mission

    NASA Technical Reports Server (NTRS)

    Latham, David W.

    2004-01-01

    This report covers work carried out at the Smithsonian Astrophysical Observatory during the period 1 December 2003 to 30 November 2004 to support efforts to prepare the Kepler Input Catalog. The Catalog will be used to select the targets observed for planetary transits by Kepler.

  9. Biomechanical Quantification of Mendelsohn Maneuver and Effortful Swallowing on Pharyngoesophageal Function.

    PubMed

    Doeltgen, Sebastian Heinrich; Ong, Ellisa; Scholten, Ingrid; Cock, Charles; Omari, Taher

    2017-11-01

    Objective To quantify the effects of 2 swallowing maneuvers used in dysphagia rehabilitation-the Mendelsohn maneuver and effortful swallowing-on pharyngoesophageal function with novel, objective pressure-flow analysis. Study Design Evaluation of intervention effects in a healthy control cohort. Setting A pharyngoesophageal motility research laboratory in a tertiary education facility. Subjects Twelve young healthy subjects (9 women, 28.6 ± 7.9 years) from the general public, without swallowing impairment, volunteered to participate in this study. Methods Surface electromyography from the floor-of-mouth musculature and high-resolution impedance manometry-based pressure flow analysis were used to assess floor-of-mouth activation and pharyngoesophageal motility, respectively. Subjects each performed 10 noneffortful control swallows, Mendelsohn maneuver swallows, and effortful swallows, with a 5-mL viscous bolus. Repeated measures analyses of variance was used to compare outcome measures across conditions. Results Effortful and Mendelsohn swallows generated greater floor-of-mouth contraction ( P = .001) and pharyngeal pressure ( P < .0001) when compared with control swallows. There were no changes at the level of the upper esophageal sphincter, except for a faster opening to maximal diameter during maneuver swallows ( P = .01). The proximal esophageal contractile integral was reduced during Mendelsohn swallows ( P = .001). Conclusion Effortful and Mendelsohn maneuver swallows significantly alter the pharyngoesophageal pressure profile. Faster opening of the upper esophageal sphincter may facilitate bolus transfer during maneuver swallows; however, reduced proximal esophageal contractility during Mendelsohn maneuver swallows may impair bolus flow and aggravate dysphagic symptoms.

  10. Drug target ontology to classify and integrate drug discovery data.

    PubMed

    Lin, Yu; Mehta, Saurabh; Küçük-McGinty, Hande; Turner, John Paul; Vidovic, Dusica; Forlin, Michele; Koleti, Amar; Nguyen, Dac-Trung; Jensen, Lars Juhl; Guha, Rajarshi; Mathias, Stephen L; Ursu, Oleg; Stathias, Vasileios; Duan, Jianbin; Nabizadeh, Nooshin; Chung, Caty; Mader, Christopher; Visser, Ubbo; Yang, Jeremy J; Bologa, Cristian G; Oprea, Tudor I; Schürer, Stephan C

    2017-11-09

    One of the most successful approaches to develop new small molecule therapeutics has been to start from a validated druggable protein target. However, only a small subset of potentially druggable targets has attracted significant research and development resources. The Illuminating the Druggable Genome (IDG) project develops resources to catalyze the development of likely targetable, yet currently understudied prospective drug targets. A central component of the IDG program is a comprehensive knowledge resource of the druggable genome. As part of that effort, we have developed a framework to integrate, navigate, and analyze drug discovery data based on formalized and standardized classifications and annotations of druggable protein targets, the Drug Target Ontology (DTO). DTO was constructed by extensive curation and consolidation of various resources. DTO classifies the four major drug target protein families, GPCRs, kinases, ion channels and nuclear receptors, based on phylogenecity, function, target development level, disease association, tissue expression, chemical ligand and substrate characteristics, and target-family specific characteristics. The formal ontology was built using a new software tool to auto-generate most axioms from a database while supporting manual knowledge acquisition. A modular, hierarchical implementation facilitate ontology development and maintenance and makes use of various external ontologies, thus integrating the DTO into the ecosystem of biomedical ontologies. As a formal OWL-DL ontology, DTO contains asserted and inferred axioms. Modeling data from the Library of Integrated Network-based Cellular Signatures (LINCS) program illustrates the potential of DTO for contextual data integration and nuanced definition of important drug target characteristics. DTO has been implemented in the IDG user interface Portal, Pharos and the TIN-X explorer of protein target disease relationships. DTO was built based on the need for a formal semantic

  11. Intensive care unit drug costs in the context of total hospital drug expenditures with suggestions for targeted cost containment efforts.

    PubMed

    Altawalbeh, Shoroq M; Saul, Melissa I; Seybert, Amy L; Thorpe, Joshua M; Kane-Gill, Sandra L

    2018-04-01

    To assess costs of intensive care unit (ICU) related pharmacotherapy relative to hospital drug expenditures, and to identify potential targets for cost-effectiveness investigations. We offer the unique advantage of comparing ICU drug costs with previously published data a decade earlier to describe changes over time. Financial transactions for all ICU patients during fiscal years (FY) 2009-2012 were retrieved from the hospital's data repository. ICU drug costs were evaluated for each FY. ICU departments' charges were also retrieved and calculated as percentages of total ICU charges. Albumin, prismasate (dialysate), voriconazole, factor VII and alteplase denoted the highest percentages of ICU drug costs. ICU drug costs contributed to an average of 31% (SD 1.0%) of the hospital's total drug costs. ICU drug costs per patient day increased by 5.8% yearly versus 7.8% yearly for non-ICU drugs. This rate was higher for ICU drugs costs at 12% a decade previous. Pharmacy charges contributed to 17.7% of the total ICU charges. Growth rates of costs per year have declined but still drug expenditures in the ICU are consistently a significant driver in this resource intensive environment with a high impact on hospital drug expenditures. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 7 CFR 622.31 - Basic planning efforts.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., DEPARTMENT OF AGRICULTURE WATER RESOURCES WATERSHED PROJECTS Planning § 622.31 Basic planning efforts. Upon... the need for planning effort. Once planning is authorized by the Chief of NRCS, a watershed plan-environmental impact statement (plan-EIS) or a watershed plan-environmental assessment (plan-EA) will be...

  13. 7 CFR 622.31 - Basic planning efforts.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., DEPARTMENT OF AGRICULTURE WATER RESOURCES WATERSHED PROJECTS Planning § 622.31 Basic planning efforts. Upon... the need for planning effort. Once planning is authorized by the Chief of NRCS, a watershed plan-environmental impact statement (plan-EIS) or a watershed plan-environmental assessment (plan-EA) will be...

  14. 7 CFR 622.31 - Basic planning efforts.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., DEPARTMENT OF AGRICULTURE WATER RESOURCES WATERSHED PROJECTS Planning § 622.31 Basic planning efforts. Upon... the need for planning effort. Once planning is authorized by the Chief of NRCS, a watershed plan-environmental impact statement (plan-EIS) or a watershed plan-environmental assessment (plan-EA) will be...

  15. 7 CFR 622.31 - Basic planning efforts.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., DEPARTMENT OF AGRICULTURE WATER RESOURCES WATERSHED PROJECTS Planning § 622.31 Basic planning efforts. Upon... the need for planning effort. Once planning is authorized by the Chief of NRCS, a watershed plan-environmental impact statement (plan-EIS) or a watershed plan-environmental assessment (plan-EA) will be...

  16. 15 CFR 930.114 - Secretarial mediation efforts.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Secretarial mediation efforts. 930.114... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.114 Secretarial mediation efforts. (a) Following the close of the hearing, the hearing officer shall transmit the...

  17. Targeting an efficient target-to-target interval for P300 speller brain–computer interfaces

    PubMed Central

    Sellers, Eric W.; Wang, Xingyu

    2013-01-01

    Longer target-to-target intervals (TTI) produce greater P300 event-related potential amplitude, which can increase brain–computer interface (BCI) classification accuracy and decrease the number of flashes needed for accurate character classification. However, longer TTIs requires more time for each trial, which will decrease the information transfer rate of BCI. In this paper, a P300 BCI using a 7 × 12 matrix explored new flash patterns (16-, 18- and 21-flash pattern) with different TTIs to assess the effects of TTI on P300 BCI performance. The new flash patterns were designed to minimize TTI, decrease repetition blindness, and examine the temporal relationship between each flash of a given stimulus by placing a minimum of one (16-flash pattern), two (18-flash pattern), or three (21-flash pattern) non-target flashes between each target flashes. Online results showed that the 16-flash pattern yielded the lowest classification accuracy among the three patterns. The results also showed that the 18-flash pattern provides a significantly higher information transfer rate (ITR) than the 21-flash pattern; both patterns provide high ITR and high accuracy for all subjects. PMID:22350331

  18. Stochastic evolutionary dynamics in minimum-effort coordination games

    NASA Astrophysics Data System (ADS)

    Li, Kun; Cong, Rui; Wang, Long

    2016-08-01

    The minimum-effort coordination game draws recently more attention for the fact that human behavior in this social dilemma is often inconsistent with the predictions of classical game theory. Here, we combine evolutionary game theory and coalescence theory to investigate this game in finite populations. Both analytic results and individual-based simulations show that effort costs play a key role in the evolution of contribution levels, which is in good agreement with those observed experimentally. Besides well-mixed populations, set structured populations have also been taken into consideration. Therein we find that large number of sets and moderate migration rate greatly promote effort levels, especially for high effort costs.

  19. The Timing and Effort of Lexical Access in Natural and Degraded Speech

    PubMed Central

    Wagner, Anita E.; Toffanin, Paolo; Başkent, Deniz

    2016-01-01

    Understanding speech is effortless in ideal situations, and although adverse conditions, such as caused by hearing impairment, often render it an effortful task, they do not necessarily suspend speech comprehension. A prime example of this is speech perception by cochlear implant users, whose hearing prostheses transmit speech as a significantly degraded signal. It is yet unknown how mechanisms of speech processing deal with such degraded signals, and whether they are affected by effortful processing of speech. This paper compares the automatic process of lexical competition between natural and degraded speech, and combines gaze fixations, which capture the course of lexical disambiguation, with pupillometry, which quantifies the mental effort involved in processing speech. Listeners’ ocular responses were recorded during disambiguation of lexical embeddings with matching and mismatching durational cues. Durational cues were selected due to their substantial role in listeners’ quick limitation of the number of lexical candidates for lexical access in natural speech. Results showed that lexical competition increased mental effort in processing natural stimuli in particular in presence of mismatching cues. Signal degradation reduced listeners’ ability to quickly integrate durational cues in lexical selection, and delayed and prolonged lexical competition. The effort of processing degraded speech was increased overall, and because it had its sources at the pre-lexical level this effect can be attributed to listening to degraded speech rather than to lexical disambiguation. In sum, the course of lexical competition was largely comparable for natural and degraded speech, but showed crucial shifts in timing, and different sources of increased mental effort. We argue that well-timed progress of information from sensory to pre-lexical and lexical stages of processing, which is the result of perceptual adaptation during speech development, is the reason why in ideal

  20. Working memory capacity may influence perceived effort during aided speech recognition in noise.

    PubMed

    Rudner, Mary; Lunner, Thomas; Behrens, Thomas; Thorén, Elisabet Sundewall; Rönnberg, Jerker

    2012-09-01

    Recently there has been interest in using subjective ratings as a measure of perceived effort during speech recognition in noise. Perceived effort may be an indicator of cognitive load. Thus, subjective effort ratings during speech recognition in noise may covary both with signal-to-noise ratio (SNR) and individual cognitive capacity. The present study investigated the relation between subjective ratings of the effort involved in listening to speech in noise, speech recognition performance, and individual working memory (WM) capacity in hearing impaired hearing aid users. In two experiments, participants with hearing loss rated perceived effort during aided speech perception in noise. Noise type and SNR were manipulated in both experiments, and in the second experiment hearing aid compression release settings were also manipulated. Speech recognition performance was measured along with WM capacity. There were 46 participants in all with bilateral mild to moderate sloping hearing loss. In Experiment 1 there were 16 native Danish speakers (eight women and eight men) with a mean age of 63.5 yr (SD = 12.1) and average pure tone (PT) threshold of 47. 6 dB (SD = 9.8). In Experiment 2 there were 30 native Swedish speakers (19 women and 11 men) with a mean age of 70 yr (SD = 7.8) and average PT threshold of 45.8 dB (SD = 6.6). A visual analog scale (VAS) was used for effort rating in both experiments. In Experiment 1, effort was rated at individually adapted SNRs while in Experiment 2 it was rated at fixed SNRs. Speech recognition in noise performance was measured using adaptive procedures in both experiments with Dantale II sentences in Experiment 1 and Hagerman sentences in Experiment 2. WM capacity was measured using a letter-monitoring task in Experiment 1 and the reading span task in Experiment 2. In both experiments, there was a strong and significant relation between rated effort and SNR that was independent of individual WM capacity, whereas the

  1. Differential impact of response effort within a response chain on use of mands in a student with autism.

    PubMed

    Buckley, Scott D; Newchok, Debra K

    2005-01-01

    We investigated the effects of response effort on the use of mands during functional communication training (FCT) in a participant with autism. The number of links in a picture exchange response chain determined two levels of response effort. Each level was paired with a fixed ratio (FR3) schedule of reinforcement for aggression in a reversal design. Responding to either schedule produced access to a preferred item. The participant opted for the low effort mand while aggression decreased significantly. However, the high effort mand did not compete with the FR3 schedule for aggression. Results are discussed in terms of response effort within a response chain of a picture exchange system and competing ratio schedules for problem behavior during mand training.

  2. Impacts on terrestrial biodiversity of moving from a 2°C to a 1.5°C target.

    PubMed

    Smith, Pete; Price, Jeff; Molotoks, Amy; Warren, Rachel; Malhi, Yadvinder

    2018-05-13

    We applied a recently developed tool to examine the reduction in climate risk to biodiversity in moving from a 2°C to a 1.5°C target. We then reviewed the recent literature examining the impact of (a) land-based mitigation options and (b) land-based greenhouse gas removal options on biodiversity. We show that holding warming to 1.5°C versus 2°C can significantly reduce the number of species facing a potential loss of 50% of their climatic range. Further, there would be an increase of 5.5-14% of the globe that could potentially act as climatic refugia for plants and animals, an area equivalent to the current global protected area network. Efforts to meet the 1.5°C target through mitigation could largely be consistent with biodiversity protection/enhancement. For impacts of land-based greenhouse gas removal technologies on biodiversity, some (e.g. soil carbon sequestration) could be neutral or positive, others (e.g. bioenergy with carbon capture and storage) are likely to lead to conflicts, while still others (e.g. afforestation/reforestation) are context-specific, when applied at scales necessary for meaningful greenhouse gas removal. Additional effort to meet the 1.5°C target presents some risks, particularly if inappropriately managed, but it also presents opportunities.This article is part of the theme issue 'The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'. © 2018 The Authors.

