Cost estimation for the active debris removal of multiple priority targets

NASA Astrophysics Data System (ADS)

Braun, Vitali; Wiedemann, Carsten; Schulz, Eugen

The increasing number of space debris objects, especially in distinct low Earth orbit (LEO) altitudes between 600 and 1000 km, leads to an increase in the potential collision risk between the objects and threatens active satellites in that region. Several recent studies show that active debris removal (ADR) has to be performed in order to prevent a collisional cascading effect, also known as the Kessler syndrome. In order to stabilize the population growth in the critical LEO region, a removal of five prioritized objects per year has been recognized as a significant figure. Various proposals are addressing the technical issues for ADR missions, including the de-orbiting of objects by means of a service satellite using a chemical or an electric propulsion system. The servicer would rendezvous with a preselected target, perform a docking maneuver and then provide a de-orbit burn to transfer the target on a trajectory where it re-enters the Earth’s atmosphere within a given time frame. In this paper the technical aspects are complemented by a cost estimation model, focusing on multi target missions, which are based on a service satellite capable of de-orbiting more than one target within a single mission. The cost model for ADR includes initial development cost, production cost, launch cost and operation cost as well as the modelling of the propulsion system of the servicer. Therefore, different scenarios are defined for chemical and electric propulsion systems as applied to multi target missions, based on a literature review of concepts currently being under discussion. The costs of multi target missions are compared to a scenario where only one target is removed. Also, the results allow to determine an optimum number of objects to be removed per mission and provide numbers which can be used in future studies, e.g. those related to ADR cost and benefit analyses.

Search for Two Categories of Target Produces Fewer Fixations to Target-Color Items

ERIC Educational Resources Information Center

Menneer, Tamaryn; Stroud, Michael J.; Cave, Kyle R.; Li, Xingshan; Godwin, Hayward J.; Liversedge, Simon P.; Donnelly, Nick

2012-01-01

Searching simultaneously for metal threats (guns and knives) and improvised explosive devices (IEDs) in X-ray images is less effective than 2 independent single-target searches, 1 for metal threats and 1 for IEDs. The goals of this study were to (a) replicate this dual-target cost for categorical targets and to determine whether the cost remains…

Thin liquid sheet target capabilities for ultra-intense laser acceleration of ions at a kHz repetition rate

NASA Astrophysics Data System (ADS)

Klim, Adam; Morrison, J.; Orban, C.; Chowdhury, E.; Frische, K.; Feister, S.; Roquemore, M.

2017-10-01

The success of laser-accelerated ion experiments depends crucially on a number of factors including how thin the targets can be created. We present experimental results demonstrating extremely thin (under 200 nm) glycol sheet targets that can be used for ultra-intense laser-accelerated ion experiments conducted at the Air Force Research Laboratory at Wright-Patterson Air Force Base. Importantly, these experiments operate at a kHz repetition rate and the recovery time of the liquid targets is fast enough to allow the laser to interact with a refreshed, thin target on every shot. These thin targets can be used to produce energetic electrons, light ions, and neutrons as well as x-rays, we present results from liquid glycol targets which are useful for proton acceleration experiments via the mechanism of Target Normal Sheath Acceleration (TNSA). In future work, we will create thin sheets from deuterated water in order to perform laser-accelerated deuteron experiments. This research was sponsored by the Quantum and Non-Equilibrium Processes Division of the AFOSR, under the management of Dr. Enrique Parra, and support from the DOD HPCMP Internship Program.

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

PubMed

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

2016-04-26

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

Cost-effectiveness of targeted and tailored interventions on colorectal cancer screening use.

PubMed

Lairson, David R; DiCarlo, Melissa; Myers, Ronald E; Wolf, Thomas; Cocroft, James; Sifri, Randa; Rosenthal, Michael; Vernon, Sally W; Wender, Richard

2008-02-15

Colorectal cancer (CRC) screening is cost-effective but underused. The objective of this study was to determine the cost-effectiveness of targeted and tailored behavioral interventions to increase CRC screening use by conducting an economic analysis associated with a randomized trial among patients in a large, racially and ethnically diverse, urban family practice in Philadelphia. The incremental costs per unit increase were measured in individuals who were screened during the 24 months after intervention. Percent increase in screening was adjusted for baseline differences in the study groups. Each intervention arm received a targeted screening invitation letter, stool blood test (SBT) cards, informational booklet, and reminder letter. Tailored interventions incrementally added tailored messages and reminder telephone calls. Program costs of the targeted intervention were 42 dollars per participant. Additional costs of adding tailored print materials and of delivering a reminder telephone call were 150 dollars and 200 dollars per participant, respectively. The cost per additional individual screened was 319 dollars when comparing the no intervention group with the targeted intervention group. The targeted intervention was more effective and less costly than the tailored intervention. Although tailoring plus reminder telephone call was the most effective strategy, it was very costly per additional individual screened. Mailed SBT cards significantly boosted CRC screening use. However, going beyond the targeted intervention to include tailoring or tailoring plus reminder calls in the manner used in this study did not appear to be an economically attractive strategy. Cancer 2008. (c) 2007 American Cancer Society.

Low, slow, small target recognition based on spatial vision network

NASA Astrophysics Data System (ADS)

Cheng, Zhao; Guo, Pei; Qi, Xin

2018-03-01

Traditional photoelectric monitoring is monitored using a large number of identical cameras. In order to ensure the full coverage of the monitoring area, this monitoring method uses more cameras, which leads to more monitoring and repetition areas, and higher costs, resulting in more waste. In order to reduce the monitoring cost and solve the difficult problem of finding, identifying and tracking a low altitude, slow speed and small target, this paper presents spatial vision network for low-slow-small targets recognition. Based on camera imaging principle and monitoring model, spatial vision network is modeled and optimized. Simulation experiment results demonstrate that the proposed method has good performance.

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.

ResStock - Targeting Energy and Cost Savings for U.S. Homes | NREL

Science.gov Websites

ResStock - Targeting Energy and Cost Savings for U.S. Homes Science and Technology Highlights Highlights in Research & Development ResStock - Targeting Energy and Cost Savings for U.S. Homes Key discovered $49 billion in potential annual utility bill savings through cost-effective energy efficiency

Ecosystem Services in Conservation Planning: Targeted Benefits vs. Co-Benefits or Costs?

PubMed Central

Chan, Kai M. A.; Hoshizaki, Lara; Klinkenberg, Brian

2011-01-01

There is growing support for characterizing ecosystem services in order to link conservation and human well-being. However, few studies have explicitly included ecosystem services within systematic conservation planning, and those that have follow two fundamentally different approaches: ecosystem services as intrinsically-important targeted benefits vs. substitutable co-benefits. We present a first comparison of these two approaches in a case study in the Central Interior of British Columbia. We calculated and mapped economic values for carbon storage, timber production, and recreational angling using a geographical information system (GIS). These ‘marginal’ values represent the difference in service-provision between conservation and managed forestry as land uses. We compared two approaches to including ecosystem services in the site-selection software Marxan: as Targeted Benefits, and as Co-Benefits/Costs (in Marxan's cost function); we also compared these approaches with a Hybrid approach (carbon and angling as targeted benefits, timber as an opportunity cost). For this analysis, the Co-Benefit/Cost approach yielded a less costly reserve network than the Hybrid approach (1.6% cheaper). Including timber harvest as an opportunity cost in the cost function resulted in a reserve network that achieved targets equivalently, but at 15% lower total cost. We found counter-intuitive results for conservation: conservation-compatible services (carbon, angling) were positively correlated with each other and biodiversity, whereas the conservation-incompatible service (timber) was negatively correlated with all other networks. Our findings suggest that including ecosystem services within a conservation plan may be most cost-effective when they are represented as substitutable co-benefits/costs, rather than as targeted benefits. By explicitly valuing the costs and benefits associated with services, we may be able to achieve meaningful biodiversity conservation at lower cost

Target Context Specification Can Reduce Costs in Nonfocal Prospective Memory

ERIC Educational Resources Information Center

Lourenço, Joana S.; White, Katherine; Maylor, Elizabeth A.

2013-01-01

Performing a nonfocal prospective memory (PM) task results in a cost to ongoing task processing, but the precise nature of the monitoring processes involved remains unclear. We investigated whether target context specification (i.e., explicitly associating the PM target with a subset of ongoing stimuli) can trigger trial-by-trial changes in task…

Repetitive output laser system and method using target reflectivity

DOEpatents

Johnson, Roy R.

1978-01-01

An improved laser system and method for implosion of a thermonuclear fuel pellet in which that portion of a laser pulse reflected by the target pellet is utilized in the laser system to initiate a succeeding target implosion, and in which the energy stored in the laser system to amplify the initial laser pulse, but not completely absorbed thereby, is used to amplify succeeding laser pulses initiated by target reflection.

Cost effectiveness of targeted HIV prevention interventions for female sex workers in India.

PubMed

Prinja, Shankar; Bahuguna, Pankaj; Rudra, Shalini; Gupta, Indrani; Kaur, Manmeet; Mehendale, S M; Chatterjee, Susmita; Panda, Samiran; Kumar, Rajesh

2011-06-01

To ascertain the cost effectiveness of targeted interventions for female sex workers (FSW) under the National AIDS Control Programme in India. A compartmental mathematical Markov state model was used over a 20-year time horizon (1995-2015) to estimate the cost effectiveness of FSW targeted interventions, with a health system perspective. The incremental costs and effects of FSW targeted interventions were compared against a baseline scenario of mass media for the general population alone. The incremental cost-effectiveness ratio was computed at a 3% discount rate using HIV infections averted and disability-adjusted life-years (DALY) as benefit measures. It was assumed that the transmission of the HIV virus moves from a high-risk group (FSW) to the client population and finally to the general population (partners of clients). Targeted interventions for FSW result in a reduction of 47% (1.6 million) prevalent and 36% (2.7 million) cumulative HIV cases, respectively, in 2015. Adult HIV prevalence in India, with and without (mass media only) FSW interventions, would be 0.25% and 0.48% in 2015. Indian government and development partners spend an average US $104 (INR4680) per HIV infection averted and US $10.7 (INR483) per DALY averted. Discounting at 3%, FSW targeted interventions cost US $105.5 (INR4748) and US $10.9 (INR490) per HIV case and DALY averted, respectively. At the current gross domestic product in India, targeted intervention is a cost-effective strategy for HIV prevention in India.

Can disease management target patients most likely to generate high costs? The impact of comorbidity.

PubMed

Charlson, Mary; Charlson, Robert E; Briggs, William; Hollenberg, James

2007-04-01

Disease management programs are increasingly used to manage costs of patients with chronic disease. We sought to examine the clinical characteristics and measure the health care expenditures of patients most likely to be targeted by disease management programs. Retrospective analysis of prospectively obtained data. A general medicine practice with both faculty and residents at an urban academic medical center. Five thousand eight hundred sixty-one patients enrolled in the practice for at least 1 year. Annual cost of diseases targeted by disease management. Patients' clinical and demographic information were collected from a computer system used to manage patients. Data included diagnostic information, medications, and resource usage over 1 year. We looked at 10 common diseases targeted by disease management programs. Unadjusted annual median costs for chronic diseases ranged between $1,100 and $1,500. Congestive heart failure ($1,500), stroke ($1,500), diabetes ($1,500), and cancer ($1,400) were the most expensive. As comorbidity increased, annual adjusted costs increased exponentially. Those with comorbidity scores of 2 or more accounted for 26% of the population but 50% of the overall costs. Costs for individual chronic conditions vary within a relatively narrow range. However, the costs for patients with multiple coexisting medical conditions increase rapidly. Reducing health care costs will require focusing on patients with multiple comorbid diseases, not just single diseases. The overwhelming impact of comorbidity on costs raises significant concerns about the potential ability of disease management programs to limit the costs of care.

How much does it cost to achieve coverage targets for primary healthcare services? A costing model from Aceh, Indonesia.

PubMed

Abdullah, Asnawi; Hort, Krishna; Abidin, Azwar Zaenal; Amin, Fadilah M

2012-01-01

Despite significant investment in improving service infrastructure and training of staff, public primary healthcare services in low-income and middle-income countries tend to perform poorly in reaching coverage targets. One of the factors identified in Aceh, Indonesia was the lack of operational funds for service provision. The objective of this study was to develop a simple and transparent costing tool that enables health planners to calculate the unit costs of providing basic health services to estimate additional budgets required to deliver services in accordance with national targets. The tool was developed using a standard economic approach that linked the input activities to achieving six national priority programs at primary healthcare level: health promotion, sanitation and environment health, maternal and child health and family planning, nutrition, immunization and communicable diseases control, and treatment of common illness. Costing was focused on costs of delivery of the programs that need to be funded by local government budgets. The costing tool consisting of 16 linked Microsoft Excel worksheets was developed and tested in several districts enabled the calculation of the unit costs of delivering of the six national priority programs per coverage target of each program (such as unit costs of delivering of maternal and child health program per pregnant mother). This costing tool can be used by health planners to estimate additional money required to achieve a certain level of coverage of programs, and it can be adjusted for different costs and program delivery parameters in different settings. Copyright © 2012 John Wiley & Sons, Ltd.

Can Disease Management Target Patients Most Likely to Generate High Costs? The Impact of Comorbidity

PubMed Central

Charlson, Robert E.; Briggs, William; Hollenberg, James

2007-01-01

Context Disease management programs are increasingly used to manage costs of patients with chronic disease. Objective We sought to examine the clinical characteristics and measure the health care expenditures of patients most likely to be targeted by disease management programs. Design Retrospective analysis of prospectively obtained data. Setting A general medicine practice with both faculty and residents at an urban academic medical center. Participants Five thousand eight hundred sixty-one patients enrolled in the practice for at least 1 year. Main Outcomes Annual cost of diseases targeted by disease management. Measurements Patients’ clinical and demographic information were collected from a computer system used to manage patients. Data included diagnostic information, medications, and resource usage over 1 year. We looked at 10 common diseases targeted by disease management programs. Results Unadjusted annual median costs for chronic diseases ranged between $1,100 and $1,500. Congestive heart failure ($1,500), stroke ($1,500), diabetes ($1,500), and cancer ($1,400) were the most expensive. As comorbidity increased, annual adjusted costs increased exponentially. Those with comorbidity scores of 2 or more accounted for 26% of the population but 50% of the overall costs. Conclusions Costs for individual chronic conditions vary within a relatively narrow range. However, the costs for patients with multiple coexisting medical conditions increase rapidly. Reducing health care costs will require focusing on patients with multiple comorbid diseases, not just single diseases. The overwhelming impact of comorbidity on costs raises significant concerns about the potential ability of disease management programs to limit the costs of care. PMID:17372794

Energy technologies evaluated against climate targets using a cost and carbon trade-off curve.

PubMed

Trancik, Jessika E; Cross-Call, Daniel

2013-06-18

Over the next few decades, severe cuts in emissions from energy will be required to meet global climate-change mitigation goals. These emission reductions imply a major shift toward low-carbon energy technologies, and the economic cost and technical feasibility of mitigation are therefore highly dependent upon the future performance of energy technologies. However, existing models do not readily translate into quantitative targets against which we can judge the dynamic performance of technologies. Here, we present a simple, new model for evaluating energy-supply technologies and their improvement trajectories against climate-change mitigation goals. We define a target for technology performance in terms of the carbon intensity of energy, consistent with emission reduction goals, and show how the target depends upon energy demand levels. Because the cost of energy determines the level of adoption, we then compare supply technologies to one another and to this target based on their position on a cost and carbon trade-off curve and how the position changes over time. Applying the model to U.S. electricity, we show that the target for carbon intensity will approach zero by midcentury for commonly cited emission reduction goals, even under a high demand-side efficiency scenario. For Chinese electricity, the carbon intensity target is relaxed and less certain because of lesser emission reductions and greater variability in energy demand projections. Examining a century-long database on changes in the cost-carbon space, we find that the magnitude of changes in cost and carbon intensity that are required to meet future performance targets is not unprecedented, providing some evidence that these targets are within engineering reach. The cost and carbon trade-off curve can be used to evaluate the dynamic performance of existing and new technologies against climate-change mitigation goals.

Targeting Health Behaviors to Reduce Health Care Costs in Pediatric Psychology: Descriptive Review and Recommendations

PubMed Central

Hommel, Kevin A.

2016-01-01

Objective Recent efforts to enhance the quality of health care in the United States while reducing costs have resulted in an increased emphasis on cost containment and the introduction of new payment plans. The purpose of this review is to summarize the impact of pediatric health behavior change interventions on health care costs. Methods A review of PubMed, PsycINFO, and PEDE databases identified 15 articles describing the economic outcomes of pediatric health behavior change interventions. Data describing the intervention, health outcome, and economic outcome were extracted. Results All interventions targeting cigarette smoking (n = 3) or the prevention of a chronic medical condition (n = 5) were predicted to avert hundreds of dollars in health care costs per patient. Five of the seven interventions targeting self-management were associated with reductions in health care costs. Conclusions Pediatric health behavior change interventions may be a valuable component of efforts to improve population health while reducing health care costs. PMID:26359311

Scrutinizing data helps team target high-cost DRGs, improve costly tracheostomy care.

PubMed

1997-10-01

Targeting high-cost DRGs using data collection, analysis: A hospital team analyzed DRGs with the highest excess charges and found DRG 483 (tracheostomy) had astronomical charges. Here's the step-by-step story of how they analyzed individual physician resource utilization, care progression through the hospital, and admission source to identify areas for clinical improvement, plus their findings and how they're putting them to use to improve care and reduce costs.

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

PubMed

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

2011-05-01

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

Trends in the Cost and Use of Targeted Cancer Therapies for the Privately Insured Nonelderly: 2001 to 2011

PubMed Central

Shih, Ya-Chen Tina; Smieliauskas, Fabrice; Geynisman, Daniel M.; Kelly, Ronan J.; Smith, Thomas J.

2015-01-01

Purpose This study sought to define and identify drivers of trends in cost and use of targeted therapeutics among privately insured nonelderly patients with cancer receiving chemotherapy between 2001 and 2011. Methods We classified oncology drugs as targeted oral anticancer medications, targeted intravenous anticancer medications, and all others. Using the LifeLink Health Plan Claims Database, we studied and disaggregated trends in use and in insurance and out-of-pocket payments per patient per month and during the first year of chemotherapy. Results We found a large increase in the use of targeted intravenous anticancer medications and a gradual increase in targeted oral anticancer medications; targeted therapies accounted for 63% of all chemotherapy expenditures in 2011. Insurance payments per patient per month and in the first year of chemotherapy for targeted oral anticancer medications more than doubled in 10 years, surpassing payments for targeted intravenous anticancer medications, which remained fairly constant throughout. Substitution toward targeted therapies and growth in drug prices both at launch and postlaunch contributed to payer spending growth. Out-of-pocket spending for targeted oral anticancer medications was ≤ half of the amount for targeted intravenous anticancer medications. Conclusion Targeted therapies now dominate anticancer drug spending. More aggressive management of pharmacy benefits for targeted oral anticancer medications and payment reform for injectable drugs hold promise. Restraining the rapid rise in spending will require more than current oral drug parity laws, such as value-based insurance that makes the benefits and costs transparent and involves the patient directly in the choice of treatment. PMID:25987701

Laser plasma cryogenic target on translating substrate for generation of continuously repetitive EUV and soft X-ray pulses

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

Amano, Sho

2014-06-15

To generate continuously repetitive EUV and soft X-ray pulses with various wavelengths from laser-produced plasmas, a one-dimensionally translating substrate system with a closed He gas cryostat that can continuously supply various cryogenic targets for ∼10 Hz laser pulses has been developed. The system was successfully operated at a lowest temperature of 15 K and at a maximum up-down speed of 12 mm/s. Solid Ar, Kr, and Xe layers were formed, and their growth rates and the laser crater sizes on them were studied. By optimization of the operational parameters in accordance with our design rule, it was shown that stablemore » output power was achieved continuously from the plasma emission at frequencies of 1–10 Hz. The average soft X-ray and EUV powers obtained were 19 mW at 3.2 nm, 33 mW at 10.0 nm, and 66 mW at 10.8 nm, with 10% bandwidths, from the Ar, Kr, and Xe solid targets, respectively, with a laser power of 1 W. We will be able to achieve higher frequencies using a high beam quality laser that produces smaller craters, and can expect higher powers. Although only Ar, Kr, and Xe gases were tested in this study, the target system achieved a temperature of 15 K and can thus solidify almost all target gases, apart from H and He, and can continuously supply the solid target. The use of various target materials will enable expansion of the EUV and soft X-ray emission wavelength range.« less

SECOND TARGET STATION MODERATOR PERFORMANCE WITH A ROTATING TARGET

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

Remec, Igor; Gallmeier, Franz X; Rennich, Mark J

2016-01-01

Oak Ridge National Laboratory manages and operates the Spallation Neutron Source and the High Flux Isotope Reactor, two of the world's most advanced neutron scattering facilities. Both facilities are funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Science, and are available to researchers from all over the world. Delivering cutting edge science requires continuous improvements and development of the facilities and instruments. The SNS was designed from the outset to accommodate an additional target station, or Second Target Station (STS), and an upgraded accelerator feeding proton beams to STS and the existing First Targetmore » Station (FTS). Upgrade of the accelerator and the design and construction of STS are being proposed. The presently considered STS configuration is driven with short (<1 s) proton pulses at 10 Hz repetition rate and 467 kW proton beam power, and is optimized for high intensity and high resolution long wavelength neutron applications. STS will allow installation of 22 beamlines and will expand and complement the current national neutron scattering capabilities. In 2015 the STS studies were performed for a compact tungsten target; first a stationary tungsten plate target was analyzed to considerable details and then dropped in favor of a rotating target. For both target options the proton beam footprint as small as acceptable from mechanical and heat removal aspects is required to arrive at a compact-volume neutron production zone in the target, which is essential for tight coupling of target and moderators and for achieving high-intensity peak neutron fluxes. This paper will present recent STS work with the emphasis on neutronics and moderator performance.« less

Cost-effective targeting of conservation investments to reduce the northern Gulf of Mexico hypoxic zone.

PubMed

Rabotyagov, Sergey S; Campbell, Todd D; White, Michael; Arnold, Jeffrey G; Atwood, Jay; Norfleet, M Lee; Kling, Catherine L; Gassman, Philip W; Valcu, Adriana; Richardson, Jeffrey; Turner, R Eugene; Rabalais, Nancy N

2014-12-30

A seasonally occurring summer hypoxic (low oxygen) zone in the northern Gulf of Mexico is the second largest in the world. Reductions in nutrients from agricultural cropland in its watershed are needed to reduce the hypoxic zone size to the national policy goal of 5,000 km(2) (as a 5-y running average) set by the national Gulf of Mexico Task Force's Action Plan. We develop an integrated assessment model linking the water quality effects of cropland conservation investment decisions on the more than 550 agricultural subwatersheds that deliver nutrients into the Gulf with a hypoxic zone model. We use this integrated assessment model to identify the most cost-effective subwatersheds to target for cropland conservation investments. We consider targeting of the location (which subwatersheds to treat) and the extent of conservation investment to undertake (how much cropland within a subwatershed to treat). We use process models to simulate the dynamics of the effects of cropland conservation investments on nutrient delivery to the Gulf and use an evolutionary algorithm to solve the optimization problem. Model results suggest that by targeting cropland conservation investments to the most cost-effective location and extent of coverage, the Action Plan goal of 5,000 km(2) can be achieved at a cost of $2.7 billion annually. A large set of cost-hypoxia tradeoffs is developed, ranging from the baseline to the nontargeted adoption of the most aggressive cropland conservation investments in all subwatersheds (estimated to reduce the hypoxic zone to less than 3,000 km(2) at a cost of $5.6 billion annually).

The grain of spatially referenced economic cost and biodiversity benefit data and the effectiveness of a cost targeting strategy.

PubMed

Sutton, N J; Armsworth, P R

2014-12-01

Facing tight resource constraints, conservation organizations must allocate funds available for habitat protection as effectively as possible. Often, they combine spatially referenced economic and biodiversity data to prioritize land for protection. We tested how sensitive these prioritizations could be to differences in the spatial grain of these data by demonstrating how the conclusion of a classic debate in conservation planning between cost and benefit targeting was altered based on the available information. As a case study, we determined parcel-level acquisition costs and biodiversity benefits of land transactions recently undertaken by a nonprofit conservation organization that seeks to protect forests in the eastern United States. Then, we used hypothetical conservation plans to simulate the types of ex ante priorities that an organization could use to prioritize areas for protection. We found the apparent effectiveness of cost and benefit targeting depended on the spatial grain of the data used when prioritizing parcels based on local species richness. However, when accounting for complementarity, benefit targeting consistently was more efficient than a cost targeting strategy regardless of the spatial grain of the data involved. More pertinently for other studies, we found that combining data collected over different spatial grains inflated the apparent effectiveness of a cost targeting strategy and led to overestimation of the efficiency gain offered by adopting a more integrative return-on-investment approach. © 2014 Society for Conservation Biology.

Targeting Health Behaviors to Reduce Health Care Costs in Pediatric Psychology: Descriptive Review and Recommendations.

PubMed

McGrady, Meghan E; Hommel, Kevin A

2016-09-01

Recent efforts to enhance the quality of health care in the United States while reducing costs have resulted in an increased emphasis on cost containment and the introduction of new payment plans. The purpose of this review is to summarize the impact of pediatric health behavior change interventions on health care costs. A review of PubMed, PsycINFO, and PEDE databases identified 15 articles describing the economic outcomes of pediatric health behavior change interventions. Data describing the intervention, health outcome, and economic outcome were extracted. All interventions targeting cigarette smoking (n = 3) or the prevention of a chronic medical condition (n = 5) were predicted to avert hundreds of dollars in health care costs per patient. Five of the seven interventions targeting self-management were associated with reductions in health care costs. Pediatric health behavior change interventions may be a valuable component of efforts to improve population health while reducing health care costs. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Magnetized Target Fusion: Prospects for Low-Cost Fusion Energy

NASA Technical Reports Server (NTRS)

Siemon, Richard E.; Turchi, Peter J.; Barnes, Daniel C.; Degnan, James; Parks, Paul; Ryutov, Dmitri D.; Thio, Y. C. Francis; Schafer, Charles (Technical Monitor)

2001-01-01

Magnetized Target Fusion (MTF) has attracted renewed interest in recent years because it has the potential to resolve one of the major problems with conventional fusion energy research - the high cost of facilities to do experiments and in general develop practical fusion energy. The requirement for costly facilities can be traced to fundamental constraints. The Lawson condition implies large system size in the case of conventional magnetic confinement, or large heating power in the case of conventional inertial confinement. The MTF approach is to use much higher fuel density than with conventional magnetic confinement (corresponding to megabar pressures), which results in a much-reduced system size to achieve Lawson conditions. Intrinsically the system must be pulsed because the pressures exceed the strength of any known material. To facilitate heating the fuel (or "target") to thermonuclear conditions with a high-power high-intensity source of energy, magnetic fields are used to insulate the high-pressure fuel from material surroundings (thus "magnetized target"). Because of magnetic insulation, the required heating power intensity is reduced by many orders of magnitude compared to conventional inertial fusion, even with relatively poor energy confinement in the magnetic field, such as that characterized by Bohm diffusion. In this paper we show semi-quantitatively why MTF-should allow fusion energy production without costly facilities within the same generally accepted physical constraints used for conventional magnetic and inertial fusion. We also briefly discuss potential applications of this technology ranging from nuclear rockets for space propulsion to a practical commercial energy system. Finally, we report on the exploratory research underway, and the interesting physics issues that arise in the MTF regime of parameters. Experiments at Los Alamos are focused on formation of a suitable plasma target for compression, utilizing the knowledge base for compact

Cost-effective targeting of conservation investments to reduce the northern Gulf of Mexico hypoxic zone

PubMed Central

Rabotyagov, Sergey S.; Campbell, Todd D.; White, Michael; Arnold, Jeffrey G.; Atwood, Jay; Norfleet, M. Lee; Kling, Catherine L.; Gassman, Philip W.; Valcu, Adriana; Richardson, Jeffrey; Turner, R. Eugene; Rabalais, Nancy N.

2014-01-01

A seasonally occurring summer hypoxic (low oxygen) zone in the northern Gulf of Mexico is the second largest in the world. Reductions in nutrients from agricultural cropland in its watershed are needed to reduce the hypoxic zone size to the national policy goal of 5,000 km2 (as a 5-y running average) set by the national Gulf of Mexico Task Force’s Action Plan. We develop an integrated assessment model linking the water quality effects of cropland conservation investment decisions on the more than 550 agricultural subwatersheds that deliver nutrients into the Gulf with a hypoxic zone model. We use this integrated assessment model to identify the most cost-effective subwatersheds to target for cropland conservation investments. We consider targeting of the location (which subwatersheds to treat) and the extent of conservation investment to undertake (how much cropland within a subwatershed to treat). We use process models to simulate the dynamics of the effects of cropland conservation investments on nutrient delivery to the Gulf and use an evolutionary algorithm to solve the optimization problem. Model results suggest that by targeting cropland conservation investments to the most cost-effective location and extent of coverage, the Action Plan goal of 5,000 km2 can be achieved at a cost of $2.7 billion annually. A large set of cost-hypoxia tradeoffs is developed, ranging from the baseline to the nontargeted adoption of the most aggressive cropland conservation investments in all subwatersheds (estimated to reduce the hypoxic zone to less than 3,000 km2 at a cost of $5.6 billion annually). PMID:25512489

Bioeconomic analysis of child-targeted subsidies for artemisinin combination therapies: a cost-effectiveness analysis

PubMed Central

Klein, Eili Y.; Smith, David L.; Cohen, Justin M.; Laxminarayan, Ramanan

2015-01-01

The Affordable Medicines Facility for malaria (AMFm) was conceived as a global market-based mechanism to increase access to effective malaria treatment and prolong effectiveness of artemisinin. Although results from a pilot implementation suggested that the subsidy was effective in increasing access to high-quality artemisinin combination therapies (ACTs), the Global Fund has converted AMFm into a country-driven mechanism whereby individual countries could choose to fund the subsidy from within their country envelopes. Because the initial costs of the subsidy in the pilot countries was higher than expected, countries are also exploring alternatives to a universal subsidy, such as subsidizing only child doses. We examined the incremental cost-effectiveness of a child-targeted policy using an age-structured bioeconomic model of malaria from the provider perspective. Because the vast majority of malaria deaths occur in children, targeting children could potentially improve the cost-effectiveness of the subsidy, though it would avert significantly fewer deaths. However, the benefits of a child-targeted subsidy (i.e. deaths averted) are eroded as leakage (i.e. older individuals taking young child-targeted doses) increases, with few of the benefits of a universal subsidy gained (i.e. reductions in overall prevalence). Although potentially more cost-effective, a child-targeted subsidy must contain measures to reduce the possibility of leakage. PMID:25994293

Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.

PubMed

Erten, Mujde Z; Fernandez, Luca P; Ng, Hank K; McKinnon, Wendy C; Heald, Brandie; Koliba, Christopher J; Greenblatt, Marc S

2016-10-01

Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. We compared targeted versus universal screening of CRCs for Lynch syndrome. In 2010-2011, we employed targeted screening (age < 60 and/or Bethesda criteria). From 2012 to 2014, we screened all CRCs. Immunohistochemistry for the four mismatch repair proteins was done in all cases, followed by other diagnostic studies as indicated. We modeled the diagnostic costs of detecting Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.

Utilizing random Forest QSAR models with optimized parameters for target identification and its application to target-fishing server.

PubMed

Lee, Kyoungyeul; Lee, Minho; Kim, Dongsup

2017-12-28

The identification of target molecules is important for understanding the mechanism of "target deconvolution" in phenotypic screening and "polypharmacology" of drugs. Because conventional methods of identifying targets require time and cost, in-silico target identification has been considered an alternative solution. One of the well-known in-silico methods of identifying targets involves structure activity relationships (SARs). SARs have advantages such as low computational cost and high feasibility; however, the data dependency in the SAR approach causes imbalance of active data and ambiguity of inactive data throughout targets. We developed a ligand-based virtual screening model comprising 1121 target SAR models built using a random forest algorithm. The performance of each target model was tested by employing the ROC curve and the mean score using an internal five-fold cross validation. Moreover, recall rates for top-k targets were calculated to assess the performance of target ranking. A benchmark model using an optimized sampling method and parameters was examined via external validation set. The result shows recall rates of 67.6% and 73.9% for top-11 (1% of the total targets) and top-33, respectively. We provide a website for users to search the top-k targets for query ligands available publicly at http://rfqsar.kaist.ac.kr . The target models that we built can be used for both predicting the activity of ligands toward each target and ranking candidate targets for a query ligand using a unified scoring scheme. The scores are additionally fitted to the probability so that users can estimate how likely a ligand-target interaction is active. The user interface of our web site is user friendly and intuitive, offering useful information and cross references.

Climate targets and cost-effective climate stabilization pathways

NASA Astrophysics Data System (ADS)

Held, H.

2015-08-01

Climate economics has developed two main tools to derive an economically adequate response to the climate problem. Cost benefit analysis weighs in any available information on mitigation costs and benefits and thereby derives an "optimal" global mean temperature. Quite the contrary, cost effectiveness analysis allows deriving costs of potential policy targets and the corresponding cost- minimizing investment paths. The article highlights pros and cons of both approaches and then focusses on the implications of a policy that strives at limiting global warming to 2 °C compared to pre-industrial values. The related mitigation costs and changes in the energy sector are summarized according to the IPCC report of 2014. The article then points to conceptual difficulties when internalizing uncertainty in these types of analyses and suggests pragmatic solutions. Key statements on mitigation economics remain valid under uncertainty when being given the adequate interpretation. Furthermore, the expected economic value of perfect climate information is found to be on the order of hundreds of billions of Euro per year if a 2°-policy were requested. Finally, the prospects of climate policy are sketched.

Targeting the probability versus cost of feared outcomes in public speaking anxiety.

PubMed

Nelson, Elizabeth A; Deacon, Brett J; Lickel, James J; Sy, Jennifer T

2010-04-01

Cognitive-behavioral theory suggests that social phobia is maintained, in part, by overestimates of the probability and cost of negative social events. Indeed, empirically supported cognitive-behavioral treatments directly target these cognitive biases through the use of in vivo exposure or behavioral experiments. While cognitive-behavioral theories and treatment protocols emphasize the importance of targeting probability and cost biases in the reduction of social anxiety, few studies have examined specific techniques for reducing probability and cost bias, and thus the relative efficacy of exposure to the probability versus cost of negative social events is unknown. In the present study, 37 undergraduates with high public speaking anxiety were randomly assigned to a single-session intervention designed to reduce either the perceived probability or the perceived cost of negative outcomes associated with public speaking. Compared to participants in the probability treatment condition, those in the cost treatment condition demonstrated significantly greater improvement on measures of public speaking anxiety and cost estimates for negative social events. The superior efficacy of the cost treatment condition was mediated by greater treatment-related changes in social cost estimates. The clinical implications of these findings are discussed. Published by Elsevier Ltd.

Longitudinal trends in use and costs of targeted therapies for common cancers in Taiwan: a retrospective observational study

PubMed Central

Hsu, Jason C; Lu, Christine Y

2016-01-01

Objectives Some targeted therapies have improved survival and overall quality of cancer care generally, but these increasingly expensive medicines have led to increases in pharmaceutical expenditure. This study examined trends in use and expenditures of antineoplastic agents in Taiwan, and estimated market shares by prescription volume and costs of targeted therapies over time. We also determined which cancer types accounted for the highest use of targeted therapies. Design This is a retrospective observational study focusing on the utilisation of targeted therapies for treatment of cancer. Setting The monthly claims data for antineoplastic agents were retrieved from Taiwan's National Health Insurance Research Database (2009–2012). Main outcome measures We calculated market shares by prescription volume and costs for each class of antineoplastic agent by cancer type. Using a time series design with Autoregressive Integrated Moving Average (ARIMA) models, we estimated trends in use and costs of targeted therapies. Results Among all antineoplastic agents, use of targeted therapies grew from 6.24% in 2009 to 12.29% in 2012, but their costs rose from 26.16% to 41.57% in that time. Monoclonal antibodies and protein kinase inhibitors contributed the most (respectively, 23.84% and 16.12% of costs for antineoplastic agents in 2012). During 2009–2012, lung (44.64% of use; 28.26% of costs), female breast (16.49% of use; 27.18% of costs) and colorectal (12.11% of use; 13.16% of costs) cancers accounted for the highest use of targeted therapies. Conclusions In Taiwan, targeted therapies are increasingly used for different cancers, representing a substantial economic burden. It is important to establish mechanisms to monitor their use and outcomes. PMID:27266775

Targeted Capture Sequencing in Whitebark Pine Reveals Range-Wide Demographic and Adaptive Patterns Despite Challenges of a Large, Repetitive Genome.

PubMed

Syring, John V; Tennessen, Jacob A; Jennings, Tara N; Wegrzyn, Jill; Scelfo-Dalbey, Camille; Cronn, Richard

2016-01-01

Whitebark pine (Pinus albicaulis) inhabits an expansive range in western North America, and it is a keystone species of subalpine environments. Whitebark is susceptible to multiple threats - climate change, white pine blister rust, mountain pine beetle, and fire exclusion - and it is suffering significant mortality range-wide, prompting the tree to be listed as 'globally endangered' by the International Union for Conservation of Nature and 'endangered' by the Canadian government. Conservation collections (in situ and ex situ) are being initiated to preserve the genetic legacy of the species. Reliable, transferrable, and highly variable genetic markers are essential for quantifying the genetic profiles of seed collections relative to natural stands, and ensuring the completeness of conservation collections. We evaluated the use of hybridization-based target capture to enrich specific genomic regions from the 27 GB genome of whitebark pine, and to evaluate genetic variation across loci, trees, and geography. Probes were designed to capture 7,849 distinct genes, and screening was performed on 48 trees. Despite the inclusion of repetitive elements in the probe pool, the resulting dataset provided information on 4,452 genes and 32% of targeted positions (528,873 bp), and we were able to identify 12,390 segregating sites from 47 trees. Variations reveal strong geographic trends in heterozygosity and allelic richness, with trees from the southern Cascade and Sierra Range showing the greatest distinctiveness and differentiation. Our results show that even under non-optimal conditions (low enrichment efficiency; inclusion of repetitive elements in baits), targeted enrichment produces high quality, codominant genotypes from large genomes. The resulting data can be readily integrated into management and gene conservation activities for whitebark pine, and have the potential to be applied to other members of 5-needle pine group (Pinus subsect. Quinquefolia) due to their

The Negative Repetition Effect

ERIC Educational Resources Information Center

Mulligan, Neil W.; Peterson, Daniel J.

2013-01-01

A fundamental property of human memory is that repetition enhances memory. Peterson and Mulligan (2012) recently documented a surprising "negative repetition effect," in which participants who studied a list of cue-target pairs twice recalled fewer targets than a group who studied the pairs only once. Words within a pair rhymed, and…

Multiple cueing dissociates location- and feature-based repetition effects

PubMed Central

Hu, Kesong; Zhan, Junya; Li, Bingzhao; He, Shuchang; Samuel, Arthur G.

