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.

Two Self-Control Procedures in the Reduction of Targeted and Nontargeted Anxieties.

ERIC Educational Resources Information Center

Deffenbacher, Jerry L.; And Others

1979-01-01

Compared effects of relaxation as self-control and a self-control variant of systematic desensitization in reducing targeted (test anxiety) and nontargeted anxieties with those of wait-list and no-treatment expectancy controls. Groups given relaxation as self-control and modified desensitization reported less debilitating test anxiety than…

Assessment of a Targeted Trap-Neuter-Return Pilot Study in Auckland, New Zealand

PubMed Central

Zito, Sarah; Vigeant, Shalsee; Dale, Arnja

2018-01-01

Simple Summary It is generally accepted that stray cats need to be managed to minimise the associated negative impacts and there is a need for effective and humane management tools. One such potential tool is trap-neuter-return (TNR), which anecdotally has been used in New Zealand to manage stray cats, but no concerted and targeted implementation of this technique has been reported, nor any formal assessments conducted. A targeted TNR (TTNR) programme for urban stray cats was implemented and assessed in one Auckland suburb. Assessment was based on the number of incoming felines; stray, unsocialised cats euthanased; unsocialised, unowned cats sterilised and returned (independently of the TTNR programme); and neonatal/underage euthanasias. Incoming stray feline, underage euthanasia, and unsocialised stray cat euthanasia numbers all reduced for the targeted suburb when these outcome measures were compared for the years before and after the programme. These outcome measures had a greater reduction in the targeted suburb compared to the other Auckland suburbs not targeted by the TTNR programme, although causation cannot be inferred, as a variety of reasons could have contributed to the changes. This pilot programme suggests that TTNR could be a valuable humane cat management tool in urban New Zealand, and further assessment is warranted. Abstract There is a need for effective and humane management tools to manage urban stray cats and minimise negative impacts associated with stray cats. One such tool is targeted trap-neuter-return (TTNR), but no concerted implementation of this technique or formal assessments have been reported. To address this deficit, a TTNR programme was implemented and assessed in one Auckland suburb from May 2015 to June 2016; the programme sterilised and returned 348 cats (4.2 cats/1000 residents). Assessment was based on the number of incoming felines; stray, unsocialised cats euthanased; unsocialised, unowned cats sterilised and returned (independently of the TTNR programme); and neonatal/underage euthanasias. Incoming stray felines, underage euthanasias, and unsocialised stray cat euthanasias were all reduced for the targeted suburb when compared for the years before and after the programme (the percentage reduction in these parameters was −39, −17, −34, −7, and −47, respectively). These outcome measures had a greater reduction in the targeted suburb compared to the Auckland suburbs not targeted by the TTNR programme (p < 0.01), although causation cannot be inferred, as a variety of reasons could have contributed to the changes. This pilot programme suggests that TTNR could be a valuable, humane cat management tool in urban New Zealand, and further assessment is warranted. PMID:29757255

MRI-guided targeting delivery of doxorubicin with reduction-responsive lipid-polymer hybrid nanoparticles.

PubMed

Wu, Bo; Lu, Shu-Ting; Deng, Kai; Yu, Hui; Cui, Can; Zhang, Yang; Wu, Ming; Zhuo, Ren-Xi; Xu, Hai-Bo; Huang, Shi-Wen

2017-01-01

In recent years, there has been increasing interest in developing a multifunctional nanoscale platform for cancer monitoring and chemotherapy. However, there is still a big challenge for current clinic contrast agents to improve their poor tumor selectivity and response. Herein, we report a new kind of Gd complex and folate-coated redox-sensitive lipid-polymer hybrid nanoparticle (Gd-FLPNP) for tumor-targeted magnetic resonance imaging and therapy. Gd-FLPNPs can simultaneously accomplish diagnostic imaging, and specific targeting and controlled release of doxorubicin (DOX). They exhibit good monodispersity, excellent size stability, and a well-defined core-shell structure. Paramagnetic nanoparticles based on gadolinium-diethylenetriaminepentaacetic acid-bis-cetylamine have paramagnetic properties with an approximately two-fold enhancement in the longitudinal relaxivity compared to clinical used Magnevist. For targeted and reduction-sensitive drug delivery, Gd-FLPNPs released DOX faster and enhanced cell uptake in vitro, and exhibited better antitumor effect both in vitro and in vivo.

Comparing effectiveness of mass media campaigns with price reductions targeting fruit and vegetable intake on US cardiovascular disease mortality and race disparities.

PubMed

Pearson-Stuttard, Jonathan; Bandosz, Piotr; Rehm, Colin D; Afshin, Ashkan; Peñalvo, Jose L; Whitsel, Laurie; Danaei, Goodarz; Micha, Renata; Gaziano, Tom; Lloyd-Williams, Ffion; Capewell, Simon; Mozaffarian, Dariush; O'Flaherty, Martin

2017-07-01

Background: A low intake of fruits and vegetables (F&Vs) is a major risk factor for cardiovascular disease (CVD) in the United States. Both mass media campaigns (MMCs) and economic incentives may increase F&V consumption. Few data exist on their comparative effectiveness. Objective: We estimated CVD mortality reductions potentially achievable by price reductions and MMC interventions targeting F&V intake in the US population. Design: We developed a US IMPACT Food Policy Model to compare 3 policies targeting F&V intake across US adults from 2015 to 2030: national MMCs and national F&V price reductions of 10% and 30%. We accounted for differences in baseline diets, CVD rates, MMC coverage, MMC duration, and declining effects over time. Outcomes included cumulative CVD (coronary heart disease and stroke) deaths prevented or postponed and life-years gained (LYGs) over the study period, stratified by age, sex, and race. Results: A 1-y MMC in 2015 would increase the average national F&V consumption by 7% for 1 y and prevent ∼18,600 CVD deaths (95% CI: 17,600, 19,500), gaining ∼280,100 LYGs by 2030. With a 15-y MMC, increased F&V consumption would be sustained, yielding a 3-fold larger reduction (56,100; 95% CI: 52,400, 57,700) in CVD deaths. In comparison, a 10% decrease in F&V prices would increase F&V consumption by ∼14%. This would prevent ∼153,300 deaths (95% CI: 146,400, 159,200), gaining ∼2.51 million LYGs. For a 30% price decrease, resulting in a 42% increase in F&V consumption, corresponding values would be 451,900 CVD deaths prevented or postponed (95% CI: 433,100, 467,500) and 7.3 million LYGs gained. Effects were similar by sex, with a smaller proportional effect and larger absolute effects at older ages. A 1-y MMC would be 35% less effective in preventing CVD deaths in non-Hispanic blacks than in whites. In comparison, price-reduction policies would have equitable proportional effects. Conclusion: Both national MMCs and price-reduction policies could reduce US CVD mortality, with price reduction being more powerful and sustainable. © 2017 American Society for Nutrition.

Drug-target interaction prediction using ensemble learning and dimensionality reduction.

PubMed

Ezzat, Ali; Wu, Min; Li, Xiao-Li; Kwoh, Chee-Keong

2017-10-01

Experimental prediction of drug-target interactions is expensive, time-consuming and tedious. Fortunately, computational methods help narrow down the search space for interaction candidates to be further examined via wet-lab techniques. Nowadays, the number of attributes/features for drugs and targets, as well as the amount of their interactions, are increasing, making these computational methods inefficient or occasionally prohibitive. This motivates us to derive a reduced feature set for prediction. In addition, since ensemble learning techniques are widely used to improve the classification performance, it is also worthwhile to design an ensemble learning framework to enhance the performance for drug-target interaction prediction. In this paper, we propose a framework for drug-target interaction prediction leveraging both feature dimensionality reduction and ensemble learning. First, we conducted feature subspacing to inject diversity into the classifier ensemble. Second, we applied three different dimensionality reduction methods to the subspaced features. Third, we trained homogeneous base learners with the reduced features and then aggregated their scores to derive the final predictions. For base learners, we selected two classifiers, namely Decision Tree and Kernel Ridge Regression, resulting in two variants of ensemble models, EnsemDT and EnsemKRR, respectively. In our experiments, we utilized AUC (Area under ROC Curve) as an evaluation metric. We compared our proposed methods with various state-of-the-art methods under 5-fold cross validation. Experimental results showed EnsemKRR achieving the highest AUC (94.3%) for predicting drug-target interactions. In addition, dimensionality reduction helped improve the performance of EnsemDT. In conclusion, our proposed methods produced significant improvements for drug-target interaction prediction. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of a Targeted Trap-Neuter-Return Pilot Study in Auckland, New Zealand.

PubMed

Zito, Sarah; Aguilar, Glenn; Vigeant, Shalsee; Dale, Arnja

2018-05-13

There is a need for effective and humane management tools to manage urban stray cats and minimise negative impacts associated with stray cats. One such tool is targeted trap-neuter-return (TTNR), but no concerted implementation of this technique or formal assessments have been reported. To address this deficit, a TTNR programme was implemented and assessed in one Auckland suburb from May 2015 to June 2016; the programme sterilised and returned 348 cats (4.2 cats/1000 residents). Assessment was based on the number of incoming felines; stray, unsocialised cats euthanased; unsocialised, unowned cats sterilised and returned (independently of the TTNR programme); and neonatal/underage euthanasias. Incoming stray felines, underage euthanasias, and unsocialised stray cat euthanasias were all reduced for the targeted suburb when compared for the years before and after the programme (the percentage reduction in these parameters was −39, −17, −34, −7, and −47, respectively). These outcome measures had a greater reduction in the targeted suburb compared to the Auckland suburbs not targeted by the TTNR programme ( p < 0.01), although causation cannot be inferred, as a variety of reasons could have contributed to the changes. This pilot programme suggests that TTNR could be a valuable, humane cat management tool in urban New Zealand, and further assessment is warranted.

Ecosystem Management and Land Conservation Can Substantially Contribute to California's Climate Mitigation Goals

NASA Astrophysics Data System (ADS)

Marvin, D.; Cameron, D. R.; Passero, M. C.; Remucal, J. M.

2017-12-01

California has been a global leader in climate change policy through its early adoption of ambitious GHG reduction goals, committing to steep reductions through 2030 and beyond. Modeling efforts focused on future greenhouse gas (GHG) emissions from energy and other sectors in California have shown varying capacity to meet the emissions reductions targets established by the state. These efforts have not included potential reductions from changes in ecosystem management, restoration, and conservation. This study simulates the future GHG reduction potential of these land-based activities (e.g., changes to forest management, avoided conversion of grasslands to agriculture) when applied to California lands at three plausible rates of policy implementation relative to current efforts. We then compare the reduction potential of the activities against "business-as-usual" (BAU) emissions projections for the California to highlight the contribution of the biosphere toward reaching the state's GHG 2030 and 2050 reduction targets. By 2030, an Ambitious land-based activity implementation scenario could contribute as much as 146.7 MMTCO2e or 17.4% of the cumulative reductions needed to meet the state's 2030 goal, greater than the individual contributions of four other economic sectors, including those from the Industrial and Agriculture sectors. On an annual basis, the Ambitious scenario could result in reductions as high as 17.93 MMTCO2e yr-1 or 13.4% of the state's 2030 reduction goal. Most reductions come from changes in forest management, such as extending rotation times for harvest and reducing stocking density, thereby promoting accelerated growth. Such changes comprise 59.8% to 67.4% of annual projected emissions reductions in 2050 for the Ambitious and Limited scenarios, respectively. Implementation of a range of land-based emissions reduction activities can materially contribute to one of the most ambitious mitigation targets globally. This study provides a flexible, dynamic framework for estimating the reductions achievable through land conservation, ecological restoration, and changes in management regimes that can account for new data and scientific understanding.

Achieving CO 2 reductions in Colombia: Effects of carbon taxes and abatement targets

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

Calderón, Silvia; Alvarez, Andres Camilo; Loboguerrero, Ana Maria

In this paper we investigate CO 2 emission scenarios for Colombia and the effects of implementing carbon taxes and abatement targets on the energy system. By comparing baseline and policy scenario results from two integrated assessment partial equilibrium models TIAM-ECN and GCAM and two general equilibrium models Phoenix and MEG4C, we provide an indication of future developments and dynamics in the Colombian energy system. Currently, the carbon intensity of the energy system in Colombia is low compared to other countries in Latin America. However, this trend may change given the projected rapid growth of the economy and the potential increasemore » in the use of carbon-based technologies. Climate policy in Colombia is under development and has yet to consider economic instruments such as taxes and abatement targets. This paper shows how taxes or abatement targets can achieve significant CO 2 reductions in Colombia. Though abatement may be achieved through different pathways, taxes and targets promote the entry of cleaner energy sources into the market and reduce final energy demand through energy efficiency improvements and other demand-side responses. The electric power sector plays an important role in achieving CO 2 emission reductions in Colombia, through the increase of hydropower, the introduction of wind technologies, and the deployment of biomass, coal and natural gas with CO 2 capture and storage (CCS). Uncertainty over the prevailing mitigation pathway reinforces the importance of climate policy to guide sectors toward low-carbon technologies. This paper also assesses the economy-wide implications of mitigation policies such as potential losses in GDP and consumption. As a result, an assessment of the legal, institutional, social and environmental barriers to economy-wide mitigation policies is critical yet beyond the scope of this paper.« less

Achieving CO 2 reductions in Colombia: Effects of carbon taxes and abatement targets

DOE PAGES

Calderón, Silvia; Alvarez, Andres Camilo; Loboguerrero, Ana Maria; ...

2015-06-03

In this paper we investigate CO 2 emission scenarios for Colombia and the effects of implementing carbon taxes and abatement targets on the energy system. By comparing baseline and policy scenario results from two integrated assessment partial equilibrium models TIAM-ECN and GCAM and two general equilibrium models Phoenix and MEG4C, we provide an indication of future developments and dynamics in the Colombian energy system. Currently, the carbon intensity of the energy system in Colombia is low compared to other countries in Latin America. However, this trend may change given the projected rapid growth of the economy and the potential increasemore » in the use of carbon-based technologies. Climate policy in Colombia is under development and has yet to consider economic instruments such as taxes and abatement targets. This paper shows how taxes or abatement targets can achieve significant CO 2 reductions in Colombia. Though abatement may be achieved through different pathways, taxes and targets promote the entry of cleaner energy sources into the market and reduce final energy demand through energy efficiency improvements and other demand-side responses. The electric power sector plays an important role in achieving CO 2 emission reductions in Colombia, through the increase of hydropower, the introduction of wind technologies, and the deployment of biomass, coal and natural gas with CO 2 capture and storage (CCS). Uncertainty over the prevailing mitigation pathway reinforces the importance of climate policy to guide sectors toward low-carbon technologies. This paper also assesses the economy-wide implications of mitigation policies such as potential losses in GDP and consumption. As a result, an assessment of the legal, institutional, social and environmental barriers to economy-wide mitigation policies is critical yet beyond the scope of this paper.« less

To Legislate or Not to Legislate? A Comparison of the UK and South African Approaches to the Development and Implementation of Salt Reduction Programs

PubMed Central

Charlton, Karen; Webster, Jacqui; Kowal, Paul

2014-01-01

The World Health Organization promotes salt reduction as a best-buy strategy to reduce chronic diseases, and Member States have agreed to a 30% reduction target in mean population salt intake by 2025. Whilst the UK has made the most progress on salt reduction, South Africa was the first country to pass legislation for salt levels in a range of processed foods. This paper compares the process of developing salt reduction strategies in both countries and highlights lessons for other countries. Like the UK, the benefits of salt reduction were being debated in South Africa long before it became a policy priority. Whilst salt reduction was gaining a higher profile internationally, undoubtedly, local research to produce context-specific, domestic costs and outcome indicators for South Africa was crucial in influencing the decision to legislate. In the UK, strong government leadership and extensive advocacy activities initiated in the early 2000s have helped drive the voluntary uptake of salt targets by the food industry. It is too early to say which strategy will be most effective regarding reductions in population-level blood pressure. Robust monitoring and transparent mechanisms for holding the industry accountable will be key to continued progress in each of the countries. PMID:25230210

Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models.

PubMed

Houben, Rein M G J; Menzies, Nicolas A; Sumner, Tom; Huynh, Grace H; Arinaminpathy, Nimalan; Goldhaber-Fiebert, Jeremy D; Lin, Hsien-Ho; Wu, Chieh-Yin; Mandal, Sandip; Pandey, Surabhi; Suen, Sze-Chuan; Bendavid, Eran; Azman, Andrew S; Dowdy, David W; Bacaër, Nicolas; Rhines, Allison S; Feldman, Marcus W; Handel, Andreas; Whalen, Christopher C; Chang, Stewart T; Wagner, Bradley G; Eckhoff, Philip A; Trauer, James M; Denholm, Justin T; McBryde, Emma S; Cohen, Ted; Salomon, Joshua A; Pretorius, Carel; Lalli, Marek; Eaton, Jeffrey W; Boccia, Delia; Hosseini, Mehran; Gomez, Gabriela B; Sahu, Suvanand; Daniels, Colleen; Ditiu, Lucica; Chin, Daniel P; Wang, Lixia; Chadha, Vineet K; Rade, Kiran; Dewan, Puneet; Hippner, Piotr; Charalambous, Salome; Grant, Alison D; Churchyard, Gavin; Pillay, Yogan; Mametja, L David; Kimerling, Michael E; Vassall, Anna; White, Richard G

2016-11-01

The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31-62%) and a 72% reduction in mortality (range 64-82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level. Bill and Melinda Gates Foundation. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Impact of hydrogeological data on measures of uncertainty, site characterization and environmental performance metrics

NASA Astrophysics Data System (ADS)

de Barros, Felipe P. J.; Ezzedine, Souheil; Rubin, Yoram

2012-02-01

The significance of conditioning predictions of environmental performance metrics (EPMs) on hydrogeological data in heterogeneous porous media is addressed. Conditioning EPMs on available data reduces uncertainty and increases the reliability of model predictions. We present a rational and concise approach to investigate the impact of conditioning EPMs on data as a function of the location of the environmentally sensitive target receptor, data types and spacing between measurements. We illustrate how the concept of comparative information yield curves introduced in de Barros et al. [de Barros FPJ, Rubin Y, Maxwell R. The concept of comparative information yield curves and its application to risk-based site characterization. Water Resour Res 2009;45:W06401. doi:10.1029/2008WR007324] could be used to assess site characterization needs as a function of flow and transport dimensionality and EPMs. For a given EPM, we show how alternative uncertainty reduction metrics yield distinct gains of information from a variety of sampling schemes. Our results show that uncertainty reduction is EPM dependent (e.g., travel times) and does not necessarily indicate uncertainty reduction in an alternative EPM (e.g., human health risk). The results show how the position of the environmental target, flow dimensionality and the choice of the uncertainty reduction metric can be used to assist in field sampling campaigns.