  3. Impacts on terrestrial biodiversity of moving from a 2°C to a 1.5°C target

    PubMed Central

    Price, Jeff; Molotoks, Amy; Warren, Rachel

    2018-01-01

    We applied a recently developed tool to examine the reduction in climate risk to biodiversity in moving from a 2°C to a 1.5°C target. We then reviewed the recent literature examining the impact of (a) land-based mitigation options and (b) land-based greenhouse gas removal options on biodiversity. We show that holding warming to 1.5°C versus 2°C can significantly reduce the number of species facing a potential loss of 50% of their climatic range. Further, there would be an increase of 5.5–14% of the globe that could potentially act as climatic refugia for plants and animals, an area equivalent to the current global protected area network. Efforts to meet the 1.5°C target through mitigation could largely be consistent with biodiversity protection/enhancement. For impacts of land-based greenhouse gas removal technologies on biodiversity, some (e.g. soil carbon sequestration) could be neutral or positive, others (e.g. bioenergy with carbon capture and storage) are likely to lead to conflicts, while still others (e.g. afforestation/reforestation) are context-specific, when applied at scales necessary for meaningful greenhouse gas removal. Additional effort to meet the 1.5°C target presents some risks, particularly if inappropriately managed, but it also presents opportunities. This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'. PMID:29610386

  4. Reproductive effort in invasive and non-invasive Rubus.

    PubMed

    McDowell, Susan C; Turner, David P

    2002-10-01

    We quantified the physiological costs and the total amount of resources allocated to reproduction in two closely related species of Rubus, one of which is invasive. These two species share several morphological and life-history characteristics and grow together in the Pacific Northwestern United States. Reproductive effort was manipulated in canes of both species by removing flower buds. The non-invasive species, R. ursinus, exhibited significantly greater water stress in the reproductive canes, as indicated by lower leaf water potential (Ψ) and reduced stomatal conductance (g s ). This species also showed a reduction in leaf nitrogen concentration ([N]) associated with reproduction. Combined, these factors led to reduced photosynthesis (A) on a diurnal basis, lower water-use efficiency as inferred from δ 13 C, and reduced photosynthetic capacity. All of these effects were more pronounced during the fruiting stage than in the flowering stage. The invasive species, R. discolor, showed no changes in water stress, [N], δ 13 C, or A associated with reproduction. A model was used to estimate total gross photosynthesis (A gross ) for reproductive and non-reproductive canes of both species over cane lifetime. Reproduction was associated with a greater decline in A gross for the non-invasive R. ursinus than for the invasive R. discolor. Although R. discolor allocated more resources directly to flowers and fruit than R. ursinus, the invasive species had significantly lower reproductive effort, or total amount of resources diverted from vegetative activity to reproduction, than the non-invasive species. By minimizing the reduction of photosynthesis associated with reproduction, this invasive species may be able to minimize the trade-offs commonly associated with reproduction.

  5. Traditional Indian spices and their health significance.

    PubMed

    Krishnaswamy, Kamala

    2008-01-01

    India has been recognized all over the world for spices and medicinal plants. Both exhibit a wide range of physiological and pharmacological properties. Current biomedical efforts are focused on their scientific merits, to provide science-based evidence for the traditional uses and to develop either functional foods or nutraceuticals. The Indian traditional medical systems use turmeric for wound healing, rheumatic disorders, gastrointestinal symptoms, deworming, rhinitis and as a cosmetic. Studies in India have explored its anti-inflammatory, cholekinetic and anti-oxidant potentials with the recent investigations focusing on its preventive effect on precarcinogenic, anti-inflammatory and anti atherosclerotic effects in biological systems both under in vitro and in vivo conditions in animals and humans. Both turmeric and curcumin were found to increase detoxifying enzymes, prevent DNA damage, improve DNA repair, decrease mutations and tumour formation and exhibit antioxidative potential in animals. Limited clinical studies suggest that turmeric can significantly impact excretion of mutagens in urine in smokers and regress precancerous palatal lesions. It reduces DNA adducts and micronuclei in oral epithelial cells. It prevents formation of nitroso compounds both in vivo and in vitro. It delays induced cataract in diabetes and reduces hyperlipidemia in obese rats. Recently several molecular targets have been identified for therapeutic / preventive effects of turmeric. Fenugreek seeds, a rich source of soluble fiber used in Indian cuisine reduces blood glucose and lipids and can be used as a food adjuvant in diabetes. Similarly garlic, onions, and ginger have been found to modulate favourably the process of carcinogenesis.

  6. Computational design of high efficiency release targets for use at ISOL facilities

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Alton, G. D.; Middleton, J. W.

    1999-06-01

    This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated vitreous carbon fiber (RVCF) or carbon-bonded-carbon-fiber (CBCF) to form highly permeable composite target matrices. Computational studies which simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived from diffusion release-rate simulation studies for selected targets and thermal analyses of temperature distributions within a prototype target/heat-sink system subjected to primary ion beam irradiation will be presented in this report.

  7. Biomechanical Comparison of Three Perceived Effort Set Shots in Team Handball Players.

    PubMed

    Plummer, Hillary A; Gascon, Sarah S; Oliver, Gretchen D

    2017-01-01

    Plummer, HA, Gascon, SS, and Oliver, GD. Biomechanical comparison of three perceived effort set shots in team handball players. J Strength Cond Res 31(1): 80-87, 2017-Shoulder injuries are prevalent in the sport of team handball; however, no guidelines currently exist in the implementation of an interval throwing protocol for players returning from an upper extremity injury. These guidelines exist for the sport of baseball, but team handball may present additional challenges due to greater ball mass that must be accounted for. The purpose of this study was to examine kinematic differences in the team handball set shot at 50, 75, and 100% effort which are common throwing intensities in throwing protocols. Eleven male team handball players (23.09 ± 3.05 years; 185.12 ± 8.33 cm; 89.65 ± 12.17 kg) volunteered. An electromagnetic tracking system was used to collect kinematic data at the pelvis, trunk, scapula, and shoulder. Kinematic differences at the shoulder, trunk, and pelvis were observed across effort levels throughout the set shot with most occurring at ball release and maximum internal rotation. Significant differences in ball speed were observed between all 3 effort level shots (p < 0.001). Team handball players are able to gauge the effort at which they shoot; however, it cannot be assumed that these speeds will be at a certain percentage of their maximum. The results of this study provide valuable evidence that can be used to prepare a team handball player to return to throwing activities.

  8. A Random Variable Approach to Nuclear Targeting and Survivability

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

    Undem, Halvor A.

    We demonstrate a common mathematical formalism for analyzing problems in nuclear survivability and targeting. This formalism, beginning with a random variable approach, can be used to interpret past efforts in nuclear-effects analysis, including targeting analysis. It can also be used to analyze new problems brought about by the post Cold War Era, such as the potential effects of yield degradation in a permanently untested nuclear stockpile. In particular, we illustrate the formalism through four natural case studies or illustrative problems, linking these to actual past data, modeling, and simulation, and suggesting future uses. In the first problem, we illustrate themore » case of a deterministically modeled weapon used against a deterministically responding target. Classic "Cookie Cutter" damage functions result. In the second problem, we illustrate, with actual target test data, the case of a deterministically modeled weapon used against a statistically responding target. This case matches many of the results of current nuclear targeting modeling and simulation tools, including the result of distance damage functions as complementary cumulative lognormal functions in the range variable. In the third problem, we illustrate the case of a statistically behaving weapon used against a deterministically responding target. In particular, we show the dependence of target damage on weapon yield for an untested nuclear stockpile experiencing yield degradation. Finally, and using actual unclassified weapon test data, we illustrate in the fourth problem the case of a statistically behaving weapon used against a statistically responding target.« less

  9. Phage protein-targeted cancer nanomedicines

    PubMed Central

    Petrenko, V.A.; Jayanna, P.K.

    2015-01-01

    Nanoencapsulation of anticancer drugs improves their therapeutic indices by virtue of the enhanced permeation and retention effect which achieves passive targeting of nanoparticles in tumors. This effect can be significantly enhanced by active targeting of nanovehicles to tumors. Numerous ligands have been proposed and used in various studies with peptides being considered attractive alternatives to antibodies. This is further reinforced by the availability of peptide phage display libraries which offer an unlimited reservoir of target-specific probes. In particular landscape phages with multivalent display of target-specific peptides which enable the phage particle itself to become a nanoplatform creates a paradigm for high throughput selection of nanoprobes setting the stage for personalized cancer management. Despite its promise, this conjugate of combinatorial chemistry and nanotechnology has not made a significant clinical impact in cancer management due to a lack of using robust processes that facilitate scale-up and manufacturing. To this end we proposed the use of phage fusion protein as the navigating modules of novel targeted nanomedicine platforms which are described in this review. PMID:24269681

  10. Targeted Inhibition of Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Sensitizes Pancreatic Cancer Cells to Doxorubicin without Exacerbating Cardiac Toxicity.

    PubMed

    Durrant, David E; Das, Anindita; Dyer, Samya; Tavallai, Seyedmehrad; Dent, Paul; Kukreja, Rakesh C

    2015-09-01

    Pancreatic cancer has the lowest 5-year survival rate of all major cancers despite decades of effort to design and implement novel, more effective treatment options. In this study, we tested whether the dual phosphoinositide 3-kinase/mechanistic target of rapamycin inhibitor BEZ235 (BEZ) potentiates the antitumor effects of doxorubicin (DOX) against pancreatic cancer. Cotreatment of BEZ235 with DOX resulted in dose-dependent inhibition of the phosphoinositide 3-kinase/mechanistic target of rapamycin survival pathway, which corresponded with an increase in poly ADP ribose polymerase cleavage. Moreover, BEZ cotreatment significantly improved the effects of DOX toward both cell viability and cell death in part through reduced Bcl-2 expression and increased expression of the shorter, more cytotoxic forms of BIM. BEZ also facilitated intracellular accumulation of DOX, which led to enhanced DNA damage and reactive oxygen species generation. Furthermore, BEZ in combination with gemcitabine reduced MiaPaca2 cell proliferation but failed to increase reactive oxygen species generation or BIM expression, resulting in reduced necrosis and apoptosis. Treatment with BEZ and DOX in mice bearing tumor xenographs significantly repressed tumor growth as compared with BEZ, DOX, or gemcitabine. Additionally, in contrast to the enhanced expression seen in MiaPaca2 cells, BEZ and DOX cotreatment reduced BIM expression in H9C2 cardiomyocytes. Also, the Bcl-2/Bax ratio was increased, which was associated with a reduction in cell death. In vivo echocardiography showed decreased cardiac function with DOX treatment, which was not improved by combination treatment with BEZ. Thus, we propose that combining BEZ with DOX would be a better option for patients than current standard of care by providing a more effective tumor response without the associated increase in toxicity. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Response effort discounts the subjective value of rewards.

    PubMed

    Nishiyama, Ryoji

    2014-09-01

    Factors associated with obtaining a reward, such as a temporal delay in receiving the reward, can influence the subjective value of the reward. Cognitive as well as physical response effort is also known to influence choice behaviors. The present study used hypothetical situations to assess whether response effort affects the subjective value of rewards. The results demonstrated that increasing response effort increases the amount of money that participants are willing to forgo to avoid engaging in work. An exponential as well as hyperbolic function provided a good fit for such discounting. The findings suggest that response effort discounts the subjective value of a reward as a function of its amount. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Life Science Professional Societies Expand Undergraduate Education Efforts

    PubMed Central

    Matyas, Marsha Lakes; Ruedi, Elizabeth A.; Engen, Katie; Chang, Amy L.

    2017-01-01

    The Vision and Change in Undergraduate Biology Education reports cite the critical role of professional societies in undergraduate life science education and, since 2008, have called for the increased involvement of professional societies in support of undergraduate education. Our study explored the level of support being provided by societies for undergraduate education and documented changes in support during the Vision and Change era. Society representatives responded to a survey on programs, awards, meetings, membership, teaching resources, publications, staffing, finances, evaluation, and collaborations that address undergraduate faculty and students. A longitudinal comparison group of societies responded to surveys in both 2008 and 2014. Results indicate that life science professional societies are extensively engaged in undergraduate education in their fields, setting standards for their discipline, providing vetted education resources, engaging students in both research and education, and enhancing professional development and recognition/status for educators. Societies are devoting funding and staff to these efforts and engaging volunteer leadership. Longitudinal comparison group responses indicate there have been significant and quantifiable expansions of undergraduate efforts in many areas since 2008. These indicators can serve as a baseline for defining, aligning, and measuring how professional societies can promote sustainable, evidence-based support of undergraduate education initiatives. PMID:28130272

  13. A structural biology perspective on bioactive small molecules and their plant targets.

    PubMed

    Kumari, Selva; van der Hoorn, Renier A L

    2011-10-01

    Structural biology efforts in recent years have generated numerous co-crystal structures of bioactive small molecules interacting with their plant targets. These studies include the targets of various phytohormones, pathogen-derived effectors, herbicides and other bioactive compounds. Here we discuss that this collection of structures contains excellent examples of nine collective observations: molecular glues, allostery, inhibitors, molecular mimicry, promiscuous binding sites, unexpected electron densities, natural selection at atomic resolution, and applications in structure-guided mutagenesis and small molecule design. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Implementing Target Value Design.