2014-01-01

There is an extensive literature on the phenomenon of inhibition of return (IOR): When attention is drawn to a peripheral location and then removed, response time is delayed if a target appears in the previously inspected location. Recent research suggests that non-spatial attribute repetition (i.e., if a target shares a feature like color with the earlier, cueing, stimulus) can have a similar inhibitory effect, at least when the target appears in the previously cued location. What remains unknown is whether location- and feature-based inhibitory effects can be dissociated. In the present study, we used a multiple cueing approach to investigate the properties of location- and feature-based repetition effects. In two experiments (detection, and discrimination), location-based IOR was absent but feature-based inhibition was consistently observed. Thus, the present results indicate that feature- and location-based inhibitory effects are dissociable. The results also provide support for the view that the attentional consequences of multiple cues reflect the overall center of gravity of the cues. We suggest that the repetition costs associated with feature and location repetition may be best understood as a consequence of the pattern of activation for object files associated with the stimuli present in the displays. PMID:24907677

Interventions That Target Criminogenic Needs for Justice-Involved Persons With Serious Mental Illnesses: A Targeted Service Delivery Approach.

PubMed

Wilson, Amy Blank; Farkas, Kathleen; Bonfine, Natalie; Duda-Banwar, Janelle

2018-05-01

This research describes the development of a targeted service delivery approach that tailors the delivery of interventions that target criminogenic needs to the specific learning and treatment needs of justice-involved people with serious mental illnesses (SMIs). This targeted service delivery approach includes five service delivery strategies: repetition and summarizing, amplification, active coaching, low-demand practice, and maximizing participation. Examples of how to apply each strategy in session are provided, as well as recommendations on when to use each strategy during the delivery of interventions that target criminogenic needs. This targeted service delivery approach makes an important contribution to the development of interventions for justice-involved people with SMI by increasing the chances that people with SMI can participate fully in and benefit from these interventions that target criminogenic needs. These developments come at a critical time in the field as the next generation of services for justice-involved people with SMI are being developed.

Depression screening with patient-targeted feedback in cardiology: The cost-effectiveness of DEPSCREEN-INFO

PubMed Central

Kohlmann, Sebastian; Gierk, Benjamin

2017-01-01

Background Although depression is common in patients with heart disease, screening for depression is much debated. DEPSCREEN-INFO showed that a patient-targeted feedback in addition to screening results in lower depression level six months after screening. The purpose of this analysis was to perform a cost-effectiveness analysis of DEPSCREEN-INFO. Methods Patients with coronary heart disease or arterial hypertension were included. Participants in both groups were screened for depression. Participants in the intervention group additionally received a patient-targeted feedback of their result and recommended treatment options. A cost-utility analysis using quality-adjusted life years (QALY) based on the EQ-5D was performed. The time horizon was 6 months. Resource utilization was assessed by a telephone interview. Multiple imputation using chained equations was used. Net-benefit regressions controlled for prognostic variables at baseline were performed to construct cost-effectiveness acceptability curves. Different sensitivity analyses were performed. Results 375 participants (intervention group: 155; control group: 220) were included at baseline. After 6 months, in the intervention group adjusted total costs were lower (-€2,098; SE: €1,717) and more QALY were gained (0.0067; SD: 0.0133); yet differences were not statistically significant. The probability of cost-effectiveness was around 80% independent of the willingness-to-pay (range: €0/QALY–€130,000/QALY). The results were robust. Conclusions A patient-targeted feedback in addition to depression screening in cardiology is cost-effective with a high probability. This underpins the use of the patient-targeted feedbacks and the PHQ-9 that are both freely available and easy to implement in routine care. PMID:28806775

Depression screening with patient-targeted feedback in cardiology: The cost-effectiveness of DEPSCREEN-INFO.

PubMed

Brettschneider, Christian; Kohlmann, Sebastian; Gierk, Benjamin; Löwe, Bernd; König, Hans-Helmut

2017-01-01

Although depression is common in patients with heart disease, screening for depression is much debated. DEPSCREEN-INFO showed that a patient-targeted feedback in addition to screening results in lower depression level six months after screening. The purpose of this analysis was to perform a cost-effectiveness analysis of DEPSCREEN-INFO. Patients with coronary heart disease or arterial hypertension were included. Participants in both groups were screened for depression. Participants in the intervention group additionally received a patient-targeted feedback of their result and recommended treatment options. A cost-utility analysis using quality-adjusted life years (QALY) based on the EQ-5D was performed. The time horizon was 6 months. Resource utilization was assessed by a telephone interview. Multiple imputation using chained equations was used. Net-benefit regressions controlled for prognostic variables at baseline were performed to construct cost-effectiveness acceptability curves. Different sensitivity analyses were performed. 375 participants (intervention group: 155; control group: 220) were included at baseline. After 6 months, in the intervention group adjusted total costs were lower (-€2,098; SE: €1,717) and more QALY were gained (0.0067; SD: 0.0133); yet differences were not statistically significant. The probability of cost-effectiveness was around 80% independent of the willingness-to-pay (range: €0/QALY-€130,000/QALY). The results were robust. A patient-targeted feedback in addition to depression screening in cardiology is cost-effective with a high probability. This underpins the use of the patient-targeted feedbacks and the PHQ-9 that are both freely available and easy to implement in routine care.

Recall of "The Real Cost" Anti-Smoking Campaign Is Specifically Associated With Endorsement of Campaign-Targeted Beliefs.

PubMed

Kranzler, Elissa C; Gibson, Laura A; Hornik, Robert C

2017-10-01

Though previous research suggests the FDA's "The Real Cost" anti-smoking campaign has reduced smoking initiation, the theorized pathway of effects (through targeted beliefs) has not been evaluated. This study assesses the relationship between recall of campaign television advertisements and ad-specific anti-smoking beliefs. Respondents in a nationally representative survey of nonsmoking youths age 13-17 (n = 4,831) reported exposure to four The Real Cost advertisements and a fake ad, smoking-relevant beliefs, and nonsmoking intentions. Analyses separately predicted each targeted belief from specific ad recall, adjusting for potential confounders and survey weights. Parallel analyses with non-targeted beliefs showed smaller effects, strengthening claims of campaign effects. Recall of four campaign ads (but not the fake ad) significantly predicted endorsement of the ad-targeted belief (Mean β = .13). Two-sided sign tests indicated stronger ad recall associations with the targeted belief relative to the non-targeted belief (p < .05). Logistic regression analyses indicated that respondents who endorsed campaign-targeted beliefs were more likely to have no intention to smoke (p < .01). This study is the first to demonstrate a relationship between recall of ads from The Real Cost campaign and the theorized pathway of effects (through targeted beliefs). These analyses also provide a methodological template for showing campaign effects despite limitations of available data.

Using cost and health impacts to prioritize the targeted testing of tuberculosis in the United States.

PubMed

Miller, Thaddeus L; Hilsenrath, Peter; Lykens, Kristine; McNabb, Scott J N; Moonan, Patrick K; Weis, Stephen E

2006-04-01

Evaluation improves efficiency and effectiveness. Current U.S. tuberculosis (TB) control policies emphasize the treatment of latent TB infection (LTBI). However, this policy, if not targeted, may be inefficient. We determined the efficiency of a state-law mandated TB screening program and a non state-law mandated one in terms of cost, morbidity, treatment, and disease averted. We evaluated two publicly funded metropolitan TB prevention and control programs through retrospective analyses and modeling. Main outcomes measured were TB incidence and prevalence, TB cases averted, and cost. A non state-law mandated TB program for homeless persons in Tarrant County screened 4.5 persons to identify one with LTBI and 82 persons to identify one with TB. A state-law mandated TB program for jail inmates screened 109 persons to identify one with LTBI and 3274 persons to identify one with TB. The number of patients with LTBI treated to prevent one TB case was 12.1 and 15.3 for the homeless and jail inmate TB programs, respectively. Treatment of LTBI by the homeless and jail inmate TB screening programs will avert 11.9 and 7.9 TB cases at a cost of 14,350 US dollars and 34,761 US dollars per TB case, respectively. Mandated TB screening programs should be risk-based, not population-based. Non mandated targeted testing for TB in congregate settings for the homeless was more efficient than state-law mandated targeted testing for TB among jailed inmates.

The impact of targeting repetitive BamHI-W sequences on the sensitivity and precision of EBV DNA quantification.

PubMed

Sanosyan, Armen; Fayd'herbe de Maudave, Alexis; Bollore, Karine; Zimmermann, Valérie; Foulongne, Vincent; Van de Perre, Philippe; Tuaillon, Edouard

2017-01-01

Viral load monitoring and early Epstein-Barr virus (EBV) DNA detection are essential in routine laboratory testing, especially in preemptive management of Post-transplant Lymphoproliferative Disorder. Targeting the repetitive BamHI-W sequence was shown to increase the sensitivity of EBV DNA quantification, but the variability of BamHI-W reiterations was suggested to be a source of quantification bias. We aimed to assess the extent of variability associated with BamHI-W PCR and its impact on the sensitivity of EBV DNA quantification using the 1st WHO international standard, EBV strains and clinical samples. Repetitive BamHI-W- and LMP2 single- sequences were amplified by in-house qPCRs and BXLF-1 sequence by a commercial assay (EBV R-gene™, BioMerieux). Linearity and limits of detection of in-house methods were assessed. The impact of repeated versus single target sequences on EBV DNA quantification precision was tested on B95.8 and Raji cell lines, possessing 11 and 7 copies of the BamHI-W sequence, respectively, and on clinical samples. BamHI-W qPCR demonstrated a lower limit of detection compared to LMP2 qPCR (2.33 log10 versus 3.08 log10 IU/mL; P = 0.0002). BamHI-W qPCR underestimated the EBV DNA load on Raji strain which contained fewer BamHI-W copies than the WHO standard derived from the B95.8 EBV strain (mean bias: - 0.21 log10; 95% CI, -0.54 to 0.12). Comparison of BamHI-W qPCR versus LMP2 and BXLF-1 qPCR showed an acceptable variability between EBV DNA levels in clinical samples with the mean bias being within 0.5 log10 IU/mL EBV DNA, whereas a better quantitative concordance was observed between LMP2 and BXLF-1 assays. Targeting BamHI-W resulted to a higher sensitivity compared to LMP2 but the variable reiterations of BamHI-W segment are associated with higher quantification variability. BamHI-W can be considered for clinical and therapeutic monitoring to detect an early EBV DNA and a dynamic change in viral load.

The impact of targeting repetitive BamHI-W sequences on the sensitivity and precision of EBV DNA quantification

PubMed Central

Fayd’herbe de Maudave, Alexis; Bollore, Karine; Zimmermann, Valérie; Foulongne, Vincent; Van de Perre, Philippe; Tuaillon, Edouard

2017-01-01

Background Viral load monitoring and early Epstein-Barr virus (EBV) DNA detection are essential in routine laboratory testing, especially in preemptive management of Post-transplant Lymphoproliferative Disorder. Targeting the repetitive BamHI-W sequence was shown to increase the sensitivity of EBV DNA quantification, but the variability of BamHI-W reiterations was suggested to be a source of quantification bias. We aimed to assess the extent of variability associated with BamHI-W PCR and its impact on the sensitivity of EBV DNA quantification using the 1st WHO international standard, EBV strains and clinical samples. Methods Repetitive BamHI-W- and LMP2 single- sequences were amplified by in-house qPCRs and BXLF-1 sequence by a commercial assay (EBV R-gene™, BioMerieux). Linearity and limits of detection of in-house methods were assessed. The impact of repeated versus single target sequences on EBV DNA quantification precision was tested on B95.8 and Raji cell lines, possessing 11 and 7 copies of the BamHI-W sequence, respectively, and on clinical samples. Results BamHI-W qPCR demonstrated a lower limit of detection compared to LMP2 qPCR (2.33 log10 versus 3.08 log10 IU/mL; P = 0.0002). BamHI-W qPCR underestimated the EBV DNA load on Raji strain which contained fewer BamHI-W copies than the WHO standard derived from the B95.8 EBV strain (mean bias: - 0.21 log10; 95% CI, -0.54 to 0.12). Comparison of BamHI-W qPCR versus LMP2 and BXLF-1 qPCR showed an acceptable variability between EBV DNA levels in clinical samples with the mean bias being within 0.5 log10 IU/mL EBV DNA, whereas a better quantitative concordance was observed between LMP2 and BXLF-1 assays. Conclusions Targeting BamHI-W resulted to a higher sensitivity compared to LMP2 but the variable reiterations of BamHI-W segment are associated with higher quantification variability. BamHI-W can be considered for clinical and therapeutic monitoring to detect an early EBV DNA and a dynamic change in viral load

Short-term and long-term attentional biases to frequently encountered target features.

PubMed

Sha, Li Z; Remington, Roger W; Jiang, Yuhong V

2017-07-01

It has long been known that frequently occurring targets are attended better than infrequent ones in visual search. But does this frequency-based attentional prioritization reflect momentary or durable changes in attention? Here we observed both short-term and long-term attentional biases for visual features as a function of different types of statistical associations between the targets, distractors, and features. Participants searched for a target, a line oriented horizontally or vertically among diagonal distractors, and reported its length. In one set of experiments we manipulated the target's color probability: Targets were more often in Color 1 than in Color 2. The distractors were in other colors. Participants found Color 1 targets more quickly than Color 2 targets, but this preference disappeared immediately when the target's color became random in the subsequent testing phase. In the other set of experiments, we manipulated the diagnostic values of the two colors: Color 1 was more often a target than a distractor; Color 2 was more often a distractor than a target. Participants found Color 1 targets more quickly than Color 2 targets. Importantly, and in contrast to the first set of experiments, the featural preference was sustained in the testing phase. These results suggest that short-term and long-term attentional biases are products of different statistical information. Finding a target momentarily activates its features, inducing short-term repetition priming. Long-term changes in attention, on the other hand, may rely on learning diagnostic features of the targets.

Exploiting target amplitude information to improve multi-target tracking

NASA Astrophysics Data System (ADS)

Ehrman, Lisa M.; Blair, W. Dale

2006-05-01

Closely-spaced (but resolved) targets pose a challenge for measurement-to-track data association algorithms. Since the Mahalanobis distances between measurements collected on closely-spaced targets and tracks are similar, several elements of the corresponding kinematic measurement-to-track cost matrix are also similar. Lacking any other information on which to base assignments, it is not surprising that data association algorithms make mistakes. One ad hoc approach for mitigating this problem is to multiply the kinematic measurement-to-track likelihoods by amplitude likelihoods. However, this can actually be detrimental to the measurement-to-track association process. With that in mind, this paper pursues a rigorous treatment of the hypothesis probabilities for kinematic measurements and features. Three simple scenarios are used to demonstrate the impact of basing data association decisions on these hypothesis probabilities for Rayleigh, fixed-amplitude, and Rician targets. The first scenario assumes that the tracker carries two tracks but only one measurement is collected. This provides insight into more complex scenarios in which there are fewer measurements than tracks. The second scenario includes two measurements and one track. This extends naturally to the case with more measurements than tracks. Two measurements and two tracks are present in the third scenario, which provides insight into the performance of this method when the number of measurements equals the number of tracks. In all cases, basing data association decisions on the hypothesis probabilities leads to good results.

Fusion energy with lasers, direct drive targets, and dry wall chambers

NASA Astrophysics Data System (ADS)

Sethian, J. D.; Friedman, M.; Lehmberg, R. H.; Myers, M.; Obenschain, S. P.; Giuliani, J.; Kepple, P.; Schmitt, A. J.; Colombant, D.; Gardner, J.; Hegeler, F.; Wolford, M.; Swanekamp, S. B.; Weidenheimer, D.; Welch, D.; Rose, D.; Payne, S.; Bibeau, C.; Baraymian, A.; Beach, R.; Schaffers, K.; Freitas, B.; Skulina, K.; Meier, W.; Latkowski, J.; Perkins, L. J.; Goodin, D.; Petzoldt, R.; Stephens, E.; Najmabadi, F.; Tillack, M.; Raffray, R.; Dragojlovic, Z.; Haynes, D.; Peterson, R.; Kulcinski, G.; Hoffer, J.; Geller, D.; Schroen, D.; Streit, J.; Olson, C.; Tanaka, T.; Renk, T.; Rochau, G.; Snead, L.; Ghoneim, N.; Lucas, G.

2003-12-01

A coordinated, focused effort is underway to develop Laser Inertial Fusion Energy. The key components are developed in concert with one another and the science and engineering issues are addressed concurrently. Recent advances include: target designs have been evaluated that show it could be possible to achieve the high gains (>100) needed for a practical fusion system.These designs feature a low-density CH foam that is wicked with solid DT and over-coated with a thin high-Z layer. These results have been verified with three independent one-dimensional codes, and are now being evaluated with two- and three-dimensional codes. Two types of lasers are under development: Krypton Fluoride (KrF) gas lasers and Diode Pumped Solid State Lasers (DPSSL). Both have recently achieved repetitive 'first light', and both have made progress in meeting the fusion energy requirements for durability, efficiency, and cost. This paper also presents the advances in development of chamber operating windows (target survival plus no wall erosion), final optics (aluminium at grazing incidence has high reflectivity and exceeds the required laser damage threshold), target fabrication (demonstration of smooth DT ice layers grown over foams, batch production of foam shells, and appropriate high-Z overcoats), and target injection (new facility for target injection and tracking studies).

Economically sustainable scaling of photovoltaics to meet climate targets

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

Needleman, David Berney; Poindexter, Jeremy R.; Kurchin, Rachel C.

To meet climate targets, power generation capacity from photovoltaics (PV) in 2030 will have to be much greater than is predicted from either steady state growth using today's manufacturing capacity or industry roadmaps. Analysis of whether current technology can scale, in an economically sustainable way, to sufficient levels to meet these targets has not yet been undertaken, nor have tools to perform this analysis been presented. Here, we use bottom-up cost modeling to predict cumulative capacity as a function of technological and economic variables. We find that today's technology falls short in two ways: profits are too small relative tomore » upfront factory costs to grow manufacturing capacity rapidly enough to meet climate targets, and costs are too high to generate enough demand to meet climate targets. We show that decreasing the capital intensity (capex) of PV manufacturing to increase manufacturing capacity and effectively reducing cost (e.g., through higher efficiency) to increase demand are the most effective and least risky ways to address these barriers to scale. We also assess the effects of variations in demand due to hard-to-predict factors, like public policy, on the necessary reductions in cost.Lastly, we review examples of redundant technology pathways for crystalline silicon PV to achieve the necessary innovations in capex, performance, and price.« less

Economically sustainable scaling of photovoltaics to meet climate targets

DOE PAGES

Needleman, David Berney; Poindexter, Jeremy R.; Kurchin, Rachel C.; ...

2016-04-21

To meet climate targets, power generation capacity from photovoltaics (PV) in 2030 will have to be much greater than is predicted from either steady state growth using today's manufacturing capacity or industry roadmaps. Analysis of whether current technology can scale, in an economically sustainable way, to sufficient levels to meet these targets has not yet been undertaken, nor have tools to perform this analysis been presented. Here, we use bottom-up cost modeling to predict cumulative capacity as a function of technological and economic variables. We find that today's technology falls short in two ways: profits are too small relative tomore » upfront factory costs to grow manufacturing capacity rapidly enough to meet climate targets, and costs are too high to generate enough demand to meet climate targets. We show that decreasing the capital intensity (capex) of PV manufacturing to increase manufacturing capacity and effectively reducing cost (e.g., through higher efficiency) to increase demand are the most effective and least risky ways to address these barriers to scale. We also assess the effects of variations in demand due to hard-to-predict factors, like public policy, on the necessary reductions in cost.Lastly, we review examples of redundant technology pathways for crystalline silicon PV to achieve the necessary innovations in capex, performance, and price.« less

Cost-effectiveness of tobacco control policies and programmes targeting adolescents: a systematic review.

PubMed

Leão, Teresa; Kunst, Anton E; Perelman, Julian

2018-02-01

Consistent evidence shows the importance of preventing smoking at young ages, when health behaviours are formed, with long-term consequences on health and survival. Although tobacco control policies and programmes targeting adolescents are widely promoted, the cost-effectiveness of such interventions has not been systematically documented. We performed a systematic review on the cost-effectiveness of policies and programmes preventing tobacco consumption targeting adolescents. We systematically reviewed literature on the (i) cost and effectiveness of (ii) prevention policies targeting (iii) smoking by (iv) adolescents. PubMed, Web of Science, Cochrane, CEA-TUFTS, Health Economic Evaluations, Wiley Online Library, Centre for Reviews and Dissemination Database, the National Institute for Health and Care Excellence and Google Scholar databases were used, and Google search engine was used for other grey literature review. We obtained 793 full-text papers and 19 grey literature documents, from which 16 studies fulfilled the inclusion criteria. Of these, only one was published in the last 5 years, and 15 were performed in high-income countries. Eight analyzed the cost-effectiveness of school-based programmes, five focused on media campaigns and three on legal bans. Policies and programmes were found to be cost-effective in all studies, and both effective and cost-saving in about half of the studies. Evidence is scarce and relatively obsolete, and rarely focused on the evaluation of legal bans. Moreover, no comparisons have been made between different interventions or across different contexts and implementation levels. However, all studies conclude that smoking prevention policies and programmes amongst adolescents are greatly worth their costs. © The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association.

Analogous selection processes in declarative and procedural working memory: N-2 list-repetition and task-repetition costs.

PubMed

Gade, Miriam; Souza, Alessandra S; Druey, Michel D; Oberauer, Klaus

2017-01-01

Working memory (WM) holds and manipulates representations for ongoing cognition. Oberauer (Psychology of Learning and Motivation, 51, 45-100, 2009) distinguishes between two analogous WM sub-systems: a declarative WM which handles the objects of thought, and a procedural WM which handles the representations of (cognitive) actions. Here, we assessed whether analogous effects are observed when participants switch between memory sets (declarative representations) and when they switch between task sets (procedural representations). One mechanism assumed to facilitate switching in procedural WM is the inhibition of previously used, but currently irrelevant task sets, as indexed by n-2 task-repetition costs (Mayr & Keele, Journal of Experimental Psychology: General, 129(1), 4-26, 2000). In this study we tested for an analogous effect in declarative WM. We assessed the evidence for n-2 list-repetition costs across eight experiments in which participants switched between memory lists to perform speeded classifications, mental arithmetic, or a local recognition test. N-2 list-repetition costs were obtained consistently in conditions assumed to increase interference between memory lists, and when lists formed chunks in long-term memory. Further analyses across experiments revealed a substantial contribution of episodic memory to n-2 list-repetition costs, thereby questioning the interpretation of n-2 repetition costs as reflecting inhibition. We reanalyzed the data of eight task-switching experiments, and observed that episodic memory also contributes to n-2 task-repetition costs. Taken together, these results show analogous processing principles in declarative and procedural WM, and question the relevance of inhibitory processes for efficient switching between mental sets.

Thermal limits on MV x-ray production by bremsstrahlung targets in the context of novel linear accelerators.

PubMed

Wang, Jinghui; Trovati, Stefania; Borchard, Philipp M; Loo, Billy W; Maxim, Peter G; Fahrig, Rebecca

2017-12-01

To study the impact of target geometrical and linac operational parameters, such as target material and thickness, electron beam size, repetition rate, and mean current on the ability of the radiotherapy treatment head to deliver high-dose-rate x-ray irradiation in the context of novel linear accelerators capable of higher repetition rates/duty cycle than conventional clinical linacs. The depth dose in a water phantom without a flattening filter and heat deposition in an x-ray target by 10 MeV pulsed electron beams were calculated using the Monte-Carlo code MCNPX, and the transient temperature behavior of the target was simulated by ANSYS. Several parameters that affect both the dose distribution and temperature behavior were investigated. The target was tungsten with a thickness ranging from 0 to 3 mm and a copper heat remover layer. An electron beam with full width at half maximum (FWHM) between 0 and3 mm and mean current of 0.05-2 mA was used as the primary beam at repetition rates of 100, 200, 400, and 800 Hz. For a 10 MeV electron beam with FWHM of 1 mm, pulse length of 5 μs, by using a thin tungsten target with thickness of 0.2 mm instead of 1 mm, and by employing a high repetition rate of 800 Hz instead of 100 Hz, the maximum dose rate delivered can increase two times from 0.57 to 1.16 Gy/s. In this simple model, the limiting factor on dose rate is the copper heat remover's softening temperature, which was considered to be 500°C in our study. A high dose rate can be obtained by employing thin targets together with high repetition rate electron beams enabled by novel linac designs, whereas the benefit of thin targets is marginal at conventional repetition rates. Next generation linacs used to increase dose rate need different target designs compared to conventional linacs. © 2017 American Association of Physicists in Medicine.

Repetition suppression of faces is modulated by emotion

NASA Astrophysics Data System (ADS)

Ishai, Alumit; Pessoa, Luiz; Bikle, Philip C.; Ungerleider, Leslie G.

2004-06-01

Single-unit recordings and functional brain imaging studies have shown reduced neural responses to repeated stimuli in the visual cortex. By using event-related functional MRI, we compared the activation evoked by repetitions of neutral and fearful faces, which were either task relevant (targets) or irrelevant (distracters). We found that within the inferior occipital gyri, lateral fusiform gyri, superior temporal sulci, amygdala, and the inferior frontal gyri/insula, targets evoked stronger responses than distracters and their repetition was associated with significantly reduced responses. Repetition suppression, as manifested by the difference in response amplitude between the first and third repetitions of a target, was stronger for fearful than neutral faces. Distracter faces, regardless of their repetition or valence, evoked negligible activation, indicating top-down attenuation of behaviorally irrelevant stimuli. Our findings demonstrate a three-way interaction between emotional valence, repetition, and task relevance and suggest that repetition suppression is influenced by high-level cognitive processes in the human brain. face perception | functional MRI

No cost-saving target too small for this hospital's product reengineering program.

PubMed

1998-02-01

It pays to put every product purchase under the microscope. By creating a multidisciplinary value analysis committee to review staff ideas on potential savings for products, as well as internal services and processes, this New Jersey health care provider is slashing costs and standardizing products across clinical service lines. Learn how the committee operates and what it's doing to get vital employee participation, plus read about specific products targeted for cost reduction.

Influence of the laser pulse repetition rate and scanning speed on the morphology of Ag nanostructures fabricated by pulsed laser ablation of solid target in water

NASA Astrophysics Data System (ADS)

Nikolov, A. S.; Balchev, I. I.; Nedyalkov, N. N.; Kostadinov, I. K.; Karashanova, D. B.; Atanasova, G. B.

2017-11-01

Nanostructures of noble metal were produced by pulsed laser ablation in liquid. A solid Ag target was immersed in double distilled water and a CuBr laser in a master oscillator—power amplifier configuration oscillating at 511 nm and emitting pulses with duration of 30 ns at a repetition rate of up to 20 kHz was employed to produce different colloids. The impact was studied of the laser pulse repetition rate and the beam scanning speed on the morphology of the nanostructures formed. Further, the optical extinction spectra of the colloids in the UV/VIS range were measured and used to make an indirect assessment of the changes in the shape and size distribution of the nanostructures. The transmission values in the near UV range were used to estimate the efficiency of the ablation process under the different experimental conditions implemented. A visualization of the nanostructures was made possible by transmission electron microscopy (TEM). The structure and phase composition of the nanoparticles were studied by high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED), while the alteration of the target surface caused by the impact of the high-repetition-rate laser illumination was investigated by X-ray photoelectron spectroscopy (XPS). The optimal conditions were determined yielding the highest efficiency in terms of amount of ablated material.

Economic evaluation of targeted cancer interventions: critical review and recommendations.

PubMed

Elkin, Elena B; Marshall, Deborah A; Kulin, Nathalie A; Ferrusi, Ilia L; Hassett, Michael J; Ladabaum, Uri; Phillips, Kathryn A

2011-10-01

Scientific advances have improved our ability to target cancer interventions to individuals who will benefit most and spare the risks and costs to those who will derive little benefit or even be harmed. Several approaches are currently used for targeting interventions for cancer risk reduction, screening, and treatment, including risk prediction algorithms for identifying high-risk subgroups and diagnostic tests for tumor markers and germline genetic mutations. Economic evaluation can inform decisions about the use of targeted interventions, which may be more costly than traditional strategies. However, assessing the impact of a targeted intervention on costs and health outcomes requires explicit consideration of the method of targeting. In this study, we describe the importance of this principle by reviewing published cost-effectiveness analyses of targeted interventions in breast cancer. Few studies we identified explicitly evaluated the relationships among the method of targeting, the accuracy of the targeting test, and outcomes of the targeted intervention. Those that did found that characteristics of targeting tests had a substantial impact on outcomes. We posit that the method of targeting and the outcomes of a targeted intervention are inextricably linked and recommend that cost-effectiveness analyses of targeted interventions explicitly consider costs and outcomes of the method of targeting.

Are national targets the right way to improve infection control practice?

PubMed

Millar, M

2009-12-01

The 'right way to improve infection control practice' should be cost-effective and lead to a fair distribution of infection control resources. Cost-effectiveness is a measure of aggregate 'good', and fairness emphasises similar treatment for individuals under similar circumstances. The UK national meticillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) target encourages National Health Service trusts to prioritise strategies aimed at MRSA BSI prevention. Under resource-limited conditions, the MRSA BSI target inevitably encourages deprioritisation of patients at risk of non-target healthcare-associated infection (HCAI), some of which are associated with an equal or larger burden of adverse outcome. Established healthcare improvement strategies, such as the Plan, Do, Study, Act (PDSA) cycle advocated by the Health Foundation, require the setting of aims (or targets). If we are to improve infection control practice then we need to decide on what to measure, how to measure it, and what the improvement (target) should be. In selecting targets for infection prevention, account should be taken of the contribution of HCAI to adverse health outcomes overall. Human risk compensation behaviour and microbial adaptation may both counteract the overall benefit of infection targets isolated from overall outcomes. Risk taking is part of a healthy healthcare system. We must be careful not to isolate HCAI outcomes from overall outcomes or to isolate 'risk takers' from 'risk controllers'. We must try to limit the scope for human risk compensation and we must watch out for microbial adaptation. Targets should be set locally, taking account of fairness and cost-effectiveness. Locally relevant information is key; positive incentives work best.

Hi-Plex for Simple, Accurate, and Cost-Effective Amplicon-based Targeted DNA Sequencing.

PubMed

Pope, Bernard J; Hammet, Fleur; Nguyen-Dumont, Tu; Park, Daniel J

2018-01-01

Hi-Plex is a suite of methods to enable simple, accurate, and cost-effective highly multiplex PCR-based targeted sequencing (Nguyen-Dumont et al., Biotechniques 58:33-36, 2015). At its core is the principle of using gene-specific primers (GSPs) to "seed" (or target) the reaction and universal primers to "drive" the majority of the reaction. In this manner, effects on amplification efficiencies across the target amplicons can, to a large extent, be restricted to early seeding cycles. Product sizes are defined within a relatively narrow range to enable high-specificity size selection, replication uniformity across target sites (including in the context of fragmented input DNA such as that derived from fixed tumor specimens (Nguyen-Dumont et al., Biotechniques 55:69-74, 2013; Nguyen-Dumont et al., Anal Biochem 470:48-51, 2015), and application of high-specificity genetic variant calling algorithms (Pope et al., Source Code Biol Med 9:3, 2014; Park et al., BMC Bioinformatics 17:165, 2016). Hi-Plex offers a streamlined workflow that is suitable for testing large numbers of specimens without the need for automation.

Hospital protocols for targeted glycemic control: Development, implementation, and models for cost justification.

PubMed

Magee, Michelle F

2007-05-15

Evolving elements of best practices for providing targeted glycemic control in the hospital setting, clinical performance measurement, basal-bolus plus correction-dose insulin regimens, components of standardized subcutaneous (s.c.) insulin order sets, and strategies for implementation and cost justification of glycemic control initiatives are discussed. Best practices for targeted glycemic control should address accurate documentation of hyperglycemia, initial patient assessment, management plan, target blood glucose range, blood glucose monitoring frequency, maintenance of glycemic control, criteria for glucose management consultations, and standardized insulin order sets and protocols. Establishing clinical performance measures, including desirable processes and outcomes, can help ensure the success of targeted hospital glycemic control initiatives. The basal-bolus plus correction-dose regimen for insulin administration will be used to mimic the normal physiologic pattern of endogenous insulin secretion. Standardized insulin order sets and protocols are being used to minimize the risk of error in insulin therapy. Components of standardized s.c. insulin order sets include specification of the hyperglycemia diagnosis, finger stick blood glucose monitoring frequency and timing, target blood glucose concentration range, cutoff values for excessively high or low blood glucose concentrations that warrant alerting the physician, basal and prandial or nutritional (i.e., bolus) insulin, correction doses, hypoglycemia treatment, and perioperative or procedural dosage adjustments. The endorsement of hospital administrators and key physician and nursing leaders is needed for glycemic control initiatives. Initiatives may be cost justified on the basis of the billings for clinical diabetes management services and/or the return- on-investment accrued to reductions in hospital length of stay, readmissions, and accurate documentation and coding of unrecognized or uncontrolled

Cost-effectiveness of clinical remission by treat to target strategy in established rheumatoid arthritis: results of the CREATE registry.

PubMed

Cárdenas, M; de la Fuente, S; Castro-Villegas, M C; Romero-Gómez, M; Ruiz-Vílchez, D; Calvo-Gutiérrez, J; Escudero-Contreras, A; Del Prado, J R; Collantes-Estévez, E; Font, P

2016-12-01

To analyse the cost-effectiveness, in daily clinical practice, of the strategy of treating to the target of clinical remission (CR) in patients with established rheumatoid arthritis (RA), after 2 years of treatment with biological therapy. Adult patients with established RA were treated with biological therapy and followed up for 2 years by a multidisciplinary team responsible for their clinical management. Treatment effectiveness was evaluated by the DAS28 score. The direct costs incurred during this period were quantified from the perspective of the healthcare system. We calculated the cost-effectiveness of obtaining a DAS28 < 2.6, considered as CR. The study included 144 RA patients treated with biological therapies. After 2 years of treatment, 32.6% of patients achieved CR. The mean cost of achieving CR at 2 years was 79,681 ± 38,880 euros. The strategy of treatment to the target of CR is considered the most effective, but in actual clinical practice in patients with established RA, it has a high cost.

Treating to the target of remission in early rheumatoid arthritis is cost-effective: results of the DREAM registry.

PubMed

Vermeer, Marloes; Kievit, Wietske; Kuper, Hillechiena H; Braakman-Jansen, Louise M A; Bernelot Moens, Hein J; Zijlstra, Theo R; den Broeder, Alfons A; van Riel, Piet L C M; Fransen, Jaap; van de Laar, Mart A F J

2013-12-13

Where health economic studies are frequently performed using modelling, with input from randomized controlled trials and best guesses, we used real-life data to analyse the cost-effectiveness and cost-utility of a treatment strategy aiming to the target of remission compared to usual care in early rheumatoid arthritis (RA). We used real-life data from comparable cohorts in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry: the DREAM remission induction cohort (treat-to-target, T2T) and the Nijmegen early RA inception cohort (usual care, UC). Both cohorts were followed prospectively using the DREAM registry methodology. All patients fulfilled the American College of Rheumatology criteria for RA and were included in the cohort at the time of diagnosis. The T2T cohort was treated according to a protocolised strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6). The UC cohort was treated without DAS28-guided treatment decisions. EuroQol-5D utility scores were estimated from the Health Assessment Questionnaire. A health care perspective was adopted and direct medical costs were collected. The incremental cost effectiveness ratio (ICER) per patient in remission and incremental cost utility ratio (ICUR) per quality-adjusted life year (QALY) gained were calculated over two and three years of follow-up. Two year data were available for 261 T2T patients and 213 UC patients; an extended follow-up of three years was available for 127 and 180 patients, respectively. T2T produced higher remission percentages and a larger gain in QALYs than UC. The ICER was € 3,591 per patient in remission after two years and T2T was dominant after three years. The ICUR was € 19,410 per QALY after two years and T2T was dominant after three years. We can conclude that treating to the target of remission in early RA is cost-effective compared with UC. The data suggest that in the third year, T2T becomes cost-saving.

Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

PubMed

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug

42 CFR 457.555 - Maximum allowable cost-sharing charges on targeted low-income children in families with income...

Code of Federal Regulations, 2012 CFR

2012-10-01

... maximum amount of $11.35 for services furnished in a hospital emergency room if those services are not... 42 Public Health 4 2012-10-01 2012-10-01 false Maximum allowable cost-sharing charges on targeted... Requirements: Enrollee Financial Responsibilities § 457.555 Maximum allowable cost-sharing charges on targeted...

Advanced Targeting Cost Function Design for Evolutionary Optimization of Control of Logistic Equation

NASA Astrophysics Data System (ADS)

Senkerik, Roman; Zelinka, Ivan; Davendra, Donald; Oplatkova, Zuzana

2010-06-01

This research deals with the optimization of the control of chaos by means of evolutionary algorithms. This work is aimed on an explanation of how to use evolutionary algorithms (EAs) and how to properly define the advanced targeting cost function (CF) securing very fast and precise stabilization of desired state for any initial conditions. As a model of deterministic chaotic system, the one dimensional Logistic equation was used. The evolutionary algorithm Self-Organizing Migrating Algorithm (SOMA) was used in four versions. For each version, repeated simulations were conducted to outline the effectiveness and robustness of used method and targeting CF.

Cost effectiveness of a targeted age-based West Nile virus vaccination program.

PubMed

Shankar, Manjunath B; Staples, J Erin; Meltzer, Martin I; Fischer, Marc

2017-05-25

West Nile virus (WNV) is the leading cause of domestically-acquired arboviral disease in the United States. Several WNV vaccines are in various stages of development. We estimate the cost-effectiveness of WNV vaccination programs targeting groups at increased risk for severe WNV disease. We used a mathematical model to estimate costs and health outcomes of vaccination with WNV vaccine compared to no vaccination among seven cohorts, spaced at 10year intervals from ages 10 to 70years, each followed until 90-years-old. U.S. surveillance data were used to estimate WNV neuroinvasive disease incidence. Data for WNV seroprevalence, acute and long-term care costs of WNV disease patients, quality-adjusted life-years (QALYs), and vaccine characteristics were obtained from published reports. We assumed vaccine efficacy to either last lifelong or for 10years with booster doses given every 10years. There was a statistically significant difference in cost-effectiveness ratios across cohorts in both models and all outcomes assessed (Kruskal-Wallis test p<0.0001). The 60-year-cohort had a mean cost per neuroinvasive disease case prevented of $664,000 and disability averted of $1,421,000 in lifelong model and $882,000 and $1,887,000, respectively in 10-year immunity model; these costs were statistically significantly lower than costs for other cohorts (p<0.0001). Vaccinating 70-year-olds had the lowest cost per death averted in both models at around $4.7 million (95%CI $2-$8 million). Cost per disease case averted was lowest among 40- and 50-year-old cohorts and cost per QALY saved lowest among 60-year cohorts in lifelong immunity model. The models were most sensitive to disease incidence, vaccine cost, and proportion of persons developing disease among infected. Age-based WNV vaccination program targeting those at higher risk for severe disease is more cost-effective than universal vaccination. Annual variation in WNV disease incidence, QALY weights, and vaccine costs impact the

Electric Vehicle Technologies and Targets | Transportation Research | NREL

Science.gov Websites

. Table showing 2022 targets for decreases in battery cost ($125/kWh) and increases in battery capacity exchanger. Table showing 2022 targets for decreases in power electronics cost ($8/kW, $440 system cost) and , high performing, and long lasting. DOE has targeted a 75% reduction in battery cost and a 75% increase

Cost-effectiveness of targeted screening for abdominal aortic aneurysm. Monte Carlo-based estimates.