X-Divertor Geometries for Deeper Detachment Without Degrading the DIII-D H-Mode

NASA Astrophysics Data System (ADS)

Covele, Brent; Kotschenreuther, M. T.; Valanju, P. M.; Mahajan, S. M.; Leonard, A. W.; Hyatt, A. W.; McLean, A. G.; Thomas, D. M.; Guo, H. Y.; Watkins, J. G.; Makowski, M. A.; Hill, D. N.

2015-11-01

Recent DIII-D experiments comparing the standard divertor (SD) and X-Divertor (XD) geometries show heat and particle flux reduction at the divertor target plate. The XD features large poloidal flux expansion, increased connection length, and poloidal field line flaring, quantified by the Divertor Index. Both SD and XD were pushed deep into detachment with increased gas puffing, until core energy confinement and pedestal pressure were substantially reduced. As expected, outboard target heat fluxes are significantly reduced in the XD compared to the SD under similar upstream plasma conditions, even at low Greenwald fraction. The high-triangularity (floor) XD cases show larger reduction in temperature, heat, and particle flux relative to the SD in all cases, while low-triangularity (shelf) XD cases show more modest reductions over the SD. Consequently, heat flux reduction and divertor detachment may be achieved in the XD with less gas puffing and higher pedestal pressures. Further causative analysis, as well as detailed modeling with SOLPS, is underway. These initial experiments suggest the XD as a promising candidate to achieve divertor heat flux control compatible with robust H-mode operation. Work supported by US DOE under DE-FC02-04ER54698, DE-AC52-07NA27344, DE-FG02-04ER54754, and DE-FG02-04ER54742.

Microbubble-assisted p53, RB, and p130 gene transfer in combination with radiation therapy in prostate cancer.

PubMed

Nande, Rounak; Greco, Adelaide; Gossman, Michael S; Lopez, Jeffrey P; Claudio, Luigi; Salvatore, Marco; Brunetti, Arturo; Denvir, James; Howard, Candace M; Claudio, Pier Paolo

2013-06-01

Combining radiation therapy and direct intratumoral (IT) injection of adenoviral vectors has been explored as a means to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates to enhance targeted delivery of systemically administered genes. Here we show that p53, pRB, and p130 gene transfer mediated by US cavitation of microbubbles at the tumor site resulted in targeted gene transduction and increased reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed significant reduction in tumor volume compared to Ad.p130 treated tumors (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05) compared to radiation alone. These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease.

Reduction-Responsive Polymeric Micelles and Vesicles for Triggered Intracellular Drug Release

PubMed Central

Sun, Huanli; Cheng, Ru; Deng, Chao

2014-01-01

Abstract Significance: The therapeutic effects of current micellar and vesicular drug formulations are restricted by slow and inefficient drug release at the pathological site. The development of smart polymeric nanocarriers that release drugs upon arriving at the target site has received a tremendous amount of attention for cancer therapy. Recent Advances: Taking advantage of a high reducing potential in the tumor tissues and in particular inside the tumor cells, various reduction-sensitive polymeric micelles and vesicles have been designed and explored for triggered anticancer drug release. These reduction-responsive nanosystems have demonstrated several unique features, such as good stability under physiological conditions, fast response to intracellular reducing environment, triggering drug release right in the cytosol and cell nucleus, and significantly improved antitumor activity, compared to traditional reduction-insensitive counterparts. Critical Issues: Although reduction-sensitive micelles and polymersomes have accomplished rapid intracellular drug release and enhanced in vitro antitumor effect, their fate inside the cells including the mechanism, site, and rate of reduction reaction remains unclear. Moreover, the systemic fate and performance of reduction-sensitive polymeric drug formulations have to be investigated. Future Directions: Biophysical studies should be carried out to gain insight into the degradation and drug release behaviors of reduction-responsive nanocarriers inside the tumor cells. Furthermore, novel ligand-decorated reduction-sensitive nanoparticulate drug formulations should be designed and explored for targeted cancer therapy in vivo. Antioxid. Redox Signal. 21, 755–767. PMID:24279980

Quasi-Experimental Evaluation of the Effectiveness of a Large-Scale Readmission Reduction Program.

PubMed

Jenq, Grace Y; Doyle, Margaret M; Belton, Beverly M; Herrin, Jeph; Horwitz, Leora I

2016-05-01

Feasibility, effectiveness, and sustainability of large-scale readmission reduction efforts are uncertain. The Greater New Haven Coalition for Safe Transitions and Readmission Reductions was funded by the Center for Medicare & Medicaid Services (CMS) to reduce readmissions among all discharged Medicare fee-for-service (FFS) patients. To evaluate whether overall Medicare FFS readmissions were reduced through an intervention applied to high-risk discharge patients. This quasi-experimental evaluation took place at an urban academic medical center. Target discharge patients were older than 64 years with Medicare FFS insurance, residing in nearby zip codes, and discharged alive to home or facility and not against medical advice or to hospice; control discharge patients were older than 54 years with the same zip codes and discharge disposition but without Medicare FFS insurance if older than 64 years. High-risk target discharge patients were selectively enrolled in the program. Personalized transitional care, including education, medication reconciliation, follow-up telephone calls, and linkage to community resources. We measured the 30-day unplanned same-hospital readmission rates in the baseline period (May 1, 2011, through April 30, 2012) and intervention period (October 1, 2012, through May 31, 2014). We enrolled 10 621 (58.3%) of 18 223 target discharge patients (73.9% of discharge patients screened as high risk) and included all target discharge patients in the analysis. The mean (SD) age of the target discharge patients was 79.7 (8.8) years. The adjusted readmission rate decreased from 21.5% to 19.5% in the target population and from 21.1% to 21.0% in the control population, a relative reduction of 9.3%. The number needed to treat to avoid 1 readmission was 50. In a difference-in-differences analysis using a logistic regression model, the odds of readmission in the target population decreased significantly more than that of the control population in the intervention period (odds ratio, 0.90; 95% CI, 0.83-0.99; P = .03). In a comparative interrupted time series analysis of the difference in monthly adjusted admission rates, the target population decreased an absolute -3.09 (95% CI, -6.47 to 0.29; P = .07) relative to the control population, a similar but nonsignificant effect. This large-scale readmission reduction program reduced readmissions by 9.3% among the full population targeted by the CMS despite being delivered only to high-risk patients. However, it did not achieve the goal reduction set by the CMS.

Core hydrophobicity tuning of a self-assembled particle results in efficient lipid reduction and favorable organ distribution.

PubMed

Banik, Bhabatosh; Wen, Ru; Marrache, Sean; Kumar, Anil; Kolishetti, Nagesh; Howerth, Elizabeth W; Dhar, Shanta

2017-12-21

Atherosclerosis, the deadliest disease in the United States, arises due to the build up of plaques in the arteries as a result of excessive cholesterol deposition and an impaired cholesterol removal process. High density lipoproteins (HDL), popularly known as "good cholesterol", are naturally occurring nano-sized particles that, along with apolipoproteins, are deployed to maintain cholesterol homeostasis in the body. Both cholesterol efflux, from the fat-laden macrophages in the arteries, and intracellular lipid transport, to deliver cholesterol to the mitochondria of liver cells for metabolism, hold key responsibilities to maintain healthy lipid levels inside the body. We designed a library of nine mitochondria targeted polymer-lipid hybrid nanoparticles (NPs), comprised of completely synthetic yet biodegradable components, that are capable of performing HDL-like functions. Using this library, we optimized a superior mitochondria targeted NP candidate, which can show favourable organ distribution, therapeutic potential, and non-toxic properties. Two targeted NP formulations with optimum NP size, zeta potential, and cholesterol binding and release properties were identified. Lipid reduction and anti-oxidative properties of these two NPs demonstrated cholesterol removal ability. In vivo therapeutic evaluation of the targeted-NP formulations in apolipoprotein E knockout (apoE - / - ) mice indicated lipid reduction and anti-inflammatory properties compared to non-targeted NPs. This synthetic targeted NP with potential abilities to participate in both extra- and intracellular cholesterol transport might potentiate therapeutic interventions for heart diseases.

Loss of TIMP3 underlies diabetic nephropathy via FoxO1/STAT1 interplay.

PubMed

Fiorentino, Loredana; Cavalera, Michele; Menini, Stefano; Marchetti, Valentina; Mavilio, Maria; Fabrizi, Marta; Conserva, Francesca; Casagrande, Viviana; Menghini, Rossella; Pontrelli, Paola; Arisi, Ivan; D'Onofrio, Mara; Lauro, Davide; Khokha, Rama; Accili, Domenico; Pugliese, Giuseppe; Gesualdo, Loreto; Lauro, Renato; Federici, Massimo

2013-03-01

ADAM17 and its inhibitor TIMP3 are involved in nephropathy, but their role in diabetic kidney disease (DKD) is unclear. Diabetic Timp3(-/-) mice showed increased albuminuria, increased membrane thickness and mesangial expansion. Microarray profiling uncovered a significant reduction of Foxo1 expression in diabetic Timp3(-/-) mice compared to WT, along with FoxO1 target genes involved in autophagy, while STAT1, a repressor of FoxO1 transcription, was increased. Re-expression of Timp3 in Timp3(-/-) mesangial cells rescued the expression of Foxo1 and its targets, and decreased STAT1 expression to control levels; abolishing STAT1 expression led to a rescue of FoxO1, evoking a role of STAT1 in linking Timp3 deficiency to FoxO1. Studies on kidney biopsies from patients with diabetic nephropathy confirmed a significant reduction in TIMP3, FoxO1 and FoxO1 target genes involved in autophagy compared to controls, while STAT1 expression was strongly increased. Our study suggests that loss of TIMP3 is a hallmark of DKD in human and mouse models and designates TIMP3 as a new possible therapeutic target for diabetic nephropathy. Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

Effect of Multifactorial Treatment Targets and Relative Importance of Hemoglobin A1c, Blood Pressure, and Low-Density Lipoprotein-Cholesterol on Cardiovascular Diseases in Chinese Primary Care Patients With Type 2 Diabetes Mellitus: A Population-Based Retrospective Cohort Study.

PubMed

Wan, Eric Yuk Fai; Fung, Colman Siu Cheung; Yu, Esther Yee Tak; Chin, Weng Yee; Fong, Daniel Yee Tak; Chan, Anca Ka Chun; Lam, Cindy Lo Kuen

2017-08-17

The relative effect of hemoglobin A1c, blood pressure, and low-density lipoprotein-cholesterol (LDL-C) ("ABC" factors) on the prevention of cardiovascular diseases (CVD) among patients with type 2 diabetes mellitus is poorly understood. This study aimed to evaluate the association of key clinical parameters on CVD risk using a multifactorial optimal control approach in Chinese primary care patients with type 2 diabetes mellitus. A population-based retrospective cohort study was conducted on 144 271 Chinese type 2 diabetes mellitus primary care patients, aged 18 to 79 and without prior clinical diagnosis of CVD in 2008-2011. Cox regressions were conducted to examine the association between the combinations of ABC targets (hemoglobin A1c <7%, blood pressure <130/90 mm Hg, and LDL-C <2.6 mmol/L) and risks of CVD (overall), coronary heart disease, stroke, and heart failure. Achieving more ABC targets incrementally reduced the incidence of total CVD and individual disease including coronary heart disease, stroke, and heart failure, irrespective of other patient characteristics. Compared with suboptimal control in all ABC levels, achieving any 1, 2, and all 3 ABC targets reduced the relative risk of CVD by 13% to 42%, 31% to 52%, and 55%, respectively. Among those achieving only 1 ABC target, LDL-C reduction was associated with the greatest CVD risk reduction (42%), followed by blood pressure reduction (18%), and hemoglobin A1c reduction (13%). To achieve the greatest risk reduction for the incidence of CVD, the ultimate goal of treatment should be to achieve target control of hemoglobin A1c, blood pressure, and LDL-C. If it is not possible to achieve all 3 targets, efforts should be prioritized on treating the LDL-C to minimize CVD risk. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

SU-E-T-625: Potential for Reduced Radiation Induced Toxicity for the Treatment of Inoperable Non-Small-Cell Lung Cancer Using RapidArc Planning

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

Pokhrel, D; Sood, S; Badkul, R

2015-06-15

Purpose: To investigate the feasibility of using RapidArc (RA) treatment planning to reduce irradiation volume of normal lung and other organs at risk (OARs) in the treatment of inoperable non-small-cell lung cancer (NSCLC) patients. Methods: A retrospective treatment planning and delivery study was performed to compare target coverage and the volumes of the normal lung, spinal cord, heart and esophagus on 4D-CT scan above their dose tolerances delivered by RA vs. IMRT for ten inoperable NSCLC patients (Stage I-IIIB). RA plans consisted of either one-full or two-partial co-planar arcs used to treat 95% of the planning target volume (PTV) withmore » 6MV beam to a prescription of 66Gy in 33 fractions. IMRT plans were generated using 5–7 co-planar fields with 6MV beam. PTV coverage, dose-volume histograms, homogeneity/conformity indices (CI), total number of monitor units(MUs), beam-on time and delivery accuracy were compared between the two treatment plans. Results: Similar target coverage was obtained between the two techniques. RA (CI=1.02) provided more conformal plans without loss of homogeneity compared to IMRT plans (CI=1.12). Compared to IMRT, RA achieved a significant median dose reduction in V10 (3%), V20 (8%), and mean lung dose (3%) on average, respectively. On average, V5 was comparable between the two treatment plans. RA reduced mean esophagus (6%), mean heart (18%), and maximum spinal cord dose (7%), on average, respectively. Total number of MUs and beam-on time were each reduced almost by a factor of 2 when compared to IMRT-patient comfort, reduced intra-fraction-motion and leakage dose. The average IMRT and RA QA pass rate was about 98% for both types of plans for 3%/3mm criterion. Conclusion: Compared to IMRT plans, RA provided not only comparable target coverage, but also improved conformity, treatment time, and significant reduction in irradiation of OARs. This may potentially allow for target dose escalation without increase in normal tissue toxicity.« less

Pricing effects on food choices.

PubMed

French, Simone A

2003-03-01

Individual dietary choices are primarily influenced by such considerations as taste, cost, convenience and nutritional value of foods. The current obesity epidemic has been linked to excessive consumption of added sugars and fat, as well as to sedentary lifestyles. Fat and sugar provide dietary energy at very low cost. Food pricing and marketing practices are therefore an essential component of the eating environment. Recent studies have applied economic theories to changing dietary behavior. Price reduction strategies promote the choice of targeted foods by lowering their cost relative to alternative food choices. Two community-based intervention studies used price reductions to promote the increased purchase of targeted foods. The first study examined lower prices and point-of-purchase promotion on sales of lower fat vending machine snacks in 12 work sites and 12 secondary schools. Price reductions of 10%, 25% and 50% on lower fat snacks resulted in an increase in sales of 9%, 39% and 93%, respectively, compared with usual price conditions. The second study examined the impact of a 50% price reduction on fresh fruit and baby carrots in two secondary school cafeterias. Compared with usual price conditions, price reductions resulted in a four-fold increase in fresh fruit sales and a two-fold increase in baby carrot sales. Both studies demonstrate that price reductions are an effective strategy to increase the purchase of more healthful foods in community-based settings such as work sites and schools. Results were generalizable across various food types and populations. Reducing prices on healthful foods is a public health strategy that should be implemented through policy initiatives and industry collaborations.

Readmissions, Observation, and the Hospital Readmissions Reduction Program.

PubMed

Zuckerman, Rachael B; Sheingold, Steven H; Orav, E John; Ruhter, Joel; Epstein, Arnold M

2016-04-21

The Hospital Readmissions Reduction Program, which is included in the Affordable Care Act (ACA), applies financial penalties to hospitals that have higher-than-expected readmission rates for targeted conditions. Some policy analysts worry that reductions in readmissions are being achieved by keeping returning patients in observation units instead of formally readmitting them to the hospital. We examined the changes in readmission rates and stays in observation units over time for targeted and nontargeted conditions and assessed whether hospitals that had greater increases in observation-service use had greater reductions in readmissions. We compared monthly, hospital-level rates of readmission and observation-service use within 30 days after hospital discharge among Medicare elderly beneficiaries from October 2007 through May 2015. We used an interrupted time-series model to determine when trends changed and whether changes differed between targeted and nontargeted conditions. We assessed the correlation between changes in readmission rates and use of observation services after adoption of the ACA in March 2010. We analyzed data from 3387 hospitals. From 2007 to 2015, readmission rates for targeted conditions declined from 21.5% to 17.8%, and rates for nontargeted conditions declined from 15.3% to 13.1%. Shortly after passage of the ACA, the readmission rate declined quickly, especially for targeted conditions, and then continued to fall at a slower rate after October 2012 for both targeted and nontargeted conditions. Stays in observation units for targeted conditions increased from 2.6% in 2007 to 4.7% in 2015, and rates for nontargeted conditions increased from 2.5% to 4.2%. Within hospitals, there was no significant association between changes in observation-unit stays and readmissions after implementation of the ACA. Readmission trends are consistent with hospitals' responding to incentives to reduce readmissions, including the financial penalties for readmissions under the ACA. We did not find evidence that changes in observation-unit stays accounted for the decrease in readmissions.