    PubMed

    Alves, Thais da C L; Lichtig, Will; Rybkowski, Zofia K

    2017-04-01

    An alternative to the traditional way of designing projects is the process of target value design (TVD), which takes different departure points to start the design process. The TVD process starts with the client defining an allowable cost that needs to be met by the design and construction teams. An expected cost in the TVD process is defined through multiple interactions between multiple stakeholders who define wishes and others who define ways of achieving these wishes. Finally, a target cost is defined based on the expected profit the design and construction teams are expecting to make. TVD follows a series of continuous improvement efforts aimed at reaching the desired goals for the project and its associated target value cost. The process takes advantage of rapid cycles of suggestions, analyses, and implementation that starts with the definition of value for the client. In the traditional design process, the goal is to identify user preferences and find solutions that meet the needs of the client's expressed preferences. In the lean design process, the goal is to educate users about their values and advocate for a better facility over the long run; this way owners can help contractors and designers to identify better solutions. This article aims to inform the healthcare community about tools and techniques commonly used during the TVD process and how they can be used to educate and support project participants in developing better solutions to meet their needs now as well as in the future.

  15. Comparative Study of State Tax Effort and the Role of Federal Government Policy in Shaping Revenue Reliance Patterns.

    ERIC Educational Resources Information Center

    Alexander, F. King

    2003-01-01

    Compared the willingness of states to invest in higher education and institutional sectors by studying state expenditures and fiscal tax effort. Findings show significant disparities in the ways states finance higher education and its sectors. Poorer states tend to exert more tax effort in public higher education, while wealthier states are less…

  16. Visual Cues and Listening Effort: Individual Variability

    ERIC Educational Resources Information Center

    Picou, Erin M.; Ricketts, Todd A; Hornsby, Benjamin W. Y.

    2011-01-01

    Purpose: To investigate the effect of visual cues on listening effort as well as whether predictive variables such as working memory capacity (WMC) and lipreading ability affect the magnitude of listening effort. Method: Twenty participants with normal hearing were tested using a paired-associates recall task in 2 conditions (quiet and noise) and…

  17. Advances in the Engineering of the Gene Editing Enzymes and the Genomes: Understanding and Handling the Off-Target Effects of CRISPR/Cas9.

    PubMed

    Yin, Yufang; Wang, Qian; Xiao, Li; Wang, Fengjiao; Song, Zhuo; Zhou, Cuilan; Liu, Xuan; Xing, Chungen; He, Nongyue; Li, Kai; Feng, Yan; Zhang, Jia

    2018-03-01

    In the past decades, significant progresses have been achieved in genetic engineering of nucleases. Among the genetically engineered nucleases, zinc finger nucleases, transcription activator-like (TAL) effector nucleases, and CRIPSPR/Cas9 system form a new field of gene editing. The gene editing efficiency or targeting effect and the off-target effect are the two major determinant factors in evaluating the usefulness of a new enzyme. Engineering strategies in improving these gene editing enzymes, particularly in minimizing their off-target effects, are the focus of this paper. Examples of using these genetically engineered enzymes in genome modification are discussed in order to better understand the requirement of engineering efforts in obtaining more powerful and useful gene editing enzymes. In addition, the identification of naturally existed anti-Cas proteins has been employed in minimizing off-target effects. Considering the future application in human gene therapy, optimization of these well recognized gene editing enzymes and exploration of more novel enzymes are both required. Before people find an ideal gene editing system having virtually no off-target effect, technologies used to screen and identify off-target effects are of importance in clinical trials employing gene therapy.

  18. Fe₃O₄ Nanoparticles in Targeted Drug/Gene Delivery Systems.

    PubMed

    Shen, Lazhen; Li, Bei; Qiao, Yongsheng

    2018-02-23

    Fe₃O₄ nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe₃O₄ NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe₃O₄ NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe₃O₄ NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe₃O₄ NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe₃O₄ NPs targeting drug/gene delivery systems.

  19. Progress in the Visualization and Mining of Chemical and Target Spaces.

    PubMed

    Medina-Franco, José L; Aguayo-Ortiz, Rodrigo

    2013-12-01

    Chemogenomics is a growing field that aims to integrate the chemical and target spaces. As part of a multi-disciplinary effort to achieve this goal, computational methods initially developed to visualize the chemical space of compound collections and mine single-target structure-activity relationships, are being adapted to visualize and mine complex relationships in chemogenomics data sets. Similarly, the growing evidence that clinical effects are many times due to the interaction of single or multiple drugs with multiple targets, is encouraging the development of novel methodologies that are integrated in multi-target drug discovery endeavors. Herein we review advances in the development and application of approaches to generate visual representations of chemical space with particular emphasis on methods that aim to explore and uncover relationships between chemical and target spaces. Also, progress in the data mining of the structure-activity relationships of sets of compounds screened across multiple targets are discussed in light of the concept of activity landscape modeling. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Understanding Laser-Imprint Effects on Plastic-Target Implosions on OMEGA with New Physics Models

    NASA Astrophysics Data System (ADS)

    Hu, S. X.; Michel, D. T.; Davis, A. K.; Betti, R.; Radha, P. B.; Campbell, E. M.; Froula, D. H.; Stoeckl, C.

    2016-10-01

    Using the state-of-the-art physics models (nonlocal thermal transport, cross-beam energy transfer, and first-principles equation of state) recently implemented in our two-dimensional hydrocode DRACO, we have performed a systematic study of laser-imprint effects on plastic-target implosions on OMEGA by both simulations and experiments. Through varying the laser picket intensity, the imploding shells were set at different adiabats ranging from α = 2 to α = 6 . As the shell adiabat α decreases, we observed: (1) the measured shell thickness at the hot spot emission becomes larger than the uniform prediction; (2) the hot-spot core emits and neutron burn starts earlier than the corresponding 1-D prediction; and (3) the measured neutron yields are significantly reduced from their 1-D designs. Most of these experimental observations are well reproduced by our DRACO simulations with laser imprints. These studies clearly identify that laser imprint is the major cause for target performance degradation of OMEGA implosions of α <= 3 . Mitigating laser imprints must be an essential effort to improve low- α target performance in direct-drive inertial confinement fusion ignition attempts. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

  1. The role of effort in influencing the effect of anxiety on performance: testing the conflicting predictions of processing efficiency theory and the conscious processing hypothesis.

    PubMed

    Wilson, Mark; Smith, Nickolas C; Holmes, Paul S

    2007-08-01

    The aim of this study was to test the conflicting predictions of processing efficiency theory (PET) and the conscious processing hypothesis (CPH) regarding effort's role in influencing the effects of anxiety on a golf putting task. Mid-handicap golfers made a series of putts to target holes under two counterbalanced conditions designed to manipulate the level of anxiety experienced. The effort exerted on each putting task was assessed though self-report, psychophysiological (heart rate variability) and behavioural (pre-putt time and glances at the target) measures. Performance was assessed by putting error. Results were generally more supportive of the predictions of PET rather than the CPH as performance was maintained for some performers despite increased state anxiety and a reduction in processing efficiency. The findings of this study support previous research suggesting that both theories offer useful theoretical frameworks for examining the relationship between anxiety and performance in sport.

  2. Important historical efforts at emergency department categorization in the United States and implications for regionalization.

    PubMed

    Mehrotra, Abhishek; Sklar, David P; Tayal, Vivek S; Kocher, Keith E; Handel, Daniel A; Myles Riner, R

    2010-12-01

    This article is drawn from a report created for the American College of Emergency Physicians (ACEP) Emergency Department (ED) Categorization Task Force and also reflects the proceedings of a breakout session, "Beyond ED Categorization-Matching Networks to Patient Needs," at the 2010 Academic Emergency Medicine consensus conference, "Beyond Regionalization: Integrated Networks of Emergency Care." The authors describe a brief history of the significant national and state efforts at categorization and suggest reasons why many of these efforts failed to persevere or gain wider implementation. The history of efforts to categorize hospital (and ED) emergency services demonstrates recognition of the potential benefits of categorization, but reflects repeated failures to implement full categorization systems or limited excursions into categorization through licensing of EDs or designation of receiving and referral facilities. An understanding of the history of hospital and ED categorization could better inform current efforts to develop categorization schemes and processes. 2010 by the Society for Academic Emergency Medicine.

  3. R.J. Reynolds' targeting of African Americans: 1988-2000.

    PubMed

    Balbach, Edith D; Gasior, Rebecca J; Barbeau, Elizabeth M

    2003-05-01

    The purpose of this study was to describe RJ Reynolds (RJR) Tobacco Company's strategy for targeting African Americans, as revealed in tobacco industry documents and magazine advertisements. The authors searched industry documents to determine RJR's strategies and analyzed magazine advertising during 2 periods: the time of the launch of the company's Uptown cigarette (1989-1990) and a decade later (1999-2000). RJR's efforts to target the African American market segment existed before and after Uptown, and the company's strategy was largely implemented via other RJR brands. Advertisements featured mentholated cigarettes, fantasy/escape, expensive objects, and nightlife. To help all populations become tobacco-free, tobacco control practitioners must understand and counter tobacco industry strategies.

  4. UAHuntsville-NASA MSFC Heliophysics REU: A Model for Recruiting Targeted Groups

    NASA Astrophysics Data System (ADS)

    Farid, S.; Heerikhuisen, J.; Winebarger, A. R.

    2014-12-01

    In 2011, researchers from the University of Alabama-Huntsville Center for Space Plasma and Aeronomic Research Center (CSPAR) and NASA Marshall Space Fight Center (MSFC) received a 3-year NSF award to create a REU site specifically designed to increase the participation of underrepresented groups in the Geo-sciences, specifically Heliophysics, and to reduce the attrition rate of sophomores by engaging them in research. This program has been highly successful. In three years of operation, we have increased in the diversity of applicant pool and selected participants, increased the number of inexperienced participants and made measurable impacts on the students' perceptions of graduate school and Heliophysics careers, and produced research with significant scientific merit. We attribute the success of the program to our proactive recruitment of first and second year students, underrepresented groups, and students from small universities. Key factors in our efforts include: 1) In person school visits of targeted schools 2.) Establishing relationships with faculty at targeted schools. 3.) An inclusive selection process that considers the availability of research at the students home institution 4.) A reduced focus on GPA and more focus on recommendation letters as indicators of success 5.) A successful cohort of experienced and inexperienced students 6.) The unique learning environment fostered by UAH-CSPAR and NASA-MSFC scientists. In this presentation, we review our strategies and suggest techniques to recruit targeted groups to similar REU programs.

  5. Heuristics Made Easy: An Effort-Reduction Framework

    ERIC Educational Resources Information Center

    Shah, Anuj K.; Oppenheimer, Daniel M.

    2008-01-01

    In this article, the authors propose a new framework for understanding and studying heuristics. The authors posit that heuristics primarily serve the purpose of reducing the effort associated with a task. As such, the authors propose that heuristics can be classified according to a small set of effort-reduction principles. The authors use this…

  6. ATR NSUF Instrumentation Enhancement Efforts

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

    Joy L. Rempe; Mitchell K. Meyer; Darrell L. Knudson

    A key component of the Advanced Test Reactor (ATR) National Scientific User Facility (NSUF) effort is to expand instrumentation available to users conducting irradiation tests in this unique facility. In particular, development of sensors capable of providing real-time measurements of key irradiation parameters is emphasized because of their potential to increase data fidelity and reduce posttest examination costs. This paper describes the strategy for identifying new instrumentation needed for ATR irradiations and the program underway to develop and evaluate new sensors to address these needs. Accomplishments from this program are illustrated by describing new sensors now available to users ofmore » the ATR NSUF. In addition, progress is reported on current research efforts to provide improved in-pile instrumentation to users.« less

  7. JTPA: Targeting, Outreach and Recruitment. A Technical Assistance and Training Series.

    ERIC Educational Resources Information Center

    Employment and Training Administration (DOL), Washington, DC.

    This guide, which was developed with input from more than 120 Job Training Partnership Act (JTPA) programs across the United States, is designed to give JTPA program staff new ideas for conducting their targeting, outreach, and recruitment efforts. Presented first are an overview of the guide's contents and suggestions for using it. The first five…

  8. Identifying Belief-Based Targets for the Promotion of Leisure-Time Walking

    ERIC Educational Resources Information Center

    Rhodes, Ryan E.; Blanchard, Chris M.; Courneya, Kerry S.; Plotnikoff, Ronald C.

    2009-01-01

    Walking is the most common type of physical activity (PA) and the likely target of efforts to increase PA. No studies, however, have identified the belief-level correlates for walking using the theory of planned behavior. This study elicits salient beliefs about walking and evaluates beliefs that may be most important for walking-promotion…

  9. Subthalamic Nucleus Local Field Potential Activity Helps Encode Motor Effort Rather Than Force in Parkinsonism

    PubMed Central

    Pogosyan, Alek; Ashkan, Keyoumars; Cheeran, Binith; FitzGerald, James J.; Green, Alexander L.; Aziz, Tipu; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Brown, Peter

    2015-01-01

    Local field potential (LFP) recordings from patients with deep brain stimulation electrodes in the basal ganglia have suggested that frequency-specific activities correlate with force or effort, but previous studies have not been able to disambiguate the two. Here, we dissociated effort from actual force generated by contrasting the force generation of different fingers while recording LFP activity from the subthalamic nucleus (STN) in patients with Parkinson's disease who had undergone functional surgery. Patients were studied while on their normal dopaminergic medication. We investigated the relationship between frequency-specific oscillatory activity in the STN and voluntary flexion of either the index or little finger at different effort levels. At each tested effort level (10%, 25%, and 40% of the maximal voluntary contraction force of each individual finger), the index finger generated larger force than the little finger. Movement-related suppression of beta-band power in the STN LFP was significantly modulated by effort, but not by which finger was used, suggesting that the beta suppression in the STN LFP during sustained contraction serves as a proxy for effort. The absolute force scaled with beta power suppression, but with the scaling determined by the maximal voluntary contraction force of the motor effector. Our results argue against the hypothesis that the basal ganglia are directly involved in the parameterization of force during movement and support a role of the STN in the control of motor effort to be attributed to a response. PMID:25878267

  10. Intensity and duration of physical efforts in Physical Education classes.

    PubMed

    Kremer, Marina Marques; Reichert, Felipe Fossati; Hallal, Pedro Curi

    2012-04-01

    To evaluate the intensity and duration of physical efforts in Physical Education classes in primary and secondary school. School-based cross-sectional study carried out by means of the observation of 218 Physical Education classes, including a total of 272 students (each one of the students was evaluated three times). The study was carried out in the city of Pelotas (Southern Brazil), between August and December 2009. In order to evaluate the intensity of the efforts, accelerometers were used and the following cut-off points were adopted (in counts per minute): sedentary activities (0-100), light activities (101-2,000), moderate (2,001-4,999), vigorous (5,000-7,999), and very vigorous activities (>8000). The mean duration of the classes was 35.6 minutes (SD 6.0). The mean proportion of time spent in moderate to vigorous physical activity was 32.7% (SD 25.2). Boys (44.1%) were involved significantly more in moderate to vigorous physical activity as compared to girls (21.0%; p<0.01). Students who practice physical activities outside the classes participated more in moderate to vigorous physical activity in the Physical Education classes. Besides the fact that Physical Education classes have a short duration, students practice moderate to vigorous physical activity during one third of the class, with a poor significant contribution to students' level of physical activity.