PubMed

Pentikäinen, T J; Sipilä, T; Rissanen, P; Soisalon-Soininen, S; Salo, J

2000-01-01

This article reports a cost-effectiveness analysis of targeted screening for abdominal aortic aneurysm (AAA). A major emphasis was on the estimation of distributions of costs and effectiveness. We performed a Monte Carlo simulation using C programming language in a PC environment. Data on survival and costs, and a majority of screening probabilities, were from our own empirical studies. Natural history data were based on the literature. Each screened male gained 0.07 life-years at an incremental cost of FIM 3,300. The expected values differed from zero very significantly. For females, expected gains were 0.02 life-years at an incremental cost of FIM 1,100, which was not statistically significant. Cost-effectiveness ratios and their 95% confidence intervals were FIM 48,000 (27,000-121,000) and 54,000 (22,000-infinity) for males and females, respectively. Sensitivity analysis revealed that the results for males were stable. Individual variation in life-year gains was high. Males seemed to benefit from targeted AAA screening, and the results were stable. As far as the cost-effectiveness ratio is considered acceptable, screening for males seemed to be justified. However, our assumptions about growth and rupture behavior of AAAs might be improved with further clinical and epidemiological studies. As a point estimate, females benefited in a similar manner, but the results were not statistically significant. The evidence of this study did not justify screening of females.

Cost-effectiveness of annual targeted larviciding campaigns in Cambodia against the dengue vector Aedes aegypti.

PubMed

Suaya, Jose A; Shepard, Donald S; Chang, Moh-Seng; Caram, Mariana; Hoyer, Stefan; Socheat, Duong; Chantha, Ngan; Nathan, Michael B

2007-09-01

To assess the cost-effectiveness (CE) of annual targeted larviciding campaigns from 2001 to 2005 against the dengue vector Aedes aegypti in two urban areas of Cambodia with a population of 2.9 million people. The intervention under analysis consisted of annual larviciding campaigns targeting medium to large water storage containers in households and other premises. The CE compared the intervention against the hypothetical alternative of no intervention. The CE was calculated as the ratio of disability adjusted life years (DALYs) saved to the net cost of the intervention (in 2005 US dollars) by year. A sensitivity analysis explored the range of study parameters. The intervention reduced the number of dengue cases and deaths by 53%. It averted an annual average of 2980 dengue hospitalizations, 11,921 dengue ambulatory cases and 23 dengue deaths, resulting in a saving of 997 DALYs per year. The gross cost of the intervention was US $567,800 per year, or US $0.20 per person covered. As the intervention averted considerable medical care, the annual net cost of the intervention was US $312,214 (US $0.11 per person covered) from a public sector perspective and US $37,137 (US $0.01 per person covered) from a societal perspective. The resulting CE ratios were: US $313/DALY gained from the public perspective and US $37/DALY gained from the societal perspective. Even under the most conservative assumption, the intervention remained cost effective from both perspectives. Annual, targeted larviciding campaigns appear to have been effective and cost-effective medium-term interventions to reduce the epidemiologic and economic burden of dengue in urban areas of Cambodia.

Cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal anti-D prophylaxis in RhD-negative pregnant women: a model-based analysis.

PubMed

Neovius, M; Tiblad, E; Westgren, M; Kublickas, M; Neovius, K; Wikman, A

2016-07-01

To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. Model based on a population-based cohort study. The Swedish health service. Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010-2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008-2009 when standard care did not include RAADP (n = 7099). Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. Additional cost per RhD immunisation averted. Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP. © 2015 Royal College of Obstetricians and Gynaecologists.

Optimized ion acceleration using high repetition rate, variable thickness liquid crystal targets

NASA Astrophysics Data System (ADS)

Poole, Patrick; Willis, Christopher; Cochran, Ginevra; Andereck, C. David; Schumacher, Douglass

2015-11-01

Laser-based ion acceleration is a widely studied plasma physics topic for its applications to secondary radiation sources, advanced imaging, and cancer therapy. Recent work has centered on investigating new acceleration mechanisms that promise improved ion energy and spectrum. While the physics of these mechanisms is not yet fully understood, it has been observed to dominate for certain ranges of target thickness, where the optimum thickness depends on laser conditions including energy, pulse width, and contrast. The study of these phenomena is uniquely facilitated by the use of variable-thickness liquid crystal films, first introduced in P. L. Poole et al. PoP21, 063109 (2014). Control of the formation parameters of these freely suspended films such as volume, temperature, and draw speed allows on-demand thickness variability between 10 nanometers and several 10s of microns, fully encompassing the currently studied thickness regimes with a single target material. The low vapor pressure of liquid crystal enables in-situ film formation and unlimited vacuum use of these targets. Details on the selection and optimization of ion acceleration mechanism with target thickness will be presented, including recent experiments on the Scarlet laser facility and others. This work was performed with support from the DARPA PULSE program through a grant from AMRDEC and by the NNSA under contract DE-NA0001976.

Analysis of the Encoding Factors That Produce the Negative Repetition Effect

ERIC Educational Resources Information Center

Mulligan, Neil W.; Peterson, Daniel J.

2014-01-01

Perhaps the most basic finding in memory research is the repetition effect--the fact that repetition enhances memory. Peterson and Mulligan (2012) recently documented a surprising "negative repetition effect," in which participants who studied a list of cue-target pairs twice recalled "fewer" targets than a group who studied…

Inhibition in task switching: The reliability of the n - 2 repetition cost.

PubMed

Kowalczyk, Agnieszka W; Grange, James A

2017-12-01

The n - 2 repetition cost seen in task switching is the effect of slower response times performing a recently completed task (e.g. an ABA sequence) compared to performing a task that was not recently completed (e.g. a CBA sequence). This cost is thought to reflect cognitive inhibition of task representations and as such, the n - 2 repetition cost has begun to be used as an assessment of individual differences in inhibitory control; however, the reliability of this measure has not been investigated in a systematic manner. The current study addressed this important issue. Seventy-two participants performed three task switching paradigms; participants were also assessed on rumination traits and processing speed-measures of individual differences potentially modulating the n - 2 repetition cost. We found significant n - 2 repetition costs for each paradigm. However, split-half reliability tests revealed that this cost was not reliable at the individual-difference level. Neither rumination tendencies nor processing speed predicted this cost. We conclude that the n - 2 repetition cost is not reliable as a measure of individual differences in inhibitory control.

Negotiating targets with patients: choice of target in relation to occupational state.

PubMed

Robinson, Sandra M; Walker, David J

2012-02-01

Following the recent National Institute for Health and Clinical Excellence guidance on the management of RA, we were interested to see if we could negotiate targets for treatment with patients in routine clinics, how they would express this and whether staying at work would be a target. One hundred RA patients were recruited. They were consecutive within clinics, but not all clinics were used. They were asked their understanding of the DAS score and a target for treatment negotiated. Any impact of the RA on their paid employment was then explored. Four participants were unable to specify a target for their RA. Negotiated targets were expressed as restricted activities and either as maintaining an activity (70) if the disease was stable, or regaining an activity (26) if the treatment was being increased. Targets were walking a distance for 50% of patients; leisure activities for 18%; domestic activities for 17%; work for 14% and personal care for 2%. For the 21 participants currently working, maintaining work was the target for 12, with 1 wishing to regain lost hours. No patient currently not working expressed returning to work as a target. There were some differences in targets between men and women. Patients are able to negotiate a target for their treatment, expressed as maintaining or regaining a physical activity. Work ceases to be a target once it is lost. Therefore, preventing loss of occupation is likely to be more effective than trying to regain it.

Assessing the relationship between toxicity and economic cost of oncological target agents: A systematic review of clinical trials

PubMed Central

Tartari, Francesca; Conti, Alessandro

2017-01-01

Target agents are peculiar oncological drugs which differ from the traditional therapies in their ability of recognizing specific molecules expressed by tumor cells and microenvironment. Thus, their toxicity is generally lower than that associated to chemotherapy, and they represent nowadays a new standard of care in a number of tumors. This paper deals with the relationship between economic costs and toxicity of target agents. At this aim, a cluster analysis-based exploration of the main features of a large collection of them is carried out, with a specific focus on the variables leading to the identification of their toxicity and related costs. The analysis of the toxicity is based on the Severe Adverse Events (SAE) and Discontinuation (D) rates of each target agent considering data published on PubMed from 1965 to 2016 in the phase II and III studies that have led to the approval of these drugs for cancer patients by US Food and Drug Administration. The construction of the dataset represents a key step of the research, and is grounded on the critical analysis of a wide set of clinical studies. In order to capture different evaluation strategies of the toxicity, clustering is performed according to three different criteria (including Voronoi tessellation). Our procedure allows us to identify 5 different groups of target agents pooled by similar SAE and D rates and, at the same time, 3 groups based on target agents’ costs for 1 month and for the median whole duration of therapy. Results highlight several specific regularities for toxicity and costs. This study present several limitations, being realized starting from clinical trials and not from individual patients’ data. However, a macroscopic perspective suggests that costs are rather heterogeneous, and they do not clearly follow the clustering based on SAE and D rates. PMID:28829823

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

Target-controlled inhalation anaesthesia: A cost-benefit analysis based on the cost per minute of anaesthesia by inhalation.

PubMed

Ponsonnard, Sébastien; Galy, Antoine; Cros, Jérôme; Daragon, Armelle Marie; Nathan, Nathalie

2017-02-01

End-tidal target-controlled inhalational anaesthesia (TCIA) with halogenated agents (HA) provides a faster and more accurately titrated anaesthesia as compared to manually-controlled anaesthesia. This study aimed to measure the macro-economic cost-benefit ratio of TCIA as compared to manually-controlled anaesthesia. This retrospective and descriptive study compared direct drug spending between two hospitals before 2011 and then after the replacement of three of six anaesthesia machines with TCIA mode machines in 2012 (Aisys carestation ® , GE). The direct costs were obtained from the pharmacy department and the number and duration of the anaesthesia procedures from the computerized files of the hospital. The cost of halogenated agents was reduced in the hospital equipped with an Aisys carestation ® by 13% as was the cost of one minute of anaesthesia by inhalation (€0.138 and €0.121/min between 2011 and 2012). The extra cost of the implementation of the 3 anaesthesia machines could be paid off with the resulting savings over 6 years. TCIA appears to have a favourable cost-benefit ratio. Despite a number of factors, which would tend to minimise the saving and increase costs, we still managed to observe a 13% savings. Shorter duration of surgery, type of induction as well as the way HA concentration is targeted may influence the savings results obtained. Copyright © 2016 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

A Nonword Repetition Task for Speakers with Misarticulations: The Syllable Repetition Task (SRT)

PubMed Central

Shriberg, Lawrence D.; Lohmeier, Heather L.; Campbell, Thomas F.; Dollaghan, Christine A.; Green, Jordan R.; Moore, Christopher A.

2010-01-01

Purpose Conceptual and methodological confounds occur when non(sense) repetition tasks are administered to speakers who do not have the target speech sounds in their phonetic inventories or who habitually misarticulate targeted speech sounds. We describe a nonword repetition task, the Syllable Repetiton Task (SRT) that eliminates this confound and report findings from three validity studies. Method Ninety-five preschool children with Speech Delay and 63 with Typical Speech, completed an assessment battery that included the Nonword Repetition Task (NRT: Dollaghan & Campbell, 1998) and the SRT. SRT stimuli include only four of the earliest occurring consonants and one early occurring vowel. Results Study 1 findings indicated that the SRT eliminated the speech confound in nonword testing with speakers who misarticulate. Study 2 findings indicated that the accuracy of the SRT to identify expressive language impairment was comparable to findings for the NRT. Study 3 findings illustrated the SRT’s potential to interrogate speech processing constraints underlying poor nonword repetition accuracy. Results supported both memorial and auditory-perceptual encoding constraints underlying nonword repetition errors in children with speech-language impairment. Conclusion The SRT appears to be a psychometrically stable and substantively informative nonword repetition task for emerging genetic and other research with speakers who misarticulate. PMID:19635944

Targeting vector construction through recombineering.

PubMed

Malureanu, Liviu A

2011-01-01

Gene targeting in mouse embryonic stem cells is an essential, yet still very expensive and highly time-consuming, tool and method to study gene function at the organismal level or to create mouse models of human diseases. Conventional cloning-based methods have been largely used for generating targeting vectors, but are hampered by a number of limiting factors, including the variety and location of restriction enzymes in the gene locus of interest, the specific PCR amplification of repetitive DNA sequences, and cloning of large DNA fragments. Recombineering is a technique that exploits the highly efficient homologous recombination function encoded by λ phage in Escherichia coli. Bacteriophage-based recombination can recombine homologous sequences as short as 30-50 bases, allowing manipulations such as insertion, deletion, or mutation of virtually any genomic region. The large availability of mouse genomic bacterial artificial chromosome (BAC) libraries covering most of the genome facilitates the retrieval of genomic DNA sequences from the bacterial chromosomes through recombineering. This chapter describes a successfully applied protocol and aims to be a detailed guide through the steps of generation of targeting vectors through recombineering.

Thermochemical energy storage with ammonia: Aiming for the sunshot cost target

NASA Astrophysics Data System (ADS)

Lavine, Adrienne S.; Lovegrove, Keith M.; Jordan, Joshua; Anleu, Gabriela Bran; Chen, Chen; Aryafar, Hamarz; Sepulveda, Abdon

2016-05-01

Thermochemical energy storage has the potential to reduce the cost of concentrating solar thermal power. This paper presents recent advances in ammonia-based thermochemical energy storage (TCES), supported by an award from the U.S. Dept. of Energy SunShot program. Advances have been made in three areas: identification of promising approaches for underground containment of the gaseous products of the dissociation reaction, demonstration that ammonia synthesis can be used to generate steam for a supercritical-steam Rankine cycle, and a preliminary design for integration of the endothermic reactors within a tower receiver. Based on these advances, ammonia-based TCES shows promise to meet the 15/kWht SunShot cost target.

DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS.

PubMed

Ahmari, Susanne E; Dougherty, Darin D

2015-08-01

Obsessive-compulsive disorder (OCD) is a chronic, severe mental illness with up to 2-3% prevalence worldwide. In fact, OCD has been classified as one of the world's 10 leading causes of illness-related disability according to the World Health Organization, largely because of the chronic nature of disabling symptoms.([1]) Despite the severity and high prevalence of this chronic and disabling disorder, there is still relatively limited understanding of its pathophysiology. However, this is now rapidly changing due to development of powerful technologies that can be used to dissect the neural circuits underlying pathologic behaviors. In this article, we describe recent technical advances that have allowed neuroscientists to start identifying the circuits underlying complex repetitive behaviors using animal model systems. In addition, we review current surgical and stimulation-based treatments for OCD that target circuit dysfunction. Finally, we discuss how findings from animal models may be applied in the clinical arena to help inform and refine targeted brain stimulation-based treatment approaches. © 2015 Wiley Periodicals, Inc.

A Negative Effect of Repetition in Episodic Memory

ERIC Educational Resources Information Center

Peterson, Daniel J.; Mulligan, Neil W.

2012-01-01

One of the foundational principles of human memory is that repetition (i.e., being presented with a stimulus multiple times) improves recall. In the current study a group of participants who studied a list of cue-target pairs twice recalled fewer targets than a group who studied the pairs only once, a negative repetition effect. Such a…

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

The cost-effectiveness of targeted or universal screening for vasa praevia at 18-20 weeks of gestation in Ontario.

PubMed

Cipriano, L E; Barth, W H; Zaric, G S

2010-08-01

To estimate the cost-effectiveness of targeted and universal screening for vasa praevia at 18-20 weeks of gestation in singleton and twin pregnancies. Cost-utility analysis based on a decision-analytic model comparing relevant strategies and life-long outcomes for mother and infant(s). Ontario, Canada. A cohort of pregnant women in 1 year. We constructed a decision-analytic model to estimate the lifetime incremental costs and benefits of screening for vasa praevia. Inputs were estimated from the literature. Costs were collected from the London Health Sciences Centre, the Ontario Health Insurance Program, and other sources. We used one-way, scenario and probabilistic sensitivity analysis to determine the robustness of the results. Incremental costs, life expectancy, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER). Universal transvaginal ultrasound screening of twin pregnancies has an ICER of $5488 per QALY-gained. Screening all singleton pregnancies with the risk factors low-lying placentas, in vitro fertilisation (IVF) conception, accessory placental lobes, or velamentous cord insertion has an ICER of $15,764 per QALY-gained even though identifying some of these risk factors requires routine use of colour Doppler during transabdominal examinations. Screening women with a marginal cord insertion costs an additional $27,603 per QALY-gained. Universal transvaginal screening for vasa praevia in singleton pregnancies costs $579,164 per QALY compared with targeted screening. Compared with current practice, screening all twin pregnancies for vasa praevia with transvaginal ultrasound is cost-effective. Among the alternatives considered, the use of colour Doppler at all transabdominal ultrasound examinations of singleton pregnancies and targeted use of transvaginal ultrasound for IVF pregnancies or when the placenta has been found to be associated with one or more risk factors is cost-effective. Universal screening of singleton pregnancies

Post-targeting strategy for ready-to-use targeted nanodelivery post cargo loading.

PubMed

Zhu, J Y; Hu, J J; Zhang, M K; Yu, W Y; Zheng, D W; Wang, X Q; Feng, J; Zhang, X Z

2017-12-14

Based on boronate formation, this study reports a post-targeting methodology capable of readily installing versatile targeting modules onto a cargo-loaded nanoplatform in aqueous mediums. This permits the targeted nanodelivery of broad-spectrum therapeutics (drug/gene) in a ready-to-use manner while overcoming the PEGylation-dilemma that frequently occurs in conventional targeting approaches.

Cost-Effectiveness of Treatment Sequences of Chemotherapies and Targeted Biologics for Elderly Metastatic Colorectal Cancer Patients.

PubMed

Parikh, Rohan C; Du, Xianglin L; Robert, Morgan O; Lairson, David R

2017-01-01

Treatment patterns for metastatic colorectal cancer (mCRC) patients have changed considerably over the last decade with the introduction of new chemotherapies and targeted biologics. These treatments are often administered in various sequences with limited evidence regarding their cost-effectiveness. To conduct a pharmacoeconomic evaluation of commonly administered treatment sequences among elderly mCRC patients. A probabilistic discrete event simulation model assuming Weibull distribution was developed to evaluate the cost-effectiveness of the following common treatment sequences: (a) first-line oxaliplatin/irinotecan followed by second-line oxaliplatin/irinotecan + bevacizumab (OI-OIB); (b) first-line oxaliplatin/irinotecan + bevacizumab followed by second-line oxaliplatin/irinotecan + bevacizumab (OIB-OIB); (c) OI-OIB followed by a third-line targeted biologic (OI-OIB-TB); and (d) OIB-OIB followed by a third-line targeted biologic (OIB-OIB-TB). Input parameters for the model were primarily obtained from the Surveillance, Epidemiology, and End Results-Medicare linked dataset for incident mCRC patients aged 65 years and older diagnosed from January 2004 through December 2009. A probabilistic sensitivity analysis was performed to account for parameter uncertainty. Costs (2014 U.S. dollars) and effectiveness were discounted at an annual rate of 3%. In the base case analyses, at the willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life-year (QALY) gained, the treatment sequence OIB-OIB (vs. OI-OIB) was not cost-effective with an incremental cost-effectiveness ratio (ICER) per patient of $119,007/QALY; OI-OIB-TB (vs. OIB-OIB) was dominated; and OIB-OIB-TB (vs. OIB-OIB) was not cost-effective with an ICER of $405,857/QALY. Results similar to the base case analysis were obtained assuming log-normal distribution. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $100,000/QALY gained, sequence

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.

TargetCompare: A web interface to compare simultaneous miRNAs targets.

PubMed

Moreira, Fabiano Cordeiro; Dustan, Bruno; Hamoy, Igor G; Ribeiro-Dos-Santos, André M; Dos Santos, Andrea Ribeiro

2014-01-01

MicroRNAs (miRNAs) are small non-coding nucleotide sequences between 17 and 25 nucleotides in length that primarily function in the regulation of gene expression. A since miRNA has thousand of predict targets in a complex, regulatory cell signaling network. Therefore, it is of interest to study multiple target genes simultaneously. Hence, we describe a web tool (developed using Java programming language and MySQL database server) to analyse multiple targets of pre-selected miRNAs. We cross validated the tool in eight most highly expressed miRNAs in the antrum region of stomach. This helped to identify 43 potential genes that are target of at least six of the referred miRNAs. The developed tool aims to reduce the randomness and increase the chance of selecting strong candidate target genes and miRNAs responsible for playing important roles in the studied tissue. http://lghm.ufpa.br/targetcompare.

Prospects of target nanostructuring for laser proton acceleration

PubMed Central

Lübcke, Andrea; Andreev, Alexander A.; Höhm, Sandra; Grunwald, Ruediger; Ehrentraut, Lutz; Schnürer, Matthias

2017-01-01

In laser-based proton acceleration, nanostructured targets hold the promise to allow for significantly boosted proton energies due to strong increase of laser absorption. We used laser-induced periodic surface structures generated in-situ as a very fast and economic way to produce nanostructured targets capable of high-repetition rate applications. Both in experiment and theory, we investigate the impact of nanostructuring on the proton spectrum for different laser–plasma conditions. Our experimental data show that the nanostructures lead to a significant enhancement of absorption over the entire range of laser plasma conditions investigated. At conditions that do not allow for efficient laser absorption by plane targets, i.e. too steep plasma gradients, nanostructuring is found to significantly enhance the proton cutoff energy and conversion efficiency. In contrast, if the plasma gradient is optimized for laser absorption of the plane target, the nanostructure-induced absorption increase is not reflected in higher cutoff energies. Both, simulation and experiment point towards the energy transfer from the laser to the hot electrons as bottleneck. PMID:28290479

Prospects of target nanostructuring for laser proton acceleration.

PubMed

Lübcke, Andrea; Andreev, Alexander A; Höhm, Sandra; Grunwald, Ruediger; Ehrentraut, Lutz; Schnürer, Matthias

2017-03-14

In laser-based proton acceleration, nanostructured targets hold the promise to allow for significantly boosted proton energies due to strong increase of laser absorption. We used laser-induced periodic surface structures generated in-situ as a very fast and economic way to produce nanostructured targets capable of high-repetition rate applications. Both in experiment and theory, we investigate the impact of nanostructuring on the proton spectrum for different laser-plasma conditions. Our experimental data show that the nanostructures lead to a significant enhancement of absorption over the entire range of laser plasma conditions investigated. At conditions that do not allow for efficient laser absorption by plane targets, i.e. too steep plasma gradients, nanostructuring is found to significantly enhance the proton cutoff energy and conversion efficiency. In contrast, if the plasma gradient is optimized for laser absorption of the plane target, the nanostructure-induced absorption increase is not reflected in higher cutoff energies. Both, simulation and experiment point towards the energy transfer from the laser to the hot electrons as bottleneck.

Prospects of target nanostructuring for laser proton acceleration

NASA Astrophysics Data System (ADS)

Lübcke, Andrea; Andreev, Alexander A.; Höhm, Sandra; Grunwald, Ruediger; Ehrentraut, Lutz; Schnürer, Matthias

2017-03-01

In laser-based proton acceleration, nanostructured targets hold the promise to allow for significantly boosted proton energies due to strong increase of laser absorption. We used laser-induced periodic surface structures generated in-situ as a very fast and economic way to produce nanostructured targets capable of high-repetition rate applications. Both in experiment and theory, we investigate the impact of nanostructuring on the proton spectrum for different laser-plasma conditions. Our experimental data show that the nanostructures lead to a significant enhancement of absorption over the entire range of laser plasma conditions investigated. At conditions that do not allow for efficient laser absorption by plane targets, i.e. too steep plasma gradients, nanostructuring is found to significantly enhance the proton cutoff energy and conversion efficiency. In contrast, if the plasma gradient is optimized for laser absorption of the plane target, the nanostructure-induced absorption increase is not reflected in higher cutoff energies. Both, simulation and experiment point towards the energy transfer from the laser to the hot electrons as bottleneck.

Targeting high-risk employees may reduce cardiovascular racial disparities.

PubMed

Burke, James F; Vijan, Sandeep; Chekan, Lynette A; Makowiec, Ted M; Thomas, Laurita; Morgenstern, Lewis B

2014-09-01

A possible remedy for health disparities is for employers to promote cardiovascular health among minority employees. We sought to quantify the financial return to employers of interventions to improve minority health, and to determine whether a race- or risk-targeted strategy was better. Retrospective claims-based cohort analysis. Unconditional per-person costs attributable to stroke and myocardial infarction (MI) were estimated for University of Michigan employees from 2006 to 2009 using a 2-part model. The model was then used to predict the costs of cardiovascular disease to the University for 2 subgroups of employees-minorities and high-risk patients-and to calculate cost-savings thresholds: the point at which the costs of hypothetical interventions (eg, workplace fitness programs) would equal the cost savings from stroke/ MI prevention. Of the 38,314 enrollees, 10% were African American. Estimated unconditional payments for stroke/MI were almost the same in African Americans ($128 per employee per year; 95% CI, $79-$177) and whites ($128 per employee per year; 95% CI, $101- $156), including higher event rates and lower payments per event in African Americans. Targeting the highest risk decile with interventions to reduce stroke/MI would result in a substantially higher cost-savings threshold ($81) compared with targeting African Americans ($13). An unanticipated consequence of risk-based targeting is that African Americans would substantially benefit: an intervention targeted at the top risk decile would prevent 75% of the events in African Americans, just as would an intervention that exclusively targeted African Americans. Targeting all high-risk employees for cardiovascular risk reduction may be a win-win-win situation for employers: improving health, decreasing costs, and reducing disparities.

[Target volume margins for lung cancer: internal target volume/clinical target volume].

PubMed

Jouin, A; Pourel, N

2013-10-01

The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. Copyright © 2013. Published by Elsevier SAS.

42 CFR 457.555 - Maximum allowable cost-sharing charges on targeted low-income children in families with income...

Code of Federal Regulations, 2013 CFR

2013-10-01

...-emergency use of the emergency room. For Federal FY 2009, for targeted low-income children whose household...-institutional services, up to a maximum amount of $11.35 for services furnished in a hospital emergency room if... 42 Public Health 4 2013-10-01 2013-10-01 false Maximum allowable cost-sharing charges on targeted...

42 CFR 457.555 - Maximum allowable cost-sharing charges on targeted low-income children in families with income...

Code of Federal Regulations, 2014 CFR

2014-10-01

...-emergency use of the emergency room. For Federal FY 2009, for targeted low-income children whose household...-institutional services, up to a maximum amount of $11.35 for services furnished in a hospital emergency room if... 42 Public Health 4 2014-10-01 2014-10-01 false Maximum allowable cost-sharing charges on targeted...

Three-dimensional calibration targets for optical coherence tomography

NASA Astrophysics Data System (ADS)

Gabriele Sandrian, Michelle; Tomlins, Pete; Woolliams, Peter; Rasakanthan, Janarthanan; Lee, Graham C.; Yang, Anna; Považay, Boris; Alex, Aneesh; Sugden, Kate; Drexler, Wolfgang

2012-03-01

The recent expansion of clinical applications for optical coherence tomography (OCT) is driving the development of approaches for consistent image acquisition. There is a simultaneous need for time-stable, easy-to-use imaging targets for calibration and standardization of OCT devices. We present calibration targets consisting of three-dimensional structures etched into nanoparticle-embedded resin. Spherical iron oxide nanoparticles with a predominant particle diameter of 400 nm were homogeneously dispersed in a two part polyurethane resin and allowed to harden overnight. These samples were then etched using a precision micromachining femtosecond laser with a center wavelength of 1026 nm, 100kHz repetition rate and 450 fs pulse duration. A series of lines in depth were etched, varying the percentage of inscription energy and speed of the translation stage moving the target with respect to the laser. Samples were imaged with a dual wavelength spectral-domain OCT system (λ=800nm, ▵λ~180nm, and λ=1325nm, ▵λ~100nm) and point-spread function of nanoparticles within the target was measured.

A new fetal RHD genotyping test: costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales.

PubMed

Szczepura, Ala; Osipenko, Leeza; Freeman, Karoline

2011-01-18

Postnatal and antenatal anti-D prophylaxis have dramatically reduced maternal sensitisations and cases of rhesus disease in babies born to women with RhD negative blood group. Recent scientific advances mean that non-invasive prenatal diagnosis (NIPD), based on the presence of cell-free fetal DNA in maternal plasma, could be used to target prophylaxis on "at risk" pregnancies where the fetus is RhD positive. This paper provides the first assessment of cost-effectiveness of NIPD-targeted prophylaxis compared to current policies. We conducted an economic analysis of NIPD implementation in England and Wales. Two scenarios were considered. Scenario 1 assumed that NIPD will be only used to target antenatal prophylaxis with serology tests continuing to direct post-delivery prophylaxis. In Scenario 2, NIPD would also displace postnatal serology testing if an RhD negative fetus was identified. Costs were estimated from the provider's perspective for both scenarios together with a threshold royalty fee per test. Incremental costs were compared with clinical implications. The basic cost of an NIPD in-house test is £16.25 per sample (excluding royalty fee). The two-dose antenatal prophylaxis policy recommended by NICE is estimated to cost the NHS £3.37 million each year. The estimated threshold royalty fee is £2.18 and £8.83 for Scenarios 1 and 2 respectively. At a £2.00 royalty fee, mass NIPD testing would produce no saving for Scenario 1 and £507,154 per annum for Scenario 2. Incremental cost-effectiveness analysis indicates that, at a test sensitivity of 99.7% and this royalty fee, NIPD testing in Scenario 2 will generate one additional sensitisation for every £9,190 saved. If a single-dose prophylaxis policy were implemented nationally, as recently recommended by NICE, Scenario 2 savings would fall. Currently, NIPD testing to target anti-D prophylaxis is unlikely to be sufficiently cost-effective to warrant its large scale introduction in England and Wales. Only

Cost-effectiveness analysis of risk-reduction measures to reach water safety targets.

PubMed

Lindhe, Andreas; Rosén, Lars; Norberg, Tommy; Bergstedt, Olof; Pettersson, Thomas J R

2011-01-01

Identifying the most suitable risk-reduction measures in drinking water systems requires a thorough analysis of possible alternatives. In addition to the effects on the risk level, also the economic aspects of the risk-reduction alternatives are commonly considered important. Drinking water supplies are complex systems and to avoid sub-optimisation of risk-reduction measures, the entire system from source to tap needs to be considered. There is a lack of methods for quantification of water supply risk reduction in an economic context for entire drinking water systems. The aim of this paper is to present a novel approach for risk assessment in combination with economic analysis to evaluate risk-reduction measures based on a source-to-tap approach. The approach combines a probabilistic and dynamic fault tree method with cost-effectiveness analysis (CEA). The developed approach comprises the following main parts: (1) quantification of risk reduction of alternatives using a probabilistic fault tree model of the entire system; (2) combination of the modelling results with CEA; and (3) evaluation of the alternatives with respect to the risk reduction, the probability of not reaching water safety targets and the cost-effectiveness. The fault tree method and CEA enable comparison of risk-reduction measures in the same quantitative unit and consider costs and uncertainties. The approach provides a structured and thorough analysis of risk-reduction measures that facilitates transparency and long-term planning of drinking water systems in order to avoid sub-optimisation of available resources for risk reduction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Achievement of cholesterol targets and prescribing of higher-cost statins: a cross-sectional study in general practice.

PubMed

Fleetcroft, Robert; Schofield, Peter; Duerden, Martin; Ashworth, Mark

2012-12-01

There is conflicting evidence as to whether achievement of cholesterol targets at the population level is dependent on the choice and cost of statin. To investigate the practice-level relationship between cholesterol quality indicators in patients with heart disease, stroke, and diabetes and prescribing of low-cost statins. Correlations and linear regression modelling of retrospective cross-sectional practice-level data with potential explanatory variables in 7909 (96.4%) general practices in England in 2008-2009. Quality indicator data were obtained from the Information Centre and prescribing data from the NHS Business Authority. A 'cholesterol quality indicator' score was constructed by dividing the numbers of patients achieving the target for cholesterol control of ≤5 mmol/l in stroke, diabetes, and heart disease by the numbers on each register. A 'low-cost statin' ratio score was constructed by dividing the numbers of defined daily doses of simvastatin and pravastatin by the total numbers of defined daily doses of statins. Simvastatin accounted for 83.3% (standard deviation [SD] = 15.7%) of low-cost statins prescribed and atorvastatin accounted for 85.7% (SD = 14.8%) of high-cost statins prescribed. The mean cholesterol score was 73.7% (SD = 6.0%). Practices using a higher proportion of the low-cost statins were less successful in achieving cholesterol targets. An increase of 10% in the prescribing of low-cost statins was associated with a decrease of 0.46% in the cholesterol quality indicator score (95% confidence interval = -0.54% to -0.38%, P<0.001). Greater use of low-cost statins was associated with a small reduction in cholesterol control.

TargetCompare: A web interface to compare simultaneous miRNAs targets

PubMed Central

Moreira, Fabiano Cordeiro; Dustan, Bruno; Hamoy, Igor G; Ribeiro-dos-Santos, André M; dos Santos, Ândrea Ribeiro

2014-01-01

MicroRNAs (miRNAs) are small non-coding nucleotide sequences between 17 and 25 nucleotides in length that primarily function in the regulation of gene expression. A since miRNA has thousand of predict targets in a complex, regulatory cell signaling network. Therefore, it is of interest to study multiple target genes simultaneously. Hence, we describe a web tool (developed using Java programming language and MySQL database server) to analyse multiple targets of pre-selected miRNAs. We cross validated the tool in eight most highly expressed miRNAs in the antrum region of stomach. This helped to identify 43 potential genes that are target of at least six of the referred miRNAs. The developed tool aims to reduce the randomness and increase the chance of selecting strong candidate target genes and miRNAs responsible for playing important roles in the studied tissue. Availability http://lghm.ufpa.br/targetcompare PMID:25352731

NREL 2012 Achievement of Ethanol Cost Targets: Biochemical Ethanol Fermentation via Dilute-Acid Pretreatment and Enzymatic Hydrolysis of Corn Stover

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

Tao, L.; Schell, D.; Davis, R.

2014-04-01

For the DOE Bioenergy Technologies Office, the annual State of Technology (SOT) assessment is an essential activity for quantifying the benefits of biochemical platform research. This assessment has historically allowed the impact of research progress achieved through targeted Bioenergy Technologies Office funding to be quantified in terms of economic improvements within the context of a fully integrated cellulosic ethanol production process. As such, progress toward the ultimate 2012 goal of demonstrating cost-competitive cellulosic ethanol technology can be tracked. With an assumed feedstock cost for corn stover of $58.50/ton this target has historically been set at $1.41/gal ethanol for conversion costsmore » only (exclusive of feedstock) and $2.15/gal total production cost (inclusive of feedstock) or minimum ethanol selling price (MESP). This year, fully integrated cellulosic ethanol production data generated by National Renewable Energy Laboratory (NREL) researchers in their Integrated Biorefinery Research Facility (IBRF) successfully demonstrated performance commensurate with both the FY 2012 SOT MESP target of $2.15/gal (2007$, $58.50/ton feedstock cost) and the conversion target of $1.41/gal through core research and process improvements in pretreatment, enzymatic hydrolysis, and fermentation.« less

Distributed Bees Algorithm Parameters Optimization for a Cost Efficient Target Allocation in Swarms of Robots

PubMed Central

Jevtić, Aleksandar; Gutiérrez, Álvaro

2011-01-01

Swarms of robots can use their sensing abilities to explore unknown environments and deploy on sites of interest. In this task, a large number of robots is more effective than a single unit because of their ability to quickly cover the area. However, the coordination of large teams of robots is not an easy problem, especially when the resources for the deployment are limited. In this paper, the Distributed Bees Algorithm (DBA), previously proposed by the authors, is optimized and applied to distributed target allocation in swarms of robots. Improved target allocation in terms of deployment cost efficiency is achieved through optimization of the DBA’s control parameters by means of a Genetic Algorithm. Experimental results show that with the optimized set of parameters, the deployment cost measured as the average distance traveled by the robots is reduced. The cost-efficient deployment is in some cases achieved at the expense of increased robots’ distribution error. Nevertheless, the proposed approach allows the swarm to adapt to the operating conditions when available resources are scarce. PMID:22346677

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

PubMed

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

2016-08-01

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

Sound segregation via embedded repetition is robust to inattention.

PubMed

Masutomi, Keiko; Barascud, Nicolas; Kashino, Makio; McDermott, Josh H; Chait, Maria

2016-03-01

The segregation of sound sources from the mixture of sounds that enters the ear is a core capacity of human hearing, but the extent to which this process is dependent on attention remains unclear. This study investigated the effect of attention on the ability to segregate sounds via repetition. We utilized a dual task design in which stimuli to be segregated were presented along with stimuli for a "decoy" task that required continuous monitoring. The task to assess segregation presented a target sound 10 times in a row, each time concurrent with a different distractor sound. McDermott, Wrobleski, and Oxenham (2011) demonstrated that repetition causes the target sound to be segregated from the distractors. Segregation was queried by asking listeners whether a subsequent probe sound was identical to the target. A control task presented similar stimuli but probed discrimination without engaging segregation processes. We present results from 3 different decoy tasks: a visual multiple object tracking task, a rapid serial visual presentation (RSVP) digit encoding task, and a demanding auditory monitoring task. Load was manipulated by using high- and low-demand versions of each decoy task. The data provide converging evidence of a small effect of attention that is nonspecific, in that it affected the segregation and control tasks to a similar extent. In all cases, segregation performance remained high despite the presence of a concurrent, objectively demanding decoy task. The results suggest that repetition-based segregation is robust to inattention. (c) 2016 APA, all rights reserved).

Adaptive optics to enhance target recognition

NASA Astrophysics Data System (ADS)

McAulay, Alastair D.

2012-06-01

Target recognition can be enhanced by reducing image degradation due to atmospheric turbulence. This is accomplished by an adaptive optic system. We discuss the forms of degradation when a target is viewed through the atmosphere1: scintillation from ground targets on a hot day in visible or infrared light; beam spreading and wavering around in time; atmospheric turbulence caused by motion of the target or by weather. In the case of targets we can use a beacon laser that reflects back from the target into a wavefront detector to measure the effects of turbulence on propagation to and from the target before imaging.1 A deformable mirror then corrects the wavefront shape of the transmitted, reflected or scattered data for enhanced imaging. Further, recognition of targets is enhanced by performing accurate distance measurements to localized parts of the target using lidar. Distance is obtained by sending a short pulse to the target and measuring the time for the pulse to return. There is inadequate time to scan the complete field of view so that the beam must be steered to regions of interest such as extremities of the image during image recognition. Distance is particularly valuable to recognize fine features in range along the target or when segmentation is required to separate a target from background or from other targets. We discuss the issues involved.

Complementary Approaches to Existing Target Based Drug Discovery for Identifying Novel Drug Targets.