Changes in the Sodium Content of Australian Processed Foods between 1980 and 2013 Using Analytical Data

PubMed Central

Zganiacz, Felicity; Wills, Ron B. H.; Mukhopadhyay, Soumi Paul; Arcot, Jayashree; Greenfield, Heather

2017-01-01

The objective of this study was to obtain analytical data on the sodium content of a range of processed foods and compare the levels obtained with their label claims and with published data of the same or equivalent processed foods in the 1980s and 1990s to investigate the extent of any change in sodium content in relation to reformulation targets. The sodium contents of 130 Australian processed foods were obtained by inductively coupled plasma optical emission spectrometry (ICP-OES) analysis and compared with previously published data. The sodium content between 1980 and 2013 across all products and by each product category were compared. There was a significant overall sodium reduction of 23%, 181 mg/100 g (p <0.001, 95% CI (Confidence Interval), 90 to 272 mg/100 g), in Australian processed foods since 1980, with a 12% (83 mg/100 g) reduction over the last 18 years. The sodium content of convenience foods (p < 0.001, 95% CI, 94 to 291 mg/100 g) and snack foods (p = 0.017, 95% CI, 44 to 398 mg/100 g) had declined significantly since 1980. Meanwhile, the sodium contents of processed meats (p = 0.655, 95% CI, −121 to 190) and bread and other bakery products (p = 0.115, 95% CI, −22 to 192) had decreased, though not significantly. Conversely, the sodium content of cheese (p = 0.781, 95% CI, −484 to 369 mg/100 g) had increased but also not significantly. Of the 130 products analysed, 62% met Australian reformulation targets. Sodium contents of the processed foods and the overall changes in comparison with previous data indicate a decrease over the 33 years period and suggest that the Australian recommended reformulation targets have been effective. Further sodium reduction of processed foods is still required and continuous monitoring of the reduction of sodium levels in processed foods is needed. PMID:28505147

Changes in the Sodium Content of Australian Processed Foods between 1980 and 2013 Using Analytical Data.

PubMed

Zganiacz, Felicity; Wills, Ron B H; Mukhopadhyay, Soumi Paul; Arcot, Jayashree; Greenfield, Heather

2017-05-15

The objective of this study was to obtain analytical data on the sodium content of a range of processed foods and compare the levels obtained with their label claims and with published data of the same or equivalent processed foods in the 1980s and 1990s to investigate the extent of any change in sodium content in relation to reformulation targets. The sodium contents of 130 Australian processed foods were obtained by inductively coupled plasma optical emission spectrometry (ICP-OES) analysis and compared with previously published data. The sodium content between 1980 and 2013 across all products and by each product category were compared. There was a significant overall sodium reduction of 23%, 181 mg/100 g ( p <0.001, 95% CI (Confidence Interval), 90 to 272 mg/100 g), in Australian processed foods since 1980, with a 12% (83 mg/100 g) reduction over the last 18 years. The sodium content of convenience foods ( p < 0.001, 95% CI, 94 to 291 mg/100 g) and snack foods ( p = 0.017, 95% CI, 44 to 398 mg/100 g) had declined significantly since 1980. Meanwhile, the sodium contents of processed meats ( p = 0.655, 95% CI, -121 to 190) and bread and other bakery products ( p = 0.115, 95% CI, -22 to 192) had decreased, though not significantly. Conversely, the sodium content of cheese ( p = 0.781, 95% CI, -484 to 369 mg/100 g) had increased but also not significantly. Of the 130 products analysed, 62% met Australian reformulation targets. Sodium contents of the processed foods and the overall changes in comparison with previous data indicate a decrease over the 33 years period and suggest that the Australian recommended reformulation targets have been effective. Further sodium reduction of processed foods is still required and continuous monitoring of the reduction of sodium levels in processed foods is needed.

Beaver Colony Density Trends on the Chequamegon-Nicolet National Forest, 1987 – 2013

PubMed Central

Ribic, Christine A.; Donner, Deahn M.; Beck, Albert J.; Reinecke, Sue; Eklund, Dan

2017-01-01

The North American beaver (Castor canadensis) is a managed species in the United States. In northern Wisconsin, as part of the state-wide beaver management program, the Chequamegon-Nicolet National Forest removes beavers from targeted trout streams on U.S. Forest Service lands. However, the success of this management program has not been evaluated. Targeted removals comprise only 3% of the annual beaver harvest, a level of effort that may not affect the beaver population. We used colony location data along Forest streams from 1987–2013 (Nicolet, northeast Wisconsin) and 1997–2013 (Chequamegon, northwest Wisconsin) to assess trends in beaver colony density on targeted trout streams compared to non-targeted streams. On the Chequamegon, colony density on non-targeted trout and non-trout streams did not change over time, while colony density on targeted trout streams declined and then stabilized. On the Nicolet, beaver colony density decreased on both non-targeted streams and targeted trout streams. However, colony density on targeted trout streams declined faster. The impact of targeted trapping was similar across the two sides of the Forest (60% reduction relative to non-targeted trout streams). Exploratory analyses of weather influences found that very dry conditions and severe winters were associated with transient reductions in beaver colony density on non-targeted streams on both sides of the Forest. Our findings may help land management agencies weigh more finely calibrated beaver control measures against continued large-scale removal programs. PMID:28081271

Beaver Colony Density Trends on the Chequamegon-Nicolet National Forest, 1987 - 2013.

PubMed

Ribic, Christine A; Donner, Deahn M; Beck, Albert J; Rugg, David J; Reinecke, Sue; Eklund, Dan

2017-01-01

The North American beaver (Castor canadensis) is a managed species in the United States. In northern Wisconsin, as part of the state-wide beaver management program, the Chequamegon-Nicolet National Forest removes beavers from targeted trout streams on U.S. Forest Service lands. However, the success of this management program has not been evaluated. Targeted removals comprise only 3% of the annual beaver harvest, a level of effort that may not affect the beaver population. We used colony location data along Forest streams from 1987-2013 (Nicolet, northeast Wisconsin) and 1997-2013 (Chequamegon, northwest Wisconsin) to assess trends in beaver colony density on targeted trout streams compared to non-targeted streams. On the Chequamegon, colony density on non-targeted trout and non-trout streams did not change over time, while colony density on targeted trout streams declined and then stabilized. On the Nicolet, beaver colony density decreased on both non-targeted streams and targeted trout streams. However, colony density on targeted trout streams declined faster. The impact of targeted trapping was similar across the two sides of the Forest (60% reduction relative to non-targeted trout streams). Exploratory analyses of weather influences found that very dry conditions and severe winters were associated with transient reductions in beaver colony density on non-targeted streams on both sides of the Forest. Our findings may help land management agencies weigh more finely calibrated beaver control measures against continued large-scale removal programs.

Beaver colony density trends on the Chequamegon-Nicolet National Forest, 1987 – 2013

USGS Publications Warehouse

Ribic, Christine; Donner, Deahn M.; Beck, Albert J.; Rugg, David J.; Reinecke, Sue; Eklund, Dan

2017-01-01

The North American beaver (Castor canadensis) is a managed species in the United States. In northern Wisconsin, as part of the state-wide beaver management program, the Chequamegon-Nicolet National Forest removes beavers from targeted trout streams on U.S. Forest Service lands. However, the success of this management program has not been evaluated. Targeted removals comprise only 3% of the annual beaver harvest, a level of effort that may not affect the beaver population. We used colony location data along Forest streams from 1987–2013 (Nicolet, northeast Wisconsin) and 1997–2013 (Chequamegon, northwest Wisconsin) to assess trends in beaver colony density on targeted trout streams compared to non-targeted streams. On the Chequamegon, colony density on non-targeted trout and non-trout streams did not change over time, while colony density on targeted trout streams declined and then stabilized. On the Nicolet, beaver colony density decreased on both non-targeted streams and targeted trout streams. However, colony density on targeted trout streams declined faster. The impact of targeted trapping was similar across the two sides of the Forest (60% reduction relative to non-targeted trout streams). Exploratory analyses of weather influences found that very dry conditions and severe winters were associated with transient reductions in beaver colony density on non-targeted streams on both sides of the Forest. Our findings may help land management agencies weigh more finely calibrated beaver control measures against continued large-scale removal programs.

Using a Reduced Spot Size for Intensity-Modulated Proton Therapy Potentially Improves Salivary Gland-Sparing in Oropharyngeal Cancer

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

Water, Tara A. van de, E-mail: t.a.van.de.water@rt.umcg.nl; Lomax, Antony J.; Bijl, Hendrik P.

2012-02-01

Purpose: To investigate whether intensity-modulated proton therapy with a reduced spot size (rsIMPT) could further reduce the parotid and submandibular gland dose compared with previously calculated IMPT plans with a larger spot size. In addition, it was investigated whether the obtained dose reductions would theoretically translate into a reduction of normal tissue complication probabilities (NTCPs). Methods: Ten patients with N0 oropharyngeal cancer were included in a comparative treatment planning study. Both IMPT plans delivered simultaneously 70 Gy to the boost planning target volume (PTV) and 54 Gy to the elective nodal PTV. IMPT and rsIMPT used identical three-field beam arrangements.more » In the IMPT plans, the parotid and submandibular salivary glands were spared as much as possible. rsIMPT plans used identical dose-volume objectives for the parotid glands as those used by the IMPT plans, whereas the objectives for the submandibular glands were tightened further. NTCPs were calculated for salivary dysfunction and xerostomia. Results: Target coverage was similar for both IMPT techniques, whereas rsIMPT clearly improved target conformity. The mean doses in the parotid glands and submandibular glands were significantly lower for three-field rsIMPT (14.7 Gy and 46.9 Gy, respectively) than for three-field IMPT (16.8 Gy and 54.6 Gy, respectively). Hence, rsIMPT significantly reduced the NTCP of patient-rated xerostomia and parotid and contralateral submandibular salivary flow dysfunction (27%, 17%, and 43% respectively) compared with IMPT (39%, 20%, and 79%, respectively). In addition, mean dose values in the sublingual glands, the soft palate and oral cavity were also decreased. Obtained dose and NTCP reductions varied per patient. Conclusions: rsIMPT improved sparing of the salivary glands and reduced NTCP for xerostomia and parotid and submandibular salivary dysfunction, while maintaining similar target coverage results. It is expected that rsIMPT improves quality of life during and after radiotherapy treatment.« less

Comparison of a new noncoplanar intensity-modulated radiation therapy technique for craniospinal irradiation with 3 coplanar techniques

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

Hansen, Anders T., E-mail: andehans@rm.dk; Lukacova, Slavka; Lassen-Ramshad, Yasmin

2015-01-01

When standard conformal x-ray technique for craniospinal irradiation is used, it is a challenge to achieve satisfactory dose coverage of the target including the area of the cribriform plate, while sparing organs at risk. We present a new intensity-modulated radiation therapy (IMRT), noncoplanar technique, for delivering irradiation to the cranial part and compare it with 3 other techniques and previously published results. A total of 13 patients who had previously received craniospinal irradiation with standard conformal x-ray technique were reviewed. New treatment plans were generated for each patient using the noncoplanar IMRT-based technique, a coplanar IMRT-based technique, and a coplanarmore » volumetric-modulated arch therapy (VMAT) technique. Dosimetry data for all patients were compared with the corresponding data from the conventional treatment plans. The new noncoplanar IMRT technique substantially reduced the mean dose to organs at risk compared with the standard radiation technique. The 2 other coplanar techniques also reduced the mean dose to some of the critical organs. However, this reduction was not as substantial as the reduction obtained by the noncoplanar technique. Furthermore, compared with the standard technique, the IMRT techniques reduced the total calculated radiation dose that was delivered to the normal tissue, whereas the VMAT technique increased this dose. Additionally, the coverage of the target was significantly improved by the noncoplanar IMRT technique. Compared with the standard technique, the coplanar IMRT and the VMAT technique did not improve the coverage of the target significantly. All the new planning techniques increased the number of monitor units (MU) used—the noncoplanar IMRT technique by 99%, the coplanar IMRT technique by 122%, and the VMAT technique by 26%—causing concern for leak radiation. The noncoplanar IMRT technique covered the target better and decreased doses to organs at risk compared with the other techniques. All the new techniques increased the number of MU compared with the standard technique.« less

Cost-Reduction Roadmap for Residential Solar Photovoltaics (PV), 2017-2030

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

Cook, Jeffrey J.; Ardani, Kristen B.; Margolis, Robert M.

The installed cost of solar photovoltaics (PV) has fallen rapidly in recent years and is expected to continue declining in the future. In this report, we focus on the potential for continued PV cost reductions in the residential market. From 2010 to 2017, the levelized cost of energy (LCOE) for residential PV declined from 52 cents per kilowatt-hour (cents/kWh) to 16 cents/kWh (Fu et al. 2017). The U.S. Department of Energy's (DOE's) Solar Energy Technologies Office (SETO) recently set new LCOE targets for 2030, including a target of 5 cents/kWh for residential PV. We present a roadmap for achieving themore » SETO 2030 residential PV target. Because the 2030 target likely will not be achieved under business-as-usual trends (NREL 2017), we examine two key market segments that demonstrate significant opportunities for cost savings and market growth: installing PV at the time of roof replacement and installing PV as part of the new home construction process. Within both market segments, we identify four key cost-reduction opportunities: market maturation, business model integration, product innovation, and economies of scale. To assess the potential impact of these cost reductions, we compare modeled residential PV system prices in 2030 to the National Renewable Energy Laboratory's (NREL's) quarter one 2017 (Q1 2017) residential PV system price benchmark (Fu et al. 2017). We use a bottom-up accounting framework to model all component and project-development costs incurred when installing a PV system. The result is a granular accounting for 11 direct and indirect costs associated with installing a residential PV system in 2030. All four modeled pathways demonstrate significant installed-system price savings over the Q1 2017 benchmark, with the visionary pathways yielding the greatest price benefits. The largest modeled cost savings are in the supply chain, sales and marketing, overhead, and installation labor cost categories. When we translate these installed-system costs into LCOE, we find that the less-aggressive pathways achieve significant cost reductions, but may not achieve the 2030 LCOE target. On the other hand, both visionary pathways could get very close to (for roof replacement) or achieve (for new construction) the 2030 target. Our analysis has two key implications. First, because installed-system soft cost reductions account for about 65 percent of the LCOE reductions in 2030 for both visionary pathways, residential PV stakeholders may need to emphasize these soft cost reductions to achieve the 2030 target. Second, capturing these savings will likely require considerable innovation in the technologies and business practices employed by the PV industry.« less

Target oriented dimensionality reduction of hyperspectral data by Kernel Fukunaga-Koontz Transform

NASA Astrophysics Data System (ADS)

Binol, Hamidullah; Ochilov, Shuhrat; Alam, Mohammad S.; Bal, Abdullah

2017-02-01

Principal component analysis (PCA) is a popular technique in remote sensing for dimensionality reduction. While PCA is suitable for data compression, it is not necessarily an optimal technique for feature extraction, particularly when the features are exploited in supervised learning applications (Cheriyadat and Bruce, 2003) [1]. Preserving features belonging to the target is very crucial to the performance of target detection/recognition techniques. Fukunaga-Koontz Transform (FKT) based supervised band reduction technique can be used to provide this requirement. FKT achieves feature selection by transforming into a new space in where feature classes have complimentary eigenvectors. Analysis of these eigenvectors under two classes, target and background clutter, can be utilized for target oriented band reduction since each basis functions best represent target class while carrying least information of the background class. By selecting few eigenvectors which are the most relevant to the target class, dimension of hyperspectral data can be reduced and thus, it presents significant advantages for near real time target detection applications. The nonlinear properties of the data can be extracted by kernel approach which provides better target features. Thus, we propose constructing kernel FKT (KFKT) to present target oriented band reduction. The performance of the proposed KFKT based target oriented dimensionality reduction algorithm has been tested employing two real-world hyperspectral data and results have been reported consequently.

Dosimetric Advantages of Midventilation Compared With Internal Target Volume for Radiation Therapy of Pancreatic Cancer

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

Lens, Eelco, E-mail: e.lens@amc.uva.nl; Horst, Astrid van der; Versteijne, Eva

2015-07-01

Purpose: The midventilation (midV) approach can be used to take respiratory-induced pancreatic tumor motion into account during radiation therapy. In this study, the dosimetric consequences for organs at risk and tumor coverage of using a midV approach compared with using an internal target volume (ITV) were investigated. Methods and Materials: For each of the 18 patients, 2 treatment plans (25 × 2.0 Gy) were created, 1 using an ITV and 1 using a midV approach. The midV dose distribution was blurred using the respiratory-induced motion from 4-dimensional computed tomography. The resulting planning target volume (PTV) coverage for this blurred dosemore » distribution was analyzed; PTV coverage was required to be at least V{sub 95%} >98%. In addition, the change in PTV size and the changes in V{sub 10Gy}, V{sub 20Gy}, V{sub 30Gy}, V{sub 40Gy}, D{sub mean} and D{sub 2cc} for the stomach and for the duodenum were analyzed; differences were tested for significance using the Wilcoxon signed-rank test. Results: Using a midV approach resulted in sufficient target coverage. A highly significant PTV size reduction of 13.9% (P<.001) was observed. Also, all dose parameters for the stomach and duodenum, except the D{sub 2cc} of the duodenum, improved significantly (P≤.002). Conclusions: By using the midV approach to account for respiratory-induced tumor motion, a significant PTV reduction and significant dose reductions to the stomach and to the duodenum can be achieved when irradiating pancreatic tumors.« less

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.

Evaluation of Australian soup manufacturer compliance with national sodium reduction targets.

PubMed

Levi, Rebecca; Probst, Yasmine; Crino, Michelle; Dunford, Elizabeth

2018-04-01

Packaged foods dominate Australia's food supply and are important contributors to nutrition-related disease. To help address this problem, the Food and Health Dialogue (FHD) was launched in 2009, setting voluntary sodium reduction targets for various categories of packaged foods. The aim of this study was to examine the food industry's progress and compliance with the FHD sodium reduction targets for soup products. Nutritional information was collected from product labels of all soup products available from four major Australian supermarkets annually between 2011 and 2014. Products were assigned to categories in line with those in the FHD. The proportion of soup products meeting sodium reduction targets was examined by (i) soup category; (ii) FHD participant status; and (iii) manufacturer. A 6% reduction in sodium levels in soups overall was found from 2011 to 2014 (P = 0.002). Significant reductions were observed for FHD participants (P < 0.05 for all) but not for non-participants. In 2014, 67% dry soups and 76% of wet soups met national sodium reduction targets. Despite the majority of soup products meeting the sodium reduction targets specified by the FHD, re-evaluation of the targets may be required to further reduce sodium levels in soups. Manufacturers participating in the FHD are likely to be driving sodium reductions in the Australian soup market, further highlighting the need for continued government leadership in this area to ensure all manufacturers are actively involved in the process. © 2017 Dietitians Association of Australia.