  11. Analyzing Body Movements within the Laban Effort Framework Using a Single Accelerometer

    PubMed Central

    Kikhia, Basel; Gomez, Miguel; Jiménez, Lara Lorna; Hallberg, Josef; Karvonen, Niklas; Synnes, Kåre

    2014-01-01

    This article presents a study on analyzing body movements by using a single accelerometer sensor. The investigated categories of body movements belong to the Laban Effort Framework: Strong—Light, Free—Bound and Sudden—Sustained. All body movements were represented by a set of activities used for data collection. The calculated accuracy of detecting the body movements was based on collecting data from a single wireless tri-axial accelerometer sensor. Ten healthy subjects collected data from three body locations (chest, wrist and thigh) simultaneously in order to analyze the locations comparatively. The data was then processed and analyzed using Machine Learning techniques. The wrist placement was found to be the best single location to record data for detecting Strong—Light body movements using the Random Forest classifier. The wrist placement was also the best location for classifying Bound—Free body movements using the SVM classifier. However, the data collected from the chest placement yielded the best results for detecting Sudden—Sustained body movements using the Random Forest classifier. The study shows that the choice of the accelerometer placement should depend on the targeted type of movement. In addition, the choice of the classifier when processing data should also depend on the chosen location and the target movement. PMID:24662408

  12. Regionally Applied Research Efforts (RARE) Report titled " ...

    EPA Pesticide Factsheets

    The traditional methodology for health risk assessment used by the U. S. Environmental Protection Agency (EPA) is based on the use of exposure assumptions (e.g. exposure duration, food ingestion rate, body weight, etc.) that represent the entire American population, either as a central tendency exposure (e.g. average, median) or as a reasonable maximum exposure (e.g. 95% upper confidence limit). Unfortunately, EPA lacked exposure information for assessing health risks for New England regional tribes sustaining a tribal subsistence way of life. As a riverine tribe, the Penobscot culture and traditions are inextricably tied to the Penobscot River watershed. It is through hunting, fishing, trapping, gathering and making baskets, pottery, moccasins, birch-bark canoes and other traditional practices that the Penobscot culture and people are sustained. The Penobscot River receives a variety of pollutant discharges leaving the Penobscot Indian Nation (PIN) questioning the ecological health and water quality of the river and how this may affect the practices that sustain their way of life. The objectives of this Regional Applied Research Effort (RARE) study were to: (1) Develop culturally sensitive methodologies for assessing the potential level of exposure to contaminants that Penobscot Indian Nation tribal members may have from maintaining tribal sustenance practices; (2) Conduct field surveys and laboratory analysis on targeted flora and fauna for chemical expo

  13. The Expanding Diversity of Mycobacterium tuberculosis Drug Targets.

    PubMed

    Wellington, Samantha; Hung, Deborah T

    2018-05-11

    After decades of relative inactivity, a large increase in efforts to discover antitubercular therapeutics has brought insights into the biology of Mycobacterium tuberculosis (Mtb) and promising new drugs such as bedaquiline, which inhibits ATP synthase, and the nitroimidazoles delamanid and pretomanid, which inhibit both mycolic acid synthesis and energy production. Despite these advances, the drug discovery pipeline remains underpopulated. The field desperately needs compounds with novel mechanisms of action capable of inhibiting multi- and extensively drug -resistant Mtb (M/XDR-TB) and, potentially, nonreplicating Mtb with the hope of shortening the duration of required therapy. New knowledge about Mtb, along with new methods and technologies, has driven exploration into novel target areas, such as energy production and central metabolism, that diverge from the classical targets in macromolecular synthesis. Here, we review new small molecule drug candidates that act on these novel targets to highlight the methods and perspectives advancing the field. These new targets bring with them the aspiration of shortening treatment duration as well as a pipeline of effective regimens against XDR-TB, positioning Mtb drug discovery to become a model for anti-infective discovery.

  14. Post Irradiation Examination Results of the NT-02 Graphite Fins NUMI Target

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

    Ammigan, K.; Hurh, P.; Sidorov, V.

    2017-02-10

    The NT-02 neutrino target in the NuMI beamline at Fermilab is a 95 cm long target made up of segmented graphite fins. It is the longest running NuMI target, which operated with a 120 GeV proton beam with maximum power of 340 kW, and saw an integrated total proton on target of 6.1 1020. Over the last half of its life, gradual degradation of neutrino yield was observed until the target was replaced. The probable causes for the target performance degradation are attributed to radiation damage, possibly including cracking caused by reduction in thermal shock resistance, as well as potentialmore » localized oxidation in the heated region of the target. Understanding the long-termstructural response of target materials exposed to proton irradiation is critical as future proton accelerator sources are becoming increasingly more powerful. As a result, an autopsy of the target was carried out to facilitate post-irradiation examination of selected graphite fins. Advanced microstructural imaging and surface elemental analysis techniques were used to characterize the condition of the fins in an effort to identify degradation mechanisms, and the relevant findings are presented in this paper.« less

  15. Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology.

    PubMed

    Salamone, John D; Yohn, Samantha E; López-Cruz, Laura; San Miguel, Noemí; Correa, Mercè

    2016-05-01

    Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work-related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort-related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson's disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort-related decision

  16. The Effect of Age on Listening Effort

    ERIC Educational Resources Information Center

    Degeest, Sofie; Keppler, Hannah; Corthals, Paul

    2015-01-01

    Purpose: The objective of this study was to investigate the effect of age on listening effort. Method: A dual-task paradigm was used to evaluate listening effort in different conditions of background noise. Sixty adults ranging in age from 20 to 77 years were included. A primary speech-recognition task and a secondary memory task were performed…

  17. NASA cryogenic fluid management space experiment efforts

    NASA Technical Reports Server (NTRS)

    Glover, Daniel

    1991-01-01

    A history of technological development for subcritical cryogenic fluid management (CFM) through space experiments is given for the period 1960 to 1990. Space experiments with liquid hydrogen were conducted in the early 1960s. Efforts since then have consisted of studies and designs of potential space experiments. A chronology of CFM space experiments and design efforts is included.

  18. Malthusian overfishing and efforts to overcome it on Kenyan coral reefs.

    PubMed

    McClanahan, Tim R; Hicks, Christina C; Darling, Emily S

    2008-09-01

    This study examined trends along a gradient of fishing intensity in an artisanal coral reef fishery over a 10-year period along 75 km of Kenya's most populated coastline. As predicted by Malthusian scenarios, catch per unit effort (CPUE), mean trophic level, the functional diversity of fished taxa, and the diversity of gear declined, while total annual catch and catch variability increased along the fishing pressure gradient. The fishery was able to sustain high (approximately 16 Mg x km(-2) x yr(-1)) but variable yields at high fishing pressure due to the dominance of a few productive herbivorous fish species in the catch. The effect of two separate management strategies to overcome this Malthusian pattern was investigated: fisheries area closure and elimination of the dominant and most "competitive" gear. We found that sites within 5 km of the enforced closure showed significantly lower total catch and CPUE, but increased yield stability and trophic level of catch than predicted by regression models normalized for fishing effort. Sites that had excluded illegal beach seine use through active gear management exhibited increased total catch and CPUE. There was a strong interaction between closure and gear management, which indicates that, for closures to be effective at increasing catch, there must be simultaneous efforts at gear management around the periphery of the closures. We propose that Malthusian effects are responsible for the variation in gear and catch and that active management through reduced effort and reductions in the most competitive gear have the greatest potential to increase the functional and trophic diversity and per-person productivity.

  19. Toward Personalized Targeted Therapeutics: An Overview.

    PubMed

    Weathers, Shiao-Pei S; Gilbert, Mark R

    2017-04-01

    In neuro-oncology, there has been a movement towards personalized medicine, or tailoring treatment to the individual patient. Ideally, tumor and patient evaluations would lead to the selection of the best treatment (based on tumor characterization) and the right dosing schedule (based on patient characterization). The recent advances in the molecular analysis of glioblastoma have created optimism that personalized targeted therapy is within reach. Although our understanding of the molecular complexity of glioblastoma has increased over the years, the path to developing effective targeted therapeutic strategies is wrought with many challenges, as described in this review. These challenges include disease heterogeneity, clinical and genomic patient variability, limited number of effective treatments, clinical trial inefficiency, drug delivery, and clinical trial support and accrual. To confront these challenges, it will be imperative to devise innovative and adaptive clinical trials in order to accelerate our efforts in improving the outcomes for our patients who have been in desperate need.

  20. Measuring cognitive load: performance, mental effort and simulation task complexity.

    PubMed

    Haji, Faizal A; Rojas, David; Childs, Ruth; de Ribaupierre, Sandrine; Dubrowski, Adam

    2015-08-01

    Interest in applying cognitive load theory in health care simulation is growing. This line of inquiry requires measures that are sensitive to changes in cognitive load arising from different instructional designs. Recently, mental effort ratings and secondary task performance have shown promise as measures of cognitive load in health care simulation. We investigate the sensitivity of these measures to predicted differences in intrinsic load arising from variations in task complexity and learner expertise during simulation-based surgical skills training. We randomly assigned 28 novice medical students to simulation training on a simple or complex surgical knot-tying task. Participants completed 13 practice trials, interspersed with computer-based video instruction. On trials 1, 5, 9 and 13, knot-tying performance was assessed using time and movement efficiency measures, and cognitive load was assessed using subjective rating of mental effort (SRME) and simple reaction time (SRT) on a vibrotactile stimulus-monitoring secondary task. Significant improvements in knot-tying performance (F(1.04,24.95)  = 41.1, p < 0.001 for movements; F(1.04,25.90)  = 49.9, p < 0.001 for time) and reduced cognitive load (F(2.3,58.5)  = 57.7, p < 0.001 for SRME; F(1.8,47.3)  = 10.5, p < 0.001 for SRT) were observed in both groups during training. The simple-task group demonstrated superior knot tying (F(1,24)  = 5.2, p = 0.031 for movements; F(1,24)  = 6.5, p = 0.017 for time) and a faster decline in SRME over the first five trials (F(1,26)  = 6.45, p = 0.017) compared with their peers. Although SRT followed a similar pattern, group differences were not statistically significant. Both secondary task performance and mental effort ratings are sensitive to changes in intrinsic load among novices engaged in simulation-based learning. These measures can be used to track cognitive load during skills training. Mental effort ratings are also sensitive to small

  1. Class I Area Significant Impact Levels

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  2. Will weight loss cause significant dosimetric changes of target volumes and organs at risk in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy?

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

    Chen, Chuanben; Fei, Zhaodong; Chen, Lisha

    This study aimed to quantify dosimetric effects of weight loss for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Overall, 25 patients with NPC treated with IMRT were enrolled. We simulated weight loss during IMRT on the computer. Weight loss model was based on the planning computed tomography (CT) images. The original external contour of head and neck was labeled plan 0, and its volume was regarded as pretreatment normal weight. We shrank the external contour with different margins (2, 3, and 5 mm) and generated new external contours of head and neck. The volumes of reconstructed external contoursmore » were regarded as weight during radiotherapy. After recontouring outlines, the initial treatment plan was mapped to the redefined CT scans with the same beam configurations, yielding new plans. The computer model represented a theoretical proportional weight loss of 3.4% to 13.7% during the course of IMRT. The dose delivered to the planning target volume (PTV) of primary gross tumor volume and clinical target volume significantly increased by 1.9% to 2.9% and 1.8% to 2.9% because of weight loss, respectively. The dose to the PTV of gross tumor volume of lymph nodes fluctuated from −2.0% to 1.0%. The dose to the brain stem and the spinal cord was increased (p < 0.001), whereas the dose to the parotid gland was decreased (p < 0.001). Weight loss may lead to significant dosimetric change during IMRT. Repeated scanning and replanning for patients with NPC with an obvious weight loss may be necessary.« less

  3. A REVIEW OF EFFORTS TO ORGANIZE INFORMATION ABOUT HUMAN LEARNING, TRANSFER, AND RETENTION.

    ERIC Educational Resources Information Center

    GINSBERG, ROSE; AND OTHERS

    FOURTEEN EFFORTS TO ORGANIZE AVAILABLE INFORMATION ON HUMAN LEARNING, TRANSFER, AND RETENTION ARE SUMMARIZED AND EVALUATED ON SIX CRITERIA--BEHAVIORAL SIGNIFICANCE OF CATEGORIES, SCOPE, OBJECTIVITY AND RELIABILITY OF CATEGORIES, PROGNOSIS FOR THE SYSTEM, LOGICAL STRUCTURE, AND HEURISTIC VALUE OF THE SYSTEM. ATTENTION IS GIVEN TO OTHER SOURCES OF…