PubMed

Vasaikar, Suhas; Bhatia, Pooja; Bhatia, Partap G; Chu Yaiw, Koon

2016-11-21

In the past decade, it was observed that the relationship between the emerging New Molecular Entities and the quantum of R&D investment has not been favorable. There might be numerous reasons but few studies stress the introduction of target based drug discovery approach as one of the factors. Although a number of drugs have been developed with an emphasis on a single protein target, yet identification of valid target is complex. The approach focuses on an in vitro single target, which overlooks the complexity of cell and makes process of validation drug targets uncertain. Thus, it is imperative to search for alternatives rather than looking at success stories of target-based drug discovery. It would be beneficial if the drugs were developed to target multiple components. New approaches like reverse engineering and translational research need to take into account both system and target-based approach. This review evaluates the strengths and limitations of known drug discovery approaches and proposes alternative approaches for increasing efficiency against treatment.

Cancer-linked targets modulated by curcumin

PubMed Central

Hasima, Noor; Aggarwal, Bharat B

2012-01-01

In spite of major advances in oncology, the World Health Organization predicts that cancer incidence will double within the next two decades. Although it is well understood that cancer is a hyperproliferative disorder mediated through dysregulation of multiple cell signaling pathways, most cancer drug development remains focused on modulation of specific targets, mostly one at a time, with agents referred to as “targeted therapies,” “smart drugs,” or “magic bullets.” How many cancer targets there are is not known, and how many targets must be attacked to control cancer growth is not well understood. Although more than 90% of cancer-linked deaths are due to metastasis of the tumor to vital organs, most drug targeting is focused on killing the primary tumor. Besides lacking specificity, the targeted drugs induce toxicity and side effects that sometimes are greater problems than the disease itself. Furthermore, the cost of some of these drugs is so high that most people cannot afford them. The present report describes the potential anticancer properties of curcumin, a component of the Indian spice turmeric (Curcuma longa), known for its safety and low cost. Curcumin can selectively modulate multiple cell signaling pathways linked to inflammation and to survival, growth, invasion, angiogenesis, and metastasis of cancer cells. More clinical trials of curcumin are needed to prove its usefulness in the cancer setting. PMID:23301199

Motor cortex guides selection of predictable movement targets

PubMed Central

Woodgate, Philip J.W.; Strauss, Soeren; Sami, Saber A.; Heinke, Dietmar

2016-01-01

The present paper asks whether the motor cortex contributes to prediction-based guidance of target selection. This question was inspired by recent evidence that suggests (i) recurrent connections from the motor system into the attentional system may extract movement-relevant perceptual information and (ii) that the motor cortex cannot only generate predictions of the sensory consequences of movements but may also operate as predictor of perceptual events in general. To test this idea we employed a choice reaching task requiring participants to rapidly reach and touch a predictable or unpredictable colour target. Motor cortex activity was modulated via transcranial direct current stimulation (tDCS). In Experiment 1 target colour repetitions were predictable. Under such conditions anodal tDCS facilitated selection versus sham and cathodal tDCS. This improvement was apparent for trajectory curvature but not movement initiation. Conversely, where no predictability of colour was embedded reach performance was unaffected by tDCS. Finally, the results of a key-press experiment suggested that motor cortex involvement is restricted to tasks where the predictable target colour is movement-relevant. The outcomes are interpreted as evidence that the motor system contributes to the top-down guidance of selective attention to movement targets. PMID:25835319

Cost-effectiveness of health promotion targeting physical activity and healthy eating in mental health care.

PubMed

Verhaeghe, Nick; De Smedt, Delphine; De Maeseneer, Jan; Maes, Lea; Van Heeringen, Cornelis; Annemans, Lieven

2014-08-18

There is a higher prevalence of obesity in individuals with mental disorders compared to the general population. The results of several studies suggested that weight reduction in this population is possible following psycho-educational and/or behavioural weight management interventions. Evidence of the effectiveness alone is however inadequate for policy making. The aim of the current study was to evaluate the cost-effectiveness of a health promotion intervention targeting physical activity and healthy eating in individuals with mental disorders. A Markov decision-analytic model using a public payer perspective was applied, projecting the one-year results of a 10-week intervention over a time horizon of 20 years, assuming a repeated yearly implementation of the programme. Scenario analysis was applied evaluating the effects on the results of alternative modelling assumptions. One-way sensitivity analysis was performed to assess the effects on the results of varying key input parameters. An incremental cost-effectiveness ratio of 27,096€/quality-adjusted life years (QALY) in men, and 40,139€/QALY in women was found in the base case. Scenario analysis assuming an increase in health-related quality of life as a result of the body mass index decrease resulted in much better cost-effectiveness in both men (3,357€/QALY) and women (3,766€/QALY). The uncertainty associated with the intervention effect had the greatest impact on the model. As far as is known to the authors, this is the first health economic evaluation of a health promotion intervention targeting physical activity and healthy eating in individuals with mental disorders. Such research is important as it provides payers and governments with better insights how to spend the available resources in the most efficient way. Further research examining the cost-effectiveness of health promotion targeting physical activity and healthy eating in individuals with mental disorders is required.

Reaching the global target to reduce stunting: an investment framework

PubMed Central

Shekar, Meera; D’Alimonte, Mary R; Rogers, Hilary E; Eberwein, Julia Dayton; Akuoku, Jon Kweku; Pereira, Audrey; Soe-Lin, Shan; Hecht, Robert

2017-01-01

Abstract Childhood stunting, being short for one’s age, has life-long consequences for health, human capital and economic growth. Being stunted in early childhood is associated with slower cognitive development, reduced schooling attainment and adult incomes decreased by 5–53%. The World Health Assembly has endorsed global nutrition targets including one to reduce the number of stunted children under five by 40% by 2025. The target has been included in the Sustainable Development Goals (SDG target 2.2). This paper estimates the cost of achieving this target and develops scenarios for generating the necessary financing. We focus on a key intervention package for stunting (KIPS) with strong evidence of effectiveness. Annual scale-up costs for the period of 2016–25 were estimated for a sample of 37 high burden countries and extrapolated to all low and middle income countries. The Lives Saved Tool was used to model the impact of the scale-up on stunting prevalence. We analysed data on KIPS budget allocations and expenditure by governments, donors and households to derive a global baseline financing estimate. We modelled two financing scenarios, a ‘business as usual’, which extends the current trends in domestic and international financing for nutrition through 2025, and another that proposes increases in financing from all sources under a set of burden-sharing rules. The 10-year financial need to scale up KIPS is US$49.5 billion. Under ‘business as usual’, this financial need is not met and the global stunting target is not reached. To reach the target, current financing will have to increase from US$2.6 billion to US$7.4 billion a year on average. Reaching the stunting target is feasible but will require large coordinated investments in KIPS and a supportive enabling environment. The example of HIV scale-up over 2001–11 is instructive in identifying the factors that could drive such a global response to childhood stunting. PMID:28453717

Reaching the global target to reduce stunting: an investment framework.

PubMed

Shekar, Meera; Kakietek, Jakub; D'Alimonte, Mary R; Rogers, Hilary E; Eberwein, Julia Dayton; Akuoku, Jon Kweku; Pereira, Audrey; Soe-Lin, Shan; Hecht, Robert

2017-06-01

Childhood stunting, being short for one's age, has life-long consequences for health, human capital and economic growth. Being stunted in early childhood is associated with slower cognitive development, reduced schooling attainment and adult incomes decreased by 5-53%. The World Health Assembly has endorsed global nutrition targets including one to reduce the number of stunted children under five by 40% by 2025. The target has been included in the Sustainable Development Goals (SDG target 2.2). This paper estimates the cost of achieving this target and develops scenarios for generating the necessary financing. We focus on a key intervention package for stunting (KIPS) with strong evidence of effectiveness. Annual scale-up costs for the period of 2016-25 were estimated for a sample of 37 high burden countries and extrapolated to all low and middle income countries. The Lives Saved Tool was used to model the impact of the scale-up on stunting prevalence. We analysed data on KIPS budget allocations and expenditure by governments, donors and households to derive a global baseline financing estimate. We modelled two financing scenarios, a 'business as usual', which extends the current trends in domestic and international financing for nutrition through 2025, and another that proposes increases in financing from all sources under a set of burden-sharing rules. The 10-year financial need to scale up KIPS is US$49.5 billion. Under 'business as usual', this financial need is not met and the global stunting target is not reached. To reach the target, current financing will have to increase from US$2.6 billion to US$7.4 billion a year on average. Reaching the stunting target is feasible but will require large coordinated investments in KIPS and a supportive enabling environment. The example of HIV scale-up over 2001-11 is instructive in identifying the factors that could drive such a global response to childhood stunting. © The Author 2017. Published by Oxford University

low-Cost, High-Performance Alternatives for Target Temperature Monitoring Using the Near-Infrared Spectrum

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

Virgo, Mathew; Quigley, Kevin J.; Chemerisov, Sergey

A process is being developed for commercial production of the medical isotope Mo-99 through a photo-nuclear reaction on a Mo-100 target using a highpower electron accelerator. This process requires temperature monitoring of the window through which a high-current electron beam is transmitted to the target. For this purpose, we evaluated two near infrared technologies: the OMEGA Engineering iR2 pyrometer and the Ocean Optics Maya2000 spectrometer with infrared-enhanced charge-coupled device (CCD) sensor. Measuring in the near infrared spectrum, in contrast to the long-wavelength infrared spectrum, offers a few immediate advantages: (1) ordinary glass or quartz optical elements can be used; (2)more » alignment can be performed without heating the target; and (3) emissivity corrections to temperature are typically less than 10%. If spatial resolution is not required, the infrared pyrometer is attractive because of its accuracy, low cost, and simplicity. If spatial resolution is required, we make recommendations for near-infrared imaging based on our data augmented by calculations« less

Can We Use Neurocognition to Predict Repetition of Self-Harm, and Why Might This Be Clinically Useful? A Perspective

PubMed Central

de Cates, Angharad N.; Broome, Matthew R.

2016-01-01

Over 800,000 people die by suicide each year globally, with non-fatal self-harm 20 times more common. With each episode of self-harm, the risks of future self-harm and suicide increase, as well as personal and healthcare costs. Therefore, early delineation of those at high risk of future self-harm is important. Historically, research has focused on clinical and demographic factors, but risk assessments based on these have low sensitivity to predict repetition. Various neurocognitive factors have been associated with self-harming behavior, but it is less certain if we can use these factors clinically (i) as risk markers to predict future self-harm and (ii) to become therapeutic targets for interventions. Recent systematic reviews and meta-analyses of behavioral tasks and fMRI studies point to an emerging hypothesis for neurocognition in self-harm: an underactive pre-frontal cortex is unable to respond appropriately to non-emotional stimuli, or inhibit a hyperactive emotionally-/threat-driven limbic system. However, there is almost no imaging data examining repetition of self-harm. Extrapolating from the non-repetition data, there may be several potential neurocognitive targets for interventions to prevent repeat self-harm: cognitive training; pharmacological regimes to promote non-emotional neurocognition; or other techniques, such as repetitive transcranial magnetic stimulation. Hence, there is an urgent need for imaging studies examining repetition and to test specific hypotheses. Until we investigate the functional neurocognitive basis underlying repetition of self-harm in a systematic manner using second-generational imaging techniques, we will be unable to inform third-generational imaging and potential future clinical applications. PMID:26858659

A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.

PubMed

Guo, Wei-Feng; Zhang, Shao-Wu; Shi, Qian-Qian; Zhang, Cheng-Ming; Zeng, Tao; Chen, Luonan

2018-01-19

The advances in target control of complex networks not only can offer new insights into the general control dynamics of complex systems, but also be useful for the practical application in systems biology, such as discovering new therapeutic targets for disease intervention. In many cases, e.g. drug target identification in biological networks, we usually require a target control on a subset of nodes (i.e., disease-associated genes) with minimum cost, and we further expect that more driver nodes consistent with a certain well-selected network nodes (i.e., prior-known drug-target genes). Therefore, motivated by this fact, we pose and address a new and practical problem called as target control problem with objectives-guided optimization (TCO): how could we control the interested variables (or targets) of a system with the optional driver nodes by minimizing the total quantity of drivers and meantime maximizing the quantity of constrained nodes among those drivers. Here, we design an efficient algorithm (TCOA) to find the optional driver nodes for controlling targets in complex networks. We apply our TCOA to several real-world networks, and the results support that our TCOA can identify more precise driver nodes than the existing control-fucus approaches. Furthermore, we have applied TCOA to two bimolecular expert-curate networks. Source code for our TCOA is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or https://github.com/WilfongGuo/guoweifeng . In the previous theoretical research for the full control, there exists an observation and conclusion that the driver nodes tend to be low-degree nodes. However, for target control the biological networks, we find interestingly that the driver nodes tend to be high-degree nodes, which is more consistent with the biological experimental observations. Furthermore, our results supply the novel insights into how we can efficiently target control a complex system, and especially many evidences on the

A new fetal RHD genotyping test: Costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales

PubMed Central

2011-01-01

Background Postnatal and antenatal anti-D prophylaxis have dramatically reduced maternal sensitisations and cases of rhesus disease in babies born to women with RhD negative blood group. Recent scientific advances mean that non-invasive prenatal diagnosis (NIPD), based on the presence of cell-free fetal DNA in maternal plasma, could be used to target prophylaxis on "at risk" pregnancies where the fetus is RhD positive. This paper provides the first assessment of cost-effectiveness of NIPD-targeted prophylaxis compared to current policies. Methods We conducted an economic analysis of NIPD implementation in England and Wales. Two scenarios were considered. Scenario 1 assumed that NIPD will be only used to target antenatal prophylaxis with serology tests continuing to direct post-delivery prophylaxis. In Scenario 2, NIPD would also displace postnatal serology testing if an RhD negative fetus was identified. Costs were estimated from the provider's perspective for both scenarios together with a threshold royalty fee per test. Incremental costs were compared with clinical implications. Results The basic cost of an NIPD in-house test is £16.25 per sample (excluding royalty fee). The two-dose antenatal prophylaxis policy recommended by NICE is estimated to cost the NHS £3.37 million each year. The estimated threshold royalty fee is £2.18 and £8.83 for Scenarios 1 and 2 respectively. At a £2.00 royalty fee, mass NIPD testing would produce no saving for Scenario 1 and £507,154 per annum for Scenario 2. Incremental cost-effectiveness analysis indicates that, at a test sensitivity of 99.7% and this royalty fee, NIPD testing in Scenario 2 will generate one additional sensitisation for every £9,190 saved. If a single-dose prophylaxis policy were implemented nationally, as recently recommended by NICE, Scenario 2 savings would fall. Conclusions Currently, NIPD testing to target anti-D prophylaxis is unlikely to be sufficiently cost-effective to warrant its large scale

Repetition Strengthens Target Recognition but Impairs Similar Lure Discrimination: Evidence for Trace Competition

ERIC Educational Resources Information Center

Reagh, Zachariah M.; Yassa, Michael A.

2014-01-01

Most theories of memory assume that representations are strengthened with repetition. We recently proposed Competitive Trace Theory, building on the hippocampus' powerful capacity to orthogonalize inputs into distinct outputs. We hypothesized that repetition elicits a similar but nonidentical memory trace, and that contextual details of…

Resource implications of a national health target: The New Zealand experience of a Shorter Stays in Emergency Departments target.

PubMed

Jones, Peter; Sopina, Elizaveta; Ashton, Toni

2014-12-01

The Shorter Stays in Emergency Departments health target was introduced in New Zealand in 2009. District Health Boards (DHBs) are expected to meet the target with no additional funding or incentives. The costs of implementing such targets have not previously been studied. A survey of clinical/service managers in ED throughout New Zealand determined the type and cost of resources used for the target. Responses to the target were classified according to their impact in ED, the hospital and the community. Quantifiable resource changes were assigned a financial value and grouped into categories: structure (facilities/beds), staff and processes. Simple statistics were used to describe the data, and the correlation between expenditure and target performance was determined. There was 100% response to the survey. Most DHBs reported some expenditure specifically on the target, with estimated total expenditure of over NZ$52 m. The majority of expenditure occurred in ED (60.8%) and hospital (38.7%) with little spent in the community. New staff accounted for 76.5% of expenditure. Per capita expenditure in the ED was associated with improved target performance (r = 0.48, P = 0.03), whereas expenditure in the hospital was not (r = 0.08, P = 0.75). The fact that estimated expenditure on the target was over $50 million without additional funding suggests that DHBs were able to make savings through improved efficiencies and/or that funds were reallocated from other services. The majority of expenditure occurred in the ED. Most of the funds were spent on staff, and this was associated with improved target performance. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis.

PubMed

Lo, Nathan C; Gurarie, David; Yoon, Nara; Coulibaly, Jean T; Bendavid, Eran; Andrews, Jason R; King, Charles H

2018-01-23

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA. Copyright © 2018 the Author(s). Published by PNAS.

Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis

PubMed Central

Yoon, Nara; Coulibaly, Jean T.; Bendavid, Eran; Andrews, Jason R.; King, Charles H.

2018-01-01

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5–20%) and high-prevalence (25–50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, “hot spots” of transmission, and noncompliance to MDA. PMID:29301964

TARGETING POLYMER THERAPEUTICS TO BONE

PubMed Central

Low, Stewart; Kopeček, Jindřich

2012-01-01

An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

Targeting the Plantar Fascia for Corticosteroid Injection.

PubMed

Salvi, Andrea Emilio

2015-01-01

Plantar fasciitis is often a difficult condition to treat. It is related to repetitive strain of the fascia at its attachment to the heel bone. This condition quite often appears with the concomitant presence of a plantar calcaneal heel spur. Corticosteroid injection is a popular treatment choice for plantar fasciitis, and accurate localization of the injected medication is essential for successful resolution of symptoms after the injection. In the present brief technical communication, a method for targeting the attachment of the plantar fascia to the medial tubercle of the tuberosity of the calcaneus is described. The targeting method uses the lateral radiograph of the foot to aid in localization of the proximal attachment of the plantar fascia to the calcaneus. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Nanopharmaceuticals to target antifilarials: a comprehensive review.

PubMed

Ali, Mohammad; Afzal, Mohammad; Bhattacharya, Shailja Misra; Ahmad, Farhan Jalees; Dinda, Amit Kumar

2013-05-01

Currently emphasized conventional chemotherapies for the elimination of lymphatic filariasis (LF) are imperfect due to unfocused targeting of poorly water-soluble antifilarial drugs. The profound location of drug targets (filarial parasites or wolbachia) within the complex anatomy of lymphatic tissues often necessitates prolonged treatment schedules with high doses leading to undesired side effects and poor patient compliance. Therefore, we need to reformulate antifilarial drugs taking the advantages of nanotechnology through a wide range of nanomedical carriers, which improve drug efficacy, increase bioavailability, and diminish toxicity. Connotations of drug delivery systems (DDSs) to target lymphatic filaroids or wolbachia and systemic microfilaria have been discussed. The potentials of liposomes and solid lipid nanoparticles for the treatment of LF are highlighted. Various critical factors, viz optimal size range, surface properties, preferred pH, mechanism of reticuloendothelial avoidance, and control of the release of antifilarial agents for safe elimination of parasites, are enclosed to design a novel DDS for LF. The review of nanotechnological approaches to improve antifilarial chemotherapy will help to resolve existing technological gaps. Precincts in the antifilarial discovery programs can never be overcome by conventional methods. Nanomedicine encompasses wide-range solution for each single problem (i.e., from poor solubility to nonspecific targeting of antifilarial agents) for the cure of LF at low costs and may reduce the economic burden of LF diseases. Advances in nanotechnology loom will certainly come forward as silver bullets in the near future for quick diagnosis, control, and elimination of this tropically neglected disease.

Target-Rich Environment

ERIC Educational Resources Information Center

Perna, Mark C.

2005-01-01

Target marketing is defining school enrollment goals and then developing a strategic plan to accomplish those goals through the use of specific communication vehicles and community focus. It is critical to reach the right audience, with the right message, at the right time, for the right cost. In this brief article, the author describes several…

A tool for cost-effectiveness analysis of field scale sediment-bound phosphorus mitigation measures and application to analysis of spatial and temporal targeting in the Lunan Water catchment, Scotland.

PubMed

Vinten, Andy; Sample, James; Ibiyemi, Adekunle; Abdul-Salam, Yakubu; Stutter, Marc

2017-05-15

The cost-effectiveness of six edge-of-field measures for mitigating diffuse pollution from sediment bound phosphorus (P) runoff from temperate arable farmland is analysed at catchment/field scales. These measures were: buffer strips, permanent grassland in the lowest 7% of arable fields, dry detention bunds, wetlands, and temporary barriers such as sediment fences. Baseline field P export was estimated using export coefficients (low risk crops) or a modified Universal Soil Loss Equation (high risk crops). The impact of measures was estimated using simple equations. Costs were estimated from gross margin losses or local data on grants. We used a net cost:benefit (NCB) factor to normalise the costs and impacts of each measure over time. Costs minimisation for target impact was done using PuLP, a linear programming module for Python, across 1634 riparian and non-riparian fields in the Lunan Water, a mixed arable catchment in Eastern Scotland. With all measures in place, average cost-effectiveness increases from £9 to £48/kg P as target P mitigation increases from 500 to 2500kg P across the catchment. Costs increase significantly when the measures available are restricted only to those currently eligible for government grants (buffers, bunds and wetlands). The assumed orientation of the average field slope makes a strong difference to the potential for storage of water by bunds and overall cost-effectiveness, but the non-funded measures can substitute for the extra expense incurred by bunds, where the slope orientation is not suitable. Economic discounting over time of impacts and costs of measures favours those measures, such as sediment fences, which are strongly targeted both spatially and temporally. This tool could be a useful guide for dialogue with land users about the potential fields to target for mitigation to achieve catchment targets. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Target selection biases from recent experience transfer across effectors.

PubMed

Moher, Jeff; Song, Joo-Hyun

2016-02-01

Target selection is often biased by an observer's recent experiences. However, not much is known about whether these selection biases influence behavior across different effectors. For example, does looking at a red object make it easier to subsequently reach towards another red object? In the current study, we asked observers to find the uniquely colored target object on each trial. Randomly intermixed pre-trial cues indicated the mode of action: either an eye movement or a visually guided reach movement to the target. In Experiment 1, we found that priming of popout, reflected in faster responses following repetition of the target color on consecutive trials, occurred regardless of whether the effector was repeated from the previous trial or not. In Experiment 2, we examined whether an inhibitory selection bias away from a feature could transfer across effectors. While priming of popout reflects both enhancement of the repeated target features and suppression of the repeated distractor features, the distractor previewing effect isolates a purely inhibitory component of target selection in which a previewed color is presented in a homogenous display and subsequently inhibited. Much like priming of popout, intertrial suppression biases in the distractor previewing effect transferred across effectors. Together, these results suggest that biases for target selection driven by recent trial history transfer across effectors. This indicates that representations in memory that bias attention towards or away from specific features are largely independent from their associated actions.

Molecular targeting agents in cancer therapy: science and society.

PubMed

Shaikh, Asim Jamal

2012-01-01

The inception of targeted agents has revolutionized the cancer therapy paradigm, both for physicians and patients. A large number of molecular targeted agents for cancer therapy are currently available for clinical use today. Many more are in making, but there are issues that remain to be resolved for the scientific as well as social community before the recommendation of their widespread use in may clinical scenarios can be done, one such issue being cost and cost effectiveness, others being resistance and lack of sustained efficacy. With the current knowledge about available targeted agents, the growing knowledge of intricate molecular pathways and unfolding of wider spectrum of molecular targets that can really matter in the disease control, calls for only the just use of the agents available now, drug companies need to make a serious attempt to reduce the cost of the agents. Research should focus on agents that show sustained responses in preclinical data. More needs to be done in laboratories and by the pharmaceutical industries, before we can truly claim to have entered a new era of targeted therapy in cancer care.

Cost-effectiveness of lower targets for blood pressure and low-density lipoprotein cholesterol in diabetes: the Stop Atherosclerosis in Native Diabetics Study (SANDS) .

PubMed

Wilson, Charlton; Huang, Chun-Chih; Shara, Nawar; Howard, Barbara V; Fleg, Jerome L; Henderson, Jeffrey A; Howard, Wm James; Huentelman, Heather; Lee, Elisa T; Mete, Mihriye; Russell, Marie; Galloway, James M; Silverman, Angela; Stylianou, Mario; Umans, Jason; Weir, Matthew R; Yeh, Fawn; Ratner, Robert E

2010-01-01

The Stop Atherosclerosis in Native Diabetics Study (SANDS) reported cardiovascular benefit of aggressive versus standard treatment targets for both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) in diabetic individuals. In this analysis, we examined within trial cost-effectiveness of aggressive targets of LDL-C ≤70 mg/dL and systolic BP ≤115 mmHg versus standard targets of LDL-C ≤100 mg/dL and systolic BP ≤130 mmHg. Randomized, open label blinded-to-endpoint 3-year trial. SANDS clinical trial database, Quality of Wellbeing survey, Centers for Medicare and Medicaid Services, Wholesale Drug Prices. American Indians ≥ age 40 years with type 2 diabetes and no previous cardiovascular events. April 2003 to July 2007. Health payer. Participants were randomized to aggressive versus standard groups with treatment algorithms defined for both. Incremental cost-effectiveness. Compared with the standard group, the aggressive group had slightly lower costs of medical services (-$116) but a 54% greater cost for BP medication ($1,242) and a 116% greater cost for lipid-lowering medication ($2,863), resulting in an increased cost of $3,988 over 3 years. Those in the aggressively treated group gained 0.0480 quality-adjusted life-years (QALY) over the standard group. When a 3% discount rate for costs and outcomes was used, the resulting cost per QALY was $82,589. The use of a 25%, 50%, and 75% reduction in drug costs resulted in a cost per QALY of $61,329, $40,070, and $18,810, respectively. This study was limited by use of a single ethnic group and by its 3-year duration. Within this 3-year study, treatment to lower BP and LDL-C below standard targets was not cost-effective because of the cost of the additional medications required to meet the lower targets. With the anticipated availability of generic versions of the BP and lipid-lowering drugs used in SANDS, the cost-effectiveness of this intervention should improve. Published by Elsevier Inc on

Switching between global and local levels: the level repetition effect and its hemispheric asymmetry

PubMed Central

Kéïta, Luc; Bedoin, Nathalie; Burack, Jacob A.; Lepore, Franco

2014-01-01

The global level of hierarchical stimuli (Navon’s stimuli) is typically processed quicker and better than the local level; further differential hemispheric dominance is described for local (left hemisphere, LH) and global (right hemisphere, RH) processing. However, neuroimaging and behavioral data indicate that stimulus category (letter or object) could modulate the hemispheric asymmetry for the local level processing. Besides, when the targets are unpredictably displayed at the global or local level, the participant has to switch between levels, and the magnitude of the switch cost increases with the number of repeated-level trials preceding the switch. The hemispheric asymmetries associated with level switching is an unresolved issue. LH areas may be involved in carrying over the target level information in case of level repetition. These areas may also largely participate in the processing of level-changed trials. Here we hypothesized that RH areas underly the inhibitory mechanism performed on the irrelevant level, as one of the components of the level switching process. In an experiment using a within-subject design, hierarchical stimuli were briefly presented either to the right or to the left visual field. 32 adults were instructed to identify the target at the global or local level. We assessed a possible RH dominance for the non-target level inhibition by varying the attentional demands through the manipulation of level repetitions (two or gour repeated-level trials before the switch). The behavioral data confirmed a LH specialization only for the local level processing of letter-based stimuli, and detrimental effect of increased level repetitions before a switch. Further, data provides evidence for a RH advantage in inhibiting the non-target level. Taken together, the data supports the notion of the existence of multiple mechanisms underlying level-switch effects. PMID:24723903

UniDrug-target: a computational tool to identify unique drug targets in pathogenic bacteria.

PubMed

Chanumolu, Sree Krishna; Rout, Chittaranjan; Chauhan, Rajinder S

2012-01-01

Targeting conserved proteins of bacteria through antibacterial medications has resulted in both the development of resistant strains and changes to human health by destroying beneficial microbes which eventually become breeding grounds for the evolution of resistances. Despite the availability of more than 800 genomes sequences, 430 pathways, 4743 enzymes, 9257 metabolic reactions and protein (three-dimensional) 3D structures in bacteria, no pathogen-specific computational drug target identification tool has been developed. A web server, UniDrug-Target, which combines bacterial biological information and computational methods to stringently identify pathogen-specific proteins as drug targets, has been designed. Besides predicting pathogen-specific proteins essentiality, chokepoint property, etc., three new algorithms were developed and implemented by using protein sequences, domains, structures, and metabolic reactions for construction of partial metabolic networks (PMNs), determination of conservation in critical residues, and variation analysis of residues forming similar cavities in proteins sequences. First, PMNs are constructed to determine the extent of disturbances in metabolite production by targeting a protein as drug target. Conservation of pathogen-specific protein's critical residues involved in cavity formation and biological function determined at domain-level with low-matching sequences. Last, variation analysis of residues forming similar cavities in proteins sequences from pathogenic versus non-pathogenic bacteria and humans is performed. The server is capable of predicting drug targets for any sequenced pathogenic bacteria having fasta sequences and annotated information. The utility of UniDrug-Target server was demonstrated for Mycobacterium tuberculosis (H37Rv). The UniDrug-Target identified 265 mycobacteria pathogen-specific proteins, including 17 essential proteins which can be potential drug targets. UniDrug-Target is expected to accelerate

Microvascular Targets for Anti-Fibrotic Therapeutics

PubMed Central

Pu, Kai-Ming T.; Sava, Parid; Gonzalez, Anjelica L.

2013-01-01

Fibrosis is characterized by excessive extracellular matrix deposition and is the pathological outcome of repetitive tissue injury in many disorders. The accumulation of matrix disrupts the structure and function of the native tissue and can affect multiple organs including the lungs, heart, liver, and skin. Unfortunately, current therapies against the deadliest and most common fibrosis are ineffective. The pathogenesis of fibrosis is the result of aberrant wound healing, therefore, the microvasculature plays an important role, contributing through regulation of leukocyte recruitment, inflammation, and angiogenesis. Further exacerbating the condition, microvascular endothelial cells and pericytes can transdifferentiate into matrix depositing myofibroblasts. The contribution of the microvasculature to fibrotic progression makes its cellular components and acellular products attractive therapeutic targets. In this review, we examine many of the cytokine, matrix, and cellular microvascular components involved in fibrosis and discuss their potential as targets for fibrotic therapies with a particular focus on developing nanotechnologies. PMID:24348218

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.

MFP scanner diagnostics using a self-printed target to measure the modulation transfer function

NASA Astrophysics Data System (ADS)

Wang, Weibao; Bauer, Peter; Wagner, Jerry; Allebach, Jan P.

2014-01-01

In the current market, reduction of warranty costs is an important avenue for improving profitability by manufacturers of printer products. Our goal is to develop an autonomous capability for diagnosis of printer and scanner caused defects with mid-range laser multifunction printers (MFPs), so as to reduce warranty costs. If the scanner unit of the MFP is not performing according to specification, this issue needs to be diagnosed. If there is a print quality issue, this can be diagnosed by printing a special test page that is resident in the firmware of the MFP unit, and then scanning it. However, the reliability of this process will be compromised if the scanner unit is defective. Thus, for both scanner and printer image quality issues, it is important to be able to properly evaluate the scanner performance. In this paper, we consider evaluation of the scanner performance by measuring its modulation transfer function (MTF). The MTF is a fundamental tool for assessing the performance of imaging systems. Several ways have been proposed to measure the MTF, all of which require a special target, for example a slanted-edge target. It is unacceptably expensive to ship every MFP with such a standard target, and to expect that the customer can keep track of it. To reduce this cost, in this paper, we develop new approach to this task. It is based on a self-printed slanted-edge target. Then, we propose algorithms to improve the results using a self-printed slanted-edge target. Finally, we present experimental results for MTF measurement using self-printed targets and compare them to the results obtained with standard targets.

Boundary conditions for the influence of unfamiliar non-target primes in unconscious evaluative priming: The moderating role of attentional task sets.

PubMed

Kiefer, Markus; Sim, Eun-Jim; Wentura, Dirk

2015-09-01

Evaluative priming by masked emotional stimuli that are not consciously perceived has been taken as evidence that affective stimulus evaluation can also occur unconsciously. However, as masked priming effects were small and frequently observed only for familiar primes that there also presented as visible targets in an evaluative decision task, priming was thought to reflect primarily response activation based on acquired S-R associations and not evaluative semantic stimulus analysis. The present study therefore assessed across three experiments boundary conditions for the emergence of masked evaluative priming effects with unfamiliar primes in an evaluative decision task and investigated the role of the frequency of target repetition on priming with pictorial and verbal stimuli. While familiar primes elicited robust priming effects in all conditions, priming effects by unfamiliar primes were reliably obtained for low repetition (pictures) or unrepeated targets (words), but not for targets repeated at a high frequency. This suggests that unfamiliar masked stimuli only elicit evaluative priming effects when the task set associated with the visible target involves evaluative semantic analysis and is not based on S-R triggered responding as for high repetition targets. The present results therefore converge with the growing body of evidence demonstrating attentional control influences on unconscious processing. Copyright © 2015 Elsevier Inc. All rights reserved.

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

SuperTarget goes quantitative: update on drug–target interactions

PubMed Central

Hecker, Nikolai; Ahmed, Jessica; von Eichborn, Joachim; Dunkel, Mathias; Macha, Karel; Eckert, Andreas; Gilson, Michael K.; Bourne, Philip E.; Preissner, Robert

2012-01-01

There are at least two good reasons for the on-going interest in drug–target interactions: first, drug-effects can only be fully understood by considering a complex network of interactions to multiple targets (so-called off-target effects) including metabolic and signaling pathways; second, it is crucial to consider drug-target-pathway relations for the identification of novel targets for drug development. To address this on-going need, we have developed a web-based data warehouse named SuperTarget, which integrates drug-related information associated with medical indications, adverse drug effects, drug metabolism, pathways and Gene Ontology (GO) terms for target proteins. At present, the updated database contains >6000 target proteins, which are annotated with >330 000 relations to 196 000 compounds (including approved drugs); the vast majority of interactions include binding affinities and pointers to the respective literature sources. The user interface provides tools for drug screening and target similarity inclusion. A query interface enables the user to pose complex queries, for example, to find drugs that target a certain pathway, interacting drugs that are metabolized by the same cytochrome P450 or drugs that target proteins within a certain affinity range. SuperTarget is available at http://bioinformatics.charite.de/supertarget. PMID:22067455

Infrared small target tracking based on SOPC

NASA Astrophysics Data System (ADS)

Hu, Taotao; Fan, Xiang; Zhang, Yu-Jin; Cheng, Zheng-dong; Zhu, Bin

2011-01-01

The paper presents a low cost FPGA based solution for a real-time infrared small target tracking system. A specialized architecture is presented based on a soft RISC processor capable of running kernel based mean shift tracking algorithm. Mean shift tracking algorithm is realized in NIOS II soft-core with SOPC (System on a Programmable Chip) technology. Though mean shift algorithm is widely used for target tracking, the original mean shift algorithm can not be directly used for infrared small target tracking. As infrared small target only has intensity information, so an improved mean shift algorithm is presented in this paper. How to describe target will determine whether target can be tracked by mean shift algorithm. Because color target can be tracked well by mean shift algorithm, imitating color image expression, spatial component and temporal component are advanced to describe target, which forms pseudo-color image. In order to improve the processing speed parallel technology and pipeline technology are taken. Two RAM are taken to stored images separately by ping-pong technology. A FLASH is used to store mass temp data. The experimental results show that infrared small target is tracked stably in complicated background.

Alternating between pro- and antisaccades: switch-costs manifest via decoupling the spatial relations between stimulus and response.

PubMed

Heath, Matthew; Gillen, Caitlin; Samani, Ashna

2016-03-01

Antisaccades are a nonstandard task requiring a response mirror-symmetrical to the location of a target. The completion of an antisaccade has been shown to delay the reaction time (RT) of a subsequent prosaccade, whereas the converse switch elicits a null RT cost (i.e., the unidirectional prosaccade switch-cost). The present study sought to determine whether the prosaccade switch-cost arises from low-level interference specific to the sensory features of a target (i.e., modality-dependent) or manifests via the high-level demands of dissociating the spatial relations between stimulus and response (i.e., modality-independent). Participants alternated between pro- and antisaccades wherein the target associated with the response alternated between visual and auditory modalities. Thus, the present design involved task-switch (i.e., switching from a pro- to antisaccade and vice versa) and modality-switch (i.e., switching from a visual to auditory target and vice versa) trials as well as their task- and modality-repetition counterparts. RTs were longer for modality-switch than modality-repetition trials. Notably, however, modality-switch trials did not nullify or lessen the unidirectional prosaccade switch-cost; that is, the magnitude of the RT cost for task-switch prosaccades was equivalent across modality-switch and modality-repetition trials. Thus, competitive interference within a sensory modality does not contribute to the unidirectional prosaccade switch-cost. Instead, the modality-independent findings evince that dissociating the spatial relations between stimulus and response instantiates a high-level and inertially persistent nonstandard task-set that impedes the planning of a subsequent prosaccade.

TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol.

PubMed

Jordan, Rachel E; Adab, Peymané; Jowett, Sue; Marsh, Jen L; Riley, Richard D; Enocson, Alexandra; Miller, Martin R; Cooper, Brendan G; Turner, Alice M; Ayres, Jon G; Cheng, Kar Keung; Jolly, Kate; Stockley, Robert A; Greenfield, Sheila; Siebert, Stanley; Daley, Amanda; Fitzmaurice, David A

2014-10-04

Many people with clinically significant chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. There are a number of small studies which have examined possible methods of case finding through primary care, but no large RCTs that have adequately assessed the most cost-effective approach. In this study, using a cluster randomised controlled trial (RCT) in 56 general practices in the West Midlands, we plan to investigate the effectiveness and cost-effectiveness of a Targeted approach to case finding for COPD compared with routine practice. Using an individual patient RCT nested in the Targeted arm, we plan also to compare the effectiveness and cost-effectiveness of Active case finding using a postal questionnaire (with supplementary opportunistic questionnaires), and Opportunistic-only case finding during routine surgery consultations.All ever-smoking patients aged 40-79 years, without a current diagnosis of COPD and registered with participating practices will be eligible. Patients in the Targeted arm who report positive respiratory symptoms (chronic cough or phlegm, wheeze or dyspnoea) using a brief questionnaire will be invited for further spirometric assessment to ascertain whether they have COPD or not. Post-bronchodilator spirometry will be conducted to ATS standards using an Easy One spirometer by trained research assistants.The primary outcomes will be new cases of COPD and cost per new case identified, comparing targeted case finding with routine care, and two types of targeted case finding (active versus opportunistic). A multilevel logistic regression model will be used to model the probability of detecting a new case of COPD for each treatment arm, with clustering of patients (by practice and household) accounted for using a multi-level structure.A trial-based analysis will be undertaken using costs and outcomes collected during the trial. Secondary outcomes include the feasibility, efficiency, long-term cost-effectiveness, patient and

Targeted therapy according to next generation sequencing-based panel sequencing.