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

PubMed

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

2001-11-01

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

A universal entropy-driven mechanism for thioredoxin–target recognition

PubMed Central

Palde, Prakash B.; Carroll, Kate S.

2015-01-01

Cysteine residues in cytosolic proteins are maintained in their reduced state, but can undergo oxidation owing to posttranslational modification during redox signaling or under conditions of oxidative stress. In large part, the reduction of oxidized protein cysteines is mediated by a small 12-kDa thiol oxidoreductase, thioredoxin (Trx). Trx provides reducing equivalents for central metabolic enzymes and is implicated in redox regulation of a wide number of target proteins, including transcription factors. Despite its importance in cellular redox homeostasis, the precise mechanism by which Trx recognizes target proteins, especially in the absence of any apparent signature binding sequence or motif, remains unknown. Knowledge of the forces associated with the molecular recognition that governs Trx–protein interactions is fundamental to our understanding of target specificity. To gain insight into Trx–target recognition, we have thermodynamically characterized the noncovalent interactions between Trx and target proteins before S-S reduction using isothermal titration calorimetry (ITC). Our findings indicate that Trx recognizes the oxidized form of its target proteins with exquisite selectivity, compared with their reduced counterparts. Furthermore, we show that recognition is dependent on the conformational restriction inherent to oxidized targets. Significantly, the thermodynamic signatures for multiple Trx targets reveal favorable entropic contributions as the major recognition force dictating these protein–protein interactions. Taken together, our data afford significant new insight into the molecular forces responsible for Trx–target recognition and should aid the design of new strategies for thiol oxidoreductase inhibition. PMID:26080424

High-Frequency Jet Ventilation for Complete Target Immobilization and Reduction of Planning Target Volume in Stereotactic High Single-Dose Irradiation of Stage I Non-Small Cell Lung Cancer and Lung Metastases

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

Fritz, Peter, E-mail: p.h.fritz@t-online.d; Kraus, Hans-Joerg; Muehlnickel, Werner

2010-09-01

Purpose: To demonstrate the feasibility of complete target immobilization by means of high-frequency jet ventilation (HFJV); and to show that the saving of planning target volume (PTV) on the stereotactic body radiation therapy (SBRT) under HFJV, compared with SBRT with respiratory motion, can be predicted with reliable accuracy by computed tomography (CT) scans at peak inspiration phase. Methods and Materials: A comparison regarding different methods for defining the PTV was carried out in 22 patients with tumors that clearly moved with respiration. A movement span of the gross tumor volume (GTV) was defined by fusing respiration-correlated CT scans. The PTVmore » enclosed the GTV positions with a safety margin throughout the breathing cycle. To create a PTV from CT scans acquired under HFJV, the same margins were drawn around the immobilized target. In addition, peak inspiration phase CT images (PIP-CTs) were used to approximate a target immobilized by HFJV. Results: The resulting HFJV-PTVs were between 11.6% and 45.4% smaller than the baseline values calculated as respiration-correlated CT-PTVs (median volume reduction, 25.4%). Tentative planning by means of PIP-CT PTVs predicted that in 19 of 22 patients, use of HFJV would lead to a reduction in volume of {>=}20%. Using this threshold yielded a positive predictive value of 0.89, as well as a sensitivity of 0.94 and a specificity of 0.5. Conclusions: In all patients, SBRT under HFJV provided a reliable immobilization of the GTVs and achieved a reduction in PTVs, regardless of patient compliance. Tentative planning facilitated the selection of patients who could better undergo radiation in respiratory standstill, both with greater accuracy and lung protection.« less

Introduction of Energy and Climate Mitigation Policy Issues in Energy - Environment Model of Latvia

NASA Astrophysics Data System (ADS)

Klavs, G.; Rekis, J.

2016-12-01

The present research is aimed at contributing to the Latvian national climate policy development by projecting total GHG emissions up to 2030, by evaluating the GHG emission reduction path in the non-ETS sector at different targets set for emissions reduction and by evaluating the obtained results within the context of the obligations defined by the EU 2030 policy framework for climate and energy. The method used in the research was bottom-up, linear programming optimisation model MARKAL code adapted as the MARKAL-Latvia model with improvements for perfecting the integrated assessment of climate policy. The modelling results in the baseline scenario, reflecting national economic development forecasts and comprising the existing GHG emissions reduction policies and measures, show that in 2030 emissions will increase by 19.1 % compared to 2005. GHG emissions stabilisation and reduction in 2030, compared to 2005, were researched in respective alternative scenarios. Detailed modelling and analysis of the Latvian situation according to the scenario of non-ETS sector GHG emissions stabilisation and reduction in 2030 compared to 2005 have revealed that to implement a cost effective strategy of GHG emissions reduction first of all a policy should be developed that ensures effective absorption of the available energy efficiency potential in all consumer sectors. The next group of emissions reduction measures includes all non-ETS sectors (industry, services, agriculture, transport, and waste management).

Gulf War Illness Inflammation Reduction Trial

DTIC Science & Technology

2015-10-01

study comparing blood samples from Gulf War veterans with and without multiple symptoms of pain, fatigue, and cognitive dysfunction. The goal of the...pilot study was to identify a potential therapeutic target for the treatment of GWI. Examination to the peripheral blood revealed the biomarker...understood. Therefore, we performed a pilot study comparing blood samples from Gulf War veterans who very GWI- with blood 6 from veterans who were

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

Translating the WHO 25×25 goals into a UK context: the PROMISE modelling study

PubMed Central

Cobiac, Linda J; Scarborough, Peter

2017-01-01

Objective Model the impact of targets for obesity, diabetes, raised blood pressure, tobacco use, salt intake, physical inactivity and harmful alcohol use, as outlined in the Global Non-Communicable Disease Action Plan 2013–2020, on mortality and morbidity in the UK population. Design Dynamic population modelling study. Setting UK population. Participants Not available. Main outcome measures Mortality and morbidity (years lived with disability) from non-communicable diseases (NCDs) that are averted or delayed. Probability of achieving a 25% reduction in premature mortality from NCDs by 2025 (current WHO target) and a 33% reduction by 2030 (proposed target). Results The largest improvements in mortality would be achieved by meeting the obesity target and the largest improvements in morbidity would be achieved by meeting the diabetes target. The UK could achieve the 2025 and 2030 targets for reducing premature mortality with only a little additional preventive effort compared with current practice. Achieving all 7 risk targets could avert a total of 300 000 deaths (95% uncertainty interval 250 000 to 350 000) and 1.3 million years lived with disability (1.2–1.4 million) from NCDs by 2025, with the majority of health gains due to reduced mortality and morbidity from heart disease and stroke, and reduced morbidity from diabetes. Potential reductions in morbidity from depression and in morbidity and mortality from dementia at older ages are also substantial. Conclusions The global premature mortality targets are a potentially achievable goal for countries such as the UK that can capitalise on many decades of effort in prevention and treatment. High morbidity diseases and diseases in later life are not addressed in the Global NCD Action Plan and targets, but must also be considered a priority for prevention in the UK where the population is ageing and the costs of health and social care are rising. PMID:28377390

Improving water quality in the Chesapeake Bay using payments for ecosystem services for perennial biomass for bioenergy and biofuel production

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

Woodbury, Peter B.; Kemanian, Armen R.; Jacobson, Michael

Replacing row crops with perennial bioenergy crops may reduce nitrogen (N) loading to surface waters. We estimated the benefits, costs, and potential for replacing maize with switchgrass to meet required N loading reduction targets for the Chesapeake Bay (CB) of 26.9 Gg -1. After subtracting the potential reduction in N loading due to improved N fertilizer practices for maize, a further 22.8 Gg reduction is required. Replacing maize with fertilized switchgrass could reduce N loading to the CB by 18 kg ha -1 y -1, meeting 31% of the N reduction target. The break-even price of fertilized switchgrass to providemore » the same profit as maize in the CB is 111 $Mg -1 (oven-dry basis throughout). Growers replacing maize with switchgrass could receive an ecosystem service payment of 148 ha -1 based on the price paid in Maryland for planting a rye cover crop. For our estimated average switchgrass yield of 9.9 Mg ha -1, and the greater N loading reduction of switchgrass compared to a cover crop, this equates to 24 dollars Mg -1. The annual cost of this ecosystem service payment to induce switchgrass planting is 13.29 dollars kg -1 of N. Using the POLYSYS model to account for competition among food, feed, and biomass markets, we found that with the ecosystem service payment for switchgrass of 25 $ Mg -1 added to a farm-gate price of 111 dollars Mg -1, 11% of the N loading reduction target could be met while also producing 1.3 Tg of switchgrass, potentially yielding 420 dam 3 y -1 of ethanol.« less

Improving water quality in the Chesapeake Bay using payments for ecosystem services for perennial biomass for bioenergy and biofuel production

DOE PAGES

Woodbury, Peter B.; Kemanian, Armen R.; Jacobson, Michael; ...

2017-02-03

Replacing row crops with perennial bioenergy crops may reduce nitrogen (N) loading to surface waters. We estimated the benefits, costs, and potential for replacing maize with switchgrass to meet required N loading reduction targets for the Chesapeake Bay (CB) of 26.9 Gg -1. After subtracting the potential reduction in N loading due to improved N fertilizer practices for maize, a further 22.8 Gg reduction is required. Replacing maize with fertilized switchgrass could reduce N loading to the CB by 18 kg ha -1 y -1, meeting 31% of the N reduction target. The break-even price of fertilized switchgrass to providemore » the same profit as maize in the CB is 111 $Mg -1 (oven-dry basis throughout). Growers replacing maize with switchgrass could receive an ecosystem service payment of 148 ha -1 based on the price paid in Maryland for planting a rye cover crop. For our estimated average switchgrass yield of 9.9 Mg ha -1, and the greater N loading reduction of switchgrass compared to a cover crop, this equates to 24 dollars Mg -1. The annual cost of this ecosystem service payment to induce switchgrass planting is 13.29 dollars kg -1 of N. Using the POLYSYS model to account for competition among food, feed, and biomass markets, we found that with the ecosystem service payment for switchgrass of 25 $ Mg -1 added to a farm-gate price of 111 dollars Mg -1, 11% of the N loading reduction target could be met while also producing 1.3 Tg of switchgrass, potentially yielding 420 dam 3 y -1 of ethanol.« less

PO calculation for reduction in radar cross section of hypersonic targets using RAM

NASA Astrophysics Data System (ADS)

Liu, Song-hua; Guo, Li-xin; Pan, Wei-tao; Chen, Wei; Xiao, Yi-fan

2018-06-01

The radar cross section (RCS) reduction of hypersonic targets by radar absorbing materials (RAM) coating under different reentry cases is analyzed in the C and X bands frequency range normally used for radar detection. The physical optics method is extended to both the inhomogeneous plasma sheath and RAM layer present simultaneously. The simulation results show that the absorbing coating can reduce the RCS of the plasma cloaking system and its effectiveness is related to the maximum plasma frequency. Moreover, the amount of the RCS decrease, its maxima, and the corresponding optimal RAM thickness depend on the non-uniformity and parameters of the plasma sheath. In addition, the backward RCS of the flight vehicle shrouded by plasma shielding and man-made absorber is calculated and compared to the bare cone.

MHI-148 Cyanine Dye Conjugated Chitosan Nanomicelle with NIR Light-Trigger Release Property as Cancer Targeting Theranostic Agent.

PubMed

Thomas, Reju George; Moon, Myeong Ju; Surendran, Suchithra Poilil; Park, Hyeong Ju; Park, In-Kyu; Lee, Byeong-Il; Jeong, Yong Yeon

2018-02-15

Paclitaxel (PTX) loaded hydrophobically modified glycol chitosan (HGC) micelle is biocompatible in nature, but it requires cancer targeting ability and stimuli release property for better efficiency. To improve tumor retention and drug release characteristic of HGC-PTX nanomicelles, we conjugated cancer targeting heptamethine dye, MHI-148, which acts as an optical imaging agent, targeting moiety and also trigger on-demand drug release on application of NIR 808 nm laser. The amine group of glycol chitosan modified with hydrophobic 5β-cholanic acid and the carboxyl group of MHI-148 were bonded by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide chemistry. Paclitaxel was loaded to MHI-HGC nanomicelle by an oil-in-water emulsion method, thereby forming MHI-HGC-PTX. Comparison of near infrared (NIR) dyes, MHI-148, and Flamma-774 conjugated to HGC showed higher accumulation for MHI-HGC in 4T1 tumor and 4T1 tumor spheroid. In vitro studies showed high accumulation of MHI-HGC-PTX in 4T1 and SCC7 cancer cell lines compared to NIH3T3 cell line. In vivo fluorescence imaging of the 4T1 and SCC7 tumor showed peak accumulation of MHI-HGC-PTX at day 1 and elimination from the body at day 6. MHI-HGC-PTX showed good photothermal heating ability (50.3 °C), even at a low concentration of 33 μg/ml in 1 W/cm 2 808 nm laser at 1 min time point. Tumor reduction studies in BALB/c nude mice with SCC7 tumor showed marked reduction in MHI-HGC-PTX in the PTT group combined with photothermal therapy compared to MHI-HGC-PTX in the group without PTT. MHI-HGC-PTX is a cancer theranostic agent with cancer targeting and optical imaging capability. Our studies also showed that it has cancer targeting property independent of tumor type and tumor reduction property by combined photothermal and chemotherapeutic effects.

SU-E-J-57: First Development of Adapting to Intrafraction Relative Motion Between Prostate and Pelvic Lymph Nodes Targets

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

Ge, Y; Colvill, E; O’Brien, R

2015-06-15

Purpose Large intrafraction relative motion of multiple targets is common in advanced head and neck, lung, abdominal, gynaecological and urological cancer, jeopardizing the treatment outcomes. The objective of this study is to develop a real-time adaptation strategy, for the first time, to accurately correct for the relative motion of multiple targets by reshaping the treatment field using the multi-leaf collimator (MLC). Methods The principle of tracking the simultaneously treated but differentially moving tumor targets is to determine the new aperture shape that conforms to the shifted targets. Three dimensional volumes representing the individual targets are projected to the beam’s eyemore » view. The leaf openings falling inside each 2D projection will be shifted according to the measured motion of each target to form the new aperture shape. Based on the updated beam shape, new leaf positions will be determined with optimized trade-off between the target underdose and healthy tissue overdose, and considerations of the physical constraints of the MLC. Taking a prostate cancer patient with pelvic lymph node involvement as an example, a preliminary dosimetric study was conducted to demonstrate the potential treatment improvement compared to the state-of- art adaptation technique which shifts the whole beam to track only one target. Results The world-first intrafraction adaptation system capable of reshaping the beam to correct for the relative motion of multiple targets has been developed. The dose in the static nodes and small bowel are closer to the planned distribution and the V45 of small bowel is decreased from 110cc to 75cc, corresponding to a 30% reduction by this technique compared to the state-of-art adaptation technique. Conclusion The developed adaptation system to correct for intrafraction relative motion of multiple targets will guarantee the tumour coverage and thus enable PTV margin reduction to minimize the high target dose to the adjacent organs-at-risk. The authors acknowledge funding support from the Australian NHMRC Australia Fellowship and NHMRC Project Grant No. APP1042375.« less

Tackling alcohol related violence in city centres: effect of emergency medicine and police intervention

PubMed Central

Warburton, A L; Shepherd, J P

2006-01-01

Objectives To identify correlates of alcohol related assault injury in the city centre of a European capital city, with particular reference to emergency department (ED) and police interventions, and number and capacity of licensed premises. Methods Assaults resulting in ED treatment were studied using a longitudinal controlled intervention, a three stage design during a three year period of rapid expansion in the night‐time economy, when ED initiated targeted police interventions were delivered. A controlled ED intervention targeted at high risk night‐clubs was carried out. Main outcome measure was ED treatment after assault in licensed premises and the street. Results Targeted police intervention was associated with substantial reductions in assaults in licensed premises but unexpected increases in street assault were also observed (34% overall: 105% in the principal entertainment thoroughfare). Combined police/ED intervention was associated with a significantly greater reduction compared with police intervention alone (OR = 0.61, 95% CI 0.40 to 0.91). Street assault correlated significantly with numbers and capacity of premises. Risk of assault was 50% greater in and around licensed premises in the city centre compared with those in the suburbs, although dispersion of violence to more licensed premises was not observed. Conclusions Marked decreases in licensed premises assaults resulting from targeted policing were enhanced by the intervention of ED and maxillofacial consultants. Capacity of licensed premises was a major predictor of assaults in the city centre street in which they are clustered. City centre assault injury prevention can be achieved through police/ED interventions targeted at high risk licensed premises, which should also target the streets around which these premises are clustered. PMID:16373796

Alternative Fuels Data Center

Science.gov Websites

Energy Committee (SGEC) will advise the State Energy Manager and the State Fleet Manager about energy the 30% reduction target compared to the 2010 metric ton baseline by 2030. The State Energy Manager , State Fleet Manager, and SGEC have developed performance metrics, and agencies and departments will

US Food Industry Progress During the National Salt Reduction Initiative: 2009-2014.

PubMed

Curtis, Christine J; Clapp, Jenifer; Niederman, Sarah A; Ng, Shu Wen; Angell, Sonia Y

2016-10-01

To assess the US packaged food industry's progress from 2009 to 2014, when the National Salt Reduction Initiative had voluntary, category-specific sodium targets with the goal of reducing sodium in packaged and restaurant foods by 25% over 5 years. Using the National Salt Reduction Initiative Packaged Food Database, we assessed target achievement and change in sales-weighted mean sodium density in top-selling products in 61 food categories in 2009 (n = 6336), 2012 (n = 6898), and 2014 (n = 7396). In 2009, when the targets were established, no categories met National Salt Reduction Initiative 2012 or 2014 targets. By 2014, 26% of categories met 2012 targets and 3% met 2014 targets. From 2009 to 2014, the sales-weighted mean sodium density declined significantly in almost half of all food categories (43%; 26/61 categories). Overall, sales-weighted mean sodium density declined significantly (by 6.8%; P < .001). National target setting with monitoring through a partnership of local, state, and national health organizations proved feasible, but industry progress was modest. The US Food and Drug Administration's proposed voluntary targets will be an important step in achieving more substantial sodium reductions.

Bacteriophage removal efficiency as a validation and operational monitoring tool for virus reduction in wastewater reclamation: Review.