  4. Inducible Glutamate Oxaloacetate Transaminase as a Therapeutic Target Against Ischemic Stroke

    PubMed Central

    Khanna, Savita; Briggs, Zachary

    2015-01-01

    Abstract Significance: Glutamate serves multi-faceted (patho)physiological functions in the central nervous system as the most abundant excitatory neurotransmitter and under pathological conditions as a potent neurotoxin. Regarding the latter, elevated extracellular glutamate is known to play a central role in ischemic stroke brain injury. Recent Advances: Glutamate oxaloacetate transaminase (GOT) has emerged as a new therapeutic target in protecting against ischemic stroke injury. Oxygen-sensitive induction of GOT expression and activity during ischemic stroke lowers glutamate levels at the stroke site while sustaining adenosine triphosphate levels in brain. The energy demands of the brain are among the highest of all organs underscoring the need to quickly mobilize alternative carbon skeletons for metabolism in the absence of glucose during ischemic stroke. Recent work builds on the important observation of Hans Krebs that GOT-mediated metabolism of glutamate generates tri-carboxylic acid (TCA) cycle intermediates in brain tissue. Taken together, outcomes suggest GOT may enable the transformative switch of otherwise excitotoxic glutamate into life-sustaining TCA cycle intermediates during ischemic stroke. Critical Issues: Neuroprotective strategies that focus solely on blocking mechanisms of glutamate-mediated excitotoxicity have historically failed in clinical trials. That GOT can enable glutamate to assume the role of a survival factor represents a paradigm shift necessary to develop the overall significance of glutamate in stroke biology. Future Directions: Ongoing efforts are focused to develop the therapeutic significance of GOT in stroke-affected brain. Small molecules that target induction of GOT expression and activity in the ischemic penumbra are the focus of ongoing studies. Antioxid. Redox Signal. 22, 175–186. PMID:25343301

  5. SU-F-J-219: Predicting Ventilation Change Due to Radiation Therapy: Dependency On Pre-RT Ventilation and Effort Correction

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

    Patton, T; Du, K; Bayouth, J

    Purpose: Ventilation change caused by radiation therapy (RT) can be predicted using four-dimensional computed tomography (4DCT) and image registration. This study tested the dependency of predicted post-RT ventilation on effort correction and pre-RT lung function. Methods: Pre-RT and 3 month post-RT 4DCT images were obtained for 13 patients. The 4DCT images were used to create ventilation maps using a deformable image registration based Jacobian expansion calculation. The post-RT ventilation maps were predicted in four different ways using the dose delivered, pre-RT ventilation, and effort correction. The pre-RT ventilation and effort correction were toggled to determine dependency. The four different predictedmore » ventilation maps were compared to the post-RT ventilation map calculated from image registration to establish the best prediction method. Gamma pass rates were used to compare the different maps with the criteria of 2mm distance-to-agreement and 6% ventilation difference. Paired t-tests of gamma pass rates were used to determine significant differences between the maps. Additional gamma pass rates were calculated using only voxels receiving over 20 Gy. Results: The predicted post-RT ventilation maps were in agreement with the actual post-RT maps in the following percentage of voxels averaged over all subjects: 71% with pre-RT ventilation and effort correction, 69% with no pre-RT ventilation and effort correction, 60% with pre-RT ventilation and no effort correction, and 58% with no pre-RT ventilation and no effort correction. When analyzing only voxels receiving over 20 Gy, the gamma pass rates were respectively 74%, 69%, 65%, and 55%. The prediction including both pre- RT ventilation and effort correction was the only prediction with significant improvement over using no prediction (p<0.02). Conclusion: Post-RT ventilation is best predicted using both pre-RT ventilation and effort correction. This is the only prediction that provided a significant

  6. Toward a Rational and Mechanistic Account of Mental Effort.

    PubMed

    Shenhav, Amitai; Musslick, Sebastian; Lieder, Falk; Kool, Wouter; Griffiths, Thomas L; Cohen, Jonathan D; Botvinick, Matthew M

    2017-07-25

    In spite of its familiar phenomenology, the mechanistic basis for mental effort remains poorly understood. Although most researchers agree that mental effort is aversive and stems from limitations in our capacity to exercise cognitive control, it is unclear what gives rise to those limitations and why they result in an experience of control as costly. The presence of these control costs also raises further questions regarding how best to allocate mental effort to minimize those costs and maximize the attendant benefits. This review explores recent advances in computational modeling and empirical research aimed at addressing these questions at the level of psychological process and neural mechanism, examining both the limitations to mental effort exertion and how we manage those limited cognitive resources. We conclude by identifying remaining challenges for theoretical accounts of mental effort as well as possible applications of the available findings to understanding the causes of and potential solutions for apparent failures to exert the mental effort required of us.

  7. Effects of video-based therapy preparation targeting experiential acceptance or the therapeutic alliance.

    PubMed

    Johansen, Ayna B; Lumley, Mark; Cano, Annmarie

    2011-06-01

    Preparation for psychotherapy may enhance the psychotherapeutic process, reduce drop-outs, and improve outcomes, but the effective mechanisms of such preparation are poorly understood. Previous studies have rarely targeted specific processes that are associated with positive therapy outcomes. This randomized experiment compared the effects of preparatory videos that targeted either the Therapeutic Alliance, Experiential Acceptance, or a Control video on early therapeutic process variables in 105 patients seen in individual therapy. Participants watched the videos just before their first therapy session. No significant differences were found between the Alliance and Experiential Acceptance videos on patient recommendations, immediate affective reactions, or working alliance and attrition after the first session. However, the Therapeutic Alliance video produced an immediate increase in negative mood relative to the Control video, whereas the Experiential acceptance video produced a slight increase in positive mood relative to the Alliance video. Surprisingly, patients who viewed the Alliance video were rated significantly lower than the control group on therapist-rated alliance after the first session. These findings suggest there may be specific process effects in the early phase of treatment based on the type of pretraining material used, and also indicate that video-based pretraining efforts could be counterproductive. Furthermore, this research contributes to the literature by providing insights into methodological considerations for future work on the use of technology in psychotherapy and challenges associated with preparing people for successful psychotherapy.

  8. Imbalanced target prediction with pattern discovery on clinical data repositories.

    PubMed

    Chan, Tak-Ming; Li, Yuxi; Chiau, Choo-Chiap; Zhu, Jane; Jiang, Jie; Huo, Yong

    2017-04-20

    Clinical data repositories (CDR) have great potential to improve outcome prediction and risk modeling. However, most clinical studies require careful study design, dedicated data collection efforts, and sophisticated modeling techniques before a hypothesis can be tested. We aim to bridge this gap, so that clinical domain users can perform first-hand prediction on existing repository data without complicated handling, and obtain insightful patterns of imbalanced targets for a formal study before it is conducted. We specifically target for interpretability for domain users where the model can be conveniently explained and applied in clinical practice. We propose an interpretable pattern model which is noise (missing) tolerant for practice data. To address the challenge of imbalanced targets of interest in clinical research, e.g., deaths less than a few percent, the geometric mean of sensitivity and specificity (G-mean) optimization criterion is employed, with which a simple but effective heuristic algorithm is developed. We compared pattern discovery to clinically interpretable methods on two retrospective clinical datasets. They contain 14.9% deaths in 1 year in the thoracic dataset and 9.1% deaths in the cardiac dataset, respectively. In spite of the imbalance challenge shown on other methods, pattern discovery consistently shows competitive cross-validated prediction performance. Compared to logistic regression, Naïve Bayes, and decision tree, pattern discovery achieves statistically significant (p-values < 0.01, Wilcoxon signed rank test) favorable averaged testing G-means and F1-scores (harmonic mean of precision and sensitivity). Without requiring sophisticated technical processing of data and tweaking, the prediction performance of pattern discovery is consistently comparable to the best achievable performance. Pattern discovery has demonstrated to be robust and valuable for target prediction on existing clinical data repositories with imbalance and

  9. Reminiscing about 15 years of interoperability efforts

    DOE PAGES

    Van de Sompel, Herbert; Nelson, Michael L.

    2015-11-01

    Over the past fifteen years, our perspective on tackling information interoperability problems for web-based scholarship has evolved significantly. In this opinion piece, we look back at three efforts that we have been involved in that aptly illustrate this evolution: OAI-PMH, OAI-ORE, and Memento. Understanding that no interoperability specification is neutral, we attempt to characterize the perspectives and technical toolkits that provided the basis for these endeavors. With that regard, we consider repository-centric and web-centric interoperability perspectives, and the use of a Linked Data or a REST/HATEAOS technology stack, respectively. In addition, we lament the lack of interoperability across nodes thatmore » play a role in web-based scholarship, but end on a constructive note with some ideas regarding a possible path forward.« less

  10. Subjective and psychophysiological indices of listening effort in a competing-talker task

    PubMed Central

    Mackersie, Carol L.; Cones, Heather

    2010-01-01

    % for all listening tasks. There was no significant change in performance across listening conditions for any listener. There was, however, a significant increase in mean skin conductance and EMG activity as task demand increased. Heart rate and skin temperature did not change significantly. There was no strong association between subjective and psychophysiological measures, but all participants with mean normalized effort ratings of greater than 4.5 (i.e. effort increased by a factor of at least 4.5) showed significant changes in skin conductance. Conclusions Even in the absence of substantial performance changes, listeners may experience changes in subjective and psychophysiological responses consistent with activation of a stress response. Skin conductance appears to be the most promising measure for evaluating individual changes in psychophysiological responses during listening tasks. PMID:21463566

  11. Subjective and psychophysiological indexes of listening effort in a competing-talker task.

    PubMed

    Mackersie, Carol L; Cones, Heather

    2011-02-01

    was no significant change in performance across listening conditions for any listener. There was, however, a significant increase in mean skin conductance and EMG activity as task demand increased. Heart rate and skin temperature did not change significantly. There was no strong association between subjective and psychophysiological measures, but all participants with mean normalized effort ratings of greater than 4.5 (i.e., effort increased by a factor of at least 4.5) showed significant changes in skin conductance. Even in the absence of substantial performance changes, listeners may experience changes in subjective and psychophysiological responses consistent with the activation of a stress response. Skin conductance appears to be the most promising measure for evaluating individual changes in psychophysiological responses during listening tasks. American Academy of Audiology.

  12. NDE research efforts at the FAA Center for Aviation Systems Reliability

    NASA Technical Reports Server (NTRS)

    Thompson, Donald O.; Brasche, Lisa J. H.

    1992-01-01

    The Federal Aviation Administration-Center for Aviation Systems Reliability (FAA-CASR), a part of the Institute for Physical Research and Technology at Iowa State University, began operation in the Fall of 1990 with funding from the FAA. The mission of the FAA-CASR is to develop quantitative nondestructive evaluation (NDE) methods for aircraft structures and materials including prototype instrumentation, software, techniques, and procedures and to develop and maintain comprehensive education and training programs in aviation specific inspection procedures and practices. To accomplish this mission, FAA-CASR brings together resources from universities, government, and industry to develop a comprehensive approach to problems specific to the aviation industry. The problem areas are targeted by the FAA, aviation manufacturers, the airline industry and other members of the aviation business community. This consortium approach ensures that the focus of the efforts is on relevant problems and also facilitates effective transfer of the results to industry.

  13. NCI Requests Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 9, 2012.

  14. NCI Requests Cancer Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, the National Cancer Institute (NCI) Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution.

  15. Low target prevalence is a stubborn source of errors in visual search tasks

    PubMed Central

    Wolfe, Jeremy M.; Horowitz, Todd S.; Van Wert, Michael J.; Kenner, Naomi M.; Place, Skyler S.; Kibbi, Nour

    2009-01-01

    In visual search tasks, observers look for targets in displays containing distractors. Likelihood that targets will be missed varies with target prevalence, the frequency with which targets are presented across trials. Miss error rates are much higher at low target prevalence (1–2%) than at high prevalence (50%). Unfortunately, low prevalence is characteristic of important search tasks like airport security and medical screening where miss errors are dangerous. A series of experiments show this prevalence effect is very robust. In signal detection terms, the prevalence effect can be explained as a criterion shift and not a change in sensitivity. Several efforts to induce observers to adopt a better criterion fail. However, a regime of brief retraining periods with high prevalence and full feedback allows observers to hold a good criterion during periods of low prevalence with no feedback. PMID:17999575

  16. An assessment of spacecraft target mode selection methods

    NASA Astrophysics Data System (ADS)

    Mercer, J. F.; Aglietti, G. S.; Remedia, M.; Kiley, A.

    2017-11-01

    Coupled Loads Analyses (CLAs), using finite element models (FEMs) of the spacecraft and launch vehicle to simulate critical flight events, are performed in order to determine the dynamic loadings that will be experienced by spacecraft during launch. A validation process is carried out on the spacecraft FEM beforehand to ensure that the dynamics of the analytical model sufficiently represent the behavior of the physical hardware. One aspect of concern is the containment of the FEM correlation and update effort to focus on the vibration modes which are most likely to be excited under test and CLA conditions. This study therefore provides new insight into the prioritization of spacecraft FEM modes for correlation to base-shake vibration test data. The work involved example application to large, unique, scientific spacecraft, with modern FEMs comprising over a million degrees of freedom. This comprehensive investigation explores: the modes inherently important to the spacecraft structures, irrespective of excitation; the particular 'critical modes' which produce peak responses to CLA level excitation; an assessment of several traditional target mode selection methods in terms of ability to predict these 'critical modes'; and an indication of the level of correlation these FEM modes achieve compared to corresponding test data. Findings indicate that, although the traditional methods of target mode selection have merit and are able to identify many of the modes of significance to the spacecraft, there are 'critical modes' which may be missed by conventional application of these methods. The use of different thresholds to select potential target modes from these parameters would enable identification of many of these missed modes. Ultimately, some consideration of the expected excitations is required to predict all modes likely to contribute to the response of the spacecraft in operation.

  17. Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1—Psychometric Characteristics of 5 Paradigms

    PubMed Central

    Reddy, L. Felice; Horan, William P.; Barch, Deanna M.; Buchanan, Robert W.; Dunayevich, Eduardo; Gold, James M.; Lyons, Naomi; Marder, Stephen R.; Treadway, Michael T.; Wynn, Jonathan K.; Young, Jared W.; Green, Michael F.

    2015-01-01

    Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials. PMID:26142081

  18. Dopamine does double duty in motivating cognitive effort

    PubMed Central

    Westbrook, Andrew; Braver, Todd S.

    2015-01-01

    Cognitive control is subjectively costly, suggesting that engagement is modulated in relationship to incentive state. Dopamine appears to play key roles. In particular, dopamine may mediate cognitive effort by two broad classes of functions: 1) modulating the functional parameters of working memory circuits subserving effortful cognition, and 2) mediating value-learning and decision-making about effortful cognitive action. Here we tie together these two lines of research, proposing how dopamine serves “double duty”, translating incentive information into cognitive motivation. PMID:26889810

  19. Respiratory Sinus Arrhythmia, Effortful Control, and Parenting as Predictors of Children’s Sympathy Across Early Childhood

    PubMed Central

    Taylor, Zoe E.; Eisenberg, Nancy; Spinrad, Tracy L.