PubMed

Saito, Motonobu; Momma, Tomoyuki; Kono, Koji

2018-04-17

Targeted therapy against actionable gene mutations shows a significantly higher response rate as well as longer survival compared to conventional chemotherapy, and has become a standard therapy for many cancers. Recent progress in next-generation sequencing (NGS) has enabled to identify huge number of genetic aberrations. Based on sequencing results, patients recommend to undergo targeted therapy or immunotherapy. In cases where there are no available approved drugs for the genetic mutations detected in the patients, it is recommended to be facilitate the registration for the clinical trials. For that purpose, a NGS-based sequencing panel that can simultaneously target multiple genes in a single investigation has been used in daily clinical practice. To date, various types of sequencing panels have been developed to investigate genetic aberrations with tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics. Because sequencing panels are efficient and cost-effective, they are quickly being adopted outside the lab, in hospitals and clinics, in order to identify personal targeted therapy for individual cancer patients.

Perceptual Repetition Blindness Effects

NASA Technical Reports Server (NTRS)

Hochhaus, Larry; Johnston, James C.; Null, Cynthia H. (Technical Monitor)

1994-01-01

The phenomenon of repetition blindness (RB) may reveal a new limitation on human perceptual processing. Recently, however, researchers have attributed RB to post-perceptual processes such as memory retrieval and/or reporting biases. The standard rapid serial visual presentation (RSVP) paradigm used in most RB studies is, indeed, open to such objections. Here we investigate RB using a "single-frame" paradigm introduced by Johnston and Hale (1984) in which memory demands are minimal. Subjects made only a single judgement about whether one masked target word was the same or different than a post-target probe. Confidence ratings permitted use of signal detection methods to assess sensitivity and bias effects. In the critical condition for RB a precue of the post-target word was provided prior to the target stimulus (identity precue), so that the required judgement amounted to whether the target did or did not repeat the precue word. In control treatments, the precue was either an unrelated word or a dummy.

Attentional Control via Parallel Target-Templates in Dual-Target Search

PubMed Central

Barrett, Doug J. K.; Zobay, Oliver

2014-01-01

Simultaneous search for two targets has been shown to be slower and less accurate than independent searches for the same two targets. Recent research suggests this ‘dual-target cost’ may be attributable to a limit in the number of target-templates than can guide search at any one time. The current study investigated this possibility by comparing behavioural responses during single- and dual-target searches for targets defined by their orientation. The results revealed an increase in reaction times for dual- compared to single-target searches that was largely independent of the number of items in the display. Response accuracy also decreased on dual- compared to single-target searches: dual-target accuracy was higher than predicted by a model restricting search guidance to a single target-template and lower than predicted by a model simulating two independent single-target searches. These results are consistent with a parallel model of dual-target search in which attentional control is exerted by more than one target-template at a time. The requirement to maintain two target-templates simultaneously, however, appears to impose a reduction in the specificity of the memory representation that guides search for each target. PMID:24489793

The Variation of Work Productivity and Muscle Activities at Different Levels of Production Target

NASA Astrophysics Data System (ADS)

Nur, Nurhayati Mohd; Dawal, Siti Zawiah Md; Dahari, Mahidzal; Zuhairah Mahmud Zuhudi, Nurul

2017-10-01

This paper aims to investigate the variation of work productivity and muscle activities among workers performing industrial repetitive tasks at four different levels of production target. The work productivity and muscle activities data were recorded from twenty workers at four levels of production target corresponding to “participative (PS1)”, “normal (PS2)”, “high (PS3)” and “very high (PS4)”. The results showed that worker productivity was found to increase at higher production target and there was a significant change (p < 0.005) in work productivity across the four different production targets. The muscle activities were found to increase at higher production target and correspond to more discomfort and a higher rate of muscle fatigue. The results indicated that working with a higher production target results in higher worker productivity, but could lead to higher risk of WMSDs.

Trapped between two tails: trading off scientific uncertainties via climate targets

NASA Astrophysics Data System (ADS)

Lemoine, Derek; McJeon, Haewon C.

2013-09-01

Climate change policies must trade off uncertainties about future warming, about the social and ecological impacts of warming, and about the cost of reducing greenhouse gas emissions. We show that laxer carbon targets produce broader distributions for climate damages, skewed towards severe outcomes. However, if potential low-carbon technologies fill overlapping niches, then more stringent carbon targets produce broader distributions for the cost of reducing emissions, skewed towards high-cost outcomes. We use the technology-rich GCAM integrated assessment model to assess the robustness of 450 and 500 ppm carbon targets to each uncertain factor. The 500 ppm target provides net benefits across a broad range of futures. The 450 ppm target provides net benefits only when impacts are greater than conventionally assumed, when multiple technological breakthroughs lower the cost of abatement, or when evaluated with a low discount rate. Policy evaluations are more sensitive to uncertainty about abatement technology and impacts than to uncertainty about warming.

Trapped Between Two Tails: Trading Off Scientific Uncertainties via Climate Targets

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

Lemoine, Derek M.; McJeon, Haewon C.

2013-08-20

Climate change policies must trade off uncertainties about future warming, about the social and ecological impacts of warming, and about the cost of reducing greenhouse gas emissions. We show that laxer carbon targets produce broader distributions for climate damages, skewed towards severe outcomes. However, if potential low-carbon technologies fill overlapping niches, then more stringent carbon targets produce broader distributions for the cost of reducing emissions, skewed towards high-cost outcomes. We use the technology- rich GCAM integrated assessment model to assess the robustness of 450 ppm and 500 ppm carbon targets to each uncertain factor. The 500 ppm target provides netmore » benefits across a broad range of futures. The 450 ppm target provides net benefits only when impacts are greater than conventionally assumed, when multiple technological breakthroughs lower the cost of abatement, or when evaluated with a low discount rate. Policy evaluations are more sensitive to uncertainty about abatement technology and impacts than to uncertainty about warming.« less

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens.

PubMed

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Defelipe, Lucas; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo; Turjanski, Adrián G; Fernández Do Porto, Darío

2018-01-04

Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens

PubMed Central

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo

2018-01-01

Abstract Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. PMID:29106651

The Air Force Needs to Improve Cost-Effectiveness and Availability of the Joint Surveillance Target Attack Radar System (Redacted)

DTIC Science & Technology

2016-11-01

Target Attack Radar System Objective We determined whether the Air Force made cost-effective purchases on the performance-based logistics contract to... contract to Northrop Grumman Corporation to provide Total System Support Responsibility services to sustain 16 E-8C JSTARS aircraft. These services...customer support. The Total System Support Responsibility contract is valued at $7 billion, with a 6-year base period and 16 annual contract option

Performing target specific band reduction using artificial neural networks and assessment of its efficacy using various target detection algorithms

NASA Astrophysics Data System (ADS)

Yadav, Deepti; Arora, M. K.; Tiwari, K. C.; Ghosh, J. K.

2016-04-01

Hyperspectral imaging is a powerful tool in the field of remote sensing and has been used for many applications like mineral detection, detection of landmines, target detection etc. Major issues in target detection using HSI are spectral variability, noise, small size of the target, huge data dimensions, high computation cost, complex backgrounds etc. Many of the popular detection algorithms do not work for difficult targets like small, camouflaged etc. and may result in high false alarms. Thus, target/background discrimination is a key issue and therefore analyzing target's behaviour in realistic environments is crucial for the accurate interpretation of hyperspectral imagery. Use of standard libraries for studying target's spectral behaviour has limitation that targets are measured in different environmental conditions than application. This study uses the spectral data of the same target which is used during collection of the HSI image. This paper analyze spectrums of targets in a way that each target can be spectrally distinguished from a mixture of spectral data. Artificial neural network (ANN) has been used to identify the spectral range for reducing data and further its efficacy for improving target detection is verified. The results of ANN proposes discriminating band range for targets; these ranges were further used to perform target detection using four popular spectral matching target detection algorithm. Further, the results of algorithms were analyzed using ROC curves to evaluate the effectiveness of the ranges suggested by ANN over full spectrum for detection of desired targets. In addition, comparative assessment of algorithms is also performed using ROC.

Pharmacophore based design of some multi-targeted compounds targeted against pathways of diabetic complications.

PubMed

Chadha, Navriti; Silakari, Om

2017-09-01

Diabetic complications is a complex metabolic disorder developed primarily due to prolonged hyperglycemia in the body. The complexity of the disease state as well as the unifying pathophysiology discussed in the literature reports exhibited that the use of multi-targeted agents with multiple complementary biological activities may offer promising therapy for the intervention of the disease over the single-target drugs. In the present study, novel thiazolidine-2,4-dione analogues were designed as multi-targeted agents implicated against the molecular pathways involved in diabetic complications using knowledge based as well as in-silico approaches such as pharmacophore mapping, molecular docking etc. The hit molecules were duly synthesized and biochemical estimation of these molecules against aldose reductase (ALR2), protein kinase Cβ (PKCβ) and poly (ADP-ribose) polymerase 1 (PARP-1) led to identification of compound 2 that showed good potency against PARP-1 and ALR2 enzymes. These positive results support the progress of a low cost multi-targeted agent with putative roles in diabetic complications. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

LyP-1 ultrasonic microbubbles targeting to cancer cell as tumor bio-acoustics markers or drug carriers: targeting efficiency evaluation in, microfluidic channels.

PubMed

Li, Xiang; Jin, Qiaofeng; Chen, Tan; Zhang, Baoyue; Zheng, Rongqin; Wang, Zhanhui; Zheng, Hairong

2009-01-01

Using ultrasonic contrast microbubbles as acoustic biomarkers and drug carrier vehicles by conjugating tumor specific antibody to microbubbles has shown great potential in ultrasonic tumor molecular imaging or drug-delivery and therapy. Microbubble probe targeting efficiency is one of the major challenges. In this study, we developed a novel method to evaluate the targeting capability and efficiency of microbubbles to cells, and more specifically, microbubbles binding LyP-1 (a cyclic nonapeptide acid peptide) target to cancer cell within a microfluidic system. The micro cell sieves within the microfludic channels could trap the tumor cells and enhance the microbubble's interaction with the cell. Assisted with the controllable fluid shear stress, the microbubble's targeting to the cell and the corresponding affinity efficiency could be quantitatively evaluated under a florescent microscope. The system provides a useful low-cost high efficient in vitro platform for studying microbubble-cell interaction for ultrasonic tumor molecular imaging or drug-delivery and therapy.

Categorical information influences conscious perception: An interaction between object-substitution masking and repetition blindness.

PubMed

Goodhew, Stephanie C; Greenwood, John A; Edwards, Mark

2016-05-01

The visual system is constantly bombarded with dynamic input. In this context, the creation of enduring object representations presents a particular challenge. We used object-substitution masking (OSM) as a tool to probe these processes. In particular, we examined the effect of target-like stimulus repetitions on OSM. In visual crowding, the presentation of a physically identical stimulus to the target reduces crowding and improves target perception, whereas in spatial repetition blindness, the presentation of a stimulus that belongs to the same category (type) as the target impairs perception. Across two experiments, we found an interaction between spatial repetition blindness and OSM, such that repeating a same-type stimulus as the target increased masking magnitude relative to presentation of a different-type stimulus. These results are discussed in the context of the formation of object files. Moreover, the fact that the inducer only had to belong to the same "type" as the target in order to exacerbate masking, without necessarily being physically identical to the target, has important implications for our understanding of OSM per se. That is, our results show the target is processed to a categorical level in OSM despite effective masking and, strikingly, demonstrate that this category-level content directly influences whether or not the target is perceived, not just performance on another task (as in priming).

Right secondary somatosensory cortex-a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation.

PubMed

Lindholm, Pauliina; Lamusuo, Salla; Taiminen, Tero; Pesonen, Ullamari; Lahti, Ari; Virtanen, Arja; Forssell, Heli; Hietala, Jarmo; Hagelberg, Nora; Pertovaara, Antti; Parkkola, Riitta; Jääskeläinen, Satu

2015-07-01

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex has analgesic effect; however, the efficacy of other cortical targets and the mode of action remain unclear. We examined the effects of rTMS in neuropathic orofacial pain, and compared 2 cortical targets against placebo. Furthermore, as dopaminergic mechanisms modulate pain responses, we assessed the influence of the functional DRD2 gene polymorphism (957C>T) and the catechol-O-methyltransferase (COMT) Val158Met polymorphism on the analgesic effect of rTMS. Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized, placebo-controlled, crossover study. Navigated high-frequency rTMS was given to the sensorimotor (S1/M1) and the right secondary somatosensory (S2) cortices. All subjects were genotyped for the DRD2 957C>T and COMT Val158Met polymorphisms. Pain, mood, and quality of life were monitored throughout the study. The numerical rating scale pain scores were significantly lower after the S2 stimulation than after the S1/M1 (P = 0.0071) or the sham (P = 0.0187) stimulations. The Brief Pain Inventory scores were also lower 3 to 5 days after the S2 stimulation than those at pretreatment baseline (P = 0.0127 for the intensity of pain and P = 0.0074 for the interference of pain) or after the S1/M1 (P = 0.001 and P = 0.0001) and sham (P = 0.0491 and P = 0.0359) stimulations. No correlations were found between the genetic polymorphisms and the analgesic effect in the present small clinical sample. The right S2 cortex is a promising new target for the treatment of neuropathic orofacial pain with high-frequency rTMS.

Feature Integration and Task Switching: Diminished Switch Costs after Controlling for Stimulus, Response, and Cue Repetitions

PubMed Central

Schmidt, James R.; Liefooghe, Baptist

2016-01-01

This report presents data from two versions of the task switching procedure in which the separate influence of stimulus repetitions, response key repetitions, conceptual response repetitions, cue repetitions, task repetitions, and congruency are considered. Experiment 1 used a simple alternating runs procedure with parity judgments of digits and consonant/vowel decisions of letters as the two tasks. Results revealed sizable effects of stimulus and response repetitions, and controlling for these effects reduced the switch cost. Experiment 2 was a cued version of the task switch paradigm with parity and magnitude judgments of digits as the two tasks. Results again revealed large effects of stimulus and response repetitions, in addition to cue repetition effects. Controlling for these effects again reduced the switch cost. Congruency did not interact with our novel “unbiased” measure of switch costs. We discuss how the task switch paradigm might be thought of as a more complex version of the feature integration paradigm and propose an episodic learning account of the effect. We further consider to what extent appeals to higher-order control processes might be unnecessary and propose that controls for feature integration biases should be standard practice in task switching experiments. PMID:26964102

The relationship between target joints and direct resource use in severe haemophilia.

PubMed

O'Hara, Jamie; Walsh, Shaun; Camp, Charlotte; Mazza, Giuseppe; Carroll, Liz; Hoxer, Christina; Wilkinson, Lars

2018-01-16

Target joints are a common complication of severe haemophilia. While factor replacement therapy constitutes the majority of costs in haemophilia, the relationship between target joints and non drug-related direct costs (NDDCs) has not been studied. Data on haemophilia patients without inhibitors was drawn from the 'Cost of Haemophilia across Europe - a Socioeconomic Survey' (CHESS) study, a cost assessment in severe haemophilia A and B across five European countries (France, Germany, Italy, Spain, and the United Kingdom) in which 139 haemophilia specialists provided demographic and clinical information for 1285 adult patients. NDDCs were calculated using publicly available cost data, including 12-month ambulatory and secondary care activity: haematologist and other specialist consultant consultations, medical tests and examinations, bleed-related hospital admissions, and payments to professional care providers. A generalized linear model was developed to investigate the relationship between NDDCs and target joints (areas of chronic synovitis), adjusted for patient covariates. Five hundred and thirteen patients (42% of the sample) had no diagnosed target joints; a total of 1376 target joints (range 1-10) were recorded in the remaining 714 patients. Mean adjusted NDDCs for persons with no target joints were EUR 3134 (standard error (SE) EUR 158); for persons with one or more target joints, mean adjusted NDDCs were EUR 3913 (SE EUR 157; average mean effect EUR 779; p < 0.001). Our analysis suggests that the presence of one or more target joints has a significant impact on NDDCs for patients with severe haemophilia, ceteris paribus. Prevention and management of target joints should be an important consideration of managing haemophilia patients.

Schema generation in recurrent neural nets for intercepting a moving target.

PubMed

Fleischer, Andreas G

2010-06-01

The grasping of a moving object requires the development of a motor strategy to anticipate the trajectory of the target and to compute an optimal course of interception. During the performance of perception-action cycles, a preprogrammed prototypical movement trajectory, a motor schema, may highly reduce the control load. Subjects were asked to hit a target that was moving along a circular path by means of a cursor. Randomized initial target positions and velocities were detected in the periphery of the eyes, resulting in a saccade toward the target. Even when the target disappeared, the eyes followed the target's anticipated course. The Gestalt of the trajectories was dependent on target velocity. The prediction capability of the motor schema was investigated by varying the visibility range of cursor and target. Motor schemata were determined to be of limited precision, and therefore visual feedback was continuously required to intercept the moving target. To intercept a target, the motor schema caused the hand to aim ahead and to adapt to the target trajectory. The control of cursor velocity determined the point of interception. From a modeling point of view, a neural network was developed that allowed the implementation of a motor schema interacting with feedback control in an iterative manner. The neural net of the Wilson type consists of an excitation-diffusion layer allowing the generation of a moving bubble. This activation bubble runs down an eye-centered motor schema and causes a planar arm model to move toward the target. A bubble provides local integration and straightening of the trajectory during repetitive moves. The schema adapts to task demands by learning and serves as forward controller. On the basis of these model considerations the principal problem of embedding motor schemata in generalized control strategies is discussed.

High purity tungsten targets

NASA Technical Reports Server (NTRS)

1975-01-01

High purity tungsten, which is used for targets in X-ray tubes was considered for space processing. The demand for X-ray tubes was calculated using the growth rates for dental and medical X-ray machines. It is concluded that the cost benefits are uncertain.

Rapid target foraging with reach or gaze: The hand looks further ahead than the eye

PubMed Central

2017-01-01

Real-world tasks typically consist of a series of target-directed actions and often require choices about which targets to act on and in what order. Such choice behavior can be assessed from an optimal foraging perspective whereby target selection is shaped by a balance between rewards and costs. Here we evaluated such decision-making in a rapid movement foraging task. On a given trial, participants were presented with 15 targets of varying size and value and were instructed to harvest as much reward as possible by either moving a handle to the targets (hand task) or by briefly fixating them (eye task). The short trial duration enabled participants to harvest about half the targets, ensuring that total reward was due to choice behavior. We developed a probabilistic model to predict target-by-target harvesting choices that considered the rewards and movement-related costs (i.e., target distance and size) associated with the current target as well as future targets. In the hand task, in comparison to the eye task, target choice was more strongly influenced by movement-related costs and took into account a greater number of future targets, consistent with the greater costs associated with arm movement. In both tasks, participants exhibited near-optimal behaviour and in a constrained version of the hand task in which choices could only be based on target positions, participants consistently chose among the shortest movement paths. Our results demonstrate that people can rapidly and effectively integrate values and movement-related costs associated with current and future targets when sequentially harvesting targets. PMID:28683138

High-intensity laser-accelerated ion beam produced from cryogenic micro-jet target

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

Gauthier, M., E-mail: maxence.gauthier@stanford.edu; Kim, J. B.; Curry, C. B.

2016-11-15

We report on the successful operation of a newly developed cryogenic jet target at high intensity laser-irradiation. Using the frequency-doubled Titan short pulse laser system at Jupiter Laser Facility, Lawrence Livermore National Laboratory, we demonstrate the generation of a pure proton beam a with maximum energy of 2 MeV. Furthermore, we record a quasi-monoenergetic peak at 1.1 MeV in the proton spectrum emitted in the laser forward direction suggesting an alternative acceleration mechanism. Using a solid-density mixed hydrogen-deuterium target, we are also able to produce pure proton-deuteron ion beams. With its high purity, limited size, near-critical density, and high-repetition ratemore » capability, this target is promising for future applications.« less

48 CFR 16.403-1 - Fixed-price incentive (firm target) contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (firm target) contracts. 16.403-1 Section 16.403-1 Federal Acquisition Regulations System FEDERAL... Fixed-price incentive (firm target) contracts. (a) Description. A fixed-price incentive (firm target) contract specifies a target cost, a target profit, a price ceiling (but not a profit ceiling or floor), and...

48 CFR 16.403-1 - Fixed-price incentive (firm target) contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (firm target) contracts. 16.403-1 Section 16.403-1 Federal Acquisition Regulations System FEDERAL... Fixed-price incentive (firm target) contracts. (a) Description. A fixed-price incentive (firm target) contract specifies a target cost, a target profit, a price ceiling (but not a profit ceiling or floor), and...

Target assessment for antiparasitic drug discovery

PubMed Central

Frearson, Julie A.; Wyatt, Paul G.; Gilbert, Ian H.; Fairlamb, Alan H.

2010-01-01

Drug discovery is a high-risk, expensive and lengthy process taking at least 12 years and costing upwards of US$500 million per drug to reach the clinic. For neglected diseases, the drug discovery process is driven by medical need and guided by pre-defined target product profiles. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success. Here we describe criteria used in our drug discovery unit for target assessment and introduce the ‘traffic light’ system as a prioritisation and management tool. We hope this brief review will stimulate basic scientists to acquire additional information necessary for drug discovery. PMID:17962072

A haemophilia disease management programme targeting cost and utilization of specialty pharmaceuticals.

PubMed

Duncan, N; Roberson, C; Lail, A; Donfield, S; Shapiro, A

2014-07-01

The high cost of clotting factor concentrate (CFC) used to treat haemophilia and von Willebrand disease (VWD) attracts health plans' attention for cost management strategies such as disease management programmes (DMPs). In 2004, Indiana's high risk insurance health plan, the Indiana Comprehensive Health Insurance Association, in partnership with the Indiana Hemophilia and Thrombosis Center developed and implemented a DMP for beneficiaries with bleeding disorders. This report evaluates the effectiveness of the DMP 5 years post implementation, with specific emphasis on the cost of CFC and other medical expenditures by severity of disease. A pre/post analysis was used. The main evaluation measures were total cost, total outpatient CFC IU dispensed and adjusted total outpatient CFC cost. Summary statistics and mean and median plots were calculated. Overall, 1000 non-parametric bootstrap replicates were created and percentile confidence limits for 95% confidence intervals (CI) are reported. Mean emergency department (ED) visits and mean and median duration of hospitalizations are also reported. The DMP was associated with a significant decrease in mean annualized total cost including decreased CFC utilization and cost in most years in the overall group, and specifically in patients with severe haemophilia. Patients with mild and moderate haemophilia contributed little to overall programme expenditures. This specialty health care provider-administered DMP exemplifies the success of targeted interventions developed and implemented through a health care facility expert in the disease state to curb the cost of specialty pharmaceuticals in conditions when their expenditures represent a significant portion of total annual costs of care. © 2014 John Wiley & Sons Ltd.

Open Targets: a platform for therapeutic target identification and validation

PubMed Central

Koscielny, Gautier; An, Peter; Carvalho-Silva, Denise; Cham, Jennifer A.; Fumis, Luca; Gasparyan, Rippa; Hasan, Samiul; Karamanis, Nikiforos; Maguire, Michael; Papa, Eliseo; Pierleoni, Andrea; Pignatelli, Miguel; Platt, Theo; Rowland, Francis; Wankar, Priyanka; Bento, A. Patrícia; Burdett, Tony; Fabregat, Antonio; Forbes, Simon; Gaulton, Anna; Gonzalez, Cristina Yenyxe; Hermjakob, Henning; Hersey, Anne; Jupe, Steven; Kafkas, Şenay; Keays, Maria; Leroy, Catherine; Lopez, Francisco-Javier; Magarinos, Maria Paula; Malone, James; McEntyre, Johanna; Munoz-Pomer Fuentes, Alfonso; O'Donovan, Claire; Papatheodorou, Irene; Parkinson, Helen; Palka, Barbara; Paschall, Justin; Petryszak, Robert; Pratanwanich, Naruemon; Sarntivijal, Sirarat; Saunders, Gary; Sidiropoulos, Konstantinos; Smith, Thomas; Sondka, Zbyslaw; Stegle, Oliver; Tang, Y. Amy; Turner, Edward; Vaughan, Brendan; Vrousgou, Olga; Watkins, Xavier; Martin, Maria-Jesus; Sanseau, Philippe; Vamathevan, Jessica; Birney, Ewan; Barrett, Jeffrey; Dunham, Ian

2017-01-01

We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org. PMID:27899665

Use of consumer survey data to target cessation messages to smokers through mass media.

PubMed

Nelson, David E; Gallogly, Meg; Pederson, Linda L; Barry, Matthew; McGoldrick, Daniel; Maibach, Edward W

2008-03-01

We identified the mass media channels that reach the most cigarette smokers in an attempt to more effectively target smoking cessation messages. Reach estimates and index scores for smokers were taken from 2002-2003 ConsumerStyles and HealthStyles national surveys of adults (N=11660) to estimate overall and demographic-specific exposure measures for television, radio, newspapers, and magazines. Smokers viewed more television, listened to more radio, and read fewer magazines and newspapers than did nonsmokers. Nearly one third of smokers were regular daytime or late-night television viewers. Selected cable television networks (USA, Lifetime, and Discovery Channel) and selected radio genres, such as classic rock and country, had high reach and were cost-efficient channels for targeting smokers. Certain mass media channels offer efficient opportunities to target smoking cessation messages so they reach relatively large audiences of smokers at relatively low cost. The approach used in this study can be applied to other types of health risk factors to improve health communication planning and increase efficiency of program media expenditures.

The role of multi-target policy instruments in agri-environmental policy mixes.

PubMed

Schader, Christian; Lampkin, Nicholas; Muller, Adrian; Stolze, Matthias

2014-12-01

The Tinbergen Rule has been used to criticise multi-target policy instruments for being inefficient. The aim of this paper is to clarify the role of multi-target policy instruments using the case of agri-environmental policy. Employing an analytical linear optimisation model, this paper demonstrates that there is no general contradiction between multi-target policy instruments and the Tinbergen Rule, if multi-target policy instruments are embedded in a policy-mix with a sufficient number of targeted instruments. We show that the relation between cost-effectiveness of the instruments, related to all policy targets, is the key determinant for an economically sound choice of policy instruments. If economies of scope with respect to achieving policy targets are realised, a higher cost-effectiveness of multi-target policy instruments can be achieved. Using the example of organic farming support policy, we discuss several reasons why economies of scope could be realised by multi-target agri-environmental policy instruments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Targeted human papillomavirus vaccination of men who have sex with men in the USA: a cost-effectiveness modelling analysis.

PubMed

Kim, Jane J

2010-12-01

A vaccine targeting human papillomavirus (HPV) types 16 and 18, which are associated with 80% of anal cancers, is efficacious in men. High-risk populations such as men who have sex with men (MSM) might especially benefit from vaccination. I aimed to estimate the cost-effectiveness of HPV vaccination of MSM in the USA. I constructed decision-analytic models to estimate the direct health and economic outcomes of HPV vaccination (against types 6, 11, 16, and 18) for prevention of HPV-related anal cancer and genital warts. The model parameters that were varied were age at vaccination (12 years, 20 years, and 26 years), previous exposure to vaccine-targeted HPV types, and prevalence of HIV-1. I used the models to conduct sensitivity analyses, including duration of vaccine protection, vaccine cost, and burden of anal cancer and genital warts. In a scenario of HPV vaccination of MSM at 12 years of age without previous exposure to HPV, compared with no vaccination, vaccination cost US$15,290 per quality-adjusted life-year gained. In scenarios where MSM are vaccinated at 20 years or 26 years of age, after exposure to HPV infections, the cost-effectiveness ratios worsened, but were less than $50,000 per quality-adjusted life-year under most scenarios. For example, HPV vaccination of MSM at 26 years cost $37,830 per quality-adjusted life-year when previous exposure to all vaccine-targeted HPV types was assumed to be 50%. Outcomes were most sensitive to variations in anal cancer incidence, duration of vaccine protection, and HIV prevalence in MSM. HPV vaccination of MSM is likely to be a cost-effective intervention for the prevention of genital warts and anal cancer. US National Cancer Institute. Copyright © 2010 Elsevier Ltd. All rights reserved.

Treat-to-target trials in diabetes.

PubMed

Wangnoo, Subhash K; Sethi, Bipin; Sahay, Rakesh K; John, Mathew; Ghosal, Samit; Sharma, Surendra K

2014-03-01

Treat-to-target is a therapeutic concept that considers well defined and specific physiologic targets as aims in controlling the pathophysiology of the disease. It has been widely used in diseases that pathophysiology includes, chronic metabolic and physiological disturbances, namely rheumatic conditions, vascular medicine and diabetes. In diabetes, the availability of "gold-standard" quantitative measures like fasting plasma glucose and glycated hemoglobin make the application of treat-to-target trials especially pertinent. Treatment modalities which have used single therapeutic agents or combinations or in combination with a variety of titration algorithms and implementation protocols have broadened our understanding of diabetes management with specific reference to insulin initiation and maintenance. Treat-to-target trials have been used to investigate a wide variety of questions including efficacy, safety, effect of treatment on comorbidities and patient satisfaction, ideal mechanisms to implement insulin initiation etc. A more generalized acceptance and implementation of treat-to-target trials may finally revolutionize diabetes management by combining aspects of individual care with standard treatment protocols.

Interpersonal and systemic aspects of emotional abuse at work: the target's perspective.

PubMed

Keashly, L

2001-06-01

The most frequent form of workplace aggression is not physical, it is emotional and psychological in nature. Known by many names, emotional abuse at work is rapidly becoming recognized as pervasive and costly both in individual and organizational terms. Most of the research to date on emotional abuse at work has utilized survey and other quantitative methodologies in an effort to document the presence, prevalence, and impact of these behaviors. However, these methodologies are based on researchers' definitions and theories of what constitutes emotional abuse rather than on the meaning given to these experiences by the targets of these behaviors. A thorough understanding of this phenomenon requires a scholarly appreciation of the target's experience. Taking "feeling abused" as the criterion variable, this study examined target's experiences based on interviews with people who self-identifed as having experienced difficulties with a boss, coworker, or subordinate. The interpersonal aspects of emotional abuse focused on the nature of behaviors exhibited and the respondents' labeling of their experience. Consistent with elements of researchers' definitions, behaviors were defined as abusive when they were repetitive, resulted in injury or harm to target, and were experienced as a lack of recognition of the individual's integrity. Judgments of violation of standards of conduct and unsolicited nature of the behaviors were also related to respondents' experiences. Relative power differential was also an important element. However, contrary to researchers' definitions, actor intent was not central in defining the experience as abusive. The systemic aspect of emotional abuse was illustrated in the nature of organizational responding to concerns raised by respondents. These responses were of critical importance in respondents' labeling of their experiences as abusive. The focus on the meaning of the behaviors for the respondents provides an enriched picture of key

A cost-effectiveness analysis of online, radio and print tobacco control advertisements targeting 25-39 year-old males.

PubMed

Clayforth, Cassandra; Pettigrew, Simone; Mooney, Katie; Lansdorp-Vogelaar, Iris; Rosenberg, Michael; Slevin, Terry

2014-06-01

To assess the relative cost-effectiveness of various non-television advertising media in encouraging 25-39 year-old male smokers to respond to a cessation-related call to action. Information about how new electronic media compare in effectiveness is important to inform the implementation of future tobacco control media campaigns. Two testimonial advertisements featuring members of the target group were developed for radio, press and online media. Multiple waves of media activity were scheduled over a period of seven weeks, including an initial integrated period that included all three media and subsequent single media phases that were interspersed with a week of no media activity. The resulting Quit website hits, Quitline telephone calls, and registrations to online and telephone counselling services were compared to advertising costs to determine the relative cost-effectiveness of each media in isolation and the integrated approach. The online-only campaign phase was substantially more cost-effective than the other phases, including the integrated approach. This finding is contrary to the current assumption that the use of a consistent message across multiple media simultaneously is the most cost-effective way of reaching and affecting target audiences. Online advertising may be a highly cost-effective channel for low-budget tobacco control media campaigns. © 2014 The Authors. ANZJPH © 2014 Public Health Association of Australia.

A review of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer.

PubMed

Diaby, Vakaramoko; Tawk, Rima; Sanogo, Vassiki; Xiao, Hong; Montero, Alberto J

2015-05-01

Breast cancer is a global health concern. In fact, breast cancer is the primary cause of death among women worldwide and constitutes the most expensive malignancy to treat. As health care resources are finite, decisions regarding the adoption and coverage of breast cancer treatments are increasingly being based on "value for money," i.e., cost-effectiveness. As the evidence about the cost-effectiveness of breast cancer treatments is abundant, therefore difficult to navigate, systematic reviews of published systematic reviews offer the advantage of bringing together the results of separate systematic reviews in a single report. As a consequence, this paper presents an overview of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer to inform policy and reimbursement decision-making. A systematic review was conducted of published systematic reviews documenting cost-effectiveness analyses of breast cancer treatments from 2000 to 2014. Systematic reviews identified through a literature search of health and economic databases were independently assessed against inclusion and exclusion criteria. Systematic reviews of original evaluations were included only if they targeted breast cancer patients and specific breast cancer treatments (hormone therapy, chemotherapy, and targeted therapy only), documented incremental cost-effectiveness ratios, and were reported in the English language. The search strategy used a combination of these key words: "breast cancer," "systematic review/meta-analysis," and "cost-effectiveness/economics." Data were extracted using predefined extraction forms and qualitatively appraised using the assessment of multiple systematic reviews (AMSTAR) tool. The literature search resulted in 511 bibliographic records, of which ten met our inclusion criteria. Five reviews were conducted in the early-stage breast cancer setting and five reviews in the metastatic setting. In early-stage breast

A review of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer

PubMed Central

Diaby, Vakaramoko; Xiao, Hong; Montero, Alberto J.

2015-01-01

Breast cancer is a global health concern. In fact, breast cancer is the primary cause of death among women worldwide and constitutes the most expensive malignancy to treat. As health care resources are finite, decisions regarding the adoption and coverage of breast cancer treatments are increasingly being based on “value for money,” i.e., cost-effectiveness. As the evidence about the cost-effectiveness of breast cancer treatments is abundant, therefore difficult to navigate, systematic reviews of published systematic reviews offer the advantage of bringing together the results of separate systematic reviews in a single report. As a consequence, this paper presents an overview of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer to inform policy and reimbursement decision-making. A systematic review was conducted of published systematic reviews documenting cost-effectiveness analyses of breast cancer treatments from 2000 to 2014. Systematic reviews identified through a literature search of health and economic databases were independently assessed against inclusion and exclusion criteria. Systematic reviews of original evaluations were included only if they targeted breast cancer patients and specific breast cancer treatments (hormone therapy, chemotherapy, and targeted therapy only), documented incremental cost-effectiveness ratios, and were reported in the English language. The search strategy used a combination of these key words: “breast cancer,” “systematic review/meta-analysis,” and “cost-effectiveness/economics.” Data were extracted using predefined extraction forms and qualitatively appraised using the assessment of multiple systematic reviews (AMSTAR) tool. The literature search resulted in 511 bibliographic records, of which ten met our inclusion criteria. Five reviews were conducted in the early-stage breast cancer setting and five reviews in the metastatic setting. In

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

PubMed Central

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

2014-01-01

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

Personal Vehicles Evaluated against Climate Change Mitigation Targets.

PubMed

Miotti, Marco; Supran, Geoffrey J; Kim, Ella J; Trancik, Jessika E

2016-10-18

Meeting global climate change mitigation goals will likely require that transportation-related greenhouse gas emissions begin to decline within the next two decades and then continue to fall. A variety of vehicle technologies and fuels are commercially available to consumers today that can reduce the emissions of the transportation sector. Yet what are the best options, and do any suffice to meet climate policy targets? Here, we examine the costs and carbon intensities of 125 light-duty vehicle models on the U.S. market today and evaluate these models against U.S. emission-reduction targets for 2030, 2040, and 2050 that are compatible with the goal of limiting mean global temperature rise to 2 °C above preindustrial levels. Our results show that consumers are not required to pay more for a low-carbon-emitting vehicle. Across the diverse set of vehicle models and powertrain technologies examined, a clean vehicle is usually a low-cost vehicle. Although the average carbon intensity of vehicles sold in 2014 exceeds the climate target for 2030 by more than 50%, we find that most hybrid and battery electric vehicles available today meet this target. By 2050, only electric vehicles supplied with almost completely carbon-free electric power are expected to meet climate-policy targets.

Attention to baseline: does orienting visuospatial attention really facilitate target detection?

PubMed

Albares, Marion; Criaud, Marion; Wardak, Claire; Nguyen, Song Chi Trung; Ben Hamed, Suliann; Boulinguez, Philippe

2011-08-01

Standard protocols testing the orientation of visuospatial attention usually present spatial cues before targets and compare valid-cue trials with invalid-cue trials. The valid/invalid contrast results in a relative behavioral or physiological difference that is generally interpreted as a benefit of attention orientation. However, growing evidence suggests that inhibitory control of response is closely involved in this kind of protocol that requires the subjects to withhold automatic responses to cues, probably biasing behavioral and physiological baselines. Here, we used two experiments to disentangle the inhibitory control of automatic responses from orienting of visuospatial attention in a saccadic reaction time task in humans, a variant of the classical cue-target detection task and a sustained visuospatial attentional task. Surprisingly, when referring to a simple target detection task in which there is no need to refrain from reacting to avoid inappropriate responses, we found no consistent evidence of facilitation of target detection at the attended location. Instead, we observed a cost at the unattended location. Departing from the classical view, our results suggest that reaction time measures of visuospatial attention probably relie on the attenuation of elementary processes involved in visual target detection and saccade initiation away from the attended location rather than on facilitation at the attended location. This highlights the need to use proper control conditions in experimental designs to disambiguate relative from absolute cueing benefits on target detection reaction times, both in psychophysical and neurophysiological studies.

Drug-targeting methodologies with applications: A review

PubMed Central

Kleinstreuer, Clement; Feng, Yu; Childress, Emily

2014-01-01

Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system. PMID:25516850

Cost-effectiveness of precision medicine in the fourth-line treatment of metastatic lung adenocarcinoma: An early decision analytic model of multiplex targeted sequencing.