PubMed

Amarasiri, Mohan; Kitajima, Masaaki; Nguyen, Thanh H; Okabe, Satoshi; Sano, Daisuke

2017-09-15

The multiple-barrier concept is widely employed in international and domestic guidelines for wastewater reclamation and reuse for microbiological risk management, in which a wastewater reclamation system is designed to achieve guideline values of the performance target of microbe reduction. Enteric viruses are one of the pathogens for which the target reduction values are stipulated in guidelines, but frequent monitoring to validate human virus removal efficacy is challenging in a daily operation due to the cumbersome procedures for virus quantification in wastewater. Bacteriophages have been the first choice surrogate for this task, because of the well-characterized nature of strains and the presence of established protocols for quantification. Here, we performed a meta-analysis to calculate the average log 10 reduction values (LRVs) of somatic coliphages, F-specific phages, MS2 coliphage and T4 phage by membrane bioreactor, activated sludge, constructed wetlands, pond systems, microfiltration and ultrafiltration. The calculated LRVs of bacteriophages were then compared with reported human enteric virus LRVs. MS2 coliphage LRVs in MBR processes were shown to be lower than those of norovirus GII and enterovirus, suggesting it as a possible validation and operational monitoring tool. The other bacteriophages provided higher LRVs compared to human viruses. The data sets on LRVs of human viruses and bacteriophages are scarce except for MBR and conventional activated sludge processes, which highlights the necessity of investigating LRVs of human viruses and bacteriophages in multiple treatment unit processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

TU-EF-304-11: Therapeutic Benefits of Collimation in Spot Scanning Proton Therapy in the Treatment of Brain Cancer

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

Moignier, A; Gelover, E; Wang, D

Purpose: A dynamic collimation system (DCS) based on two orthogonal pairs of mobile trimmer blades has recently been proposed to reduce the lateral penumbra in spot scanning proton therapy (SSPT). The purpose of this work is to quantify the therapeutic benefit of using the DCS for SSPT of brain cancer by comparing un-collimated and collimated treatment plans. Methods: Un-collimated and collimated brain treatment plans were created for five patients, previously treated with SSPT, using an in-house treatment planning system capable of modeling collimated and un-collimated beamlets. Un-collimated plans reproduced the clinically delivered plans in terms of target coverage and organ-at-riskmore » (OAR) sparing, whereas collimated plans were re-optimized to improve the organ-at-risk sparing while maintaining target coverage. Physical and biological comparison metrics such as dose distribution conformity, mean and maximum doses, normal tissue complication probability (NTCP) and risk of secondary brain cancer were used to evaluate the plans. Results: The DCS systematically improved the dose distribution conformity while preserving the target coverage. The average reduction of the mean dose to the 10-mm ring surrounding the target and the healthy brain were 7.1% (95% CI: 4.2%–9.9%; p<0.01) and 14.3% (95% CI: 7.8%–20.8%; p<0.01), respectively. This yielded an average reduction of 12.0% (95% CI: 8.2%–15.7%; p<0.01) for the brain necrosis NTCP using the Flickinger model, and 14.2% (95% CI: 7.7%–20.8%; p<0.01) for the risk of secondary brain cancer. The average maximum dose reductions for the brainstem, chiasm, optic nerves, cochleae and pituitary gland when comparing un-collimated and collimated plans were 14.3%, 10.4%, 11.2%, 13.0%, 12.9% and 3.4%, respectively. Evaluating individual plans using the Lyman-Kutcher-Burman NTCP model also yielded improvements. Conclusion: The lateral penumbra reduction performed by the DCS increases the normal tissue sparing capabilities of SSPT for brain tumor treatment while preserving the target coverage. This research was financially supported by Ion Beam Applications S.A. (IBA, Louvain-La-Neuve, Belgium)« less

DVH- and NTCP-based dosimetric comparison of different longitudinal margins for VMAT-IMRT of esophageal cancer.

PubMed

Münch, S; Oechsner, M; Combs, S E; Habermehl, D

2017-08-15

To cover the microscopic tumor spread in squamous cell carcinoma of the esophagus (SCC), longitudinal margins of 3-4 cm are used for radiotherapy (RT) protocols. However, smaller margins of 2-3 cm might be reasonable when advanced diagnostic imaging is integrated into target volume delineation. Purpose of this study was to compare the dose distribution and deposition to the organs at risk (OAR) for different longitudinal margins using a DVH- and NTCP-based approach. Ten patients with SCC of the middle or lower third were retrospectively selected. Three planning target volumes (PTV) with longitudinal margins of 4 cm, 3 cm and 2 cm and an axial margin of 1.5 cm to the gross target volume (GTV) were defined for each patient. For each PTV two treatment plans with total doses of 41.4 Gy (neoadjuvant treatment) and 50.4 Gy (definite treatment) were calculated. Dose to the lungs, heart, myelon and liver were then evaluated and compared between different PTVs. When using a longitudinal margin of 3 cm instead of 4 cm, all dose parameters (Dmin, Dmean, Dmedian and V5-V35), except Dmax could be significantly reduced for the lungs. Regarding the heart, a significant reduction was seen for Dmean and V5, but not for Dmin, Dmax, Dmedian and V10-V35. When comparing a longitudinal margin of 4 cm to a longitudinal margin of 2 cm, a significant difference was calculated for Dmin, Dmean, Dmedian and V5-V35 of the lungs and for Dmax, Dmean and V5-V35 of the heart. Nevertheless, no difference was seen for median heart dose. An additional dose reduction for V10 of the heart was achieved for definite treatment plans when using a longitudinal margin of 3 cm. The NTCP-based risk of pneumonitis was significantly reduced by a margin reduction to 2 cm for neoadjuvant and definite treatment plans. Reduction of longitudinal margins from 4 cm to 3 cm can significantly reduce the dose to lungs and Dmean of the heart. Despite clinical benefit and oncologic outcome remain unclear, reduction of the longitudinal margins might provide the opportunity to reduce side effects of chemoradiation (CRT) for SCC in upcoming studies.

MERLIN: a Franco-German LIDAR space mission for atmospheric methane

NASA Astrophysics Data System (ADS)

Bousquet, P.; Ehret, G.; Pierangelo, C.; Marshall, J.; Bacour, C.; Chevallier, F.; Gibert, F.; Armante, R.; Crevoisier, C. D.; Edouart, D.; Esteve, F.; Julien, E.; Kiemle, C.; Alpers, M.; Millet, B.

2017-12-01

The Methane Remote Sensing Lidar Mission (MERLIN), currently in phase C, is a joint cooperation between France and Germany on the development, launch and operation of a space LIDAR dedicated to the retrieval of total weighted methane (CH4) atmospheric columns. Atmospheric methane is the second most potent anthropogenic greenhouse gas, contributing 20% to climate radiative forcing but also plying an important role in atmospheric chemistry as a precursor of tropospheric ozone and low-stratosphere water vapour. Its short lifetime ( 9 years) and the nature and variety of its anthropogenic sources also offer interesting mitigation options in regards to the 2° objective of the Paris agreement. For the first time, measurements of atmospheric composition will be performed from space thanks to an IPDA (Integrated Path Differential Absorption) LIDAR (Light Detecting And Ranging), with a precision (target ±27 ppb for a 50km aggregation along the trace) and accuracy (target <3.7 ppb at 68%) sufficient to significantly reduce the uncertainties on methane emissions. The very low targeted systematic error target is particularly ambitious compared to current passive methane space mission. It is achievable because of the differential active measurements of MERLIN, which guarantees almost no contamination by aerosols or water vapour cross-sensitivity. As an active mission, MERLIN will deliver global methane weighted columns (XCH4) for all seasons and all latitudes, day and night Here, we recall the MERLIN objectives and mission characteristics. We also propose an end-to-end error analysis, from the causes of random and systematic errors of the instrument, of the platform and of the data treatment, to the error on methane emissions. To do so, we propose an OSSE analysis (observing system simulation experiment) to estimate the uncertainty reduction on methane emissions brought by MERLIN XCH4. The originality of our inversion system is to transfer both random and systematic errors from the observation space to the flux space, thus providing more realistic error reductions than usually provided in OSSE only using the random part of errors. Uncertainty reductions are presented using two different atmospheric transport models, TM3 and LMDZ, and compared with error reduction achieved with the GOSAT passive mission.

Reconciling sectoral abatement strategies with global climate targets: the case of the Chinese passenger vehicle fleet.

PubMed

Pauliuk, Stefan; Dhaniati, Ni Made A; Müller, Daniel B

2012-01-03

The IPCC Forth Assessment Report postulates that global warming can be limited to 2 °C by deploying technologies that are currently available or expected to be commercialized in the coming decades. However, neither specific technological pathways nor internationally binding reduction targets for different sectors or countries have been established yet. Using the passenger car stock in China as example we compute direct CO(2) emissions until 2050 depending on population, car utilization, and fuel efficiency and compare them to benchmarks derived by assuming even contribution of all sectors and a unitary global per capita emission quota. Compared to present car utilization in industrialized countries, massive deployment of prototypes of fuel efficient cars could reduce emissions by about 45%, and moderately lower car use could contribute with another 33%. Still, emissions remain about five times higher than the benchmark for the 2 °C global warming target. Therefore an extended analysis, including in particular low-carbon fuels and the impact of urban and transport planning on annual distance traveled and car ownership, should be considered. A cross-sectoral comparison could reveal whether other sectors could bear an overproportional reduction quota instead. The proposed model offers direct interfaces to material industries, fuel production, and scrap vehicle supply.

Probability cueing of distractor locations: both intertrial facilitation and statistical learning mediate interference reduction.

PubMed

Goschy, Harriet; Bakos, Sarolta; Müller, Hermann J; Zehetleitner, Michael

2014-01-01

Targets in a visual search task are detected faster if they appear in a probable target region as compared to a less probable target region, an effect which has been termed "probability cueing." The present study investigated whether probability cueing cannot only speed up target detection, but also minimize distraction by distractors in probable distractor regions as compared to distractors in less probable distractor regions. To this end, three visual search experiments with a salient, but task-irrelevant, distractor ("additional singleton") were conducted. Experiment 1 demonstrated that observers can utilize uneven spatial distractor distributions to selectively reduce interference by distractors in frequent distractor regions as compared to distractors in rare distractor regions. Experiments 2 and 3 showed that intertrial facilitation, i.e., distractor position repetitions, and statistical learning (independent of distractor position repetitions) both contribute to the probability cueing effect for distractor locations. Taken together, the present results demonstrate that probability cueing of distractor locations has the potential to serve as a strong attentional cue for the shielding of likely distractor locations.

Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug.

PubMed

Shim, Gayong; Han, Su-Eun; Yu, Yong-Hee; Lee, Sangbin; Lee, Han Young; Kim, Kwangmeyung; Kwon, Ick Chan; Park, Tae Gwan; Kim, Young Bong; Choi, Yong Seok; Kim, Chan-Wha; Oh, Yu-Kyoung

2011-10-10

Oligolysine-based cationic lipid derivatives were synthesized for delivery of siRNA, and formulated into cationic liposomes. Among various oligolysine-based lipid derivatives differing in lysine residue number and lipid moiety, trilysinoyl oleylamide (TLO)-based liposomes (TLOL) showed the highest delivery efficiency combined with minimal cytotoxicity. Delivery of siRNA using TLOL silenced target genes both in vitro and in vivo. In green fluorescent protein (GFP)-expressing tumor tissue, a significant reduction of fluorescence was observed after intratumoral administration of siGFP using TLOL compared with control siGL2. Intravenous administration of siMcl1 employing pegylated TLOL (pTLOL) reduced the expression of human Mcl1 protein in KB-xenografted tumor tissue. Despite the reduction in target protein Mcl1 expression following such systemic delivery, tumor growth was only slightly reduced compared to a siGL2-treated control group. To potentiate the anticancer activity of siMcl1, the anticancer drug suberoylanilide hydroxamic acid (SAHA) was additionally encapsulated in pTLOL. After intravenous administration of siMcl1 using SAHA-loaded pTLOL (pSTLOL), a significant reduction in tumor growth was observed compared to that seen in animals treated with free SAHA or siGL2 complexed with pSTLOL. The results indicate that pTLOL could be further developed as a systemic delivery system for synergistic anticancer siRNA and a drug. Copyright © 2010 Elsevier B.V. All rights reserved.

Location detection and tracking of moving targets by a 2D IR-UWB radar system.

PubMed

Nguyen, Van-Han; Pyun, Jae-Young

2015-03-19

In indoor environments, the Global Positioning System (GPS) and long-range tracking radar systems are not optimal, because of signal propagation limitations in the indoor environment. In recent years, the use of ultra-wide band (UWB) technology has become a possible solution for object detection, localization and tracking in indoor environments, because of its high range resolution, compact size and low cost. This paper presents improved target detection and tracking techniques for moving objects with impulse-radio UWB (IR-UWB) radar in a short-range indoor area. This is achieved through signal-processing steps, such as clutter reduction, target detection, target localization and tracking. In this paper, we introduce a new combination consisting of our proposed signal-processing procedures. In the clutter-reduction step, a filtering method that uses a Kalman filter (KF) is proposed. Then, in the target detection step, a modification of the conventional CLEAN algorithm which is used to estimate the impulse response from observation region is applied for the advanced elimination of false alarms. Then, the output is fed into the target localization and tracking step, in which the target location and trajectory are determined and tracked by using unscented KF in two-dimensional coordinates. In each step, the proposed methods are compared to conventional methods to demonstrate the differences in performance. The experiments are carried out using actual IR-UWB radar under different scenarios. The results verify that the proposed methods can improve the probability and efficiency of target detection and tracking.

A randomized clinical trial to compare the immediate effects of seated thoracic manipulation and targeted supine thoracic manipulation on cervical spine flexion range of motion and pain.

PubMed

Karas, Steve; Olson Hunt, Megan J

2014-05-01

Randomized clinical trial. To determine the effectiveness of seated thoracic manipulation versus targeted supine thoracic manipulation on cervical spine pain and flexion range of motion (ROM). There is evidence that thoracic spine manipulation is an effective treatment for patients with cervical spine pain. This evidence includes a variety of techniques to manipulate the thoracic spine. Although each of them is effective, no research has compared techniques to determine which produces the best outcomes. A total of 39 patients with cervical spine pain were randomly assigned to either a seated thoracic manipulation or targeted supine thoracic manipulation group. Pain and flexion ROM measures were taken before and after the intervention. Pain reduction (post-treatment-pre-treatment) was significantly greater in those patients receiving the targeted supine thoracic manipulation compared to the seated thoracic manipulation (P<0.05). Although not significant, we did observe greater improvement in flexion ROM in the targeted supine thoracic manipulation group. The results of this study indicate that a targeted supine thoracic manipulation may be more effective in reducing cervical spine pain and improving cervical flexion ROM than a seated thoracic manipulation. Future studies should include a variety of patients and physical therapists (PTs) to validate our findings.

[Subnational analysis of probability of premature mortality caused by four main non-communicable diseases in China during 1990-2015 and " Health China 2030" reduction target].

PubMed

Zeng, X Y; Li, Y C; Liu, S W; Wang, L J; Liu, Y N; Liu, J M; Zhou, M G

2017-03-06

Objective: To investigate the current status, temporal trend and achieving Health China 2030 reduction target of probability of premature mortality caused by four main non-communicable diseases (NCDs) including cardiovascular and cerebrovascular diseases, tumour, diabetes, and chronic respiratory disease in China both at national and provincial level during 1990 to 2015. Methods: Using the results of Global Burden of Disease study 2015 (GBD 2015), according to the method of calculating premature mortality probability recommended by WHO, the current status and temporal trend by different gender from 1990 to 2015 were calculated, analyzed, and compared. Referring to " Health China 2030" target of reduction 30% of probability of premature mortality caused by major NCDs, we evaluated the difficulty of achieving the reduction target among provinces (not including Taiwan). Results: From 1990 to 2015, the probabilities of premature mortality in cardiovascular and cerebrovascular diseases, tumour, and chronic respiratory disease were all declined consistently for both men and women in China, the total of four main NCDs decreased from 30.69% to 18.54% with higher decreasing in women (from 25.97% to 12.40%) than that in men (from 34.94% to 24.19%). In 2015, the top five provinces in terms of probability of premature mortality caused by four main NCDs were Qinghai (28.81%), Tibet (25.88%), Guizhou (24.67%), Guangxi (23.56%), and Xinjiang (23.21%) in turn, while the top five provinces with the lowest probability were Shanghai (8.40%), Beijing (9.39%), Hong Kong (10.10%), Macao (10.31%), and Zhejiang (11.70%). If achieving the " Health China 2030" target, the probabilities of premature mortality in Qinghai and Tibet with the highest probability should decline to about 20.17%, and 18.12%, respectively in 2030, while 5.88%, and 6.57% in Shanghai and Beijing, respectively. From 1990 to 2015, the probability of premature mortality of four main NCDs declined by 2.00% a year on average, the top five provinces with the fastest decline were Beijing (3.48%), Shanghai (3.24%), Zhejiang (2.81%), Fujian (2.75%), and Guangdong (2.67%), and 11 provinces including these five provinces could achieve the " Health China 2030" target by the usual rate of decline, while other 22 provinces could not achieve the target, they need greater rate of decline in order to achieve the target. Conclusion: From 1990 to 2015, the probabilities of premature mortality of four main NCDs were declined consistently in China both at national and provincial level, compared with women, the men had higher probabilities and declined slower, there were significant different in probabilities of premature mortality and their change speed among provinces. Based on the results from 1990 to 2015, there were about two thirds of the provinces, which the task of achieving the Health China 2030 target will be daunting.

Reduced dose CT with model-based iterative reconstruction compared to standard dose CT of the chest, abdomen, and pelvis in oncology patients: intra-individual comparison study on image quality and lesion conspicuity.