    2015-01-01

    The goal of this study was to examine physiological and environmental predictors of children’s sympathy (an emotional response consisting of feelings of concern or sorrow for others who are distressed or in need) and whether temperamental effortful control mediated these relations. Specifically, in a study of 192 children (23% Hispanic; 54% male), respiratory sinus arrhythmia (RSA), a measure thought to reflect physiological regulation, and observed authoritative parenting (both at 42 months) were examined as predictors of children’s effortful control (at 54 months) and, in turn, children’s sympathy (at 72 and 84 months). Measures of both baseline RSA and RSA suppression were examined. In a structural equation model, observed parenting was positively related to children’s subsequent sympathy through its positive relation to effortful control. Furthermore, the indirect path from baseline RSA to higher sympathy through effortful control was marginally significant. Authoritative parenting and baseline RSA uniquely predicted individual differences in children’s effortful control. Findings highlight the potential role of both authoritative parenting and physiological regulation in the development of children’s sympathy. PMID:25329555

  20. Cognitive Load and Listening Effort: Concepts and Age-Related Considerations.

    PubMed

    Lemke, Ulrike; Besser, Jana

    2016-01-01

    Listening effort has been recognized as an important dimension of everyday listening, especially with regard to the comprehension of spoken language. At constant levels of comprehension performance, the level of effort exerted and perceived during listening can differ considerably across listeners and situations. In this article, listening effort is used as an umbrella term for two different types of effort that can arise during listening. One of these types is processing effort, which is used to denote the utilization of "extra" mental processing resources in listening conditions that are adverse for an individual. A conceptual description is introduced how processing effort could be defined in terms of situational influences, the listener's auditory and cognitive resources, and the listener's personal state. Also, the proposed relationship between processing effort and subjectively perceived listening effort is discussed. Notably, previous research has shown that the availability of mental resources, as well as the ability to use them efficiently, changes over the course of adult aging. These common age-related changes in cognitive abilities and their neurocognitive organization are discussed in the context of the presented concept, especially regarding situations in which listening effort may be increased for older people.

  1. Student effort expectations and their learning in first-year introductory physics: A case study in Thailand

    NASA Astrophysics Data System (ADS)

    Wutchana, U.; Emarat, N.

    2011-06-01

    The Maryland Physics Expectations (MPEX) survey was designed to probe students’ expectations about their understanding of the process of learning physics and the structure of physics knowledge—cognitive expectations. This survey was administered to first-year university students in Thailand in the first semester of an introductory calculus-based physics course during academic years 2007 and 2008, to assess their expectations at the beginning of the course. The precourse MPEX results were compared and correlated with two separate measures of student learning: (1) individual students’ normalized gains from pre and post Force and Motion Conceptual Evaluation (FMCE) results, which measure students’ conceptual understanding, and (2) student’s scores on the final exam, which measure their more general problem-solving ability. The results showed a significant positive correlation between their overall MPEX score and five of the six MPEX cluster scores, with their normalized learning gains on the FMCE for both academic years. The results also showed significant positive correlations between student MPEX scores and their final exam scores for the overall MPEX score and all MPEX cluster scores except for the effort cluster. We interviewed two groups of five students each, one group with small favorable scores on the precourse MPEX effort cluster and one with high favorable scores on the precourse MPEX effort cluster, to see how the students’ learning efforts compared with their MPEX results. We concluded from the interviews that what the students think or expect about the MPEX effort involved in learning physics does not match what they actually do.

  2. Targeting an asteroid: The DSPSE encounter with asteroid 1620 Geographos

    NASA Technical Reports Server (NTRS)

    Yeomans, Donald K.

    1993-01-01

    Accurate targeting of the Deep Space Program Science Experiment (DSPSE) spacecraft to achieve a 100 km sunward flyby of asteroid 1620 Geographos will require that the ground-based ephemeris of Geographos be well known in advance of the encounter. Efforts are underway to ensure that precision optical and radar observations are available for the final asteroid orbit update that takes place several hours prior to the DSPSE flyby. Because the asteroid passes very close to the Earth six days prior to the DSPSE encounter, precision ground-based optical and radar observations should be available. These ground-based data could reduce the asteroid's position uncertainties (1-sigma) to about 10 km. This ground-based target ephemeris error estimate is far lower than for any previous comet or asteroid that has been under consideration as a mission target.

  3. Significance of autobiographical episodes and spacing effects in incidental memory.

    PubMed

    Toyota, Hiroshi

    2013-10-01

    Participants were presented with target words on two occasions, and were asked each time to generate a memory of a past episode associated with the targets. Participants were also instructed to rate the importance (significance elaboration) or pleasantness of the pisode (pleasantness elaboration) in an orienting task, followed by an unexpect d recall test. Significance elaboration led to better recall than pleasantness elaboration, but only in the spaced presentation. The spaced presentation led to better tree recall than massed presentation with significance elaboration, but the difference between the two types of presentation was not observed with pleasantness elaboration. These results suggest that the significance of an episode is more critical than the pleasantness of an episode in determining the effectiveness of autobiographical elaboration in facilitating recall.

  4. Subcellular Targeting of Methylmercury Lyase Enhances Its Specific Activity for Organic Mercury Detoxification in Plants1

    PubMed Central

    Bizily, Scott P.; Kim, Tehryung; Kandasamy, Muthugapatti K.; Meagher, Richard B.

    2003-01-01

    Methylmercury is an environmental pollutant that biomagnifies in the aquatic food chain with severe consequences for humans and other animals. In an effort to remove this toxin in situ, we have been engineering plants that express the bacterial mercury resistance enzymes organomercurial lyase MerB and mercuric ion reductase MerA. In vivo kinetics experiments suggest that the diffusion of hydrophobic organic mercury to MerB limits the rate of the coupled reaction with MerA (Bizily et al., 2000). To optimize reaction kinetics for organic mercury compounds, the merB gene was engineered to target MerB for accumulation in the endoplasmic reticulum and for secretion to the cell wall. Plants expressing the targeted MerB proteins and cytoplasmic MerA are highly resistant to organic mercury and degrade organic mercury at 10 to 70 times higher specific activity than plants with the cytoplasmically distributed wild-type MerB enzyme. MerB protein in endoplasmic reticulum-targeted plants appears to accumulate in large vesicular structures that can be visualized in immunolabeled plant cells. These results suggest that the toxic effects of organic mercury are focused in microenvironments of the secretory pathway, that these hydrophobic compartments provide more favorable reaction conditions for MerB activity, and that moderate increases in targeted MerB expression will lead to significant gains in detoxification. In summary, to maximize phytoremediation efficiency of hydrophobic pollutants in plants, it may be beneficial to target enzymes to specific subcellular environments. PMID:12586871

  5. A Bioinorganic Approach to Fragment-Based Drug Discovery Targeting Metalloenzymes.

    PubMed

    Cohen, Seth M

    2017-08-15

    fragments, how one can identify the best fragments for a given metalloenzyme, and many others. Among the most significant, and concerning, questions for metalloenzyme inhibition are those that reside around issues of specificity and whether metalloenzyme inhibitors can be as selective and specific as other small molecule inhibitors (i.e., compounds that inhibit enzymes that do not utilize a metal at their active site). This also leads to the question of whether metalloenzyme inhibitors might interfere more broadly with the metallome. Efforts to address these and related questions are discussed, with the expectation that our findings will illuminate some of these topics, alleviate some of these concerns, and encourage greater interest in this important, undervalued class of drug targets.

  6. Information campaign and advocacy efforts to promote access to emergency contraception in Mexico.

    PubMed

    Ellertson, Charlotte; Heimburger, Angela; Acevedo-Garcia, Dolores; Schiavon, Raffaela; Mejia, Guillermina; Corona, Georgina; del Castillo, Eduardo; Langer, Ana

    2002-11-01

    Emergency contraception (EC) has the potential to reduce unwanted pregnancy significantly, in Mexico as elsewhere. Recent years have seen tremendous growth in programs and research devoted to expanding access to emergency methods worldwide. In Mexico we developed a comprehensive model introduction effort that included four components: provider training, public information (through a dedicated hotline and website, free media, paid radio and TV spots, participation in talk shows, and alternative media channels), collaboration with the public sector to include EC in the official family planning norms, and assistance to partner with commercial firms to register a dedicated EC product. Ongoing efforts to combat misperceptions and overcome opposition are crucial to informing the public and ensuring greater access to the method.

  7. The E-3 Project: A Collaborative Curriculum Development Effort.

    ERIC Educational Resources Information Center

    Nelson, Lynn R.; And Others

    This paper chronicles the effort of a curriculum development team to alter the high school social studies curriculum, its content, and instructional methods. Specifically, Entrepreneur/Economic Education (E-3) is the focus of this curriculum reform effort. The E-3 program is designed as a four-year cooperative effort involving selected teachers,…

  8. A Pilot Study of Perceived Mouth Dryness, Perceived Swallowing Effort, and Saliva Substitute Effects in Healthy Adults Across the Age Range.

    PubMed

    Rogus-Pulia, Nicole M; Gangnon, Ronald; Kind, Amy; Connor, Nadine P; Asthana, Sanjay

    2018-04-01

    Xerostomia, or perceived mouth dryness, increases with advancing age, but its influence on swallowing effort is unknown. This study: (1) quantified relationships among age, perceived sense of swallowing effort, and ratings of perceived mouth dryness, and (2) examined changes in swallowing effort following application of a gel-based saliva substitute in healthy participants. This was a cross-sectional observational study and data were collected from attendees of a community healthy aging fair. Forty-two healthy participants (mean age = 65 years; 20 female) were enrolled. Each participant rated perceived effort with swallowing and perceived mouth dryness on a 10-cm horizontal, undifferentiated line. After participants applied a gel-based saliva substitute (Biotene ® Oral Balance) to their tongue and oral mucosa, they rated perceived effort with swallowing again. Age was associated with greater perceived mouth dryness (r = 0.37, p < 0.03) but not with perceived swallowing effort (r = 0.16, p = 0.32). Perceived mouth dryness was associated with greater perceived swallowing effort (r = 0.62, p < 0.001). Perceived swallowing effort declined following application of the salivary substitute (mean difference = 9.39 mm, p < 0.002). Age was found to be a significant predictor of perceived mouth dryness (p < .02); and perceived mouth dryness was found to significantly predict perceived swallow effort (p < .001). Perceived mouth dryness increased with advancing age, but perceived swallowing effort did not. Regardless of age, participants with higher levels of perceived mouth dryness also reported more perceived effort with swallowing suggesting a role for adequate oral lubrication in this perception. Even in healthy participants, use of a gel-based saliva substitute lowered perceived swallowing effort.

  9. Altering Effort Costs in Parkinson's Disease with Noninvasive Cortical Stimulation

    PubMed Central

    Salimpour, Yousef; Mari, Zoltan K.

    2015-01-01

    In Parkinson's disease (PD), the human brain is capable of producing motor commands, but appears to require greater than normal subjective effort, particularly for the more-affected side. What is the nature of this subjective effort and can it be altered? We used an isometric task in which patients produced a goal force by engaging both arms, but were free to assign any fraction of that force to each arm. The patients preferred their less-affected arm, but only in some directions. This preference was correlated with lateralization of signal-dependent noise: the direction of force for which the brain was less willing to assign effort to an arm was generally the direction for which that arm exhibited greater noise. Therefore, the direction-dependent noise in each arm acted as an implicit cost that discouraged use of that arm. To check for a causal relationship between noise and motor cost, we used bilateral transcranial direct current stimulation of the motor cortex, placing the cathode on the more-affected side and the anode on the less-affected side. This stimulation not only reduced the noise on the more-affected arm, it also increased the willingness of the patients to assign force to that arm. In a 3 d double-blind study and in a 10 d repeated stimulation study, bilateral stimulation of the two motor cortices with cathode on the more-affected side reduced noise and increased the willingness of the patients to exert effort. This stimulation also improved the clinical motor symptoms of the disease. SIGNIFICANCE STATEMENT In Parkinson's disease, patients are less willing to assign force to their affected arm. Here, we find that this pattern is direction dependent: directions for which the arm is noisier coincide with directions for which the brain is less willing to assign force. We hypothesized that if we could reduce the noise on the affected arm, then we may increase the willingness for the brain to assign force to that arm. We found a way to do this via

  10. Perception of Muscular Effort During Dynamic Elbow Extension in Multiple Sclerosis.

    PubMed

    Heller, Mario; Retzl, Irene; Kiselka, Anita; Greisberger, Andrea

    2016-02-01

    To investigate the perception of muscular effort in individuals with multiple sclerosis (MS) and healthy controls during dynamic contractions. Case-control study. MS day care center. Individuals with MS (n=28) and controls (n=28) (N=56). Not applicable. Perceived muscular effort during dynamic elbow extensions was rated at 9 different weight intensities (10%-90% of 1-repetition maximum) in a single-blind, randomized order using the OMNI-Resistance Exercise Scale. Muscle activity of the triceps brachii muscle (lateral head) was measured via surface electromyography and normalized to maximal voluntary excitation. According to OMNI-level ratings, significant main effects were found for the diagnostic condition (F=27.33, P<.001, η(2)=.11), indicating 0.7 (95% confidence interval [CI], 0.3-1.1) lower mean OMNI-level ratings for MS, and for the intensity level (F=46.81, P<.001, η(2)=.46), showing increased OMNI-level ratings for increased intensity levels for both groups. Furthermore, significant main effects were found for the diagnostic condition (F=16.52, P<.001, η(2)=.07), indicating 7.1% (95% CI, -8.6 to 22.8) higher maximal voluntary excitation values for MS, and for the intensity level (F=33.09, P<.001, η(2)=.36), showing higher relative muscle activities for increasing intensity levels in both groups. Similar to controls, individuals with MS were able to differentiate between different intensities of weight during dynamic elbow extensions when provided in a single-blind, randomized order. Therefore, perceived muscular effort might be considered to control resistance training intensities in individuals with MS. However, training intensity for individuals with MS should be chosen at approximately 1 OMNI level lower than recommended, at least for dynamic elbow extension exercises. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  11. About miRNAs, miRNA seeds, target genes and target pathways.