PubMed

Doble, Brett; John, Thomas; Thomas, David; Fellowes, Andrew; Fox, Stephen; Lorgelly, Paula

2017-05-01

To identify parameters that drive the cost-effectiveness of precision medicine by comparing the use of multiplex targeted sequencing (MTS) to select targeted therapy based on tumour genomic profiles to either no further testing with chemotherapy or no further testing with best supportive care in the fourth-line treatment of metastatic lung adenocarcinoma. A combined decision tree and Markov model to compare costs, life-years, and quality-adjusted life-years over a ten-year time horizon from an Australian healthcare payer perspective. Data sources included the published literature and a population-based molecular cohort study (Cancer 2015). Uncertainty was assessed using deterministic sensitivity analyses and quantified by estimating expected value of perfect/partial perfect information. Uncertainty due to technological/scientific advancement was assessed through a number of plausible future scenario analyses. Point estimate incremental cost-effective ratios indicate that MTS is not cost-effective for selecting fourth-line treatment of metastatic lung adenocarcinoma. Lower mortality rates during testing and for true positive patients, lower health state utility values for progressive disease, and targeted therapy resulting in reductions in inpatient visits, however, all resulted in more favourable cost-effectiveness estimates for MTS. The expected value to decision makers of removing all current decision uncertainty was estimated to be between AUD 5,962,843 and AUD 13,196,451, indicating that additional research to reduce uncertainty may be a worthwhile investment. Plausible future scenarios analyses revealed limited improvements in cost-effectiveness under scenarios of improved test performance, decreased costs of testing/interpretation, and no biopsy costs/adverse events. Reductions in off-label targeted therapy costs, when considered together with the other scenarios did, however, indicate more favourable cost-effectiveness of MTS. As more clinical evidence is

Optoelectronic System Measures Distances to Multiple Targets

NASA Technical Reports Server (NTRS)

Liebe, Carl Christian; Abramovici, Alexander; Bartman, Randall; Chapsky, Jacob; Schmalz, John; Coste, Keith; Litty, Edward; Lam, Raymond; Jerebets, Sergei

2007-01-01

An optoelectronic metrology apparatus now at the laboratory-prototype stage of development is intended to repeatedly determine distances of as much as several hundred meters, at submillimeter accuracy, to multiple targets in rapid succession. The underlying concept of optoelectronic apparatuses that can measure distances to targets is not new; such apparatuses are commonly used in general surveying and machining. However, until now such apparatuses have been, variously, constrained to (1) a single target or (2) multiple targets with a low update rate and a requirement for some a priori knowledge of target geometry. When fully developed, the present apparatus would enable measurement of distances to more than 50 targets at an update rate greater than 10 Hz, without a requirement for a priori knowledge of target geometry. The apparatus (see figure) includes a laser ranging unit (LRU) that includes an electronic camera (photo receiver), the field of view of which contains all relevant targets. Each target, mounted at a fiducial position on an object of interest, consists of a small lens at the output end of an optical fiber that extends from the object of interest back to the LRU. For each target and its optical fiber, there is a dedicated laser that is used to illuminate the target via the optical fiber. The targets are illuminated, one at a time, with laser light that is modulated at a frequency of 10.01 MHz. The modulated laser light is emitted by the target, from where it returns to the camera (photodetector), where it is detected. Both the outgoing and incoming 10.01-MHz laser signals are mixed with a 10-MHz local-oscillator to obtain beat notes at 10 kHz, and the difference between the phases of the beat notes is measured by a phase meter. This phase difference serves as a measure of the total length of the path traveled by light going out through the optical fiber and returning to the camera (photodetector) through free space. Because the portion of the path

A Deterministic Approach to Active Debris Removal Target Selection

NASA Astrophysics Data System (ADS)

Lidtke, A.; Lewis, H.; Armellin, R.

2014-09-01

Many decisions, with widespread economic, political and legal consequences, are being considered based on space debris simulations that show that Active Debris Removal (ADR) may be necessary as the concerns about the sustainability of spaceflight are increasing. The debris environment predictions are based on low-accuracy ephemerides and propagators. This raises doubts about the accuracy of those prognoses themselves but also the potential ADR target-lists that are produced. Target selection is considered highly important as removal of many objects will increase the overall mission cost. Selecting the most-likely candidates as soon as possible would be desirable as it would enable accurate mission design and allow thorough evaluation of in-orbit validations, which are likely to occur in the near-future, before any large investments are made and implementations realized. One of the primary factors that should be used in ADR target selection is the accumulated collision probability of every object. A conjunction detection algorithm, based on the smart sieve method, has been developed. Another algorithm is then applied to the found conjunctions to compute the maximum and true probabilities of collisions taking place. The entire framework has been verified against the Conjunction Analysis Tools in AGIs Systems Toolkit and relative probability error smaller than 1.5% has been achieved in the final maximum collision probability. Two target-lists are produced based on the ranking of the objects according to the probability they will take part in any collision over the simulated time window. These probabilities are computed using the maximum probability approach, that is time-invariant, and estimates of the true collision probability that were computed with covariance information. The top-priority targets are compared, and the impacts of the data accuracy and its decay are highlighted. General conclusions regarding the importance of Space Surveillance and Tracking for the

Targeted human papillomavirus vaccination for young men who have sex with men in Australia yields significant population benefits and is cost-effective.

PubMed

Zhang, Lei; Regan, David G; Ong, Jason J; Gambhir, Manoj; Chow, Eric P F; Zou, Huachun; Law, Matthew; Hocking, Jane; Fairley, Christopher K

2017-09-05

We investigated the effectiveness and cost-effectiveness of a targeted human papillomavirus (HPV) vaccination program for young (15-26) men who have sex with men (MSM). We developed a compartmental model to project HPV epidemic trajectories in MSM for three vaccination scenarios: a boys program, a targeted program for young MSM only and the combination of the two over 2017-2036. We assessed the gain in quality-adjusted-life-years (QALY) in 190,000 Australian MSM. A targeted program for young MSM only that achieved 20% coverage per year, without a boys program, will prevent 49,283 (31,253-71,500) cases of anogenital warts, 191 (88-319) person-years living with anal cancer through 2017-2036 but will only stablise anal cancer incidence. In contrast, a boys program will prevent 82,056 (52,100-117,164) cases of anogenital warts, 447 (204-725) person-years living with anal cancers through 2017-2036 and see major declines in anal cancer. This can reduce 90% low- and high-risk HPV in young MSM by 2024 and 2032, respectively, but will require vaccinating ≥84% of boys. Adding a targeted program for young MSM to an existing boys program would prevent an additional 14,912 (8479-21,803) anogenital wart and 91 (42-152) person-years living with anal cancer. In combination with a boys' program, a catch-up program for young MSM will cost an additional $AUD 6788 ($4628-11,989) per QALY gained, but delaying its implementation reduced its cost-effectiveness. A boys program that achieved coverage of about 84% will result in a 90% reduction in HPV. A targeted program for young MSM is cost-effective if timely implemented. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sources of Phoneme Errors in Repetition: Perseverative, Neologistic, and Lesion Patterns in Jargon Aphasia

PubMed Central

Pilkington, Emma; Keidel, James; Kendrick, Luke T.; Saddy, James D.; Sage, Karen; Robson, Holly

2017-01-01

This study examined patterns of neologistic and perseverative errors during word repetition in fluent Jargon aphasia. The principal hypotheses accounting for Jargon production indicate that poor activation of a target stimulus leads to weakly activated target phoneme segments, which are outcompeted at the phonological encoding level. Voxel-lesion symptom mapping studies of word repetition errors suggest a breakdown in the translation from auditory-phonological analysis to motor activation. Behavioral analyses of repetition data were used to analyse the target relatedness (Phonological Overlap Index: POI) of neologistic errors and patterns of perseveration in 25 individuals with Jargon aphasia. Lesion-symptom analyses explored the relationship between neurological damage and jargon repetition in a group of 38 aphasia participants. Behavioral results showed that neologisms produced by 23 jargon individuals contained greater degrees of target lexico-phonological information than predicted by chance and that neologistic and perseverative production were closely associated. A significant relationship between jargon production and lesions to temporoparietal regions was identified. Region of interest regression analyses suggested that damage to the posterior superior temporal gyrus and superior temporal sulcus in combination was best predictive of a Jargon aphasia profile. Taken together, these results suggest that poor phonological encoding, secondary to impairment in sensory-motor integration, alongside impairments in self-monitoring result in jargon repetition. Insights for clinical management and future directions are discussed. PMID:28522967

Independent and additive repetition priming of motion direction and color in visual search.

PubMed

Kristjánsson, Arni

2009-03-01

Priming of visual search for Gabor patch stimuli, varying in color and local drift direction, was investigated. The task relevance of each feature varied between the different experimental conditions compared. When the target defining dimension was color, a large effect of color repetition was seen as well as a smaller effect of the repetition of motion direction. The opposite priming pattern was seen when motion direction defined the target--the effect of motion direction repetition was this time larger than for color repetition. Finally, when neither was task relevant, and the target defining dimension was the spatial frequency of the Gabor patch, priming was seen for repetition of both color and motion direction, but the effects were smaller than in the previous two conditions. These results show that features do not necessarily have to be task relevant for priming to occur. There is little interaction between priming following repetition of color and motion, these two features show independent and additive priming effects, most likely reflecting that the two features are processed at separate processing sites in the nervous system, consistent with previous findings from neuropsychology & neurophysiology. The implications of the findings for theoretical accounts of priming in visual search are discussed.

Repetition priming across distinct contexts: effects of lexical status, word frequency, and retrieval test.

PubMed

Coane, Jennifer H; Balota, David A

2010-12-01

Repetition priming, the facilitation observed when a target is preceded by an identity prime, is a robust phenomenon that occurs across a variety of conditions. Oliphant (1983), however, failed to observe repetition priming for targets embedded in the instructions to an experiment in a subsequent lexical decision task. In the present experiments, we examined the roles of priming context (list or instructions), target lexicality, and target frequency in both lexical decision and episodic recognition performance. Initial encoding context did not modulate priming in lexical decision or recognition memory for low-frequency targets or nonwords, whereas context strongly modulated episodic recognition for high-frequency targets. The results indicate that priming across contexts is sensitive to the distinctiveness of the trace and the reliance on episodic retrieval mechanisms. These results also shed light on the influence of event boundaries, such that priming occurs across different events for relatively distinct (low-frequency) items.

Initial observations of cavitation-induced erosion of liquid metal spallation target vessels at the Spallation Neutron Source

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

McClintock, David A; Riemer, Bernie; Ferguson, Phillip D

2012-01-01

During operation of the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory the mechanical properties of the AISI 316L target module are altered by high-energy neutron and proton radiation. The interior surfaces of the target vessel are also damaged by cavitation-induced erosion, which results from repetitive rapid heating of the liquid mercury by high-energy proton beam pulses. Until recently no observations of cavitation-induced erosion were possible for conditions prototypical to the SNS. Post irradiation examination (PIE) of the first and second operational SNS targets was performed to gain insight into the radiation-induced changes in mechanical properties of the 316Lmore » target material and the extent of cavitation-induced erosion to the target vessel inner surfaces. Observations of cavitation-induced erosion of the first and second operational SNS target modules are presented here, including images of the target vessel interiors and specimens removed from the target beam-entrance regions.« less

Identifying Drug-Target Interactions with Decision Templates.

PubMed

Yan, Xiao-Ying; Zhang, Shao-Wu

2018-01-01

During the development process of new drugs, identification of the drug-target interactions wins primary concerns. However, the chemical or biological experiments bear the limitation in coverage as well as the huge cost of both time and money. Based on drug similarity and target similarity, chemogenomic methods can be able to predict potential drug-target interactions (DTIs) on a large scale and have no luxurious need about target structures or ligand entries. In order to reflect the cases that the drugs having variant structures interact with common targets and the targets having dissimilar sequences interact with same drugs. In addition, though several other similarity metrics have been developed to predict DTIs, the combination of multiple similarity metrics (especially heterogeneous similarities) is too naïve to sufficiently explore the multiple similarities. In this paper, based on Gene Ontology and pathway annotation, we introduce two novel target similarity metrics to address above issues. More importantly, we propose a more effective strategy via decision template to integrate multiple classifiers designed with multiple similarity metrics. In the scenarios that predict existing targets for new drugs and predict approved drugs for new protein targets, the results on the DTI benchmark datasets show that our target similarity metrics are able to enhance the predictive accuracies in two scenarios. And the elaborate fusion strategy of multiple classifiers has better predictive power than the naïve combination of multiple similarity metrics. Compared with other two state-of-the-art approaches on the four popular benchmark datasets of binary drug-target interactions, our method achieves the best results in terms of AUC and AUPR for predicting available targets for new drugs (S2), and predicting approved drugs for new protein targets (S3).These results demonstrate that our method can effectively predict the drug-target interactions. The software package can

Study of target and non-target interplay in spatial attention task.

PubMed

Sweeti; Joshi, Deepak; Panigrahi, B K; Anand, Sneh; Santhosh, Jayasree

2018-02-01

Selective visual attention is the ability to selectively pay attention to the targets while inhibiting the distractors. This paper aims to study the targets and non-targets interplay in spatial attention task while subject attends to the target object present in one visual hemifield and ignores the distractor present in another visual hemifield. This paper performs the averaged evoked response potential (ERP) analysis and time-frequency analysis. ERP analysis agrees to the left hemisphere superiority over late potentials for the targets present in right visual hemifield. Time-frequency analysis performed suggests two parameters i.e. event-related spectral perturbation (ERSP) and inter-trial coherence (ITC). These parameters show the same properties for the target present in either of the visual hemifields but show the difference while comparing the activity corresponding to the targets and non-targets. In this way, this study helps to visualise the difference between targets present in the left and right visual hemifields and, also the targets and non-targets present in the left and right visual hemifields. These results could be utilised to monitor subjects' performance in brain-computer interface (BCI) and neurorehabilitation.

Semantic congruence affects hippocampal response to repetition of visual associations.

PubMed

McAndrews, Mary Pat; Girard, Todd A; Wilkins, Leanne K; McCormick, Cornelia

2016-09-01

Recent research has shown complementary engagement of the hippocampus and medial prefrontal cortex (mPFC) in encoding and retrieving associations based on pre-existing or experimentally-induced schemas, such that the latter supports schema-congruent information whereas the former is more engaged for incongruent or novel associations. Here, we attempted to explore some of the boundary conditions in the relative involvement of those structures in short-term memory for visual associations. The current literature is based primarily on intentional evaluation of schema-target congruence and on study-test paradigms with relatively long delays between learning and retrieval. We used a continuous recognition paradigm to investigate hippocampal and mPFC activation to first and second presentations of scene-object pairs as a function of semantic congruence between the elements (e.g., beach-seashell versus schoolyard-lamp). All items were identical at first and second presentation and the context scene, which was presented 500ms prior to the appearance of the target object, was incidental to the task which required a recognition response to the central target only. Very short lags 2-8 intervening stimuli occurred between presentations. Encoding the targets with congruent contexts was associated with increased activation in visual cortical regions at initial presentation and faster response time at repetition, but we did not find enhanced activation in mPFC relative to incongruent stimuli at either presentation. We did observe enhanced activation in the right anterior hippocampus, as well as regions in visual and lateral temporal and frontal cortical regions, for the repetition of incongruent scene-object pairs. This pattern demonstrates rapid and incidental effects of schema processing in hippocampal, but not mPFC, engagement during continuous recognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing

PubMed Central

Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang

2016-01-01

The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397

LIQUID TARGET

DOEpatents

Martin, M.D.; Salsig, W.W. Jr.

1959-01-13

A liquid handling apparatus is presented for a liquid material which is to be irradiated. The apparatus consists essentially of a reservoir for the liquid, a target element, a drain tank and a drain lock chamber. The target is in the form of a looped tube, the upper end of which is adapted to be disposed in a beam of atomic particles. The lower end of the target tube is in communication with the liquid in the reservoir and a means is provided to continuously circulate the liquid material to be irradiated through the target tube. Means to heat the reservoir tank is provided in the event that a metal is to be used as the target material. The apparatus is provided with suitable valves and shielding to provide maximum safety in operation.

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

PubMed

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

2018-01-01

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

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

PubMed Central

Chen, Mengni; Lloyd, Chris J.

2018-01-01

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

Timing of saccadic eye movements during visual search for multiple targets

PubMed Central

Wu, Chia-Chien; Kowler, Eileen

2013-01-01

Visual search requires sequences of saccades. Many studies have focused on spatial aspects of saccadic decisions, while relatively few (e.g., Hooge & Erkelens, 1999) consider timing. We studied saccadic timing during search for targets (thin circles containing tilted lines) located among nontargets (thicker circles). Tasks required either (a) estimating the mean tilt of the lines, or (b) looking at targets without a concurrent psychophysical task. The visual similarity of targets and nontargets affected both the probability of hitting a target and the saccade rate in both tasks. Saccadic timing also depended on immediate conditions, specifically, (a) the type of currently fixated location (dwell time was longer on targets than nontargets), (b) the type of goal (dwell time was shorter prior to saccades that hit targets), and (c) the ordinal position of the saccade in the sequence. The results show that timing decisions take into account the difficulty of finding targets, as well as the cost of delays. Timing strategies may be a compromise between the attempt to find and locate targets, or other suitable landing locations, using eccentric vision (at the cost of increased dwell times) versus a strategy of exploring less selectively at a rapid rate. PMID:24049045

Literature evidence in open targets - a target validation platform.

PubMed

Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

2017-06-06

We present the Europe PMC literature component of Open Targets - a target validation platform that integrates various evidence to aid drug target identification and validation. The component identifies target-disease associations in documents and ranks the documents based on their confidence from the Europe PMC literature database, by using rules utilising expert-provided heuristic information. The confidence score of a given document represents how valuable the document is in the scope of target validation for a given target-disease association by taking into account the credibility of the association based on the properties of the text. The component serves the platform regularly with the up-to-date data since December, 2015. Currently, there are a total number of 1168365 distinct target-disease associations text mined from >26 million PubMed abstracts and >1.2 million Open Access full text articles. Our comparative analyses on the current available evidence data in the platform revealed that 850179 of these associations are exclusively identified by literature mining. This component helps the platform's users by providing the most relevant literature hits for a given target and disease. The text mining evidence along with the other types of evidence can be explored visually through https://www.targetvalidation.org and all the evidence data is available for download in json format from https://www.targetvalidation.org/downloads/data .

Optimizing emissions targets for residential recycling programmes: Why 'more' is not necessarily better with respect to diversion.

PubMed

Lakhan, Calvin

2016-11-01

This study highlights the economic and environmental challenges of recycling in Ontario, specifically examining the effect of attempting to increase the emissions target for the province's household recycling programme. The findings from the cost model analysis found that Ontario's Blue Box programme reduces overall carbon emissions by approximately 1.8 million tonnes every year. This study also found that targeting specific materials for recovery could result in a scenario where the province could improve both overall diversion and emissions offsets while reducing material management costs. Under our modelled scenario, as the tonnes of greenhouse gases (GHGs) avoided increases, the system cost per tonne of GHG avoided initial declines. However, after avoiding 2.05 million tonnes of GHGs, the system cost/tonne GHG avoided increases. To achieve an emissions target in excess of 2.05 million tonnes, the province will have to start recycling higher cost non-core materials (composite materials, other plastics, etc.). © The Author(s) 2016.

Entanglement-enhanced Neyman-Pearson target detection using quantum illumination

NASA Astrophysics Data System (ADS)

Zhuang, Quntao; Zhang, Zheshen; Shapiro, Jeffrey H.

2017-08-01

Quantum illumination (QI) provides entanglement-based target detection---in an entanglement-breaking environment---whose performance is significantly better than that of optimum classical-illumination target detection. QI's performance advantage was established in a Bayesian setting with the target presumed equally likely to be absent or present and error probability employed as the performance metric. Radar theory, however, eschews that Bayesian approach, preferring the Neyman-Pearson performance criterion to avoid the difficulties of accurately assigning prior probabilities to target absence and presence and appropriate costs to false-alarm and miss errors. We have recently reported an architecture---based on sum-frequency generation (SFG) and feedforward (FF) processing---for minimum error-probability QI target detection with arbitrary prior probabilities for target absence and presence. In this paper, we use our results for FF-SFG reception to determine the receiver operating characteristic---detection probability versus false-alarm probability---for optimum QI target detection under the Neyman-Pearson criterion.

SeedVicious: Analysis of microRNA target and near-target sites.

PubMed

Marco, Antonio

2018-01-01

Here I describe seedVicious, a versatile microRNA target site prediction software that can be easily fitted into annotation pipelines and run over custom datasets. SeedVicious finds microRNA canonical sites plus other, less efficient, target sites. Among other novel features, seedVicious can compute evolutionary gains/losses of target sites using maximum parsimony, and also detect near-target sites, which have one nucleotide different from a canonical site. Near-target sites are important to study population variation in microRNA regulation. Some analyses suggest that near-target sites may also be functional sites, although there is no conclusive evidence for that, and they may actually be target alleles segregating in a population. SeedVicious does not aim to outperform but to complement existing microRNA prediction tools. For instance, the precision of TargetScan is almost doubled (from 11% to ~20%) when we filter predictions by the distance between target sites using this program. Interestingly, two adjacent canonical target sites are more likely to be present in bona fide target transcripts than pairs of target sites at slightly longer distances. The software is written in Perl and runs on 64-bit Unix computers (Linux and MacOS X). Users with no computing experience can also run the program in a dedicated web-server by uploading custom data, or browse pre-computed predictions. SeedVicious and its associated web-server and database (SeedBank) are distributed under the GPL/GNU license.

Screening for microsatellite instability target genes in colorectal cancers

PubMed Central

Vilkki, S; Launonen, V; Karhu, A; Sistonen, P; Vastrik, I; Aaltonen, L

2002-01-01

Background: Defects in the DNA repair system lead to genetic instability because replication errors are not corrected. This type of genetic instability is a key event in the malignant progression of HNPCC and a subset of sporadic colon cancers and mutation rates are particularly high at short repetitive sequences. Somatic deletions of coding mononucleotide repeats have been detected, for example, in the TGFßRII and BAX genes, and recently many novel target genes for microsatellite instability (MSI) have been proposed. Novel target genes are likely to be discovered in the future. More data should be created on background mutation rates in MSI tumours to evaluate mutation rates observed in the candidate target genes. Methods: Mutation rates in 14 neutral intronic repeats were evaluated in MSI tumours. Bioinformatic searches combined with keywords related to cancer and tumour suppressor or CRC related gene homology were used to find new candidate MSI target genes. By comparison of mutation frequencies observed in intronic mononucleotide repeats versus exonic coding repeats of potential MSI target genes, the significance of the exonic mutations was estimated. Results: As expected, the length of an intronic mononucleotide repeat correlated positively with the number of slippages for both G/C and A/T repeats (p=0.0020 and p=0.0012, respectively). BRCA1, CtBP1, and Rb1 associated CtIP and other candidates were found in a bioinformatic search combined with keywords related to cancer. Sequencing showed a significantly increased mutation rate in the exonic A9 repeat of CtIP (25/109=22.9%) as compared with similar intronic repeats (p≤0.001). Conclusions: We propose a new candidate MSI target gene CtIP to be evaluated in further studies. PMID:12414815

Using personal glucose meters and functional DNA sensors to quantify a variety of analytical targets

PubMed Central

Xiang, Yu; Lu, Yi

2012-01-01

Portable, low-cost and quantitative detection of a broad range of targets at home and in the field has the potential to revolutionize medical diagnostics and environmental monitoring. Despite many years of research, very few such devices are commercially available. Taking advantage of the wide availability and low cost of the pocket-sized personal glucose meter—used worldwide by diabetes sufferers—we demonstrate a method to use such meters to quantify non-glucose targets, ranging from a recreational drug (cocaine, 3.4 μM detection limit) to an important biological cofactor (adenosine, 18 μM detection limit), to a disease marker (interferon-gamma of tuberculosis, 2.6 nM detection limit) and a toxic metal ion (uranium, 9.1 nM detection limit). The method is based on the target-induced release of invertase from a functional-DNA–invertase conjugate. The released invertase converts sucrose into glucose, which is detectable using the meter. The approach should be easily applicable to the detection of many other targets through the use of suitable functional-DNA partners (aptamers DNAzymes or aptazymes). PMID:21860458

Using personal glucose meters and functional DNA sensors to quantify a variety of analytical targets

NASA Astrophysics Data System (ADS)

Xiang, Yu; Lu, Yi

2011-09-01

Portable, low-cost and quantitative detection of a broad range of targets at home and in the field has the potential to revolutionize medical diagnostics and environmental monitoring. Despite many years of research, very few such devices are commercially available. Taking advantage of the wide availability and low cost of the pocket-sized personal glucose meter—used worldwide by diabetes sufferers—we demonstrate a method to use such meters to quantify non-glucose targets, ranging from a recreational drug (cocaine, 3.4 µM detection limit) to an important biological cofactor (adenosine, 18 µM detection limit), to a disease marker (interferon-gamma of tuberculosis, 2.6 nM detection limit) and a toxic metal ion (uranium, 9.1 nM detection limit). The method is based on the target-induced release of invertase from a functional-DNA-invertase conjugate. The released invertase converts sucrose into glucose, which is detectable using the meter. The approach should be easily applicable to the detection of many other targets through the use of suitable functional-DNA partners (aptamers, DNAzymes or aptazymes).

Electrically charged targets

DOEpatents

Goodman, Ronald K.; Hunt, Angus L.

1984-01-01

Electrically chargeable laser targets and method for forming such charged targets in order to improve their guidance along a predetermined desired trajectory. This is accomplished by the incorporation of a small amount of an additive to the target material which will increase the electrical conductivity thereof, and thereby enhance the charge placed upon the target material for guidance thereof by electrostatic or magnetic steering mechanisms, without adversely affecting the target when illuminated by laser energy.

Does practicing a wide range of joint angle configurations lead to higher flexibility in a manual obstacle-avoidance target-pointing task?

PubMed Central

Bootsma, Reinoud J.; Schoemaker, Marina M.; Otten, Egbert; Mouton, Leonora J.; Bongers, Raoul M.

2017-01-01

Flexibility in motor actions can be defined as variability in the use of degrees of freedom (e.g., joint angles in the arm) over repetitions while keeping performance (e.g., fingertip position) stabilized. We examined whether flexibility can be increased through enlarging the joint angle range during practice in a manual obstacle-avoidance target-pointing task. To establish differences in flexibility we partitioned the variability in joint angles over repetitions in variability within (GEV) and variability outside the solution space (NGEV). More GEV than NGEV reflects flexibility; when the ratio of the GEV and NGEV is higher, flexibility is higher. The pretest and posttest consisted of 30 repetitions of manual pointing to a target while moving over a 10 cm high obstacle. To enlarge the joint angle range during practice participants performed 600 target-pointing movements while moving over obstacles of different heights (5–9 cm, 11–15 cm). The results indicated that practicing movements over obstacles of different heights led participants to use enlarged range of joint angles compared to the range of joint angles used in movements over the 10 cm obstacle in the pretest. However, for each individual obstacle neither joint angle variance nor flexibility were higher during practice. We also did not find more flexibility after practice. In the posttest, joint angle variance was in fact smaller than before practice, primarily in GEV. The potential influences of learning effects and the task used that could underlie the results obtained are discussed. We conclude that with this specific type of practice in this specific task, enlarging the range of joint angles does not lead to more flexibility. PMID:28700695

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.

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

PubMed

Kim, Soo-Youl

2015-03-01

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

Camouflage target detection via hyperspectral imaging plus information divergence measurement

NASA Astrophysics Data System (ADS)

Chen, Yuheng; Chen, Xinhua; Zhou, Jiankang; Ji, Yiqun; Shen, Weimin

2016-01-01

Target detection is one of most important applications in remote sensing. Nowadays accurate camouflage target distinction is often resorted to spectral imaging technique due to its high-resolution spectral/spatial information acquisition ability as well as plenty of data processing methods. In this paper, hyper-spectral imaging technique together with spectral information divergence measure method is used to solve camouflage target detection problem. A self-developed visual-band hyper-spectral imaging device is adopted to collect data cubes of certain experimental scene before spectral information divergences are worked out so as to discriminate target camouflage and anomaly. Full-band information divergences are measured to evaluate target detection effect visually and quantitatively. Information divergence measurement is proved to be a low-cost and effective tool for target detection task and can be further developed to other target detection applications beyond spectral imaging technique.

Biosonar adjustments to target range of echolocating bottlenose dolphins (Tursiops sp.) in the wild.

PubMed

Jensen, F H; Bejder, L; Wahlberg, M; Madsen, P T

2009-04-01

Toothed whales use echolocation to locate and track prey. Most knowledge of toothed whale echolocation stems from studies on trained animals, and little is known about how toothed whales regulate and use their biosonar systems in the wild. Recent research suggests that an automatic gain control mechanism in delphinid biosonars adjusts the biosonar output to the one-way transmission loss to the target, possibly a consequence of pneumatic restrictions in how fast the sound generator can be actuated and still maintain high outputs. This study examines the relationships between target range (R), click intervals, and source levels of wild bottlenose dolphins (Tursiops sp.) by recording regular (non-buzz) echolocation clicks with a linear hydrophone array. Dolphins clicked faster with decreasing distance to the array, reflecting a decreasing delay between the outgoing echolocation click and the returning array echo. However, for interclick intervals longer than 30-40 ms, source levels were not limited by the repetition rate. Thus, pneumatic constraints in the sound-production apparatus cannot account for source level adjustments to range as a possible automatic gain control mechanism for target ranges longer than a few body lengths of the dolphin. Source level estimates drop with reducing range between the echolocating dolphins and the target as a function of 17 log(R). This may indicate either (1) an active form of time-varying gain in the biosonar independent of click intervals or (2) a bias in array recordings towards a 20 log(R) relationship for apparent source levels introduced by a threshold on received click levels included in the analysis.

Repetition Priming within and between the Two Cerebral Hemispheres

ERIC Educational Resources Information Center

Weems, S.A.; Zaidel, E.

2005-01-01

Two experiments explored repetition priming benefits in the left and right cerebral hemispheres. In both experiments, a lateralized lexical decision task was employed using repeated target stimuli. In the first experiment, all targets were repeated in the same visual field, and in the second experiment the visual field of presentation was switched…

Subliminal repetition primes help detection of phonemes in a picture: Evidence for a phonological level of the priming effects.

PubMed

Manoiloff, Laura; Segui, Juan; Hallé, Pierre

2016-01-01

In this research, we combine a cross-form word-picture visual masked priming procedure with an internal phoneme monitoring task to examine repetition priming effects. In this paradigm, participants have to respond to pictures whose names begin with a prespecified target phoneme. This task unambiguously requires retrieving the word-form of the target picture's name and implicitly orients participants' attention towards a phonological level of representation. The experiments were conducted within Spanish, whose highly transparent orthography presumably promotes fast and automatic phonological recoding of subliminal, masked visual word primes. Experiments 1 and 2 show that repetition primes speed up internal phoneme monitoring in the target, compared to primes beginning with a different phoneme from the target, or sharing only their first phoneme with the target. This suggests that repetition primes preactivate the phonological code of the entire target picture's name, hereby speeding up internal monitoring, which is necessarily based on such a code. To further qualify the nature of the phonological code underlying internal phoneme monitoring, a concurrent articulation task was used in Experiment 3. This task did not affect the repetition priming effect. We propose that internal phoneme monitoring is based on an abstract phonological code, prior to its translation into articulation.

Pricise Target Geolocation and Tracking Based on Uav Video Imagery

NASA Astrophysics Data System (ADS)

Hosseinpoor, H. R.; Samadzadegan, F.; Dadrasjavan, F.

2016-06-01

There is an increasingly large number of applications for Unmanned Aerial Vehicles (UAVs) from monitoring, mapping and target geolocation. However, most of commercial UAVs are equipped with low-cost navigation sensors such as C/A code GPS and a low-cost IMU on board, allowing a positioning accuracy of 5 to 10 meters. This low accuracy cannot be used in applications that require high precision data on cm-level. This paper presents a precise process for geolocation of ground targets based on thermal video imagery acquired by small UAV equipped with RTK GPS. The geolocation data is filtered using an extended Kalman filter, which provides a smoothed estimate of target location and target velocity. The accurate geo-locating of targets during image acquisition is conducted via traditional photogrammetric bundle adjustment equations using accurate exterior parameters achieved by on board IMU and RTK GPS sensors, Kalman filtering and interior orientation parameters of thermal camera from pre-flight laboratory calibration process. The results of this study compared with code-based ordinary GPS, indicate that RTK observation with proposed method shows more than 10 times improvement of accuracy in target geolocation.

DrugE-Rank: improving drug–target interaction prediction of new candidate drugs or targets by ensemble learning to rank

PubMed Central

Yuan, Qingjun; Gao, Junning; Wu, Dongliang; Zhang, Shihua; Mamitsuka, Hiroshi; Zhu, Shanfeng

2016-01-01

Motivation: Identifying drug–target interactions is an important task in drug discovery. To reduce heavy time and financial cost in experimental way, many computational approaches have been proposed. Although these approaches have used many different principles, their performance is far from satisfactory, especially in predicting drug–target interactions of new candidate drugs or targets. Methods: Approaches based on machine learning for this problem can be divided into two types: feature-based and similarity-based methods. Learning to rank is the most powerful technique in the feature-based methods. Similarity-based methods are well accepted, due to their idea of connecting the chemical and genomic spaces, represented by drug and target similarities, respectively. We propose a new method, DrugE-Rank, to improve the prediction performance by nicely combining the advantages of the two different types of methods. That is, DrugE-Rank uses LTR, for which multiple well-known similarity-based methods can be used as components of ensemble learning. Results: The performance of DrugE-Rank is thoroughly examined by three main experiments using data from DrugBank: (i) cross-validation on FDA (US Food and Drug Administration) approved drugs before March 2014; (ii) independent test on FDA approved drugs after March 2014; and (iii) independent test on FDA experimental drugs. Experimental results show that DrugE-Rank outperforms competing methods significantly, especially achieving more than 30% improvement in Area under Prediction Recall curve for FDA approved new drugs and FDA experimental drugs. Availability: http://datamining-iip.fudan.edu.cn/service/DrugE-Rank Contact: zhusf@fudan.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307615

DrugE-Rank: improving drug-target interaction prediction of new candidate drugs or targets by ensemble learning to rank.

PubMed

Yuan, Qingjun; Gao, Junning; Wu, Dongliang; Zhang, Shihua; Mamitsuka, Hiroshi; Zhu, Shanfeng

2016-06-15

Identifying drug-target interactions is an important task in drug discovery. To reduce heavy time and financial cost in experimental way, many computational approaches have been proposed. Although these approaches have used many different principles, their performance is far from satisfactory, especially in predicting drug-target interactions of new candidate drugs or targets. Approaches based on machine learning for this problem can be divided into two types: feature-based and similarity-based methods. Learning to rank is the most powerful technique in the feature-based methods. Similarity-based methods are well accepted, due to their idea of connecting the chemical and genomic spaces, represented by drug and target similarities, respectively. We propose a new method, DrugE-Rank, to improve the prediction performance by nicely combining the advantages of the two different types of methods. That is, DrugE-Rank uses LTR, for which multiple well-known similarity-based methods can be used as components of ensemble learning. The performance of DrugE-Rank is thoroughly examined by three main experiments using data from DrugBank: (i) cross-validation on FDA (US Food and Drug Administration) approved drugs before March 2014; (ii) independent test on FDA approved drugs after March 2014; and (iii) independent test on FDA experimental drugs. Experimental results show that DrugE-Rank outperforms competing methods significantly, especially achieving more than 30% improvement in Area under Prediction Recall curve for FDA approved new drugs and FDA experimental drugs. http://datamining-iip.fudan.edu.cn/service/DrugE-Rank zhusf@fudan.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

PubMed

Gibiansky, Leonid; Gibiansky, Ekaterina

2018-02-01

The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations. The model was shown to be remarkably successful, not only in describing the observed data for drug-target interactions, but also in advancing the qualitative and quantitative understanding of those interactions and their role in pharmacokinetic and pharmacodynamic properties of biologics. The TMDD model in its original formulation describes the interaction of the drug that has one binding site with the target that also has only one binding site. Following the framework developed earlier for drugs with one-to-one binding, this work aims to describe a rigorous approach for working with similar systems and to apply it to drugs that bind to targets with two binding sites. The quasi-steady-state, quasi-equilibrium, irreversible binding, and Michaelis-Menten approximations of the model are also derived. These equations can be used, in particular, to predict concentrations of the partially bound target (RC). This could be clinically important if RC remains active and has slow internalization rate. In this case, introduction of the drug aimed to suppress target activity may lead to the opposite effect due to RC accumulation.

Lead (Pb) Hohlraum: Target for Inertial Fusion Energy

PubMed Central

Ross, J. S.; Amendt, P.; Atherton, L. J.; Dunne, M.; Glenzer, S. H.; Lindl, J. D.; Meeker, D.; Moses, E. I.; Nikroo, A.; Wallace, R.

2013-01-01

Recent progress towards demonstrating inertial confinement fusion (ICF) ignition at the National Ignition Facility (NIF) has sparked wide interest in Laser Inertial Fusion Energy (LIFE) for carbon-free large-scale power generation. A LIFE-based fleet of power plants promises clean energy generation with no greenhouse gas emissions and a virtually limitless, widely available thermonuclear fuel source. For the LIFE concept to be viable, target costs must be minimized while the target material efficiency or x-ray albedo is optimized. Current ICF targets on the NIF utilize a gold or depleted uranium cylindrical radiation cavity (hohlraum) with a plastic capsule at the center that contains the deuterium and tritium fuel. Here we show a direct comparison of gold and lead hohlraums in efficiently ablating deuterium-filled plastic capsules with soft x rays. We report on lead hohlraum performance that is indistinguishable from gold, yet costing only a small fraction. PMID:23486285

Lead (Pb) hohlraum: target for inertial fusion energy.

PubMed

Ross, J S; Amendt, P; Atherton, L J; Dunne, M; Glenzer, S H; Lindl, J D; Meeker, D; Moses, E I; Nikroo, A; Wallace, R

2013-01-01

Recent progress towards demonstrating inertial confinement fusion (ICF) ignition at the National Ignition Facility (NIF) has sparked wide interest in Laser Inertial Fusion Energy (LIFE) for carbon-free large-scale power generation. A LIFE-based fleet of power plants promises clean energy generation with no greenhouse gas emissions and a virtually limitless, widely available thermonuclear fuel source. For the LIFE concept to be viable, target costs must be minimized while the target material efficiency or x-ray albedo is optimized. Current ICF targets on the NIF utilize a gold or depleted uranium cylindrical radiation cavity (hohlraum) with a plastic capsule at the center that contains the deuterium and tritium fuel. Here we show a direct comparison of gold and lead hohlraums in efficiently ablating deuterium-filled plastic capsules with soft x rays. We report on lead hohlraum performance that is indistinguishable from gold, yet costing only a small fraction.

Tracking 20 Years of Compound-to-Target Output from Literature and Patents

PubMed Central

Southan, Christopher; Varkonyi, Peter; Boppana, Kiran; Jagarlapudi, Sarma A.R.P.; Muresan, Sorel

2013-01-01

The statistics of drug development output and declining yield of approved medicines has been the subject of many recent reviews. However, assessing research productivity that feeds development is more difficult. Here we utilise an extensive database of structure-activity relationships extracted from papers and patents. We have used this database to analyse published compounds cumulatively linked to nearly 4000 protein target identifiers from multiple species over the last 20 years. The compound output increases up to 2005 followed by a decline that parallels a fall in pharmaceutical patenting. Counts of protein targets have plateaued but not fallen. We extended these results by exploring compounds and targets for one large pharmaceutical company. In addition, we examined collective time course data for six individual protease targets, including average molecular weight of the compounds. We also tracked the PubMed profile of these targets to detect signals related to changes in compound output. Our results show that research compound output had decreased 35% by 2012. The major causative factor is likely to be a contraction in the global research base due to mergers and acquisitions across the pharmaceutical industry. However, this does not rule out an increasing stringency of compound quality filtration and/or patenting cost control. The number of proteins mapped to compounds on a yearly basis shows less decline, indicating the cumulative published target capacity of global research is being sustained in the region of 300 proteins for large companies. The tracking of six individual targets shows uniquely detailed patterns not discernible from cumulative snapshots. These are interpretable in terms of events related to validation and de-risking of targets that produce detectable follow-on surges in patenting. Further analysis of the type we present here can provide unique insights into the process of drug discovery based on the data it actually generates. PMID

Targeting therapeutics to the glomerulus with nanoparticles.