PubMed

Morimoto, Linda Nayeli; Kamaya, Aya; Boulay-Coletta, Isabelle; Fleischmann, Dominik; Molvin, Lior; Tian, Lu; Fisher, George; Wang, Jia; Willmann, Jürgen K

2017-09-01

To compare image quality and lesion conspicuity of reduced dose (RD) CT with model-based iterative reconstruction (MBIR) compared to standard dose (SD) CT in patients undergoing oncological follow-up imaging. Forty-four cancer patients who had a staging SD CT within 12 months were prospectively included to undergo a weight-based RD CT with MBIR. Radiation dose was recorded and tissue attenuation and image noise of four tissue types were measured. Reproducibility of target lesion size measurements of up to 5 target lesions per patient were analyzed. Subjective image quality was evaluated for three readers independently utilizing 4- or 5-point Likert scales. Median radiation dose reduction was 46% using RD CT (P < 0.01). Median image noise across all measured tissue types was lower (P < 0.01) in RD CT. Subjective image quality for RD CT was higher (P < 0.01) in regard to image noise and overall image quality; however, there was no statistically significant difference regarding image sharpness (P = 0.59). There were subjectively more artifacts on RD CT (P < 0.01). Lesion conspicuity was subjectively better in RD CT (P < 0.01). Repeated target lesion size measurements were highly reproducible both on SD CT (ICC = 0.987) and RD CT (ICC = 0.97). RD CT imaging with MBIR provides diagnostic imaging quality and comparable lesion conspicuity on follow-up exams while allowing dose reduction by a median of 46% compared to SD CT imaging.

After the master settlement agreement: targeting and exposure of youth to magazine tobacco advertising.

PubMed

Alpert, Hillel R; Koh, Howard K; Connolly, Gregory N

2008-01-01

Targeting and exposure of youth to magazine advertising of tobacco products is associated with increased smoking initiation. National magazine advertising and youth exposure declined in the period following the Master Settlement Agreement (MSA). However, tobacco companies continued targeting youth with brands that were popular among them through magazine advertising and placement of ads in magazines with high youth readership. Existing restrictions, followed by enforcement through litigation, have achieved a marked reduction in overall magazine advertising but may be less adequate compared with pending federal legislation to fully protect youth from the marketing of tobacco products designed to appeal to them.

Reduction of Energy Intake using Just-In-Time Feedback from a Wearable Sensor System

PubMed Central

Farooq, Muhammad; McCrory, Megan A.; Sazonov, Edward

2017-01-01

Objective This work explored the potential use of a wearable sensor system for providing just-in-time (JIT) feedback on the progression of a meal and tested its ability to reduce the total food mass intake. Methods Eighteen participants each consumed three meals in a lab while monitored by a wearable sensor system capable of accurately tracking chew counts. The baseline visit was used to establish the self-determined ingested mass and the associated chew counts. Real-time feedback on chew counts was provided in the next two visits during which the target chew counts was either the same as that at baseline or the baseline chew counts reduced by 25%, in randomized order. The target was concealed from the participant and from the experimenter. Nonparametric repeated-measures ANOVA were performed to compare mass of intake, meal duration, and ratings of hunger, appetite, and thirst across 3 meals. Results JIT feedback targeting a 25% reduction in chew counts resulted in a reduction in mass and energy intake without affecting perceived hunger or fullness. Conclusion JIT feedback on chewing behavior may reduce intake within a meal. This system can be further used to help develop individualized strategies to provide just-in-time adaptive interventions for reducing energy intake. PMID:28233942

Reduction of energy intake using just-in-time feedback from a wearable sensor system.

PubMed

Farooq, Muhammad; McCrory, Megan A; Sazonov, Edward

2017-04-01

This work explored the potential use of a wearable sensor system for providing just-in-time (JIT) feedback on the progression of a meal and tested its ability to reduce the total food mass intake. Eighteen participants consumed three meals each in a lab while monitored by a wearable sensor system capable of accurately tracking chew counts. The baseline visit was used to establish the self-determined ingested mass and the associated chew counts. Real-time feedback on chew counts was provided in the next two visits, during which the target chew count was either the same as that at baseline or the baseline chew count reduced by 25% (in randomized order). The target was concealed from the participant and from the experimenter. Nonparametric repeated-measures ANOVAs were performed to compare mass of intake, meal duration, and ratings of hunger, appetite, and thirst across three meals. JIT feedback targeting a 25% reduction in chew counts resulted in a reduction in mass and energy intake without affecting perceived hunger or fullness. JIT feedback on chewing behavior may reduce intake within a meal. This system can be further used to help develop individualized strategies to provide JIT adaptive interventions for reducing energy intake. © 2017 The Obesity Society.

Treatment outcomes of overweight children and parents in the medical home.

PubMed

Quattrin, Teresa; Roemmich, James N; Paluch, Rocco; Yu, Jihnhee; Epstein, Leonard H; Ecker, Michelle A

2014-08-01

To test in the primary care setting the short- and long-term efficacy of a behavioral intervention that simultaneously targeted an overweight child and parent versus an information control (IC) targeting weight control only in the child. Two- to 5-year-old children who had BMI ≥85th percentile and an overweight parent (BMI >25 kg/m2) were randomized to Intervention or IC, both receiving diet and activity education over 12 months (13 sessions) followed by 12-month follow-up (3 sessions). Parents in the Intervention group were also targeted for weight control and received behavioral intervention. Pediatricians in 4 practices enrolled their patients with the assistance of embedded recruiters (Practice Enhancement Assistants) who assisted with treatment too. A total of 96 of the 105 children randomized (Intervention n = 46; IC n = 50) started the program and had data at baseline. Children in the Intervention experienced greater reductions in percent over BMI (group × months; P = .002) and z-BMI (group × months; P < 0.001) compared with IC throughout treatment and follow-up. Greater BMI reduction was observed over time for parents in the Intervention compared with IC (P < .001) throughout treatment and follow-up. Child weight changes were correlated with parent weight changes at 12 and 24 months (r = 0.38 and 0.26; P < .001 and P = .03). Concurrently targeting preschool-aged overweight and obese youth and their parents in primary care with behavioral intervention results in greater decreases in child percent over BMI, z-BMI, and parent BMI compared with IC. The difference between Intervention and IC persists after 12 months of follow-up. Copyright © 2014 by the American Academy of Pediatrics.

Cost-Reduction Roadmap Outlines Two Pathways to Meet DOE Residential Solar

Science.gov Websites

Cost Target for 2030 | News | NREL Cost-Reduction Roadmap Outlines Two Pathways to Meet DOE Residential Solar Cost Target for 2030 News Release: Cost-Reduction Roadmap Outlines Two Pathways to Meet DOE Residential Solar Cost Target for 2030 Installing photovoltaics at the time of roof replacement or as part of

Target weight achievement and ultrafiltration rate thresholds: potential patient implications.

PubMed

Flythe, Jennifer E; Assimon, Magdalene M; Overman, Robert A

2017-06-02

Higher ultrafiltration (UF) rates and extracellular hypo- and hypervolemia are associated with adverse outcomes among maintenance hemodialysis patients. The Centers for Medicare and Medicaid Services recently considered UF rate and target weight achievement measures for ESRD Quality Incentive Program inclusion. The dual measures were intended to promote balance between too aggressive and too conservative fluid removal. The National Quality Forum endorsed the UF rate measure but not the target weight measure. We examined the proposed target weight measure and quantified weight gains if UF rate thresholds were applied without treatment time (TT) extension or interdialytic weight gain (IDWG) reduction. Data were taken from the 2012 database of a large dialysis organization. Analyses considered 152,196 United States hemodialysis patients. We described monthly patient and dialysis facility target weight achievement patterns and examined differences in patient characteristics across target weight achievement status and differences in facilities across target weight measure scores. We computed the cumulative, theoretical 1-month fluid-related weight gain that would occur if UF rates were capped at 13 mL/h/kg without concurrent TT extension or IDWG reduction. Target weight achievement patterns were stable over the year. Patients who did not achieve target weight (post-dialysis weight ≥ 1 kg above or below target weight) tended to be younger, black and dialyze via catheter, and had shorter dialysis vintage, greater body weight, higher UF rate and more missed treatments compared with patients who achieved target weight. Facilities had, on average, 27.1 ± 9.7% of patients with average post-dialysis weight ≥ 1 kg above or below the prescribed target weight. In adjusted analyses, facilities located in the midwest and south and facilities with higher proportions of black and Hispanic patients and higher proportions of patients with shorter TTs were more likely to have unfavorable facility target weight measure scores. Without TT extension or IDWG reduction, UF rate threshold (13 mL/h/kg) implementation led to an average theoretical 1-month, fluid-related weight gain of 1.4 ± 3.0 kg. Target weight achievement patterns vary across clinical subgroups. Implementation of a maximum UF rate threshold without adequate attention to extracellular volume status may lead to fluid-related weight gain.

Quantifying Spot Size Reduction of a 1.8 kA Electron Beam for Flash Radiography

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

Burris-Mog, Trevor John; Moir, David C.

The spot size of Axis-I at the Dual Axis Radiographic Hydrodynamic Test facility was reduced by 15.5% by including a small diameter drift tube that acts to aperture the outer diameter of the electron beam. Comparing the measured values to both analytic calculations and results from a particle-in-cell model shows that one-third to one-half of the spot size reduction is due to a drop in beam emittance. We infer that one-half to two-thirds of the spot-size reduction is due to a reduction in beam-target interactions. Sources of emittance growth and the scaling of the final focal spot size with emittancemore » and solenoid aberrations are also presented.« less

Quantifying Spot Size Reduction of a 1.8 kA Electron Beam for Flash Radiography

DOE PAGES

Burris-Mog, Trevor John; Moir, David C.

2018-03-14

The spot size of Axis-I at the Dual Axis Radiographic Hydrodynamic Test facility was reduced by 15.5% by including a small diameter drift tube that acts to aperture the outer diameter of the electron beam. Comparing the measured values to both analytic calculations and results from a particle-in-cell model shows that one-third to one-half of the spot size reduction is due to a drop in beam emittance. We infer that one-half to two-thirds of the spot-size reduction is due to a reduction in beam-target interactions. Sources of emittance growth and the scaling of the final focal spot size with emittancemore » and solenoid aberrations are also presented.« less

Folate-containing reduction-sensitive lipid-polymer hybrid nanoparticles for targeted delivery of doxorubicin.

PubMed

Wu, Bo; Yu, Ping; Cui, Can; Wu, Ming; Zhang, Yang; Liu, Lei; Wang, Cai-Xia; Zhuo, Ren-Xi; Huang, Shi-Wen

2015-04-01

The development and evaluation of folate-targeted and reduction-triggered biodegradable nanoparticles are introduced to the research on targeted delivery of doxorubicin (DOX). This type of folate-targeted lipid-polymer hybrid nanoparticles (FLPNPs) is comprised of a poly(D,L-lactide-co-glycolide) (PLGA) core, a soybean lecithin monolayer, a monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16) reduction-sensitive shell, and a folic acid-targeted ligand. FLPNPs exhibited high size stability but fast disassembly in a simulated cancer cell reductive environment. The experiments on the release process in vitro revealed that as a reduction-sensitive drug delivery system, FLPNPs released DOX faster in the presence of 10 mM dithiothreitol (DTT). Results from flow cytometry, confocal image and in vitro cytotoxicity assays revealed that FLPNPs further enhanced cell uptake and generated higher cytotoxicity against human epidermoid carcinoma in the oral cavity than non-targeted redox-sensitive and targeted redox-insensitive controls. Furthermore, in vivo animal experiments demonstrated that systemic administration of DOX-loaded FLPNPs remarkably reduced tumor growth. Experiments on biodistribution of DOX-loaded FLPNPs showed that an increasing amount of DOX accumulated in the tumor. Therefore, FLPNPs formulations have proved to be a stable, controllable and targeted anticancer drug delivery system.

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

PubMed Central

Cale, Tabitha M.; Reams, Margaret A.

2016-01-01

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

Assessing the INDCs' land use, land use change, and forest emission projections.

PubMed

Forsell, Nicklas; Turkovska, Olga; Gusti, Mykola; Obersteiner, Michael; Elzen, Michel den; Havlik, Petr

2016-12-01

In preparation for the 2015 international climate negotiations in Paris, Parties submitted Intended Nationally Determined Contributions (INDCs) to the United Nations Framework Convention on Climate Change (UNFCCC) expressing each countries' respective post-2020 climate actions. In this paper we assess individual Parties' expected reduction of emissions/removals from land use, land use change, and forest (LULUCF) sector for reaching their INDC target, and the aggregate global effect on the INDCs on the future development of emission and removals from the LULUCF sector. This has been done through analysis Parties' official information concerning the role of LULUCF mitigation efforts for reaching INDC targets as presented in National Communications, Biennial Update Reports, and Additional file 1. On the aggregate global level, the Parties themselves perceive that net LULUCF emissions will increase over time. Overall, the net LULUCF emissions are estimated to increase by 0.6 Gt CO 2 e year -1 (range: 0.1-1.1) in 2020 and 1.3 Gt CO 2 e year -1 (range: 0.7-2.1) in 2030, both compared to 2010 levels. On the other hand, the full implementation of the INDCs is estimated to lead to a reduction of net LULUCF emissions in 2030 compared to 2010 levels. It is estimated that if all conditional and unconditional INDCs are implemented, net LULUCF emissions would decrease by 0.5 Gt CO 2 e year -1 (range: 0.2-0.8) by 2020 and 0.9 Gt CO 2 e year -1 (range: 0.5-1.3) by 2030, both compared to 2010 levels. The largest absolute reductions of net LULUCF emissions (compared to 2010 levels) are expected from Indonesia and Brazil, followed by China and Ethiopia. The results highlights that countries are expecting a significant contribution from the LULUCF sector to meet their INDC mitigation targets. At the global level, the LULUCF sector is expected to contribute to as much as 20% of the full mitigation potential of all the conditional and unconditional INDC targets. However, large uncertainties still surround how Parties estimate, project and account for emissions and removals from the LULUCF sector. While INDCs represent a new source of land-use information, further information and updates of the INDCs will be required to reduce uncertainty of the LULUCF projections.

Comparison of the Effects of a Sweetened Beverage Intervention on Self-Selected Food Intake

USDA-ARS?s Scientific Manuscript database

Evidence suggests that the intake of added sugar increases the risk of chronic disease and should be targeted for reduction. It is unclear if all types of added sugar have equivalent effects on food intake. This prospective, blinded intervention study compared parallel groups consuming one of five t...

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

PubMed Central

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

2011-01-01

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

Study of μDBO overlay target size reduction for application broadening

NASA Astrophysics Data System (ADS)

Calado, Victor; Dépré, Jérôme; Massacrier, Clément; Tarabrin, Sergey; van Haren, Richard; Dettoni, Florent; Bouyssou, Régis; Dezauzier, Christophe

2018-03-01

With these proceedings we present μ-diffraction-based overlay (μDBO) targets that are well below the currently supported minimum size of 10×10 μm2 . We have been capable of measuring overlay targets as small as 4×4 μm2 with our latest generation YieldStar system. Furthermore we find an excellent precision (TMU < 0.33 nm for 6 × 6 μm2 ) without any compromise on throughput (MAM time < 60 ms). At last a study that compares four generations of YieldStar systems show clearly that the latest generation YieldStar systems is much better capable of reading small overlay targets such that the performance of a 16 × 16 μm2 on an early generation YieldStar 2nd-gen is comparable to that of a 8 × 8 μm2 on the latest YieldStar 5th-gen. This work enables a smaller metrology footprint, more placement flexibility and in-die overlay metrology solutions.

Validation of a method to evaluate future impact of road safety interventions, a comparison between fatal passenger car crashes in Sweden 2000 and 2010.

PubMed

Strandroth, Johan

2015-03-01

When targeting a society free from serious and fatal road-traffic injuries, it has been a common practice in many countries and organizations to set up time-limited and quantified targets for the reduction of fatalities and injuries. In setting these targets EU and other organizations have recognized the importance to monitor and predict the development toward the target as well as the efficiency of road safety policies and interventions. This study aims to validate a method to forecast future road safety challenges by applying it to the fatal crashes in Sweden in 2000 and using the method to explain the change in fatalities based on the road safety interventions made until 2010. The estimation of the method is then compared to the true outcome in 2010. The aim of this study was to investigate if a residual of crashes produced by a partial analysis could constitute a sufficient base to describe the characteristics of future crashes. show that out of the 332 car occupants killed in 2000, 197 were estimated to constitute the residual in 2010. Consequently, 135 fatalities from 2000 were estimated by the model to be prevented by 2010. That is a predicted reduction of 41% compared to the reduction in the real outcome of 53%, from 332 in 2000 to 156 in 2010. The method was found able to generate a residual of crashes in 2010 from the crashes in 2000 that had a very similar nature, with regards to crash type, as the true outcome of 2010. It was also found suitable to handle double counting and system effects. However, future research is needed in order to investigate how external factors as well as random and systematic variation should be taken into account in a reliable manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

A comparative study of the tail ion distribution with reduced Fokker-Planck models

NASA Astrophysics Data System (ADS)

McDevitt, C. J.; Tang, Xian-Zhu; Guo, Zehua; Berk, H. L.

2014-03-01

A series of reduced models are used to study the fast ion tail in the vicinity of a transition layer between plasmas at disparate temperatures and densities, which is typical of the gas and pusher interface in inertial confinement fusion targets. Emphasis is placed on utilizing progressively more comprehensive models in order to identify the essential physics for computing the fast ion tail at energies comparable to the Gamow peak. The resulting fast ion tail distribution is subsequently used to compute the fusion reactivity as a function of collisionality and temperature. While a significant reduction of the fusion reactivity in the hot spot compared to the nominal Maxwellian case is present, this reduction is found to be partially recovered by an increase of the fusion reactivity in the neighboring cold region.

The treatment of extensive scalp lesions combining electrons with intensity-modulated photons.

PubMed

Chan, Maria F; Song, Yulin; Burman, Chandra; Chui, Chen S; Schupak, Karen

2006-01-01

This study was to investigate the feasibility and potential benefits of combining electrons with intensity modulated photons (IMRT+e) for patients with extensive scalp lesions. A case of a patient with an extensive scalp lesion, in which the target volume covered the entire front half of the scalp, is presented. This approach incorporated the electron dose into the inverse treatment planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Thermoluminescent dosimeters (TLD), diodes, and GAFCHROMIC EBT films were used to verify the accuracy of the techniques. The IMRT+e plan produced a superior dose distribution to the patient as compared to the IMRT plan in terms of reduction of the dose to the brain with the same dose conformity and homogeneity in the target volumes. This study showed that IMRT+e is a viable treatment modality for extensive scalp lesions patients. It provides a feasible alternative to existing treatment techniques, resulting in improved homogeneity of dose to the PTV compared to conventional electron techniques and a decrease in dose to the brain compared to photon IMRT alone.