    PubMed

    Kehl, Tim; Backes, Christina; Kern, Fabian; Fehlmann, Tobias; Ludwig, Nicole; Meese, Eckart; Lenhof, Hans-Peter; Keller, Andreas

    2017-12-05

    miRNAs are typically repressing gene expression by binding to the 3' UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways. By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions. Respective results were obtained for both, predicted target genes as well as experimentally validated targets. We note that miRNAs target gene set similarity follows a bimodal distribution, pointing at a set of 282 miRNAs that seems to target genes with very high specificity. Further, we discuss miRNAs with different (seed) sequences that nonetheless regulate similar gene sets or pathways. Most intriguingly, we found miRNA pairs that regulate different gene sets but similar pathways such as miR-6886-5p and miR-3529-5p. These are jointly targeting different parts of the MAPK signaling cascade. The main goal of this study is to provide a general overview on the results, to highlight a selection of relevant results on miRNAs, miRNA seeds, target genes and target pathways and to raise awareness for artifacts in respective comparisons. The full set of information that allows to infer detailed results on each miRNA has been included in miRPathDB, the miRNA target pathway database (https://mpd.bioinf.uni-sb.de).

  12. Mapping Fishing Effort through AIS Data

    PubMed Central

    Natale, Fabrizio; Gibin, Maurizio; Alessandrini, Alfredo; Vespe, Michele; Paulrud, Anton

    2015-01-01

    Several research initiatives have been undertaken to map fishing effort at high spatial resolution using the Vessel Monitoring System (VMS). An alternative to the VMS is represented by the Automatic Identification System (AIS), which in the EU became compulsory in May 2014 for all fishing vessels of length above 15 meters. The aim of this paper is to assess the uptake of the AIS in the EU fishing fleet and the feasibility of producing a map of fishing effort with high spatial and temporal resolution at European scale. After analysing a large AIS dataset for the period January-August 2014 and covering most of the EU waters, we show that AIS was adopted by around 75% of EU fishing vessels above 15 meters of length. Using the Swedish fleet as a case study, we developed a method to identify fishing activity based on the analysis of individual vessels’ speed profiles and produce a high resolution map of fishing effort based on AIS data. The method was validated using detailed logbook data and proved to be sufficiently accurate and computationally efficient to identify fishing grounds and effort in the case of trawlers, which represent the largest portion of the EU fishing fleet above 15 meters of length. Issues still to be addressed before extending the exercise to the entire EU fleet are the assessment of coverage levels of the AIS data for all EU waters and the identification of fishing activity in the case of vessels other than trawlers. PMID:26098430

  13. Mapping Fishing Effort through AIS Data.

    PubMed

    Natale, Fabrizio; Gibin, Maurizio; Alessandrini, Alfredo; Vespe, Michele; Paulrud, Anton

    2015-01-01

    Several research initiatives have been undertaken to map fishing effort at high spatial resolution using the Vessel Monitoring System (VMS). An alternative to the VMS is represented by the Automatic Identification System (AIS), which in the EU became compulsory in May 2014 for all fishing vessels of length above 15 meters. The aim of this paper is to assess the uptake of the AIS in the EU fishing fleet and the feasibility of producing a map of fishing effort with high spatial and temporal resolution at European scale. After analysing a large AIS dataset for the period January-August 2014 and covering most of the EU waters, we show that AIS was adopted by around 75% of EU fishing vessels above 15 meters of length. Using the Swedish fleet as a case study, we developed a method to identify fishing activity based on the analysis of individual vessels' speed profiles and produce a high resolution map of fishing effort based on AIS data. The method was validated using detailed logbook data and proved to be sufficiently accurate and computationally efficient to identify fishing grounds and effort in the case of trawlers, which represent the largest portion of the EU fishing fleet above 15 meters of length. Issues still to be addressed before extending the exercise to the entire EU fleet are the assessment of coverage levels of the AIS data for all EU waters and the identification of fishing activity in the case of vessels other than trawlers.

  14. Evolutionary dynamics of the traveler's dilemma and minimum-effort coordination games on complex networks.

    PubMed

    Iyer, Swami; Killingback, Timothy

    2014-10-01

    The traveler's dilemma game and the minimum-effort coordination game are social dilemmas that have received significant attention resulting from the fact that the predictions of classical game theory are inconsistent with the results found when the games are studied experimentally. Moreover, both the traveler's dilemma and the minimum-effort coordination games have potentially important applications in evolutionary biology. Interestingly, standard deterministic evolutionary game theory, as represented by the replicator dynamics in a well-mixed population, is also inadequate to account for the behavior observed in these games. Here we study the evolutionary dynamics of both these games in populations with interaction patterns described by a variety of complex network topologies. We investigate the evolutionary dynamics of these games through agent-based simulations on both model and empirical networks. In particular, we study the effects of network clustering and assortativity on the evolutionary dynamics of both games. In general, we show that the evolutionary behavior of the traveler's dilemma and minimum-effort coordination games on complex networks is in good agreement with that observed experimentally. Thus, formulating the traveler's dilemma and the minimum-effort coordination games on complex networks neatly resolves the paradoxical aspects of these games.

  15. Evolutionary dynamics of the traveler's dilemma and minimum-effort coordination games on complex networks

    NASA Astrophysics Data System (ADS)

    Iyer, Swami; Killingback, Timothy

    2014-10-01

    The traveler's dilemma game and the minimum-effort coordination game are social dilemmas that have received significant attention resulting from the fact that the predictions of classical game theory are inconsistent with the results found when the games are studied experimentally. Moreover, both the traveler's dilemma and the minimum-effort coordination games have potentially important applications in evolutionary biology. Interestingly, standard deterministic evolutionary game theory, as represented by the replicator dynamics in a well-mixed population, is also inadequate to account for the behavior observed in these games. Here we study the evolutionary dynamics of both these games in populations with interaction patterns described by a variety of complex network topologies. We investigate the evolutionary dynamics of these games through agent-based simulations on both model and empirical networks. In particular, we study the effects of network clustering and assortativity on the evolutionary dynamics of both games. In general, we show that the evolutionary behavior of the traveler's dilemma and minimum-effort coordination games on complex networks is in good agreement with that observed experimentally. Thus, formulating the traveler's dilemma and the minimum-effort coordination games on complex networks neatly resolves the paradoxical aspects of these games.

  16. [Effort-Reward Imbalance in Household and Family Work--Analysing the Psychometric Properties among Fathers of Underage Children].

    PubMed

    Sperlich, Stefanie; Barre, Felix; Otto, Friederike

    2016-02-01

    Recently, the concept of effort-reward imbalance (ERI) developed by Siegrist had been applied to unpaid household and family work (ERI-HF). Evidence suggests that the imbalance between effort spent and reward received in family and domestic labor is associated with poor mental and physical health. However, so far, the adopted questionnaire ERI-HF was exclusively used among women in childcare responsibility. This paper reports on the application of the model to men in childcare responsibility using data from a clinical sample of fathers in rehabilitation clinics (N=415). Analogous to the original version, ERI-HF is divided into 2 components: (i) dysbalance of effort and reward, and (ii) overcommitment. For both components, confirmatory factor analyses revealed good to satisfactory properties. Overall, 13.4% of men in childcare responsibility showed a dysbalance between high effort and low reward of household and family work. High levels of effort were more frequently reported than high levels of low reward. With percentages ranging between 24.3 and 59.6%, a significant proportion of fathers reported difficulties to withdraw from household and family work obligations. Analyses of construct validity revealed significant associations between ERI and socio-demographic factors (number of children, employment status, single fatherhood, work-family-conflict) as well as subjective health. Taken together, our findings suggest that the instrument is applicable to men in childcare responsibility. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Manipulation of parental effort affects plumage bacterial load in a wild passerine.

    PubMed

    Alt, Grete; Saag, Pauli; Mägi, Marko; Kisand, Veljo; Mänd, Raivo

    2015-06-01

    It has been suggested that plumage microorganisms play an important role in shaping the life histories of wild birds. Some bacteria may act as pathogens or cause damage to feathers, and thereby reduce individual fitness. Intense parental care in birds can result in a reduction of self-maintenance and preening behavior in parents and therefore might affect the dynamics of microbiota living on their feathers. However, experimental evidence of this relationship is virtually absent. We manipulated the parental effort of wild breeding pied flycatcher (Ficedula hypoleuca) females by modifying their brood size or temporarily removing male partners. We expected that experimentally decreasing or increasing parental effort would affect feather sanitation in females and therefore also bacterial density on their plumage. In accordance with this hypothesis, manipulation affected the density of free-living bacteria: females with reduced broods had the lowest number of free-living bacteria on their feathers, while females left without male partners had the highest. However, manipulation did not have a significant effect on the densities of attached bacteria. Our results provide experimental evidence that a trade-off between self-maintenance and parental effort affects plumage bacterial densities in birds.

  18. Effort-based cost-benefit valuation and the human brain

    PubMed Central

    Croxson, Paula L; Walton, Mark E; O'Reilly, Jill X; Behrens, Timothy EJ; Rushworth, Matthew FS

    2010-01-01

    In both the wild and the laboratory, animals' preferences for one course of action over another reflect not just reward expectations but also the cost in terms of effort that must be invested in pursuing the course of action. The ventral striatum and dorsal anterior cingulate cortex (ACCd) are implicated in the making of cost-benefit decisions in the rat but there is little information about how effort costs are processed and influence calculations of expected net value in other mammals including the human. We carried out a functional magnetic resonance imaging (fMRI) study to determine whether and where activity in the human brain was available to guide effort-based cost-benefit valuation. Subjects were scanned while they performed a series of effortful actions to obtain secondary reinforcers. At the beginning of each trial, subjects were presented with one of eight different visual cues which they had learned indicated how much effort the course of action would entail and how much reward could be expected at its completion. Cue-locked activity in the ventral striatum and midbrain reflected the net value of the course of action, signaling the expected amount of reward discounted by the amount of effort to be invested. Activity in ACCd also reflected the interaction of both expected reward and effort costs. Posterior orbitofrontal and insular activity, however, only reflected the expected reward magnitude. The ventral striatum and anterior cingulate cortex may be the substrate of effort-based cost-benefit valuation in primates as well as in rats. PMID:19357278

  19. Closed-loop adaptation of neurofeedback based on mental effort facilitates reinforcement learning of brain self-regulation.

    PubMed

    Bauer, Robert; Fels, Meike; Royter, Vladislav; Raco, Valerio; Gharabaghi, Alireza

    2016-09-01

    Considering self-rated mental effort during neurofeedback may improve training of brain self-regulation. Twenty-one healthy, right-handed subjects performed kinesthetic motor imagery of opening their left hand, while threshold-based classification of beta-band desynchronization resulted in proprioceptive robotic feedback. The experiment consisted of two blocks in a cross-over design. The participants rated their perceived mental effort nine times per block. In the adaptive block, the threshold was adjusted on the basis of these ratings whereas adjustments were carried out at random in the other block. Electroencephalography was used to examine the cortical activation patterns during the training sessions. The perceived mental effort was correlated with the difficulty threshold of neurofeedback training. Adaptive threshold-setting reduced mental effort and increased the classification accuracy and positive predictive value. This was paralleled by an inter-hemispheric cortical activation pattern in low frequency bands connecting the right frontal and left parietal areas. Optimal balance of mental effort was achieved at thresholds significantly higher than maximum classification accuracy. Rating of mental effort is a feasible approach for effective threshold-adaptation during neurofeedback training. Closed-loop adaptation of the neurofeedback difficulty level facilitates reinforcement learning of brain self-regulation. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Data-Driven Approach To Determine Popular Proteins for Targeted Proteomics Translation of Six Organ Systems.

    PubMed

    Lam, Maggie P Y; Venkatraman, Vidya; Xing, Yi; Lau, Edward; Cao, Quan; Ng, Dominic C M; Su, Andrew I; Ge, Junbo; Van Eyk, Jennifer E; Ping, Peipei

    2016-11-04

    Amidst the proteomes of human tissues lie subsets of proteins that are closely involved in conserved pathophysiological processes. Much of biomedical research concerns interrogating disease signature proteins and defining their roles in disease mechanisms. With advances in proteomics technologies, it is now feasible to develop targeted proteomics assays that can accurately quantify protein abundance as well as their post-translational modifications; however, with rapidly accumulating number of studies implicating proteins in diseases, current resources are insufficient to target every protein without judiciously prioritizing the proteins with high significance and impact for assay development. We describe here a data science method to prioritize and expedite assay development on high-impact proteins across research fields by leveraging the biomedical literature record to rank and normalize proteins that are popularly and preferentially published by biomedical researchers. We demonstrate this method by finding priority proteins across six major physiological systems (cardiovascular, cerebral, hepatic, renal, pulmonary, and intestinal). The described method is data-driven and builds upon the collective knowledge of previous publications referenced on PubMed to lend objectivity to target selection. The method and resulting popular protein lists may also be useful for exploring biological processes associated with various physiological systems and research topics, in addition to benefiting ongoing efforts to facilitate the broad translation of proteomics technologies.