PubMed

Zuckerman, Jonathan E; Davis, Mark E

2013-11-01

Nanoparticles are an enabling technology for the creation of tissue-/cell-specific therapeutics that have been investigated extensively as targeted therapeutics for cancer. The kidney, specifically the glomerulus, is another accessible site for nanoparticle delivery that has been relatively overlooked as a target organ. Given the medical need for the development of more potent, kidney-targeted therapies, the use of nanoparticle-based therapeutics may be one such solution to this problem. Here, we review the literature on nanoparticle targeting of the glomerulus. Specifically, we provide a broad overview of nanoparticle-based therapeutics and how the unique structural characteristics of the glomerulus allow for selective, nanoparticle targeting of this area of the kidney. We then summarize literature examples of nanoparticle delivery to the glomerulus and elaborate on the appropriate nanoparticle design criteria for glomerular targeting. Finally, we discuss the behavior of nanoparticles in animal models of diseased glomeruli and review examples of nanoparticle therapeutic approaches that have shown promise in animal models of glomerulonephritic disease. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Computational-experimental approach to drug-target interaction mapping: A case study on kinase inhibitors

PubMed Central

Ravikumar, Balaguru; Parri, Elina; Timonen, Sanna; Airola, Antti; Wennerberg, Krister

2017-01-01

Due to relatively high costs and labor required for experimental profiling of the full target space of chemical compounds, various machine learning models have been proposed as cost-effective means to advance this process in terms of predicting the most potent compound-target interactions for subsequent verification. However, most of the model predictions lack direct experimental validation in the laboratory, making their practical benefits for drug discovery or repurposing applications largely unknown. Here, we therefore introduce and carefully test a systematic computational-experimental framework for the prediction and pre-clinical verification of drug-target interactions using a well-established kernel-based regression algorithm as the prediction model. To evaluate its performance, we first predicted unmeasured binding affinities in a large-scale kinase inhibitor profiling study, and then experimentally tested 100 compound-kinase pairs. The relatively high correlation of 0.77 (p < 0.0001) between the predicted and measured bioactivities supports the potential of the model for filling the experimental gaps in existing compound-target interaction maps. Further, we subjected the model to a more challenging task of predicting target interactions for such a new candidate drug compound that lacks prior binding profile information. As a specific case study, we used tivozanib, an investigational VEGF receptor inhibitor with currently unknown off-target profile. Among 7 kinases with high predicted affinity, we experimentally validated 4 new off-targets of tivozanib, namely the Src-family kinases FRK and FYN A, the non-receptor tyrosine kinase ABL1, and the serine/threonine kinase SLK. Our sub-sequent experimental validation protocol effectively avoids any possible information leakage between the training and validation data, and therefore enables rigorous model validation for practical applications. These results demonstrate that the kernel-based modeling approach

Fulfilling the pedestrian protection directive using a long-wavelength infrared camera designed to meet both performance and cost targets

NASA Astrophysics Data System (ADS)

Källhammer, Jan-Erik; Pettersson, Håkan; Eriksson, Dick; Junique, Stéphane; Savage, Susan; Vieider, Christian; Andersson, Jan Y.; Franks, John; Van Nylen, Jan; Vercammen, Hans; Kvisterøy, Terje; Niklaus, Frank; Stemme, Göran

2006-04-01

Pedestrian fatalities are around 15% of the traffic fatalities in Europe. A proposed EU regulation requires the automotive industry to develop technologies that will substantially decrease the risk for Vulnerable Road Users when hit by a vehicle. Automatic Brake Assist systems, activated by a suitable sensor, will reduce the speed of the vehicle before the impact, independent of any driver interaction. Long Wavelength Infrared technology is an ideal candidate for such sensors, but requires a significant cost reduction. The target necessary for automotive serial applications are well below the cost of systems available today. Uncooled bolometer arrays are the most mature technology for Long Wave Infrared with low-cost potential. Analyses show that sensor size and production yield along with vacuum packaging and the optical components are the main cost drivers. A project has been started to design a new Long Wave Infrared system with a ten times cost reduction potential, optimized for the pedestrian protection requirement. It will take advantage of the progress in Micro Electro-Mechanical Systems and Long Wave Infrared optics to keep the cost down. Deployable and pre-impact braking systems can become effective alternatives to passive impact protection systems solutions fulfilling the EU pedestrian protection regulation. Low-cost Long Wave Infrared sensors will be an important enabler to make such systems cost competitive, allowing high market penetration.

Pre-capture multiplexing improves efficiency and cost-effectiveness of targeted genomic enrichment.

PubMed

Shearer, A Eliot; Hildebrand, Michael S; Ravi, Harini; Joshi, Swati; Guiffre, Angelica C; Novak, Barbara; Happe, Scott; LeProust, Emily M; Smith, Richard J H

2012-11-14

Targeted genomic enrichment (TGE) is a widely used method for isolating and enriching specific genomic regions prior to massively parallel sequencing. To make effective use of sequencer output, barcoding and sample pooling (multiplexing) after TGE and prior to sequencing (post-capture multiplexing) has become routine. While previous reports have indicated that multiplexing prior to capture (pre-capture multiplexing) is feasible, no thorough examination of the effect of this method has been completed on a large number of samples. Here we compare standard post-capture TGE to two levels of pre-capture multiplexing: 12 or 16 samples per pool. We evaluated these methods using standard TGE metrics and determined the ability to identify several classes of genetic mutations in three sets of 96 samples, including 48 controls. Our overall goal was to maximize cost reduction and minimize experimental time while maintaining a high percentage of reads on target and a high depth of coverage at thresholds required for variant detection. We adapted the standard post-capture TGE method for pre-capture TGE with several protocol modifications, including redesign of blocking oligonucleotides and optimization of enzymatic and amplification steps. Pre-capture multiplexing reduced costs for TGE by at least 38% and significantly reduced hands-on time during the TGE protocol. We found that pre-capture multiplexing reduced capture efficiency by 23 or 31% for pre-capture pools of 12 and 16, respectively. However efficiency losses at this step can be compensated by reducing the number of simultaneously sequenced samples. Pre-capture multiplexing and post-capture TGE performed similarly with respect to variant detection of positive control mutations. In addition, we detected no instances of sample switching due to aberrant barcode identification. Pre-capture multiplexing improves efficiency of TGE experiments with respect to hands-on time and reagent use compared to standard post-capture TGE

Target/error overlap in jargonaphasia: The case for a one-source model, lexical and non-lexical summation, and the special status of correct responses.

PubMed

Olson, Andrew; Halloran, Elizabeth; Romani, Cristina

2015-12-01

We present three jargonaphasic patients who made phonological errors in naming, repetition and reading. We analyse target/response overlap using statistical models to answer three questions: 1) Is there a single phonological source for errors or two sources, one for target-related errors and a separate source for abstruse errors? 2) Can correct responses be predicted by the same distribution used to predict errors or do they show a completion boost (CB)? 3) Is non-lexical and lexical information summed during reading and repetition? The answers were clear. 1) Abstruse errors did not require a separate distribution created by failure to access word forms. Abstruse and target-related errors were the endpoints of a single overlap distribution. 2) Correct responses required a special factor, e.g., a CB or lexical/phonological feedback, to preserve their integrity. 3) Reading and repetition required separate lexical and non-lexical contributions that were combined at output. Copyright © 2015 Elsevier Ltd. All rights reserved.

Targeting Neural Endophenotypes of Eating Disorders with Non-invasive Brain Stimulation

PubMed Central

Dunlop, Katharine A.; Woodside, Blake; Downar, Jonathan

2016-01-01

The term “eating disorders” (ED) encompasses a wide variety of disordered eating and compensatory behaviors, and so the term is associated with considerable clinical and phenotypic heterogeneity. This heterogeneity makes optimizing treatment techniques difficult. One class of treatments is non-invasive brain stimulation (NIBS). NIBS, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), are accessible forms of neuromodulation that alter the cortical excitability of a target brain region. It is crucial for NIBS to be successful that the target is well selected for the patient population in question. Targets may best be selected by stepping back from conventional DSM-5 diagnostic criteria to identify neural substrates of more basic phenotypes, including behavior related to rewards and punishment, cognitive control, and social processes. These phenotypic dimensions have been recently laid out by the Research Domain Criteria (RDoC) initiative. Consequently, this review is intended to identify potential dimensions as outlined by the RDoC and the underlying behavioral and neurobiological targets associated with ED. This review will also identify candidate targets for NIBS based on these dimensions and review the available literature on rTMS and tDCS in ED. This review systematically reviews abnormal neural circuitry in ED within the RDoC framework, and also systematically reviews the available literature investigating NIBS as a treatment for ED. PMID:26909013

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

PubMed

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

2014-06-30

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

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

PubMed

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

2014-06-01

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

Forward and Backward Repetition Blindness in Speed and Accuracy

ERIC Educational Resources Information Center

Wong, Kin Fai Ellick; Chen, Hsuan-Chih

2009-01-01

Repetition blindness (RB) was investigated in a new paradigm in which effects could stem from items preceding or following a target. Speeded-response tasks in which 3 critical items (C1, C2, and C3) were sequentially presented on each trial. In Experiments 1 and 2, participants were asked to judge whether C2 (the target) was present on each trial.…

Changes in predictive cuing modulate the hemispheric distribution of the P1 inhibitory response to attentional targets.

PubMed

Lasaponara, Stefano; D' Onofrio, Marianna; Dragone, Alessio; Pinto, Mario; Caratelli, Ludovica; Doricchi, Fabrizio

2017-05-01

Brain activity related to orienting of attention with spatial cues and brain responses to attentional targets are influenced the probabilistic contingency between cues and targets. Compared to predictive cues, cues predicting at chance the location of targets reduce the filtering out of uncued locations and the costs in reorienting attention to targets presented at these locations. Slagter et al. (2016) have recently suggested that the larger target related P1 component that is found in the hemisphere ipsilateral to validly cued targets reflects stimulus-driven inhibition in the processing of the unstimulated side of space contralateral to the same hemisphere. Here we verified whether the strength of this inhibition and the amplitude of the corresponding P1 wave are modulated by the probabilistic link between cues and targets. Healthy participants performed a task of endogenous orienting once with predictive and once with non-predictive directional cues. In the non-predictive condition we observed a drop in the amplitude of the P1 ipsilateral to the target and in the costs of reorienting. No change in the inter-hemispheric latencies of the P1 was found between the two predictive conditions. The N1 facilitatory component was unaffected by predictive cuing. These results show that the predictive context modulates the strength of the inhibitory P1 response and that this modulation is not matched with changes in the inter-hemispheric interaction between the P1 generators of the two hemispheres. Copyright © 2017. Published by Elsevier Ltd.

Action-perception dissociation in response to target acceleration.

PubMed

Dubrowski, Adam; Carnahan, Heather

2002-05-01

The purpose of this study was to investigate whether information about the acceleration characteristics of a moving target can be used for both action and perception. Also of interest was whether prior movement experience altered perceptual judgements. Participants manually intercepted targets moving with various acceleration, velocity and movement time characteristics. They also made perceptual judgements about the acceleration characteristics of these targets either with or without prior manual interception experience. Results showed that while aiming kinematics were sensitive to the acceleration characteristics of the target, participants were only able to perceptually discriminate the velocity characteristics of target motion, even after performing interceptive actions to the same targets. These results are discussed in terms of a two channel (action-perception) model of visuomotor control.

Laser ``M'egajoule'' cryogenic target program: from target fabrication to conformation of the deuterium-tritium ice layer

NASA Astrophysics Data System (ADS)

Collier, Rémy; Durut, Frédéric; Reneaume, Benoît; Chicane, Cédric; Théobald, Marc; Breton, Olivier; Martin, Michel; Fleury, Emmanuel; Vincent-Viry, Olivier; Bachelet, Franck; Jeannot, Laurent; Geoffray, Isabelle; Botrel, Ronan; Dauteuil, Christophe; Hermerel, Cyril; Choux, Alexandre; Bednarczyk, Sophie; Legaie, Olivier

2008-11-01

For the French inertial confinement fusion (ICF) experiments, cryogenic target assemblies (CTAs) for the LMJ program are manufactured and filled at CEA Valduc (Dijon) in the cryogenic targets filling station (IRCC). They will be moved at about 20 K into a transport cryostat for cryogenic targets and will be driven from CEA/Valduc to CEA/CESTA (Bordeaux). Cryogenic targets will then be transferred by several cryogenic grippers on the cryogenic target positioner before shots. The CTA has to meet severe specifications and involves a lot of challenging tasks for its manufacture. To fill CTAs by permeation with deuterium-tritium (DT), the IRCC need to meet strict thermal, mechanical and dimensional specifications. To obtain a good combustion yield, a very homogenous DT ice layer and very smooth roughness at 1.5 K below the DT triple point are also required. This paper deals with the up to date main issues in the different fields of the LMJ cryogenic target program.

Brain activation underlying threat detection to targets of different races.

PubMed

Senholzi, Keith B; Depue, Brendan E; Correll, Joshua; Banich, Marie T; Ito, Tiffany A

2015-01-01

The current study examined blood oxygen level-dependent signal underlying racial differences in threat detection. During functional magnetic resonance imaging, participants determined whether pictures of Black or White individuals held weapons. They were instructed to make shoot responses when the picture showed armed individuals but don't shoot responses to unarmed individuals, with the cost of not shooting armed individuals being greater than that of shooting unarmed individuals. Participants were faster to shoot armed Blacks than Whites, but faster in making don't shoot responses to unarmed Whites than Blacks. Brain activity differed to armed versus unarmed targets depending on target race, suggesting different mechanisms underlying threat versus safety decisions. Anterior cingulate cortex was preferentially engaged for unarmed Whites than Blacks. Parietal and visual cortical regions exhibited greater activity for armed Blacks than Whites. Seed-based functional connectivity of the amygdala revealed greater coherence with parietal and visual cortices for armed Blacks than Whites. Furthermore, greater implicit Black-danger associations were associated with increased amygdala activation to armed Blacks, compared to armed Whites. Our results suggest that different neural mechanisms may underlie racial differences in responses to armed versus unarmed targets.

Inertial Fusion Target Physics Advantages with the Krypton Fluoride Laser

NASA Astrophysics Data System (ADS)

Obenschain, Stephen

2010-11-01

The krypton fluoride (KrF) laser's short wavelength, broad bandwidth and capability to provide extremely uniform target illumination are advantages towards obtaining high gain direct drive implosions. The short wavelength helps suppress deleterious laser-plasma instabilities, and allows one to employ higher ablation pressures. In addition, the KrF architecture allows one to zoom down the focal diameter to follow the size of the imploding pellet, thereby improving the coupling efficiency. The NRL researchers have been conducting theoretical and experimental studies to quantify the beneficial effects of utilizing KrF light. Experiments using the Nike facility have confirmed that KrF light significantly increases the threshold for laser-plasma instability. This presentation will discuss the observed target physics with KrF light and its effects towards facilitating the high gains needed for power production with inertial fusion. Simulations indicate that shock ignited designs can achieve gains above 200 with KrF energies as low a 1 megajoule. For fusion energy a laser driver must be capable of high repetition rates (5-10 Hz) along with adequate efficiency and durability. The Electra KrF 30-cm aperture electron-beam-pumped amplifier has demonstrated long duration continuous operation at high-repetition rates. This and other advances show that the KrF laser should be able to meet the requirements.

The drug target genes show higher evolutionary conservation than non-target genes.

PubMed

Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

2016-01-26

Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

A review of the ligands and related targeting strategies for active targeting of paclitaxel to tumours.

PubMed

Li, Juan; Wang, Fengshan; Sun, Deqing; Wang, Rongmei

2016-08-01

It has been 30 years since the discovery of the anti-tumour property of paclitaxel (PTX), which has been successfully applied in clinic for the treatment of carcinomas of the lungs, breast and ovarian. However, PTX is poorly soluble in water and has no targeting and selectivity to tumour tissue. Recent advances in active tumour targeting of PTX delivery vehicles have addressed some of the issues related to lack of solubility in water and non-specific toxicities associated with PTX. These PTX delivery vehicles are designed for active targeting to specific cancer cells by the addition of ligands for recognition by specific receptors/antigens on cancer cells. This article will focus on various ligands and related targeting strategies serving as potential tools for active targeting of PTX to tumour tissues, illustrating their use in different tumour models. This review also highlights the need of further studies on the discovery of receptors in different cells of specific organ and ligands with binding efficiency to these specific receptors.

Oak Ridge Spallation Neutron Source (ORSNS) target station design integration

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

McManamy, T.; Booth, R.; Cleaves, J.

1996-06-01

The conceptual design for a 1- to 3-MW short pulse spallation source with a liquid mercury target has been started recently. The design tools and methods being developed to define requirements, integrate the work, and provide early cost guidance will be presented with a summary of the current target station design status. The initial design point was selected with performance and cost estimate projections by a systems code. This code was developed recently using cost estimates from the Brookhaven Pulsed Spallation Neutron Source study and experience from the Advanced Neutron Source Project`s conceptual design. It will be updated and improvedmore » as the design develops. Performance was characterized by a simplified figure of merit based on a ratio of neutron production to costs. A work breakdown structure was developed, with simplified systems diagrams used to define interfaces and system responsibilities. A risk assessment method was used to identify potential problems, to identify required research and development (R&D), and to aid contingency development. Preliminary 3-D models of the target station are being used to develop remote maintenance concepts and to estimate costs.« less

Upper Limb Kinematics in Stroke and Healthy Controls Using Target-to-Target Task in Virtual Reality.

PubMed

Hussain, Netha; Alt Murphy, Margit; Sunnerhagen, Katharina S

2018-01-01

Kinematic analysis using virtual reality (VR) environment provides quantitative assessment of upper limb movements. This technique has rarely been used in evaluating motor function in stroke despite its availability in stroke rehabilitation. To determine the discriminative validity of VR-based kinematics during target-to-target pointing task in individuals with mild or moderate arm impairment following stroke and in healthy controls. Sixty-seven participants with moderate (32-57 points) or mild (58-65 points) stroke impairment as assessed with Fugl-Meyer Assessment for Upper Extremity were included from the Stroke Arm Longitudinal study at the University of Gothenburg-SALGOT cohort of non-selected individuals within the first year of stroke. The stroke groups and 43 healthy controls performed the target-to-target pointing task, where 32 circular targets appear one after the other and disappear when pointed at by the haptic handheld stylus in a three-dimensional VR environment. The kinematic parameters captured by the stylus included movement time, velocities, and smoothness of movement. The movement time, mean velocity, and peak velocity were discriminative between groups with moderate and mild stroke impairment and healthy controls. The movement time was longer and mean and peak velocity were lower for individuals with stroke. The number of velocity peaks, representing smoothness, was also discriminative and significantly higher in both stroke groups (mild, moderate) compared to controls. Movement trajectories in stroke more frequently showed clustering (spider's web) close to the target indicating deficits in movement precision. The target-to-target pointing task can provide valuable and specific information about sensorimotor impairment of the upper limb following stroke that might not be captured using traditional clinical scale. The trial was registered with register number NCT01115348 at clinicaltrials.gov, on May 4, 2010. URL: https://clinicaltrials.gov/ct2

First demonstration of multi-MeV proton acceleration from a cryogenic hydrogen ribbon target

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

Kraft, Stephan; Obst, Lieselotte; Metzkes-Ng, Josefine

We show efficient laser driven proton acceleration up to 14 MeV from a 50 μm thick cryogenic hydrogen ribbon. Pulses of the short pulse laser ELFIE at LULI with a pulse length of ≈ 350 fs at an energy of 8 J per pulse are directed onto the target. The results were then compared to proton spectra from metal and plastic foils with different thicknesses and show a similar good performance both in maximum energy as well as in proton number. Thus, this target type is a promising candidate for experiments with high repetition rate laser systems.

First demonstration of multi-MeV proton acceleration from a cryogenic hydrogen ribbon target

NASA Astrophysics Data System (ADS)

Kraft, Stephan D.; Obst, Lieselotte; Metzkes-Ng, Josefine; Schlenvoigt, Hans-Peter; Zeil, Karl; Michaux, Sylvain; Chatain, Denis; Perin, Jean-Paul; Chen, Sophia N.; Fuchs, Julien; Gauthier, Maxence; Cowan, Thomas E.; Schramm, Ulrich

2018-04-01

We show efficient laser driven proton acceleration up to 14 MeV from a 62 μm thick cryogenic hydrogen ribbon. Pulses of the short pulse laser ELFIE at LULI with a pulse length of ≈350 fs at an energy of 8 J per pulse are directed onto the target. The results are compared to proton spectra from metal and plastic foils with different thicknesses and show a similarly good performance both in maximum energy as well as in proton number. Thus, this target type is a promising candidate for experiments with high repetition rate laser systems.

First demonstration of multi-MeV proton acceleration from a cryogenic hydrogen ribbon target

DOE PAGES

Kraft, Stephan; Obst, Lieselotte; Metzkes-Ng, Josefine; ...

2018-02-09

We show efficient laser driven proton acceleration up to 14 MeV from a 50 μm thick cryogenic hydrogen ribbon. Pulses of the short pulse laser ELFIE at LULI with a pulse length of ≈ 350 fs at an energy of 8 J per pulse are directed onto the target. The results were then compared to proton spectra from metal and plastic foils with different thicknesses and show a similar good performance both in maximum energy as well as in proton number. Thus, this target type is a promising candidate for experiments with high repetition rate laser systems.

Challenges Surrounding the Injection and Arrival of Targets at LIFE Fusion Chamber Center

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

Miles, R; Spaeth, M; Manes, K

2010-12-01

IFE target designers must consider several engineering requirements in addition to the physics requirements for successful target implosion. These considerations include low target cost, high manufacturing throughput, the ability of the target to survive the injection into the fusion chamber and arrive in a condition and physical position consistent with proper laser-target interaction and ease of post-implosion debris removal. This article briefly describes these considerations for the Laser Inertial Fusion-based Energy (LIFE) targets currently being designed.

Nanomedicine Strategies to Target Tumor-Associated Macrophages

PubMed Central

Binnemars-Postma, Karin; Storm, Gert; Prakash, Jai

2017-01-01

In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail. PMID:28471401

Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine.

PubMed

Arrue, Lily; Ratjen, Lars

2017-12-07

The photochemical control of structure and reactivity bears great potential for chemistry, biology, and life sciences. A key feature of photochemistry is the spatiotemporal control over secondary events. Well-established applications of photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology (PP). However, although both are highly localizable through the application of light, they lack cell- and tissue-specificity. The combination of nanomaterial-based drug delivery and targeting has the potential to overcome limitations for many established therapy concepts. Even more privileged seems the merger of nanomedicine and cell-specific targeting (internal targeting) controlled by light (external control), as it can potentially be applied to many different areas of medicine and pharmaceutical research, including the aforementioned PDT and PP. In this review a survey of the interface of photochemistry, medicine and targeted drug delivery is given, especially focusing on phototriggered targeting in nanomedicine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Target-responsive DNA hydrogel mediated "stop-flow" microfluidic paper-based analytic device for rapid, portable and visual detection of multiple targets.

PubMed

Wei, Xiaofeng; Tian, Tian; Jia, Shasha; Zhu, Zhi; Ma, Yanli; Sun, Jianjun; Lin, Zhenyu; Yang, Chaoyong James

2015-04-21

A versatile point-of-care assay platform was developed for simultaneous detection of multiple targets based on a microfluidic paper-based analytic device (μPAD) using a target-responsive hydrogel to mediate fluidic flow and signal readout. An aptamer-cross-linked hydrogel was used as a target-responsive flow regulator in the μPAD. In the absence of a target, the hydrogel is formed in the flow channel, stopping the flow in the μPAD and preventing the colored indicator from traveling to the final observation spot, thus yielding a "signal off" readout. In contrast, in the presence of a target, no hydrogel is formed because of the preferential interaction of target and aptamer. This allows free fluidic flow in the μPAD, carrying the indicator to the observation spot and producing a "signal on" readout. The device is inexpensive to fabricate, easy to use, and disposable after detection. Testing results can be obtained within 6 min by the naked eye via a simple loading operation without the need for any auxiliary equipment. Multiple targets, including cocaine, adenosine, and Pb(2+), can be detected simultaneously, even in complex biological matrices such as urine. The reported method offers simple, low cost, rapid, user-friendly, point-of-care testing, which will be useful in many applications.

Facebook targeted advertisement for research recruitment: A primer for nurse researchers.

PubMed

Carter-Harris, Lisa

2016-11-01

Recruiting participants for research studies can be challenging and costly. Innovative recruitment methods are needed. Facebook targeted advertisement offers a low-cost alternative to traditional methods that has been successfully used in research study recruitment. This primer offers nurse researchers a method utilizing social media as a recruitment tool and details Facebook targeted advertisement for research recruitment. Copyright © 2016 Elsevier Inc. All rights reserved.

Memory for found targets interferes with subsequent performance in multiple-target visual search.

PubMed

Cain, Matthew S; Mitroff, Stephen R

2013-10-01

Multiple-target visual searches--when more than 1 target can appear in a given search display--are commonplace in radiology, airport security screening, and the military. Whereas 1 target is often found accurately, additional targets are more likely to be missed in multiple-target searches. To better understand this decrement in 2nd-target detection, here we examined 2 potential forms of interference that can arise from finding a 1st target: interference from the perceptual salience of the 1st target (a now highly relevant distractor in a known location) and interference from a newly created memory representation for the 1st target. Here, we found that removing found targets from the display or making them salient and easily segregated color singletons improved subsequent search accuracy. However, replacing found targets with random distractor items did not improve subsequent search accuracy. Removing and highlighting found targets likely reduced both a target's visual salience and its memory load, whereas replacing a target removed its visual salience but not its representation in memory. Collectively, the current experiments suggest that the working memory load of a found target has a larger effect on subsequent search accuracy than does its perceptual salience. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Margin selection to compensate for loss of target dose coverage due to target motion during external‐beam radiation therapy of the lung

PubMed Central

Osei, Ernest; Barnett, Rob

2015-01-01

The aim of this study is to provide guidelines for the selection of external‐beam radiation therapy target margins to compensate for target motion in the lung during treatment planning. A convolution model was employed to predict the effect of target motion on the delivered dose distribution. The accuracy of the model was confirmed with radiochromic film measurements in both static and dynamic phantom modes. 502 unique patient breathing traces were recorded and used to simulate the effect of target motion on a dose distribution. A 1D probability density function (PDF) representing the position of the target throughout the breathing cycle was generated from each breathing trace obtained during 4D CT. Changes in the target D95 (the minimum dose received by 95% of the treatment target) due to target motion were analyzed and shown to correlate with the standard deviation of the PDF. Furthermore, the amount of target D95 recovered per millimeter of increased field width was also shown to correlate with the standard deviation of the PDF. The sensitivity of changes in dose coverage with respect to target size was also determined. Margin selection recommendations that can be used to compensate for loss of target D95 were generated based on the simulation results. These results are discussed in the context of clinical plans. We conclude that, for PDF standard deviations less than 0.4 cm with target sizes greater than 5 cm, little or no additional margins are required. Targets which are smaller than 5 cm with PDF standard deviations larger than 0.4 cm are most susceptible to loss of coverage. The largest additional required margin in this study was determined to be 8 mm. PACS numbers: 87.53.Bn, 87.53.Kn, 87.55.D‐, 87.55.Gh

Dual-targeting siRNAs

PubMed Central

Tiemann, Katrin; Höhn, Britta; Ehsani, Ali; Forman, Stephen J.; Rossi, John J.; Sætrom, Pål

2010-01-01

We have developed an algorithm for the prediction of dual-targeting short interfering RNAs (siRNAs) in which both strands are deliberately designed to separately target different mRNA transcripts with complete complementarity. An advantage of this approach versus the use of two separate duplexes is that only two strands, as opposed to four, are competing for entry into the RNA-induced silencing complex. We chose to design our dual-targeting siRNAs as Dicer substrate 25/27mer siRNAs, since design features resembling pre-microRNAs (miRNAs) can be introduced for Dicer processing. Seven different dual-targeting siRNAs targeting genes that are potential targets in cancer therapy have been developed including Bcl2, Stat3, CCND1, BIRC5, and MYC. The dual-targeting siRNAs have been characterized for dual target knockdown in three different cell lines (HEK293, HCT116, and PC3), where they were as effective as their corresponding single-targeting siRNAs in target knockdown. The algorithm developed in this study should prove to be useful for predicting dual-targeting siRNAs in a variety of different targets and is available from http://demo1.interagon.com/DualTargeting/. PMID:20410240

The Effect of N-3 on N-2 Repetition Costs in Task Switching

ERIC Educational Resources Information Center

Schuch, Stefanie; Grange, James A.

2015-01-01

N-2 task repetition cost is a response time and error cost returning to a task recently performed after one intervening trial (i.e., an ABA task sequence) compared with returning to a task not recently performed (i.e., a CBA task sequence). This cost is considered a robust measure of inhibitory control during task switching. The present article…

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).

SuperTarget and Matador: resources for exploring drug-target relationships.

PubMed

Günther, Stefan; Kuhn, Michael; Dunkel, Mathias; Campillos, Monica; Senger, Christian; Petsalaki, Evangelia; Ahmed, Jessica; Urdiales, Eduardo Garcia; Gewiess, Andreas; Jensen, Lars Juhl; Schneider, Reinhard; Skoblo, Roman; Russell, Robert B; Bourne, Philip E; Bork, Peer; Preissner, Robert

2008-01-01

The molecular basis of drug action is often not well understood. This is partly because the very abundant and diverse information generated in the past decades on drugs is hidden in millions of medical articles or textbooks. Therefore, we developed a one-stop data warehouse, SuperTarget that integrates drug-related information about medical indication areas, adverse drug effects, drug metabolization, pathways and Gene Ontology terms of the target proteins. An easy-to-use query interface enables the user to pose complex queries, for example to find drugs that target a certain pathway, interacting drugs that are metabolized by the same cytochrome P450 or drugs that target the same protein but are metabolized by different enzymes. Furthermore, we provide tools for 2D drug screening and sequence comparison of the targets. The database contains more than 2500 target proteins, which are annotated with about 7300 relations to 1500 drugs; the vast majority of entries have pointers to the respective literature source. A subset of these drugs has been annotated with additional binding information and indirect interactions and is available as a separate resource called Matador. SuperTarget and Matador are available at http://insilico.charite.de/supertarget and http://matador.embl.de.

Clinical outcomes and incremental costs from a medication adherence pilot intervention targeting low-income patients with diabetes at risk of cost-related medication nonadherence.

PubMed

Ryan, John G; Fedders, Mark; Jennings, Terri; Vittoria, Isabel; Yanes, Melissa

2014-12-01

The extent to which reducing cost-related barriers affects diabetes outcomes and medication adherence among uninsured patients is not known. The purpose of these analyses was to understand the clinical impact and cost considerations of a prescription assistance program targeting low-income, minority patients with diabetes and at high risk for cost-related medication nonadherence. Patients received diabetes medications without copayments for 12 months. Change in diabetes control was calculated by using glycosylated hemoglobin (HbA1c) level at follow-up compared with baseline. Clinical data were collected from the electronic health record. Medication adherence for diabetes medications was estimated by using proportion of days covered (PDC). Incremental acquisition and per-patient costs, based on actual hospital medication costs, were calculated for different baseline HbA1c levels. Patients with baseline HbA1c levels ≥7%, ≥8%, and ≥9% experienced mean HbA1c reductions of 0.82% (P = 0.008), 1.02% (P = 0.010), and 1.47% (P = 0.010), respectively, during the 12-month period. The average PDC was 70.55%; 45.24% had a PDC ≥80%, indicating an adequate level of medication adherence. Medication adherence ≥80% was associated with ethnicity (P = 0.015), whereas mean PDC was associated with number of diabetes medication classes used (P = 0.031). Acquisition cost for 1242 prescriptions filled by 103 patients was $13,365.82, representing per-patient costs of $132.39; however, as baseline targets increased, acquisition costs decreased and per-patient costs increased from $10,682.59 and $169.56 to $6509.91 and $192.27, respectively. Clinically significant reductions in HbA1c levels were achieved for all patients, although greater reductions were achieved with modest per-patient cost increases when considering patients with uncontrolled diabetes. Incorporating a multifactorial intervention to address cost-related medication nonadherence with a behavior change component may

High-Value, Cost-Conscious Care: Iterative Systems-Based Interventions to Reduce Unnecessary Laboratory Testing.

PubMed

Sadowski, Brett W; Lane, Alison B; Wood, Shannon M; Robinson, Sara L; Kim, Chin Hee

2017-09-01

Inappropriate testing contributes to soaring healthcare costs within the United States, and teaching hospitals are vulnerable to providing care largely for academic development. Via its "Choosing Wisely" campaign, the American Board of Internal Medicine recommends avoiding repetitive testing for stable inpatients. We designed systems-based interventions to reduce laboratory orders for patients admitted to the wards at an academic facility. We identified the computer-based order entry system as an appropriate target for sustainable intervention. The admission order set had allowed multiple routine tests to be ordered repetitively each day. Our iterative study included interventions on the automated order set and cost displays at order entry. The primary outcome was number of routine tests controlled for inpatient days compared with the preceding year. Secondary outcomes included cost savings, delays in care, and adverse events. Data were collected over a 2-month period following interventions in sequential years and compared with the year prior. The first intervention led to 0.97 fewer laboratory tests per inpatient day (19.4%). The second intervention led to sustained reduction, although by less of a margin than order set modifications alone (15.3%). When extrapolating the results utilizing fees from the Centers for Medicare and Medicaid Services, there was a cost savings of $290,000 over 2 years. Qualitative survey data did not suggest an increase in care delays or near-miss events. This series of interventions targeting unnecessary testing demonstrated a sustained reduction in the number of routine tests ordered, without adverse effects on clinical care. Published by Elsevier Inc.

Processing Lexical and Speaker Information in Repetition and Semantic/Associative Priming

ERIC Educational Resources Information Center

Lee, Chao-Yang; Zhang, Yu

2018-01-01

The purpose of this study is to investigate the interaction between processing lexical and speaker-specific information in spoken word recognition. The specific question is whether repetition and semantic/associative priming is reduced when the prime and target are produced by different speakers. In Experiment 1, the prime and target were repeated…

A Secure and Privacy-Preserving Targeted Ad-System

NASA Astrophysics Data System (ADS)

Androulaki, Elli; Bellovin, Steven M.

Thanks to its low product-promotion cost and its efficiency, targeted online advertising has become very popular. Unfortunately, being profile-based, online advertising methods violate consumers' privacy, which has engendered resistance to the ads. However, protecting privacy through anonymity seems to encourage click-fraud. In this paper, we define consumer's privacy and present a privacy-preserving, targeted ad system (PPOAd) which is resistant towards click fraud. Our scheme is structured to provide financial incentives to all entities involved.

Reducing emissions from agriculture to meet the 2 °C target.

PubMed

Wollenberg, Eva; Richards, Meryl; Smith, Pete; Havlík, Petr; Obersteiner, Michael; Tubiello, Francesco N; Herold, Martin; Gerber, Pierre; Carter, Sarah; Reisinger, Andrew; van Vuuren, Detlef P; Dickie, Amy; Neufeldt, Henry; Sander, Björn O; Wassmann, Reiner; Sommer, Rolf; Amonette, James E; Falcucci, Alessandra; Herrero, Mario; Opio, Carolyn; Roman-Cuesta, Rosa Maria; Stehfest, Elke; Westhoek, Henk; Ortiz-Monasterio, Ivan; Sapkota, Tek; Rufino, Mariana C; Thornton, Philip K; Verchot, Louis; West, Paul C; Soussana, Jean-François; Baedeker, Tobias; Sadler, Marc; Vermeulen, Sonja; Campbell, Bruce M

2016-12-01

More than 100 countries pledged to reduce agricultural greenhouse gas (GHG) emissions in the 2015 Paris Agreement of the United Nations Framework Convention on Climate Change. Yet technical information about how much mitigation is needed in the sector vs. how much is feasible remains poor. We identify a preliminary global target for reducing emissions from agriculture of ~1 GtCO 2 e yr -1 by 2030 to limit warming in 2100 to 2 °C above pre-industrial levels. Yet plausible agricultural development pathways with mitigation cobenefits deliver only 21-40% of needed mitigation. The target indicates that more transformative technical and policy options will be needed, such as methane inhibitors and finance for new practices. A more comprehensive target for the 2 °C limit should be developed to include soil carbon and agriculture-related mitigation options. Excluding agricultural emissions from mitigation targets and plans will increase the cost of mitigation in other sectors or reduce the feasibility of meeting the 2 °C limit. © 2016 The Authors Global Change Biology Published by John Wiley & Sons Ltd.

Eye tracking a self-moved target with complex hand-target dynamics

PubMed Central

Landelle, Caroline; Montagnini, Anna; Madelain, Laurent

2016-01-01

Previous work has shown that the ability to track with the eye a moving target is substantially improved when the target is self-moved by the subject's hand compared with when being externally moved. Here, we explored a situation in which the mapping between hand movement and target motion was perturbed by simulating an elastic relationship between the hand and target. Our objective was to determine whether the predictive mechanisms driving eye-hand coordination could be updated to accommodate this complex hand-target dynamics. To fully appreciate the behavioral effects of this perturbation, we compared eye tracking performance when self-moving a target with a rigid mapping (simple) and a spring mapping as well as when the subject tracked target trajectories that he/she had previously generated when using the rigid or spring mapping. Concerning the rigid mapping, our results confirmed that smooth pursuit was more accurate when the target was self-moved than externally moved. In contrast, with the spring mapping, eye tracking had initially similar low spatial accuracy (though shorter temporal lag) in the self versus externally moved conditions. However, within ∼5 min of practice, smooth pursuit improved in the self-moved spring condition, up to a level similar to the self-moved rigid condition. Subsequently, when the mapping unexpectedly switched from spring to rigid, the eye initially followed the expected target trajectory and not the real one, thereby suggesting that subjects used an internal representation of the new hand-target dynamics. Overall, these results emphasize the stunning adaptability of smooth pursuit when self-maneuvering objects with complex dynamics. PMID:27466129

A biochemical approach to identifying microRNA targets

PubMed Central

Karginov, Fedor V.; Conaco, Cecilia; Xuan, Zhenyu; Schmidt, Bryan H.; Parker, Joel S.; Mandel, Gail; Hannon, Gregory J.

2007-01-01

Identifying the downstream targets of microRNAs (miRNAs) is essential to understanding cellular regulatory networks. We devised a direct biochemical method for miRNA target discovery that combined RNA-induced silencing complex (RISC) purification with microarray analysis of bound mRNAs. Because targets of miR-124a have been analyzed, we chose it as our model. We honed our approach both by examining the determinants of stable binding between RISC and synthetic target RNAs in vitro and by determining the dependency of both repression and RISC coimmunoprecipitation on miR-124a seed sites in two of its well characterized targets in vivo. Examining the complete spectrum of miR-124 targets in 293 cells yielded both a set that were down-regulated at the mRNA level, as previously observed, and a set whose mRNA levels were unaffected by miR-124a. Reporter assays validated both classes, extending the spectrum of mRNA targets that can be experimentally linked to the miRNA pathway. PMID:18042700

Sputter target

DOEpatents

Gates, Willard G.; Hale, Gerald J.

1980-01-01

The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy.

Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

PubMed

Yang, Ye; Zhang, Jianyun; Yao, Yijun

2017-01-01

Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective.

PubMed

Li, Ying Hong; Wang, Pan Pan; Li, Xiao Xu; Yu, Chun Yan; Yang, Hong; Zhou, Jin; Xue, Wei Wei; Tan, Jun; Zhu, Feng

2016-01-01

The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

Advances in targeted genome editing.