Light Video Game Play is Associated with Enhanced Visual Processing of Rapid Serial Visual Presentation Targets.

PubMed

Howard, Christina J; Wilding, Robert; Guest, Duncan

2017-02-01

There is mixed evidence that video game players (VGPs) may demonstrate better performance in perceptual and attentional tasks than non-VGPs (NVGPs). The rapid serial visual presentation task is one such case, where observers respond to two successive targets embedded within a stream of serially presented items. We tested light VGPs (LVGPs) and NVGPs on this task. LVGPs were better at correct identification of second targets whether they were also attempting to respond to the first target. This performance benefit seen for LVGPs suggests enhanced visual processing for briefly presented stimuli even with only very moderate game play. Observers were less accurate at discriminating the orientation of a second target within the stream if it occurred shortly after presentation of the first target, that is to say, they were subject to the attentional blink (AB). We find no evidence for any reduction in AB in LVGPs compared with NVGPs.

Cross-sectional survey of salt content in cheese: a major contributor to salt intake in the UK

PubMed Central

Hashem, Kawther M; He, Feng J; Jenner, Katharine H; MacGregor, Graham A

2014-01-01

Objective To investigate the salt (sodium chloride) content in cheese sold in UK supermarkets. Study design We carried out a cross-sectional survey in 2012, including 612 cheeses available in UK supermarkets. Methods The salt content (g/100 g) was collected from product packaging and nutrient information panels of cheeses available in the top seven retailers. Results Salt content in cheese was high with a mean (±SD) of 1.7±0.58 g/100 g. There was a large variation in salt content between different types of cheeses and within the same type of cheese. On average, halloumi (2.71±0.34 g/100 g) and imported blue cheese (2.71±0.83 g/100 g) contained the highest amounts of salt and cottage cheese (0.55±0.14 g/100 g) contained the lowest amount of salt. Overall, among the 394 cheeses that had salt reduction targets, 84.5% have already met their respective Department of Health 2012 salt targets. Cheddar and cheddar-style cheese is the most popular/biggest selling cheese in the UK and has the highest number of products in the analysis (N=250). On average, salt level was higher in branded compared with supermarket own brand cheddar and cheddar-style products (1.78±0.13 vs 1.72±0.14 g/100 g, p<0.01). Ninety per cent of supermarket own brand products met the 2012 target for cheddar and cheddar-style cheese compared with 73% of branded products (p=0.001). Conclusions Salt content in cheese in the UK is high. There is a wide variation in the salt content of different types of cheeses and even within the same type of cheese. Despite this, 84.5% of cheeses have already met their respective 2012 targets. These findings demonstrate that much larger reductions in the amount of salt added to cheese could be made and more challenging targets need to be set, so that the UK can continue to lead the world in salt reduction. PMID:25099933

SU-E-T-29: A Dosimetric Study of Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost for Rectal Cancer

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

Sun, T; Lin, X; Yin, Y

Purpose: To compare the dosimetric differences among fixed field intensity-modulated radiotherapy (IMRT) and double-arc volumetricmodulated arc therapy (VMAT) plans with simultaneous integrated boost in rectal cancer. Methods: Ten patients with rectal cancer previously treated with IMRT were included in this analysis. For each patient, two treatment techniques were designed for each patient: the fixed 7 fields IMRT and double-arc VMAT with RapidArc technique. The treatment plan was designed to deliver in one process with simultaneous integrated boost (SIB). The prescribed doses to the planning target volume of the subclinical disease (PTV1) and the gross disease (PTV2) were 45 Gy andmore » 55 Gy in 25 fractions, respectively. The dose distribution in the target, the dose to the organs at risk, total MU and the delivery time in two techniques were compared to explore the dosimetric differences. Results: For the target dose and homogeneity in PTV1 and PTV2, no statistically differences were observed in the two plans. VMAT plans showed a better conformity in PTV1. VMAT plans reduced the mean dose to bladder, small bowel, femur heads and iliac wings. For iliac wings, VMAT plans resulted in a statistically significant reduction in irradiated volume of 15 Gy, 20 Gy, 30 Gy but increased the 10 Gy irradiated volume. VMAT plans reduced the small bowel irradiated volume of 20 Gy and 30 Gy. Compared with IMRT plans, VMAT plans showed a significant reduction of monitor units by nearly 30% and reduced treatment time by an average of 70% Conclusion: Compared to IMRT plans, VMAT plans showed the similar target dose and reduced the dose of the organs at risk, especially for small bowel and iliac wings. For rectal cancer, VMAT with simultaneous integrated boost can be carried out with high quality and efficiency.« less

Drift studies--comparison of field and wind tunnel experiments.

PubMed

Stadler, R; Regenauer, W

2005-01-01

Drift at pesticide application leads to a pollution of non-target crops, non-target species and surface water. Spray drift is influenced by many factors like environmental conditions, vegetation, technical conditions, and physical properties of the tank mixes and influenced by Chemicals. Field experiments to characterise spray drift effects with the risk of permanent changing weather conditions can be supported by wind tunnel experiments. Wind tunnel experiments do not lead to the same soil deposition curves like field experiments, but the ratio of drift reduction potential is comparable.

Changes in the Healthy Beverage Index in Response to an Intervention Targeting a Reduction in Sugar-Sweetened Beverage Consumption as Compared to an Intervention Targeting Improvements in Physical Activity: Results from the Talking Health Trial.

PubMed

Hedrick, Valisa E; Davy, Brenda M; Myers, Emily A; You, Wen; Zoellner, Jamie M

2015-12-04

The recently developed Healthy Beverage Index (HBI) was designed to evaluate overall beverage intake quality (including total fluid consumption and beverage calories), yet no known intervention studies have assessed longitudinal changes to the HBI. The objective of this investigation was to assess changes in HBI scores in response to a sugar-sweetened beverage (SSB) reduction trial as compared to a physical activity comparison group. Participants were enrolled into a six-month, community-based, controlled behavioral trial and randomized into either a SSB reduction group (SIPsmartER) or a physical activity group (MoveMore). Correlations and multilevel mixed-effects linear regression with intention-to-treat analyses are presented. Total HBI score significantly increased for SIPsmartER (n = 149) (mean increase = 7.5 points (5.4, 9.7), p ≤ 0.001) and MoveMore (n = 143) (mean increase = 3.4 points (1.6, 5.2), p ≤ 0.001) participants, with a significant between group effect (p ≤ 0.05), over the six-month intervention. Other significant changes in HBI components for SIPsmartER included increased SSB and total beverage calorie scores, and decreased low-fat milk and diet soda scores. Changes in total HBI scores were significantly correlated with changes in total Healthy Eating Index-2010 scores (r = 0.15, p ≤ 0.01). Our findings suggest that individual HBI component scores, beyond the SSB component, are influenced by intervention strategies that primarily focus on SSB reduction.

SU-F-J-17: Patient Localization Using MRI-Guided Soft Tissue for Head-And-Neck Radiotherapy: Indication for Margin Reduction and Its Feasibility

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

Qi, X; Yang, Y; Jack, N

Purpose: On-board MRI provides superior soft-tissue contrast, allowing patient alignment using tumor or nearby critical structures. This study aims to study H&N MRI-guided IGRT to analyze inter-fraction patient setup variations using soft-tissue targets and design appropriate CTV-to-PTV margin and clinical implication. Methods: 282 MR images for 10 H&N IMRT patients treated on a ViewRay system were retrospectively analyzed. Patients were immobilized using a thermoplastic mask on a customized headrest fitted in a radiofrequency coil and positioned to soft-tissue targets. The inter-fraction patient displacements were recorded to compute the PTV margins using the recipe: 2.5∑+0.7σ. New IMRT plans optimized on themore » revised PTVs were generated to evaluate the delivered dose distributions. An in-house dose deformation registration tool was used to assess the resulting dosimetric consequences when margin adaption is performed based on weekly MR images. The cumulative doses were compared to the reduced margin plans for targets and critical structures. Results: The inter-fraction displacements (and standard deviations), ∑ and σ were tabulated for MRI and compared to kVCBCT. The computed CTV-to-PTV margin was 3.5mm for soft-tissue based registration. There were minimal differences between the planned and delivered doses when comparing clinical and the PTV reduced margin plans: the paired t-tests yielded p=0.38 and 0.66 between the planned and delivered doses for the adapted margin plans for the maximum cord and mean parotid dose, respectively. Target V95 received comparable doses as planned for the reduced margin plans. Conclusion: The 0.35T MRI offers acceptable soft-tissue contrast and good spatial resolution for patient alignment and target visualization. Better tumor conspicuity from MRI allows soft-tissue based alignments with potentially improved accuracy, suggesting a benefit of margin reduction for H&N radiotherapy. The reduced margin plans (i.e., 2 mm) resulted in improved normal structure sparing and accurate dose delivery to achieve intended treatment goal under MR guidance.« less

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

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

Feng, Y

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. Themore » margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.« less

Universalism under siege? Exploring the association between targeting, child benefits and child poverty across 26 countries.

PubMed

Van Lancker, Wim; Van Mechelen, Natascha

2015-03-01

The long-standing wisdom that universally designed benefits outperform targeted benefits in terms of poverty reduction has come under siege. Recent empirical studies tend to find that targeting is not necessarily associated anymore with lower levels of poverty reduction. In this study, we investigate for a broad set of European countries (1) the relationship between child benefits and child poverty reduction; (2) whether a universal or targeted approach is more effective in reducing child poverty; and (3) the causal mechanisms explaining the link between (1) and (2). In doing so, we take into account the general characteristics of the child benefit system, the size of the redistributive budget and the generosity of benefit levels. In contrast to previous studies, we construct an indicator of targeting that captures the design instead of the outcomes of child benefit systems. We find that targeting towards lower incomes is associated with higher levels of child poverty reduction, conditional on the direction of targeting and the characteristics of the benefit system. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of Intensive Blood Pressure Control and Kidney Disease Progression in Nondiabetic Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis.

PubMed

Tsai, Wan-Chuan; Wu, Hon-Yen; Peng, Yu-Sen; Yang, Ju-Yeh; Chen, Hung-Yuan; Chiu, Yen-Ling; Hsu, Shih-Ping; Ko, Mei-Ju; Pai, Mei-Fen; Tu, Yu-Kang; Hung, Kuan-Yu; Chien, Kuo-Liong

2017-06-01

The optimal blood pressure (BP) target remains debated in nondiabetic patients with chronic kidney disease (CKD). To compare intensive BP control (<130/80 mm Hg) with standard BP control (<140/90 mm Hg) on major renal outcomes in patients with CKD without diabetes. Searches of PubMed, MEDLINE, Embase, and Cochrane Library for publications up to March 24, 2016. Randomized clinical trials that compared an intensive vs a standard BP target in nondiabetic adults with CKD, reporting changes in glomerular filtration rate (GFR), doubling of serum creatinine level, 50% reduction in GFR, end-stage renal disease (ESRD), or all-cause mortality. Random-effects meta-analyses for pooling effect measures. Meta-regression and subgroup analyses for exploring heterogeneity. Differences in annual rate of change in GFR were expressed as mean differences with 95% CIs. Differences in doubling of serum creatinine or 50% reduction in GFR, ESRD, composite renal outcome, and all-cause mortality were expressed as risk ratios (RRs) with 95% CIs. We identified 9 trials with 8127 patients and a median follow-up of 3.3 years. Compared with standard BP control, intensive BP control did not show a significant difference on the annual rate of change in GFR (mean difference, 0.07; 95% CI, -0.16 to 0.29 mL/min/1.73 m2/y), doubling of serum creatinine level or 50% reduction in GFR (RR, 0.99; 95% CI, 0.76-1.29), ESRD (RR, 0.96; 95% CI, 0.78-1.18), composite renal outcome (RR, 0.99; 95% CI, 0.81-1.21), or all-cause mortality (RR, 0.95; 95% CI, 0.66-1.37). Nonblacks and patients with higher levels of proteinuria showed a trend of lower risk of kidney disease progression with intensive BP control. Targeting BP below the current standard did not provide additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes. However, nonblack patients or those with higher levels of proteinuria might benefit from the intensive BP-lowering treatments.

Extinction with multiple excitors

PubMed Central

McConnell, Bridget L.; Miguez, Gonzalo; Miller, Ralph R.

2012-01-01

Four conditioned suppression experiments with rats, using an ABC renewal design, investigated the effects of compounding the target conditioned excitor with additional, nontarget conditioned excitors during extinction. Experiment 1 showed stronger extinction, as evidenced by less renewal, when the target excitor was extinguished in compound with a second excitor, relative to when it was extinguished with associatively neutral stimuli. Critically, this deepened extinction effect was attenuated (i.e., more renewal occurred) when a third excitor was added during extinction training. This novel demonstration contradicts the predictions of associative learning models based on total error reduction, but it is explicable in terms of a counteraction effect within the framework of the extended comparator hypothesis. The attenuated deepened extinction effect was replicated in Experiments 2a and 3, which also showed that pretraining consisting of weakening the association between the two additional excitors (Experiments 2a and 2b) or weakening the association between one of the additional excitors and the unconditioned stimulus (Experiment 3) attenuated the counteraction effect, thereby resulting in a decrease in responding to the target excitor. These results suggest that more than simple total error reduction determines responding after extinction. PMID:23055103

Do I Know What I'm Doing? Cognitive Dissonance and Action Identification Theory.

PubMed

Fointiat, Valérie; Pelt, Audrey

2015-11-27

Our main purpose was to explore hypotheses derived from the Identification of Action Theory in a particular situation that is, a dissonant situation. Thus, we varied the identification (low versus high-level) of a problematic behavior (to stop speaking for 24 hours) in the forced compliance paradigm. Two modes of dissonance reduction were presented: cognitive rationalization (classical attitude-change) and behavioral rationalization (target behavior: to stop speaking for 48 hours). As predicted, the results showed that high-level identity of action leads to cognitive rationalization whereas low-level identity leads to behavioural rationalization. Thus, participants identifying the problematic behavior at a low-level were more inclined to accept the target behavior, compared with participants identifying their problematic behavior at a higher-level. These results are of particular interest for understanding the extent to which the understanding of the discrepant act interferes with the cognitive processes of dissonance reduction.

The importance of the Montreal Protocol in protecting climate.

PubMed

Velders, Guus J M; Andersen, Stephen O; Daniel, John S; Fahey, David W; McFarland, Mack

2007-03-20

The 1987 Montreal Protocol on Substances that Deplete the Ozone Layer is a landmark agreement that has successfully reduced the global production, consumption, and emissions of ozone-depleting substances (ODSs). ODSs are also greenhouse gases that contribute to the radiative forcing of climate change. Using historical ODSs emissions and scenarios of potential emissions, we show that the ODS contribution to radiative forcing most likely would have been much larger if the ODS link to stratospheric ozone depletion had not been recognized in 1974 and followed by a series of regulations. The climate protection already achieved by the Montreal Protocol alone is far larger than the reduction target of the first commitment period of the Kyoto Protocol. Additional climate benefits that are significant compared with the Kyoto Protocol reduction target could be achieved by actions under the Montreal Protocol, by managing the emissions of substitute fluorocarbon gases and/or implementing alternative gases with lower global warming potentials.

The importance of the Montreal Protocol in protecting climate

PubMed Central

Velders, Guus J. M.; Andersen, Stephen O.; Daniel, John S.; Fahey, David W.; McFarland, Mack

2007-01-01

The 1987 Montreal Protocol on Substances that Deplete the Ozone Layer is a landmark agreement that has successfully reduced the global production, consumption, and emissions of ozone-depleting substances (ODSs). ODSs are also greenhouse gases that contribute to the radiative forcing of climate change. Using historical ODSs emissions and scenarios of potential emissions, we show that the ODS contribution to radiative forcing most likely would have been much larger if the ODS link to stratospheric ozone depletion had not been recognized in 1974 and followed by a series of regulations. The climate protection already achieved by the Montreal Protocol alone is far larger than the reduction target of the first commitment period of the Kyoto Protocol. Additional climate benefits that are significant compared with the Kyoto Protocol reduction target could be achieved by actions under the Montreal Protocol, by managing the emissions of substitute fluorocarbon gases and/or implementing alternative gases with lower global warming potentials. PMID:17360370

A randomized clinical trial to compare the immediate effects of seated thoracic manipulation and targeted supine thoracic manipulation on cervical spine flexion range of motion and pain

PubMed Central

Karas, Steve; Olson Hunt, Megan J

2014-01-01

Design Randomized clinical trial. Objectives To determine the effectiveness of seated thoracic manipulation versus targeted supine thoracic manipulation on cervical spine pain and flexion range of motion (ROM). There is evidence that thoracic spine manipulation is an effective treatment for patients with cervical spine pain. This evidence includes a variety of techniques to manipulate the thoracic spine. Although each of them is effective, no research has compared techniques to determine which produces the best outcomes. Methods A total of 39 patients with cervical spine pain were randomly assigned to either a seated thoracic manipulation or targeted supine thoracic manipulation group. Pain and flexion ROM measures were taken before and after the intervention. Results Pain reduction (post-treatment–pre-treatment) was significantly greater in those patients receiving the targeted supine thoracic manipulation compared to the seated thoracic manipulation (P<0.05). Although not significant, we did observe greater improvement in flexion ROM in the targeted supine thoracic manipulation group. The results of this study indicate that a targeted supine thoracic manipulation may be more effective in reducing cervical spine pain and improving cervical flexion ROM than a seated thoracic manipulation. Future studies should include a variety of patients and physical therapists (PTs) to validate our findings. PMID:24976754

The costs of emotional attention: affective processing inhibits subsequent lexico-semantic analysis.