  1. Effort-based decision making as an objective paradigm for the assessment of motivational deficits in schizophrenia.

    PubMed

    Fervaha, Gagan; Duncan, Mark; Foussias, George; Agid, Ofer; Faulkner, Guy E; Remington, Gary

    2015-10-01

    Negative symptoms and motivational deficits are prevalent features of schizophrenia, and represent robust predictors of real-world functional outcomes. The standard for assessment of these symptoms is clinical interview and severity ratings on standardized rating scales. In the present study we examined the psychometric properties of a performance-based measure of motivational deficits in patients with schizophrenia. Ninety-seven patients with schizophrenia were included in this investigation. Patients' willingness to expend effort for reward (i.e., motivation) was evaluated using an effort-based decision making paradigm where participants chose over a series of trials whether to expend a greater amount of effort for a larger monetary reward versus less effort for a smaller reward. Effort performance was evaluated twice, separated by a two-week interval. Patients with schizophrenia opted to expend greater effort for trials with higher reward value and greater likelihood of reward receipt. Patients did not find the task overly difficult and reported being motivated to perform well, underscoring the tolerability of the task for patients. Test-retest consistency was good and there was only minimal change in scores over time. Effort performance was not related to sociodemographic or clinical variables (e.g., positive symptoms); however, deficit syndrome patients exerted effort for reward at a significantly lower rate than nondeficit patients. The effort-based decision making task used in the present study represents an objective paradigm that can be used to evaluate motivational impairments in patients with schizophrenia. Such performance-based measures of motivation may also serve as viable endpoints in clinical trials. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. A unique role of endogenous visual-spatial attention in rapid processing of multiple targets

    PubMed Central

    Guzman, Emmanuel; Grabowecky, Marcia; Palafox, German; Suzuki, Satoru

    2012-01-01

    Visual spatial attention can be exogenously captured by a salient stimulus or can be endogenously allocated by voluntary effort. Whether these two attention modes serve distinctive functions is debated, but for processing of single targets the literature suggests superiority of exogenous attention (it is faster acting and serves more functions). We report that endogenous attention uniquely contributes to processing of multiple targets. For speeded visual discrimination, response times are faster for multiple redundant targets than for single targets due to probability summation and/or signal integration. This redundancy gain was unaffected when attention was exogenously diverted from the targets, but was completely eliminated when attention was endogenously diverted. This was not due to weaker manipulation of exogenous attention because our exogenous and endogenous cues similarly affected overall response times. Thus, whereas exogenous attention is superior for processing single targets, endogenous attention plays a unique role in allocating resources crucial for rapid concurrent processing of multiple targets. PMID:21517209

  3. NCI Requests Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through February 5, 2016.

  4. NCI Requests Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 12, 2013.

  5. Hybrid-drive implosion system for ICF targets

    DOEpatents

    Mark, J.W.K.

    1987-10-14

    Hybrid-drive implosion systems for ICF targets are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator surroundingly disposed around fusion fuel. The ablator is first compressed to higher density by a laser system, or by an ion beam system, that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system that is optimized for this second phase of operation of the target. The fusion fuel is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion. 3 figs.

  6. Systematic Identification of Combinatorial Drivers and Targets in Cancer Cell Lines

    PubMed Central

    Tabchy, Adel; Eltonsy, Nevine; Housman, David E.; Mills, Gordon B.

    2013-01-01

    There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance. PMID:23577104

  7. Systematic identification of combinatorial drivers and targets in cancer cell lines.

    PubMed

    Tabchy, Adel; Eltonsy, Nevine; Housman, David E; Mills, Gordon B

    2013-01-01

    There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

  8. Significant Figures in Measurements with Uncertainty: A Working Criterion

    NASA Astrophysics Data System (ADS)

    Vilchis, Abraham

    2017-03-01

    Generally speaking, students have difficulty reporting out measurements and estimates of quantities used in the laboratory, and with handling the significant figures associated with them. When required to make calculation involving quantities with different numbers of significant figures, they have difficulty in assigning the corresponding digits to the final result. When in addition, the quantities have uncertainty, the operations entailed pose an even greater challenge. The article advocates for some working rules for students (and teachers) in an effort to combat this problem.

  9. EA Shuttle Document Retention Effort

    NASA Technical Reports Server (NTRS)

    Wagner, Howard A.

    2010-01-01

    This slide presentation reviews the effort of code EA at Johnson Space Center (JSC) to identify and acquire databases and documents from the space shuttle program that are adjudged important for retention after the retirement of the space shuttle.

  10. Significant Revisions to OSHA 29 CFR 1910.269.

    PubMed

    Neitzel, Dennis K

    2015-06-01

    The updated OSHA 29 CFR 1910.269 requirements are significant for assisting employers in their efforts to protect their employees from electrical hazards. In addition, OSHA based these revisions on the latest consensus standards and improvements in electrical safety technology. Together, the updated regulation creates a unified and up-to-date set of requirements to help employers more effectively establish safe work practices to protect their workers.

  11. User behaviour, best practice and the risks of non-target exposure associated with anticoagulant rodenticide use.

    PubMed

    Tosh, David G; Shore, Richard F; Jess, Stephen; Withers, Alan; Bearhop, Stuart; Ian Montgomery, W; McDonald, Robbie A

    2011-06-01

    Usage of anticoagulant rodenticides (ARs) is an integral component of modern agriculture and is essential for the control of commensal rodent populations. However, the extensive deployment of ARs has led to widespread exposure of a range of non-target predatory birds and mammals to some compounds, in particular the second-generation anticoagulant rodenticides (SGARs). As a result, there has been considerable effort placed into devising voluntary best practice guidelines that increase the efficacy of rodent control and reduce the risk of non-target exposure. Currently, there is limited published information on actual practice amongst users or implementation of best practice. We assessed the behaviour of a typical group of users using an on-farm questionnaire survey. Most baited for rodents every year using SGARs. Most respondents were apparently aware of the risks of non-target exposure and adhered to some of the best practice recommendations but total compliance was rare. Our questionnaire revealed that users of first generation anticoagulant rodenticides rarely protected or checked bait stations, and so took little effort to prevent primary exposure of non-targets. Users almost never searched for and removed poisoned carcasses and many baited for prolonged periods or permanently. These factors are all likely to enhance the likelihood of primary and secondary exposure of non-target species. Copyright © 2010. Published by Elsevier Ltd.

  12. High blood sugar levels significantly impact the prognosis of colorectal cancer patients through down-regulation of microRNA-16 by targeting Myb and VEGFR2

    PubMed Central

    Huang, Ching-Wen; Lu, Chien-Yu; Miao, Zhi-Feng; Chang, Se-Fen; Juo, Suh-Hang Hank; Wang, Jaw-Yuan

    2016-01-01

    The high prevalence of type 2 diabetes mellitus in colorectal cancer patients is a crucial public health issue worldwide. The deregulation of microRNAs has been shown to be associated with the progression of CRC; however, the effects of high blood sugar levels on miR deregulation and, in turn, CRC remain unexplored. In this study, 520 CRC patients were classified into two groups according to their blood sugar levels (≧110 or <110 mg/dL). Clinicopathologic features, clinical outcomes, and serum miR-16 levels of the two groups were then analyzed, while cell cycles, cell proliferation, migration, and cellular miR-16 expression were investigated via D-(+)-glucose administration. Additionally, the target genes of miR-16 were identified. Through multivariate analysis, both the disease-free survival and overall survival of the CRC patients were found to be associated with the UICC stage, perineural invasion, and blood glucose levels (P < 0.05). Serum miR-16 levels were significantly lower in the high blood glucose patients than in the normal blood glucose patients (P = 0.0329). With D-(+)-glucose administration, the proliferation and migration of CRC cells in vitro increased remarkably (P < 0.05), while their accumulation in the G1 phase decreased significantly. Cellular miR-16 expression was suppressed by D-(+)-glucose administration. The expression levels of two target genes, Myb and VEGFR2, were affected significantly by miR-16, while glucose administration inhibited miR-16 expression and enhanced tumor cell proliferation and migration. Hyperglycemia can impact the clinical outcomes of CRC patients, likely by inhibiting miR-16 expression and the expression of its downstream genes Myb and VEGFR2. PMID:26934556

  13. Liquid Hydrogen Target Experience at SLAC

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

    Weisend, J.G.; Boyce, R.; Candia, A.

    2005-08-29

    Liquid hydrogen targets have played a vital role in the physics program at SLAC for the past 40 years. These targets have ranged from small ''beer can'' targets to the 1.5 m long E158 target that was capable of absorbing up to 800 W without any significant density changes. Successful use of these targets has required the development of thin wall designs, liquid hydrogen pumps, remote positioning and alignment systems, safety systems, control and data acquisition systems, cryogenic cooling circuits and heat exchangers. Detailed operating procedures have been created to ensure safety and operational reliability. This paper surveys the evolutionmore » of liquid hydrogen targets at SLAC and discusses advances in several of the enabling technologies that made these targets possible.« less

  14. Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1—Psychometric Characteristics of 5 Paradigms.

    PubMed

    Reddy, L Felice; Horan, William P; Barch, Deanna M; Buchanan, Robert W; Dunayevich, Eduardo; Gold, James M; Lyons, Naomi; Marder, Stephen R; Treadway, Michael T; Wynn, Jonathan K; Young, Jared W; Green, Michael F

    2015-09-01

    Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2015.

  15. High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious.

    PubMed

    Morais, Caio C A; Koyama, Yukiko; Yoshida, Takeshi; Plens, Glauco M; Gomes, Susimeire; Lima, Cristhiano A S; Ramos, Ozires P S; Pereira, Sérgio M; Kawaguchi, Naomasa; Yamamoto, Hirofumi; Uchiyama, Akinori; Borges, João B; Vidal Melo, Marcos F; Tucci, Mauro R; Amato, Marcelo B P; Kavanagh, Brian P; Costa, Eduardo L V; Fujino, Yuji

    2018-05-15

    In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious. To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP). Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS. Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients). Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.

  16. Targeting LKB1 in cancer – exposing and exploiting vulnerabilities

    PubMed Central

    Momcilovic, M; Shackelford, D B

    2015-01-01

    The LKB1 tumour suppressor is a serine/threonine kinase that functions as master regulator of cell growth, metabolism, survival and polarity. LKB1 is frequently mutated in human cancers and research spanning the last two decades have begun decoding the cellular pathways deregulated following LKB1 inactivation. This work has led to the identification of vulnerabilities present in LKB1-deficient tumour cells. Pre-clinical studies have now identified therapeutic strategies targeting this subset of tumours that promise to benefit this large patient population harbouring LKB1 mutations. Here, we review the current efforts that are underway to translate pre-clinical discovery of therapeutic strategies targeting LKB1 mutant cancers into clinical practice. PMID:26196184

  17. Evaluating Practice-Based Learning and Improvement: Efforts to Improve Acceptance of Portfolios

    PubMed Central

    Fragneto, Regina Y.; DiLorenzo, Amy Noel; Schell, Randall M.; Bowe, Edwin A.

    2010-01-01

    Introduction The Accreditation Council for Graduate Medical Education (ACGME) recommends resident portfolios as 1 method for assessing competence in practice-based learning and improvement. In July 2005, when anesthesiology residents in our department were required to start a portfolio, the residents and their faculty advisors did not readily accept this new requirement. Intensive education efforts addressing the goals and importance of portfolios were undertaken. We hypothesized that these educational efforts improved acceptance of the portfolio and retrospectively audited the portfolio evaluation forms completed by faculty advisors. Methods Intensive education about the goals and importance of portfolios began in January 2006, including presentations at departmental conferences and one-on-one education sessions. Faculty advisors were instructed to evaluate each resident's portfolio and complete a review form. We retrospectively collected data to determine the percentage of review forms completed by faculty. The portfolio reviews also assessed the percentage of 10 required portfolio components residents had completed. Results Portfolio review forms were completed by faculty advisors for 13% (5/38) of residents during the first advisor-advisee meeting in December 2005. Initiation of intensive education efforts significantly improved compliance, with review forms completed for 68% (26/38) of residents in May 2006 (P < .0001) and 95% (36/38) in December 2006 (P < .0001). Residents also significantly improved the completeness of portfolios between May and December of 2006. Discussion Portfolios are considered a best methods technique by the ACGME for evaluation of practice-based learning and improvment. We have found that intensive education about the goals and importance of portfolios can enhance acceptance of this evaluation tool, resulting in improved compliance in completion and evaluation of portfolios. PMID:22132291

  18. Evaluating practice-based learning and improvement: efforts to improve acceptance of portfolios.

    PubMed

    Fragneto, Regina Y; Dilorenzo, Amy Noel; Schell, Randall M; Bowe, Edwin A

    2010-12-01

    The Accreditation Council for Graduate Medical Education (ACGME) recommends resident portfolios as 1 method for assessing competence in practice-based learning and improvement. In July 2005, when anesthesiology residents in our department were required to start a portfolio, the residents and their faculty advisors did not readily accept this new requirement. Intensive education efforts addressing the goals and importance of portfolios were undertaken. We hypothesized that these educational efforts improved acceptance of the portfolio and retrospectively audited the portfolio evaluation forms completed by faculty advisors. Intensive education about the goals and importance of portfolios began in January 2006, including presentations at departmental conferences and one-on-one education sessions. Faculty advisors were instructed to evaluate each resident's portfolio and complete a review form. We retrospectively collected data to determine the percentage of review forms completed by faculty. The portfolio reviews also assessed the percentage of 10 required portfolio components residents had completed. Portfolio review forms were completed by faculty advisors for 13% (5/38) of residents during the first advisor-advisee meeting in December 2005. Initiation of intensive education efforts significantly improved compliance, with review forms completed for 68% (26/38) of residents in May 2006 (P < .0001) and 95% (36/38) in December 2006 (P < .0001). Residents also significantly improved the completeness of portfolios between May and December of 2006. Portfolios are considered a best methods technique by the ACGME for evaluation of practice-based learning and improvment. We have found that intensive education about the goals and importance of portfolios can enhance acceptance of this evaluation tool, resulting in improved compliance in completion and evaluation of portfolios.

  19. Transferrin-Conjugated Nanocarriers as Active-Targeted Drug Delivery Platforms for Cancer Therapy.

    PubMed

    Nogueira-Librelotto, Daniele R; Codevilla, Cristiane F; Farooqi, Ammad; Rolim, Clarice M B

    2017-01-01

    A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Assessing country-level efforts to link research to action.

    PubMed Central

    Lavis, John N.; Lomas, Jonathan; Hamid, Maimunah; Sewankambo, Nelson K.

    2006-01-01

    We developed a framework for assessing country-level efforts to link research to action. The framework has four elements. The first element assesses the general climate (how those who fund research, universities, researchers and users of research support or place value on efforts to link research to action). The second element addresses the production of research (how priority setting ensures that users' needs are identified and how scoping reviews, systematic reviews and single studies are undertaken to address these needs). The third element addresses the mix of four clusters of activities used to link research to action. These include push efforts (how strategies are used to support action based on the messages arising from research), efforts to facilitate "user pull" (how "one-stop shopping" is provided for optimally packaged high-quality reviews either alone or as part of a national electronic library for health, how these reviews are profiled during "teachable moments" such as intense media coverage, and how rapid-response units meet users' needs for the best research), "user pull" efforts undertaken by those who use research (how users assess their capacity to use research and how structures and processes are changed to support the use of research) and exchange efforts (how meaningful partnerships between researchers and users help them to jointly ask and answer relevant questions). The fourth element addresses approaches to evaluation (how support is provided for rigorous evaluations of efforts to link research to action). PMID:16917649