PubMed

Perez-Pinera, Pablo; Ousterout, David G; Gersbach, Charles A

2012-08-01

New technologies have recently emerged that enable targeted editing of genomes in diverse systems. This includes precise manipulation of gene sequences in their natural chromosomal context and addition of transgenes to specific genomic loci. This progress has been facilitated by advances in engineering targeted nucleases with programmable, site-specific DNA-binding domains, including zinc finger proteins and transcription activator-like effectors (TALEs). Recent improvements have enhanced nuclease performance, accelerated nuclease assembly, and lowered the cost of genome editing. These advances are driving new approaches to many areas of biotechnology, including biopharmaceutical production, agriculture, creation of transgenic organisms and cell lines, and studies of genome structure, regulation, and function. Genome editing is also being investigated in preclinical and clinical gene therapies for many diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Systems biology-embedded target validation: improving efficacy in drug discovery.

PubMed

Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

2014-01-01

The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. © 2013 Wiley Periodicals, Inc.

The Holistic Targeting (HOT) Methodology as the Means to Improve Information Operations (IO) Target Development and Prioritization

DTIC Science & Technology

2008-09-01

software facilitate targeting problem understanding and the network analysis tool, Palantir , as an efficient and tailored semi-automated means to...the use of compendium software facilitate targeting problem understanding and the network analysis tool, Palantir , as an efficient and tailored semi...OBJECTIVES USING COMPENDIUM SOFTWARE .....63 E. HOT TARGET PRIORITIZATION AND DEVELOPMENT USING PALANTIR SOFTWARE .................................69 1

Does Prevention Pay? Costs and Potential Cost-savings of School Interventions Targeting Children with Mental Health Problems.

PubMed

Wellander, Lisa; Wells, Michael B; Feldman, Inna

2016-06-01

In Sweden, the local government is responsible for funding schools in their district. One funding initiative is for schools to provide students with mental health problems with additional support via extra teachers, personal assistants, and special education classes. There are evidence-based preventive interventions delivered in schools, which have been shown to decrease the levels of students' mental health problems. However, little is known about how much the local government currently spends on students' mental health support and if evidence-based interventions could be financially beneficial. The aim of this study was to estimate the costs of providing additional support for students' mental health problems and the potential cost-offsets, defined as reduced school-based additional support, if two evidence-based school interventions targeting children's mental health problems were implemented in routine practice. This study uses data on the additional support students with mental health problems received in schools. Data was collected from one school district for students aged 6 to 16 years. We modeled two Swedish school interventions, Comet for Teachers and Social and Emotional Training (SET), which both had evidence of reducing mental health problems. We used a cost-offset analysis framework, assuming both interventions were fully implemented throughout the whole school district. Based on the published studies, the expected effects and the costs of the interventions were calculated. We defined the cost-offsets as the amount of predicted averted additional support for students with ongoing mental health problems who might no longer require receiving services such as one-on-one time with an extra teacher, a personal assistant, or to be placed in a special education classroom. A cost-offset analysis, from a payer's perspective (the local government responsible for school financing), was conducted comparing the costs of both interventions with the potential cost

Predicting oligonucleotide affinity to nucleic acid targets.

PubMed Central

Mathews, D H; Burkard, M E; Freier, S M; Wyatt, J R; Turner, D H

1999-01-01

A computer program, OligoWalk, is reported that predicts the equilibrium affinity of complementary DNA or RNA oligonucleotides to an RNA target. This program considers the predicted stability of the oligonucleotide-target helix and the competition with predicted secondary structure of both the target and the oligonucleotide. Both unimolecular and bimolecular oligonucleotide self structure are considered with a user-defined concentration. The application of OligoWalk is illustrated with three comparisons to experimental results drawn from the literature. PMID:10580474

Electrophysiological evidence for size invariance in masked picture repetition priming

PubMed Central

Eddy, Marianna D.; Holcomb, Phillip J.

2009-01-01

This experiment examined invariance in object representations through measuring event-related potentials (ERPs) to pictures in a masked repetition priming paradigm. Pairs of pictures were presented where the prime was either the same size or half the size of the target object and the target was either presented in a normal orientation or was a normal sized mirror reflection of the prime object. Previous masked repetition priming studies have found a cascade of priming effect sensitive to perceptual (N190/P190) and semantic (N400) properties of the stimulus. This experiment found that both early (N190/P190 effects) and later effects (N400) were invariant to size, whereas only the N190/P190 effect was invariant to mirror reflection. The combination of a small prime and a mirror reflected target led to no significant priming effects. Taken together, the results of this set of experiments suggests that object recognition, more specifically, activating an object representation, occurs in a hierarchical fashion where overlapping perceptual information between the prime and target is necessary, although not always sufficient, to activate a higher level semantic representation. PMID:19560248

Pathways to Mexico’s climate change mitigation targets: A multi-model analysis

DOE PAGES

Veysey, Jason; Octaviano, Claudia; Calvin, Katherine; ...

2015-04-25

Mexico’s climate policy sets ambitious national greenhouse gas (GHG) emission reduction targets—30% versus a business-as-usual baseline by 2020, 50% versus 2000 by 2050. However, these goals are at odds with recent energy and emission trends in the country. Both energy use and GHG emissions in Mexico have grown substantially over the last two decades. Here, we investigate how Mexico might reverse current trends and reach its mitigation targets by exploring results from energy system and economic models involved in the CLIMACAP-LAMP project. To meet Mexico’s emission reduction targets, all modeling groups agree that decarbonization of electricity is needed, along withmore » changes in the transport sector, either to more efficient vehicles or a combination of more efficient vehicles and lower carbon fuels. These measures reduce GHG emissions as well as emissions of other air pollutants. The models find different energy supply pathways, with some solutions based on renewable energy and others relying on biomass or fossil fuels with carbon capture and storage. The economy-wide costs of deep mitigation could range from 2% to 4% of GDP in 2030, and from 7% to 15% of GDP in 2050. Our results suggest that Mexico has some flexibility in designing deep mitigation strategies, and that technological options could allow Mexico to achieve its emission reduction targets, albeit at a cost to the country.« less

Context-dependent sequential effects of target selection for action.

PubMed

Moher, Jeff; Song, Joo-Hyun

2013-07-11

Humans exhibit variation in behavior from moment to moment even when performing a simple, repetitive task. Errors are typically followed by cautious responses, minimizing subsequent distractor interference. However, less is known about how variation in the execution of an ultimately correct response affects subsequent behavior. We asked participants to reach toward a uniquely colored target presented among distractors and created two categories to describe participants' responses in correct trials based on analyses of movement trajectories; partial errors referred to trials in which observers initially selected a nontarget for action before redirecting the movement and accurately pointing to the target, and direct movements referred to trials in which the target was directly selected for action. We found that latency to initiate a hand movement was shorter in trials following partial errors compared to trials following direct movements. Furthermore, when the target and distractor colors were repeated, movement time and reach movement curvature toward distractors were greater following partial errors compared to direct movements. Finally, when the colors were repeated, partial errors were more frequent than direct movements following partial-error trials, and direct movements were more frequent following direct-movement trials. The dependence of these latter effects on repeated-task context indicates the involvement of higher-level cognitive mechanisms in an integrated attention-action system in which execution of a partial-error or direct-movement response affects memory representations that bias performance in subsequent trials. Altogether, these results demonstrate that whether a nontarget is selected for action or not has a measurable impact on subsequent behavior.

Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial.

PubMed

Khan, Fakhar Z; Virdee, Mumohan S; Palmer, Christopher R; Pugh, Peter J; O'Halloran, Denis; Elsik, Maros; Read, Philip A; Begley, David; Fynn, Simon P; Dutka, David P

2012-04-24

This study sought to assess the impact of targeted left ventricular (LV) lead placement on outcomes of cardiac resynchronization therapy (CRT). Placement of the LV lead to the latest sites of contraction and away from the scar confers the best response to CRT. We conducted a randomized, controlled trial to compare a targeted approach to LV lead placement with usual care. A total of 220 patients scheduled for CRT underwent baseline echocardiographic speckle-tracking 2-dimensional radial strain imaging and were then randomized 1:1 into 2 groups. In group 1 (TARGET [Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy]), the LV lead was positioned at the latest site of peak contraction with an amplitude of >10% to signify freedom from scar. In group 2 (control) patients underwent standard unguided CRT. Patients were classified by the relationship of the LV lead to the optimal site as concordant (at optimal site), adjacent (within 1 segment), or remote (≥2 segments away). The primary endpoint was a ≥15% reduction in LV end-systolic volume at 6 months. Secondary endpoints were clinical response (≥1 improvement in New York Heart Association functional class), all-cause mortality, and combined all-cause mortality and heart failure-related hospitalization. The groups were balanced at randomization. In the TARGET group, there was a greater proportion of responders at 6 months (70% vs. 55%, p = 0.031), giving an absolute difference in the primary endpoint of 15% (95% confidence interval: 2% to 28%). Compared with controls, TARGET patients had a higher clinical response (83% vs. 65%, p = 0.003) and lower rates of the combined endpoint (log-rank test, p = 0.031). Compared with standard CRT treatment, the use of speckle-tracking echocardiography to the target LV lead placement yields significantly improved response and clinical status and lower rates of combined death and heart failure-related hospitalization. (Targeted Left Ventricular Lead

Research on the underwater target imaging based on the streak tube laser lidar

NASA Astrophysics Data System (ADS)

Cui, Zihao; Tian, Zhaoshuo; Zhang, Yanchao; Bi, Zongjie; Yang, Gang; Gu, Erdan

2018-03-01

A high frame rate streak tube imaging lidar (STIL) for real-time 3D imaging of underwater targets is presented in this paper. The system uses 532nm pulse laser as the light source, the maximum repetition rate is 120Hz, and the pulse width is 8ns. LabVIEW platform is used in the system, the system control, synchronous image acquisition, 3D data processing and display are realized through PC. 3D imaging experiment of underwater target is carried out in a flume with attenuation coefficient of 0.2, and the images of different depth and different material targets are obtained, the imaging frame rate is 100Hz, and the maximum detection depth is 31m. For an underwater target with a distance of 22m, the high resolution 3D image real-time acquisition is realized with range resolution of 1cm and space resolution of 0.3cm, the spatial relationship of the targets can be clearly identified by the image. The experimental results show that STIL has a good application prospect in underwater terrain detection, underwater search and rescue, and other fields.

Drug-induced amplification of nanoparticle targeting to tumors

PubMed Central

Lin, Kevin Y.; Kwon, Ester J.; Lo, Justin H.; Bhatia, Sangeeta N.

2018-01-01

Summary Nanomedicines have the potential to significantly impact cancer therapy by improving drug efficacy and decreasing off-target effects, yet our ability to efficiently home nanoparticles to disease sites remains limited. One frequently overlooked constraint of current active targeting schemes is the relative dearth of targetable antigens within tumors, which restricts the amount of cargo that can be delivered in a tumor-specific manner. To address this limitation, we exploit tumor-specific responses to drugs to construct a cooperative targeting system where a small molecule therapeutic modulates the disease microenvironment to amplify nanoparticle recruitment in vivo. We first administer a vascular disrupting agent, ombrabulin, which selectively affects tumors and leads to locally elevated presentation of the stress-related protein, p32. This increase in p32 levels provides more binding sites for circulating p32-targeted nanoparticles, enhancing their delivery of diagnostic or therapeutic cargos to tumors. We show that this cooperative targeting system recruits over five times higher doses of nanoparticles to tumors and decreases tumor burden when compared with non-cooperative controls. These results suggest that using nanomedicine in conjunction with drugs that enhance the presentation of target antigens in the tumor environment may be an effective strategy for improving the diagnosis and treatment of cancer. PMID:29731806

Magnetically attached sputter targets

DOEpatents

Makowiecki, Daniel M.; McKernan, Mark A.

1994-01-01

An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly.

Targeted Nanomaterials for Phototherapy

PubMed Central

Chitgupi, Upendra; Qin, Yiru; Lovell, Jonathan F.

2017-01-01

Phototherapies involve the irradiation of target tissues with light. To further enhance selectivity and potency, numerous molecularly targeted photosensitizers and photoactive nanoparticles have been developed. Active targeting typically involves harnessing the affinity between a ligand and a cell surface receptor for improved accumulation in the targeted tissue. Targeting ligands including peptides, proteins, aptamers and small molecules have been explored for phototherapy. In this review, recent examples of targeted nanomaterials used in phototherapy are summarized. PMID:29071178

Repetition priming in selective attention: A TVA analysis.

PubMed

Ásgeirsson, Árni Gunnar; Kristjánsson, Árni; Bundesen, Claus

2015-09-01

Current behavior is influenced by events in the recent past. In visual attention, this is expressed in many variations of priming effects. Here, we investigate color priming in a brief exposure digit-recognition task. Observers performed a masked odd-one-out singleton recognition task where the target-color either repeated or changed between subsequent trials. Performance was measured by recognition accuracy over exposure durations. The purpose of the study was to replicate earlier findings of perceptual priming in brief displays and to model those results based on a Theory of Visual Attention (TVA; Bundesen, 1990). We tested 4 different definitions of a generic TVA-model and assessed their explanatory power. Our hypothesis was that priming effects could be explained by selective mechanisms, and that target-color repetitions would only affect the selectivity parameter (α) of our models. Repeating target colors enhanced performance for all 12 observers. As predicted, this was only true under conditions that required selection of a target among distractors, but not when a target was presented alone. Model fits by TVA were obtained with a trial-by-trial maximum likelihood estimation procedure that estimated 4-15 free parameters, depending on the particular model. We draw two main conclusions. Color priming can be modeled simply as a change in selectivity between conditions of repetition or swap of target color. Depending on the desired resolution of analysis; priming can accurately be modeled by a simple four parameter model, where VSTM capacity and spatial biases of attention are ignored, or more fine-grained by a 10 parameter model that takes these aspects into account. Copyright © 2015 Elsevier B.V. All rights reserved.

Masked Repetition Priming Treatment for Anomia

ERIC Educational Resources Information Center

Silkes, JoAnn P.

2018-01-01

Purpose: Masked priming has been suggested as a way to directly target implicit lexical retrieval processes in aphasia. This study was designed to investigate repeated use of masked repetition priming to improve picture naming in individuals with anomia due to aphasia. Method: A single-subject, multiple-baseline design was used across 6 people…

WFIRST: Exoplanet Target Selection and Scheduling with Greedy Optimization

NASA Astrophysics Data System (ADS)

Keithly, Dean; Garrett, Daniel; Delacroix, Christian; Savransky, Dmitry

2018-01-01

We present target selection and scheduling algorithms for missions with direct imaging of exoplanets, and the Wide Field Infrared Survey Telescope (WFIRST) in particular, which will be equipped with a coronagraphic instrument (CGI). Optimal scheduling of CGI targets can maximize the expected value of directly imaged exoplanets (completeness). Using target completeness as a reward metric and integration time plus overhead time as a cost metric, we can maximize the sum completeness for a mission with a fixed duration. We optimize over these metrics to create a list of target stars using a greedy optimization algorithm based off altruistic yield optimization (AYO) under ideal conditions. We simulate full missions using EXOSIMS by observing targets in this list for their predetermined integration times. In this poster, we report the theoretical maximum sum completeness, mean number of detected exoplanets from Monte Carlo simulations, and the ideal expected value of the simulated missions.

Optimal resource allocation for defense of targets based on differing measures of attractiveness.

PubMed

Bier, Vicki M; Haphuriwat, Naraphorn; Menoyo, Jaime; Zimmerman, Rae; Culpen, Alison M

2008-06-01

This article describes the results of applying a rigorous computational model to the problem of the optimal defensive resource allocation among potential terrorist targets. In particular, our study explores how the optimal budget allocation depends on the cost effectiveness of security investments, the defender's valuations of the various targets, and the extent of the defender's uncertainty about the attacker's target valuations. We use expected property damage, expected fatalities, and two metrics of critical infrastructure (airports and bridges) as our measures of target attractiveness. Our results show that the cost effectiveness of security investment has a large impact on the optimal budget allocation. Also, different measures of target attractiveness yield different optimal budget allocations, emphasizing the importance of developing more realistic terrorist objective functions for use in budget allocation decisions for homeland security.

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.

Treat to target in gout.

PubMed

Perez-Ruiz, Fernando; Moreno-Lledó, Aitana; Urionagüena, Irati; Dickson, Alastair J

2018-01-01

The treat-to-target (T2T) approach has been successfully implemented in a number of diseases. T2T has been proposed for rheumatic diseases such as RA, spondyloarthritis, lupus, and recently for gout. The level of evidence for such approaches differs from one condition to the other (moderate to high for hyperlipidaemia, for example). Practice is based on the best available evidence at any time, and in absence of good evidence for T2T in gout, some suggest a conservative only-treat-symptoms approach. Evidence suggests that not treating gout to target in the long term is overall associated with worsening outcomes, such as flares, tophi and structural damage, which is associated to loss of quality of life and mortality. Different targets have been proposed for hyperuricaemia in gout; lower than 6 mg/dl (0.36 mmol/l) for all patients, at least <5 mg/dl (0.30 mmol/l) for patients with severe-polyarticular or tophaceous-gout. © The Author 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

GWASeq: targeted re-sequencing follow up to GWAS.

PubMed

Salomon, Matthew P; Li, Wai Lok Sibon; Edlund, Christopher K; Morrison, John; Fortini, Barbara K; Win, Aung Ko; Conti, David V; Thomas, Duncan C; Duggan, David; Buchanan, Daniel D; Jenkins, Mark A; Hopper, John L; Gallinger, Steven; Le Marchand, Loïc; Newcomb, Polly A; Casey, Graham; Marjoram, Paul

2016-03-03

For the last decade the conceptual framework of the Genome-Wide Association Study (GWAS) has dominated the investigation of human disease and other complex traits. While GWAS have been successful in identifying a large number of variants associated with various phenotypes, the overall amount of heritability explained by these variants remains small. This raises the question of how best to follow up on a GWAS, localize causal variants accounting for GWAS hits, and as a consequence explain more of the so-called "missing" heritability. Advances in high throughput sequencing technologies now allow for the efficient and cost-effective collection of vast amounts of fine-scale genomic data to complement GWAS. We investigate these issues using a colon cancer dataset. After QC, our data consisted of 1993 cases, 899 controls. Using marginal tests of associations, we identify 10 variants distributed among six targeted regions that are significantly associated with colorectal cancer, with eight of the variants being novel to this study. Additionally, we perform so-called 'SNP-set' tests of association and identify two sets of variants that implicate both common and rare variants in the etiology of colorectal cancer. Here we present a large-scale targeted re-sequencing resource focusing on genomic regions implicated in colorectal cancer susceptibility previously identified in several GWAS, which aims to 1) provide fine-scale targeted sequencing data for fine-mapping and 2) provide data resources to address methodological questions regarding the design of sequencing-based follow-up studies to GWAS. Additionally, we show that this strategy successfully identifies novel variants associated with colorectal cancer susceptibility and can implicate both common and rare variants.

Polarized internal target apparatus

DOEpatents

Holt, Roy J.

1986-01-01

A polarized internal target apparatus with a polarized gas target of improved polarization and density achieved by mixing target gas atoms with a small amount of alkali metal gas atoms, and passing a high intensity polarized light source into the mixture to cause the alkali metal gas atoms to become polarized which interact in spin exchange collisions with target gas atoms yielding polarized target gas atoms.

Single molecule targeted sequencing for cancer gene mutation detection.

PubMed

Gao, Yan; Deng, Liwei; Yan, Qin; Gao, Yongqian; Wu, Zengding; Cai, Jinsen; Ji, Daorui; Li, Gailing; Wu, Ping; Jin, Huan; Zhao, Luyang; Liu, Song; Ge, Liangjin; Deem, Michael W; He, Jiankui

2016-05-19

With the rapid decline in cost of sequencing, it is now affordable to examine multiple genes in a single disease-targeted clinical test using next generation sequencing. Current targeted sequencing methods require a separate step of targeted capture enrichment during sample preparation before sequencing. Although there are fast sample preparation methods available in market, the library preparation process is still relatively complicated for physicians to use routinely. Here, we introduced an amplification-free Single Molecule Targeted Sequencing (SMTS) technology, which combined targeted capture and sequencing in one step. We demonstrated that this technology can detect low-frequency mutations using artificially synthesized DNA sample. SMTS has several potential advantages, including simple sample preparation thus no biases and errors are introduced by PCR reaction. SMTS has the potential to be an easy and quick sequencing technology for clinical diagnosis such as cancer gene mutation detection, infectious disease detection, inherited condition screening and noninvasive prenatal diagnosis.

Magnetically attached sputter targets

DOEpatents

Makowiecki, D.M.; McKernan, M.A.

1994-02-15

An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material is described. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly. 11 figures.

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

Polarized internal target apparatus

DOEpatents

Holt, R.J.

1984-10-10

A polarized internal target apparatus with a polarized gas target of improved polarization and density (achieved by mixing target gas atoms with a small amount of alkali metal gas atoms, and passing a high intensity polarized light source into the mixture to cause the alkali metal gas atoms to become polarized which interact in spin exchange collisions with target gas atoms yielding polarized target gas atoms) is described.

Cooperative Robots to Observe Moving Targets: Review.

PubMed

Khan, Asif; Rinner, Bernhard; Cavallaro, Andrea

2018-01-01

The deployment of multiple robots for achieving a common goal helps to improve the performance, efficiency, and/or robustness in a variety of tasks. In particular, the observation of moving targets is an important multirobot application that still exhibits numerous open challenges, including the effective coordination of the robots. This paper reviews control techniques for cooperative mobile robots monitoring multiple targets. The simultaneous movement of robots and targets makes this problem particularly interesting, and our review systematically addresses this cooperative multirobot problem for the first time. We classify and critically discuss the control techniques: cooperative multirobot observation of multiple moving targets, cooperative search, acquisition, and track, cooperative tracking, and multirobot pursuit evasion. We also identify the five major elements that characterize this problem, namely, the coordination method, the environment, the target, the robot and its sensor(s). These elements are used to systematically analyze the control techniques. The majority of the studied work is based on simulation and laboratory studies, which may not accurately reflect real-world operational conditions. Importantly, while our systematic analysis is focused on multitarget observation, our proposed classification is useful also for related multirobot applications.

Artificial testing targets with controllable blur for adaptive optics microscopes

NASA Astrophysics Data System (ADS)

Hattori, Masayuki; Tamada, Yosuke; Murata, Takashi; Oya, Shin; Hasebe, Mitsuyasu; Hayano, Yutaka; Kamei, Yasuhiro

2017-08-01

This letter proposes a method of configuring a testing target to evaluate the performance of adaptive optics microscopes. In this method, a testing slide with fluorescent beads is used to simultaneously determine the point spread function and the field of view. The point spread function is reproduced to simulate actual biological samples by etching a microstructure on the cover glass. The fabrication process is simplified to facilitate an onsite preparation. The artificial tissue consists of solid materials and silicone oil and is stable for use in repetitive experiments.

Hospitals: Soft Target for Terrorism?

PubMed

De Cauwer, Harald; Somville, Francis; Sabbe, Marc; Mortelmans, Luc J

2017-02-01

In recent years, the world has been rocked repeatedly by terrorist attacks. Arguably, the most remarkable were: the series of four coordinated suicide plane attacks on September 11, 2001 on buildings in New York, Virginia, and Pennsylvania, USA; and the recent series of two coordinated attacks in Brussels (Belgium), on March 22, 2016, involving two bombings at the departure hall of Brussels International Airport and a bombing at Maalbeek Metro Station located near the European Commission headquarters in the center of Brussels. This statement paper deals with different aspects of hospital policy and disaster response planning that interface with terrorism. Research shows that the availability of necessary equipment and facilities (eg, personal protective clothing, decontamination rooms, antidotes, and anti-viral drugs) in hospitals clearly is insufficient. Emergency teams are insufficiently prepared: adequate and repetitive training remain necessary. Unfortunately, there are many examples of health care workers and physicians or hospitals being targeted in both political or religious conflicts and wars. Many health workers were kidnapped and/or killed by insurgents of various ideology. Attacks on hospitals also could cause long-term effects: hospital units could be unavailable for a long time and replacing staff could take several months, further compounding hospital operations. Both physical and psychological (eg, posttraumatic stress disorder [PTSD]) after-effects of a terrorist attack can be detrimental to health care services. On the other hand, physicians and other hospital employees have shown to be involved in terrorism. As data show that some offenders had a previous history with the location of the terror incident, the possibility of hospitals or other health care services being targeted by insiders is discussed. The purpose of this report was to consider how past terrorist incidents can inform current hospital preparedness and disaster response planning

Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges

PubMed Central

Toporkiewicz, Monika; Meissner, Justyna; Matusewicz, Lucyna; Czogalla, Aleksander; Sikorski, Aleksander F

2015-01-01

There are many problems directly correlated with the systemic administration of drugs and how they reach their target site. Targeting promises to be a hopeful strategy as an improved means of drug delivery, with reduced toxicity and minimal adverse side effects. Targeting exploits the high affinity of cell-surface-targeted ligands, either directly or as carriers for a drug, for specific retention and uptake by the targeted diseased cells. One of the most important parameters which should be taken into consideration in the selection of an appropriate ligand for targeting is the binding affinity (KD). In this review we focus on the importance of binding affinities of monoclonal antibodies, antibody derivatives, peptides, aptamers, DARPins, and small targeting molecules in the process of selection of the most suitable ligand for targeting of nanoparticles. In order to provide a critical comparison between these various options, we have also assessed each technology format across a range of parameters such as molecular size, immunogenicity, costs of production, clinical profiles, and examples of the level of selectivity and toxicity of each. Wherever possible, we have also assessed how incorporating such a targeted approach compares with, or is superior to, original treatments. PMID:25733832

Maximizing in vivo target clearance by design of pH-dependent target binding antibodies with altered affinity to FcRn.

PubMed

Yang, Danlin; Giragossian, Craig; Castellano, Steven; Lasaro, Marcio; Xiao, Haiguang; Saraf, Himanshu; Hess Kenny, Cynthia; Rybina, Irina; Huang, Zhong-Fu; Ahlberg, Jennifer; Bigwarfe, Tammy; Myzithras, Maria; Waltz, Erica; Roberts, Simon; Kroe-Barrett, Rachel; Singh, Sanjaya

2017-10-01

Antibodies with pH-dependent binding to both target antigens and neonatal Fc receptor (FcRn) provide an alternative tool to conventional neutralizing antibodies, particularly for therapies where reduction in antigen level is challenging due to high target burden. However, the requirements for optimal binding kinetic framework and extent of pH dependence for these antibodies to maximize target clearance from circulation are not well understood. We have identified a series of naturally-occurring high affinity antibodies with pH-dependent target binding properties. By in vivo studies in cynomolgus monkeys, we show that pH-dependent binding to the target alone is not sufficient for effective target removal from circulation, but requires Fc mutations that increase antibody binding to FcRn. Affinity-enhanced pH-dependent FcRn binding that is double-digit nM at pH 7.4 and single-digit nM at pH 6 achieved maximal target reduction when combined with similar target binding affinities in reverse pH directions. Sustained target clearance below the baseline level was achieved 3 weeks after single-dose administration at 1.5 mg/kg. Using the experimentally derived mechanistic model, we demonstrate the essential kinetic interplay between target turnover and antibody pH-dependent binding during the FcRn recycling, and identify the key components for achieving maximal target clearance. These results bridge the demand for improved patient dosing convenience with the "know-how" of therapeutic modality by design.

Molecular-Targeted Immunotherapeutic Strategy for Melanoma via Dual-Targeting Nanoparticles Delivering Small Interfering RNA to Tumor-Associated Macrophages.

PubMed

Qian, Yuan; Qiao, Sha; Dai, Yanfeng; Xu, Guoqiang; Dai, Bolei; Lu, Lisen; Yu, Xiang; Luo, Qingming; Zhang, Zhihong

2017-09-26

Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors. We confirmed the validity of SR-B1 for M2-like TAM targeting and demonstrated the synergistic effect of the two targeting units (α-peptide and M2pep) in the fusion peptide (α-M2pep). After being administered to tumor-bearing mice, M2NPs had higher affinity to M2-like TAMs than to tissue-resident macrophages in liver, spleen, and lung. Compared with control treatment groups, M2NP-based siRNA delivery resulted in a dramatic elimination of M2-like TAMs (52%), decreased tumor size (87%), and prolonged survival. Additionally, this molecular-targeted strategy inhibited immunosuppressive IL-10 and TGF-β production and increased immunostimulatory cytokines (IL-12 and IFN-γ) expression and CD8 + T cell infiltration (2.9-fold) in the tumor microenvironment. Moreover, the siRNA-carrying M2NPs down-regulated expression of the exhaustion markers (PD-1 and Tim-3) on the infiltrating CD8 + T cells and stimulated their IFN-γ secretion (6.2-fold), indicating the restoration of T cell immune function. Thus, the dual-targeting property of M2NPs combined with RNA interference provides a potential strategy of molecular-targeted cancer immunotherapy for clinical application.

Genomic Target Database (GTD): A database of potential targets in human pathogenic bacteria

PubMed Central

Barh, Debmalya; Kumar, Anil; Misra, Amarendra Narayana

2009-01-01

A Genomic Target Database (GTD) has been developed having putative genomic drug targets for human bacterial pathogens. The selected pathogens are either drug resistant or vaccines are yet to be developed against them. The drug targets have been identified using subtractive genomics approaches and these are subsequently classified into Drug targets in pathogen specific unique metabolic pathways,Drug targets in host-pathogen common metabolic pathways, andMembrane localized drug targets. HTML code is used to link each target to its various properties and other available public resources. Essential resources and tools for subtractive genomic analysis, sub-cellular localization, vaccine and drug designing are also mentioned. To the best of authors knowledge, no such database (DB) is presently available that has listed metabolic pathways and membrane specific genomic drug targets based on subtractive genomics. Listed targets in GTD are readily available resource in developing drug and vaccine against the respective pathogen, its subtypes, and other family members. Currently GTD contains 58 drug targets for four pathogens. Shortly, drug targets for six more pathogens will be listed. Availability GTD is available at IIOAB website http://www.iioab.webs.com/GTD.htm. It can also be accessed at http://www.iioabdgd.webs.com.GTD is free for academic research and non-commercial use only. Commercial use is strictly prohibited without prior permission from IIOAB. PMID:20011153

Modeling criterion shifts and target checking in prospective memory monitoring.

PubMed

Horn, Sebastian S; Bayen, Ute J

2015-01-01

Event-based prospective memory (PM) involves remembering to perform intended actions after a delay. An important theoretical issue is whether and how people monitor the environment to execute an intended action when a target event occurs. Performing a PM task often increases the latencies in ongoing tasks. However, little is known about the reasons for this cost effect. This study uses diffusion model analysis to decompose monitoring processes in the PM paradigm. Across 4 experiments, performing a PM task increased latencies in an ongoing lexical decision task. A large portion of this effect was explained by consistent increases in boundary separation; additional increases in nondecision time emerged in a nonfocal PM task and explained variance in PM performance (Experiment 1), likely reflecting a target-checking strategy before and after the ongoing decision (Experiment 2). However, we found that possible target-checking strategies may depend on task characteristics. That is, instructional emphasis on the importance of ongoing decisions (Experiment 3) or the use of focal targets (Experiment 4) eliminated the contribution of nondecision time to the cost of PM, but left participants in a mode of increased cautiousness. The modeling thus sheds new light on the cost effect seen in many PM studies and suggests that people approach ongoing activities more cautiously when they need to remember an intended action. PsycINFO Database Record (c) 2015 APA, all rights reserved.

TargetSpy: a supervised machine learning approach for microRNA target prediction.

PubMed

Sturm, Martin; Hackenberg, Michael; Langenberger, David; Frishman, Dmitrij

2010-05-28

Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila

TargetSpy: a supervised machine learning approach for microRNA target prediction

PubMed Central

2010-01-01

Background Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. Results We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences. In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Conclusion Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well

The Influence of Lexical Status and Neighborhood Density on Children's Nonword Repetition

ERIC Educational Resources Information Center

Metsala, Jamie L.; Chisholm, Gina M.

2010-01-01

This study examined effects of lexical status and neighborhood density of constituent syllables on children's nonword repetition and interactions with nonword length. Lexical status of the target syllable impacted repetition accuracy for the longest nonwords. In addition, children made more errors that changed a nonword syllable to a word syllable…

A General Strategy for Targeting Drugs to Bone.

PubMed

Jahnke, Wolfgang; Bold, Guido; Marzinzik, Andreas L; Ofner, Silvio; Pellé, Xavier; Cotesta, Simona; Bourgier, Emmanuelle; Lehmann, Sylvie; Henry, Chrystelle; Hemmig, René; Stauffer, Frédéric; Hartwieg, J Constanze D; Green, Jonathan R; Rondeau, Jean-Michel

2015-11-23

Targeting drugs to their desired site of action can increase their safety and efficacy. Bisphosphonates are prototypical examples of drugs targeted to bone. However, bisphosphonate bone affinity is often considered too strong and cannot be significantly modulated without losing activity on the enzymatic target, farnesyl pyrophosphate synthase (FPPS). Furthermore, bisphosphonate bone affinity comes at the expense of very low and variable oral bioavailability. FPPS inhibitors were developed with a monophosphonate as a bone-affinity tag that confers moderate affinity to bone, which can furthermore be tuned to the desired level, and the relationship between structure and bone affinity was evaluated by using an NMR-based bone-binding assay. The concept of targeting drugs to bone with moderate affinity, while retaining oral bioavailability, has broad application to a variety of other bone-targeted drugs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Insulin-Like Growth Factor II Targets the mTOR Pathway to Reverse Autism-Like Phenotypes in Mice.

PubMed

Steinmetz, Adam B; Stern, Sarah A; Kohtz, Amy S; Descalzi, Giannina; Alberini, Cristina M

2018-01-24

Autism spectrum disorder (ASD) is a developmental disability characterized by impairments in social interaction and repetitive behavior, and is also associated with cognitive deficits. There is no current treatment that can ameliorate most of the ASD symptomatology; thus, identifying novel therapies is urgently needed. We used male BTBR T + Itpr3 tf /J (BTBR) mice, a model that reproduces most of the core behavioral phenotypes of ASD, to test the effects of systemic administration of insulin-like growth factor II (IGF-II), a polypeptide that crosses the blood-brain barrier and acts as a cognitive enhancer. We show that systemic IGF-II treatments reverse the typical defects in social interaction, cognitive/executive functions, and repetitive behaviors reflective of ASD-like phenotypes. In BTBR mice, IGF-II, via IGF-II receptor, but not via IGF-I receptor, reverses the abnormal levels of the AMPK-mTOR-S6K pathway and of active translation at synapses. Thus, IGF-II may represent a novel potential therapy for ASD. SIGNIFICANCE STATEMENT Currently, there is no effective treatment for autism spectrum disorder (ASD), a developmental disability affecting a high number of children. Using a mouse model that expresses most of the key core as well as associated behavioral deficits of ASD, that are, social, cognitive, and repetitive behaviors, we report that a systemic administration of the polypeptide insulin-like growth factor II (IGF-II) reverses all these deficits. The effects of IGF-II occur via IGF-II receptors, and not IGF-I receptors, and target both basal and learning-dependent molecular abnormalities found in several ASD mice models, including those of identified genetic mutations. We suggest that IGF-II represents a potential novel therapeutic target for ASD. Copyright © 2018 the authors 0270-6474/18/371015-15$15.00/0.

Heterogeneous CPU-GPU moving targets detection for UAV video

NASA Astrophysics Data System (ADS)

Li, Maowen; Tang, Linbo; Han, Yuqi; Yu, Chunlei; Zhang, Chao; Fu, Huiquan

2017-07-01

Moving targets detection is gaining popularity in civilian and military applications. On some monitoring platform of motion detection, some low-resolution stationary cameras are replaced by moving HD camera based on UAVs. The pixels of moving targets in the HD Video taken by UAV are always in a minority, and the background of the frame is usually moving because of the motion of UAVs. The high computational cost of the algorithm prevents running it at higher resolutions the pixels of frame. Hence, to solve the problem of moving targets detection based UAVs video, we propose a heterogeneous CPU-GPU moving target detection algorithm for UAV video. More specifically, we use background registration to eliminate the impact of the moving background and frame difference to detect small moving targets. In order to achieve the effect of real-time processing, we design the solution of heterogeneous CPU-GPU framework for our method. The experimental results show that our method can detect the main moving targets from the HD video taken by UAV, and the average process time is 52.16ms per frame which is fast enough to solve the problem.

Target-directed catalytic metallodrugs

PubMed Central

Joyner, J.C.; Cowan, J.A.

2013-01-01

Most drugs function by binding reversibly to specific biological targets, and therapeutic effects generally require saturation of these targets. One means of decreasing required drug concentrations is incorporation of reactive metal centers that elicit irreversible modification of targets. A common approach has been the design of artificial proteases/nucleases containing metal centers capable of hydrolyzing targeted proteins or nucleic acids. However, these hydrolytic catalysts typically provide relatively low rate constants for target inactivation. Recently, various catalysts were synthesized that use oxidative mechanisms to selectively cleave/inactivate therapeutic targets, including HIV RRE RNA or angiotensin converting enzyme (ACE). These oxidative mechanisms, which typically involve reactive oxygen species (ROS), provide access to comparatively high rate constants for target inactivation. Target-binding affinity, co-reactant selectivity, reduction potential, coordination unsaturation, ROS products (metal-associated vs metal-dissociated; hydroxyl vs superoxide), and multiple-turnover redox chemistry were studied for each catalyst, and these parameters were related to the efficiency, selectivity, and mechanism(s) of inactivation/cleavage of the corresponding target for each catalyst. Important factors for future oxidative catalyst development are 1) positioning of catalyst reduction potential and redox reactivity to match the physiological environment of use, 2) maintenance of catalyst stability by use of chelates with either high denticity or other means of stabilization, such as the square planar geometric stabilization of Ni- and Cu-ATCUN complexes, 3) optimal rate of inactivation of targets relative to the rate of generation of diffusible ROS, 4) targeting and linker domains that afford better control of catalyst orientation, and 5) general bio-availability and drug delivery requirements. PMID:23828584

Targeted delivery of anti-tuberculosis drugs to macrophages: targeting mannose receptors

NASA Astrophysics Data System (ADS)

Filatova, L. Yu; Klyachko, N. L.; Kudryashova, E. V.

2018-04-01

The development of systems for targeted delivery of anti-tuberculosis drugs is a challenge of modern biotechnology. Currently, these drugs are encapsulated in a variety of carriers such as liposomes, polymers, emulsions and so on. Despite successful in vitro testing of these systems, virtually no success was achieved in vivo, because of low accessibility of the foci of infection located in alveolar macrophage cells. A promising strategy for increasing the efficiency of therapeutic action of anti-tuberculosis drugs is to encapsulate the agents into mannosylated carriers targeting the mannose receptors of alveolar macrophages. The review addresses the methods for modification of drug substance carriers, such as liposomes and biodegradable polymers, with mannose residues. The use of mannosylated carriers to deliver anti-tuberculosis agents increases the drug circulation time in the blood stream and increases the drug concentration in alveolar macrophage cells. The bibliography includes 113 references.

Targeted Capture and High-Throughput Sequencing Using Molecular Inversion Probes (MIPs).

PubMed