PubMed

Ihssen, Niklas; Heim, Sabine; Keil, Andreas

2007-12-01

The human brain has evolved to process motivationally relevant information in an optimized manner. The perceptual benefit for emotionally arousing material, termed motivated attention, is indexed by electrocortical amplification at various levels of stimulus analysis. An outstanding issue, particularly on a neuronal level, refers to whether and how perceptual enhancement for arousing signals translates into modified processing of information presented in temporal or spatial proximity to the affective cue. The present studies aimed to examine facilitation and interference effects of task-irrelevant emotional pictures on subsequent word identification. In the context of forced-choice lexical decision tasks, pictures varying in hedonic valence and emotional arousal preceded word/ pseudoword targets. Across measures and experiments, high-arousing compared to low-arousing pictures were associated with impaired processing of word targets. Arousing pleasant and unpleasant pictures prolonged word reaction times irrespective of stimulus-onset asynchrony (80 msec, 200 msec, 440 msec) and salient semantic category differences (e.g., erotica vs. mutilation pictures). On a neuronal level, interference was reflected in reduced N1 responses (204-264 msec) to both target types. Paralleling behavioral effects, suppression of the late positivity (404-704 msec) was more pronounced for word compared to pseudoword targets. Regional source modeling indicated that early reduction effects originated from inhibited cortical activity in posterior areas of the left inferior temporal cortex associated with orthographic processing. Modeling of later reduction effects argues for interference in distributed semantic networks comprising left anterior temporal and parietal sources. Thus, affective processing interferes with subsequent lexico-semantic analysis along the ventral stream.

Intervention related reductions in perceived burdensomeness mediates incidence of suicidal thoughts.

PubMed

Allan, Nicholas P; Boffa, Joseph W; Raines, Amanda M; Schmidt, Norman B

2018-07-01

Interventions aimed at preventing suicidal thoughts target people at risk for suicide based on risk factor elevations. Based on the interpersonal psychological theory of suicide, elevated perceived burdensomeness (PB) and thwarted belongingness (TB) are potential targets for prevention of the occurrence of suicidal thoughts. PB is the belief that one is a burden to others. TB is the perceived lack of social connectedness. This study was designed to examine the effects of a preventative intervention targeting PB and TB on the 6-month incidence of suicide ideation in a sample of 138 people (M = 38.01 years, SD = 16.40; 50.7% female) with elevated levels of these variables but no current suicidal thoughts at baseline. The three-session intervention included psychoeducation and cognitive bias modification. PB was reduced in the intervention condition, compared to the repeated contact control condition (B = 2.50, p < .05) and TB was not (B = 1.42, p = .43). The likelihood of a reported incident of suicidal thoughts was reduced for those in the active intervention compared to those in the repeated contact control condition, through reductions in PB (B = .12, 95% confidence interval [.01, .32]). There were two components of the intervention, cognitive bias modification and psychoeducation; thus, it is unclear whether one or both components contributed to these findings. This intervention can be used as a preventative intervention for suicidal thoughts by targeting PB. These results further confirm PB as a causal risk factor for suicidal thoughts. Copyright © 2018 Elsevier B.V. All rights reserved.

Safety and Efficacy of D-Tagatose in Glycemic Control in Subjects with Type 2 Diabetes.

PubMed

Ensor, Mark; Banfield, Amy B; Smith, Rebecca R; Williams, Jarrod; Lodder, Robert A

The primary objectives of this study were to evaluate the treatment effect of D-tagatose on glycemic control, determined by a statistically significant decrease in hemoglobin A1c (HbA1c), and safety profile of D-tagatose compared to placebo. The secondary objectives were to evaluate the treatment effects on fasting blood glucose, insulin, lipid profiles, changes in BMI, and the proportion of subjects achieving HbA1c targets of <7%. Type 2 diabetic patients not taking any blood glucose lowering medications were administered either 15 g of D-tagatose dissolved in 125-250 ml of water three times a day or placebo with meals. Reduction in HbA1c was statistically significant compared to placebo at all post-baseline time points in the ITT population. Additionally, secondary endpoints were achieved in the ITT population with regard to LDL, total cholesterol, fasting blood glucose, and proportion of subjects achieving HbA1c targets of <7%. D-tagatose was unable to lower triglycerides or raise HDL compared to placebo. A subgroup LOCF analysis on the ITT US population showed a greater and statistically significant LS mean reduction in HbA1c in the D-tagatose group at all post-baseline visits. Based on these results it is concluded that in the ITT population D-tagatose is an effective single agent at treating many of the therapy targets of type 2 diabetes including lowering fasting blood glucose and HbA1c, and lowering of LDL and total cholesterol.

Safety and Efficacy of D-Tagatose in Glycemic Control in Subjects with Type 2 Diabetes

PubMed Central

Ensor, Mark; Banfield, Amy B.; Smith, Rebecca R.; Williams, Jarrod; Lodder, Robert A.

2015-01-01

The primary objectives of this study were to evaluate the treatment effect of D-tagatose on glycemic control, determined by a statistically significant decrease in hemoglobin A1c (HbA1c), and safety profile of D-tagatose compared to placebo. The secondary objectives were to evaluate the treatment effects on fasting blood glucose, insulin, lipid profiles, changes in BMI, and the proportion of subjects achieving HbA1c targets of <7%. Type 2 diabetic patients not taking any blood glucose lowering medications were administered either 15 g of D-tagatose dissolved in 125–250 ml of water three times a day or placebo with meals. Reduction in HbA1c was statistically significant compared to placebo at all post-baseline time points in the ITT population. Additionally, secondary endpoints were achieved in the ITT population with regard to LDL, total cholesterol, fasting blood glucose, and proportion of subjects achieving HbA1c targets of <7%. D-tagatose was unable to lower triglycerides or raise HDL compared to placebo. A subgroup LOCF analysis on the ITT US population showed a greater and statistically significant LS mean reduction in HbA1c in the D-tagatose group at all post-baseline visits. Based on these results it is concluded that in the ITT population D-tagatose is an effective single agent at treating many of the therapy targets of type 2 diabetes including lowering fasting blood glucose and HbA1c, and lowering of LDL and total cholesterol. PMID:27054147

Blood Pressure Lowering and Safety Improvements With Liver Angiotensinogen Inhibition in Models of Hypertension and Kidney Injury.

PubMed

Mullick, Adam E; Yeh, Steve T; Graham, Mark J; Engelhardt, Jeffery A; Prakash, Thazha P; Crooke, Rosanne M

2017-09-01

Uncontrolled hypertension is an important contributor to cardiovascular disease. Despite the armamentarium of antihypertensive treatments, there remains a need for novel agents effective in individuals who cannot reach acceptable blood pressure levels. Inhibitors targeting the renin-angiotensin-aldosterone system (RAAS) are widely used but may not optimally inhibit RAAS and demonstrate an acceptable safety profile. Experiments were conducted to characterize a series of AGT (angiotensinogen) antisense oligonucleotides (ASOs) and compare their efficacy and tolerability to traditional RAAS blockade. AGT ASOs which target multiple systemic sites of AGT versus an N-acetylgalactosamine-conjugated AGT ASO that targets the liver were compared with captopril and losartan. Spontaneously hypertensive rats fed an 8% NaCl diet, a model of malignant hypertension resistant to standard RAAS inhibitors, demonstrated robust and durable blood pressure reductions with AGT ASO treatments, which was not observed with standard RAAS blockade. Studies in rat models of acute kidney injury produced by salt deprivation revealed kidney injury with ASO treatment that reduced kidney-expressed AGT, but not in animals treated with the N-acetylgalactosamine AGT ASO despite comparable plasma AGT reductions. Administration of either captopril or losartan also produced acute kidney injury during salt deprivation. Thus, intrarenal RAAS derived from kidney AGT, and inhibited by the standard of care, contributes to the maintenance of renal function during severe RAAS challenge. Such improvements in efficacy and tolerability by a liver-selective AGT inhibitor could be desirable in individuals not at their blood pressure goal with existing RAAS blockade. © 2017 American Heart Association, Inc.

Falls in Scottish homicide: lessons for homicide reduction in mental health patients

PubMed Central

Crichton, John H. M.

2017-01-01

The sustained fall in Scottish homicide rates follows crime reduction measures informed by the epidemiology of suicide. The violence reduction unit targeted young men carrying knives in public. The restriction of weapons immediately to hand appears to have caused an absolute fall in homicide just as suicide reduction was observed following changes to domestic gas supply. Further homicide reduction may be accomplished in the domestic setting with targeted changes in kitchen knife design in home safety planning for high-risk households. Most commonly homicides involving those in recent contact with mental health services in the UK have domestic characteristics and similar safety planning may be targeted at those with mental disorder and a history of violence. PMID:28811910

Assessment of Clmate Change Mitigation Strategies for the Road Transport Sector of India

NASA Astrophysics Data System (ADS)

Singh, N.; Mishra, T.; Banerjee, R.

2017-12-01

India is one of the fastest growing major economies of the world. It imports three quarters of its oil demand, making transport sector major contributor of greenhouse gas (GHG) emissions. 40% of oil consumption in India comes from transport sector and over 90% of energy demand is from road transport sector. This has led to serious increase in CO2 emission and concentration of air pollutants in India. According to Intergovernmental Panel on Climate Change (IPCC), transport can play a crucial role for mitigation of global greenhouse gas emissions. Therefore, assessment of appropriate mitigation policies is required for emission reduction and cost benefit potential. The present study aims to estimate CO2, SO2, PM and NOx emissions from the road transport sector for the base year (2014) and target year (2030) by applying bottom up emission inventory model. Effectiveness of different mitigation strategies like inclusion of natural gas as alternate fuel, penetration of electric vehicle as alternate vehicle, improvement of fuel efficiency and increase share of public transport is evaluated for the target year. Emission reduction achieved from each mitigation strategies in the target year (2030) is compared with the business as usual scenario for the same year. To obtain cost benefit analysis, marginal abatement cost for each mitigation strategy is estimated. The study evaluates mitigation strategies not only on the basis of emission reduction potential but also on their cost saving potential.

Can private land conservation reduce wildfire risk to homes? A case study in San Diego County, California, USA

USGS Publications Warehouse

Butsic, Van; Syphard, Alexandra D.; Keeley, Jon E.; Bar-Massada, Avi

2017-01-01

The purchase of private land for conservation purposes is a common way to prevent the exploitation of sensitive ecological areas. However, private land conservation can also provide other benefits, one of these being natural hazard reduction. Here, we investigated the impacts of private land conservation on fire risk to homes in San Diego County, California. We coupled an econometric land use change model with a model that estimates the probability of house loss due to fire in order to compare fire risk at the county and municipality scale under alternative private land purchasing schemes and over a 20 year time horizon. We found that conservation purchases could reduce fire risk on this landscape, and the amount of risk reduction was related to the targeting approach used to choose which parcels were conserved. Conservation land purchases that targeted parcels designated as high fire hazard resulted in lower fire risk to homes than purchases that targeted low costs or high likelihood to subdivide. This result was driven by (1) preventing home placement in fire prone areas and (2) taking land off the market, and hence increasing development densities in other areas. These results raise the possibility that resource conservation and fire hazard reduction may benefit from combining efforts. With adequate planning, future conservation purchases could have synergistic effects beyond just protecting ecologically sensitive areas.

Implication of Paris Agreement in the context of long-term climate mitigation goals.

PubMed

Fujimori, Shinichiro; Su, Xuanming; Liu, Jing-Yu; Hasegawa, Tomoko; Takahashi, Kiyoshi; Masui, Toshihiko; Takimi, Maho

2016-01-01

The Paris Agreement confirmed the global aim to achieve a long-term climate goal, in which the global increase in mean temperature is kept below 2 °C compared to the preindustrial level. We investigated the implications of the near-term emissions targets (for around the year 2030) in the context of the long-term climate mitigation goal using the Asia-Pacific Integrated Model framework. To achieve the 2 °C goal, a large greenhouse gas emissions reduction is required, either in the early or latter half of this century. In the mid-term (from 2030 to 2050), it may be necessary to consider rapid changes to the existing energy or socioeconomic systems, while long-term measures (after 2050) will rely on the substantial use of biomass combined with carbon capture and storage technology or afforestation, which will eventually realize so-called negative CO2 emissions. With respect to the policy context, two suggestions are provided here. The first is the review and revision of the nationally determined contributions (NDCs) in 2020, with an additional reduction target to the current NDCs being one workable alternative. The second suggestion is a concrete and numerical mid-term emissions reduction target, for example to be met by 2040 or 2050, which could also help to achieve the long-term climate goal.

Achieving the WHO sodium target: estimation of reductions required in the sodium content of packaged foods and other sources of dietary sodium.

PubMed

Eyles, Helen; Shields, Emma; Webster, Jacqui; Ni Mhurchu, Cliona

2016-08-01

Excess sodium intake is one of the top 2 dietary risk factors contributing to the global burden of disease. As such, many countries are now developing national sodium reduction strategies, a key component of which is a sodium reduction model that includes sodium targets for packaged foods and other sources of dietary sodium. We sought to develop a sodium reduction model to determine the reductions required in the sodium content of packaged foods and other dietary sources of sodium to reduce adult population salt intake by ∼30% toward the optimal WHO target of 5 g/d. Nationally representative household food-purchasing data for New Zealand were linked with branded food composition information to determine the mean contribution of major packaged food categories to total population sodium consumption. Discretionary salt use and the contribution of sodium from fresh foods and foods consumed away from the home were estimated with the use of national nutrition survey data. Reductions required in the sodium content of packaged foods and other dietary sources of sodium to achieve a 30% reduction in dietary sodium intakes were estimated. A 36% reduction (1.6 g salt or 628 mg Na) in the sodium content of packaged foods in conjunction with a 40% reduction in discretionary salt use and the sodium content of foods consumed away from the home would reduce total population salt intake in New Zealand by 35% (from 8.4 to 5.5 g/d) and thus meet the WHO 2025 30% relative reduction target. Key reductions required include a decrease of 21% in the sodium content of white bread, 27% for hard cheese, 42% for sausages, and 54% for ready-to-eat breakfast cereals. Achieving the WHO sodium target in New Zealand will take considerable efforts by both food manufacturers and consumers and will likely require a national government-led sodium reduction strategy. © 2016 American Society for Nutrition.

Factors influencing the difference between forecasted and actual drug sales volumes under the price-volume agreement in South Korea.

PubMed

Park, Sun-Young; Han, Euna; Kim, Jini; Lee, Eui-Kyung

2016-08-01

This study analyzed factors contributing to increases in the actual sales volumes relative to forecasted volumes of drugs under price-volume agreement (PVA) policy in South Korea. Sales volumes of newly listed drugs on the national formulary are monitored under PVA policy. When actual sales volume exceeds the pre-agreed forecasted volume by 30% or more, the drug is subject to price-reduction. Logistic regression assessed the factors related to whether drugs were the PVA price-reduction drugs. A generalized linear model with gamma distribution and log-link assessed the factors influencing the increase in actual volumes compared to forecasted volume in the PVA price-reduction drugs. Of 186 PVA monitored drugs, 34.9% were price-reduction drugs. Drugs marketed by pharmaceutical companies with previous-occupation in the therapeutic markets were more likely to be PVA price-reduction drugs than drugs marketed by firms with no previous-occupation. Drugs of multinational pharmaceutical companies were more likely to be PVA price-reduction drugs than those of domestic companies. Having more alternative existing drugs was significantly associated with higher odds of being PVA price-reduction drugs. Among the PVA price-reduction drugs, the increasing rate of actual volume compared to forecasted volume was significantly higher in drugs with clinical usefulness. By focusing the negotiation efforts on those target drugs, PVA policy can be administered more efficiently with the improved predictability of the drug sales volumes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effect of interventions targeting screen time reduction: A systematic review and meta-analysis.

PubMed

Wu, Lei; Sun, Samio; He, Yao; Jiang, Bin

2016-07-01

Previous studies have evaluated the effectiveness of interventions aimed at screen time reduction, but the results have been inconsistent. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to summarize the accumulating evidence of the impact of interventions targeting screen time reduction on body mass index (BMI) reduction and screen time reduction. The PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for RCTs on the effect of interventions targeting screen time reduction. The primary and secondary outcomes were the mean difference between the treatment and control groups in the changes in BMI and changes in screen viewing time. A random effects model was used to calculate the pooled mean differences. Fourteen trials including 2238 participants were assessed. The pooled analysis suggested that interventions targeting screen time reduction had a significant effect on BMI reduction (-0.15 kg/m, P < 0.001, I = 0) and on screen time reduction (-4.63 h/w, P = 0.003, I = 94.6%). Subgroup analysis showed that a significant effect of screen time reduction was observed in studies in which the duration of intervention was <7 months and that the types of interventions in those studies were health promotion curricula or counseling. Interventions for screen time reduction might be effective in reducing screen time and preventing excess weight. Further rigorous investigations with larger samples and longer follow-up periods are still needed to evaluate the efficacy of screen time reduction both in children and in adults.

Review of pathogen treatment reductions for onsite non ...

EPA Pesticide Factsheets

Communities face a challenge when implementing onsite reuse of collected waters for non-potable purposes given the lack of national microbial standards. Quantitative Microbial Risk Assessment (QMRA) can be used to predict the pathogen risks associated with the non-potable reuse of onsite-collected waters; the present work reviewed the relevant QMRA literature to prioritize knowledge gaps and identify health-protective pathogen treatment reduction targets. The review indicated that ingestion of untreated, onsite-collected graywater, rainwater, seepage water and stormwater from a variety of exposure routes resulted in gastrointestinal infection risks greater than the traditional acceptable level of risk. We found no QMRAs that estimated the pathogen risks associated with onsite, non-potable reuse of blackwater. Pathogen treatment reduction targets for non-potable, onsite reuse that included a suite of reference pathogens (i.e., including relevant bacterial, protozoan, and viral hazards) were limited to graywater (for a limited set of domestic uses) and stormwater (for domestic and municipal uses). These treatment reductions corresponded with the health benchmark of a probability of infection or illness of 10−3 per person per year or less. The pathogen treatment reduction targets varied depending on the target health benchmark, reference pathogen, source water, and water reuse application. Overall, there remains a need for pathogen reduction targets that are heal

Reduction of emission level in approach signals of greater mouse-eared bats (Myotis myotis): No evidence for a closed loop control system for intensity compensation.

PubMed

Budenz, Tobias; Denzinger, Annette; Schnitzler, Hans-Ulrich

2018-01-01

Bats lower the emission SPL when approaching a target. The SPL reduction has been explained by intensity compensation which implies that bats adjust the emission SPL to perceive the retuning echoes at the same level. For a better understanding of this control mechanism we recorded the echolocation signals of four Myotis myotis with an onboard microphone when foraging in the passive mode for rustling mealworms offered in two feeding dishes with different target strength, and determined the reduction rate for the emission SPL and the increase rate for the SPL of the returning echoes. When approaching the dish with higher target strength bats started the reduction of the emission SPL at a larger reaction distance (1.05 ± 0.21 m) and approached it with a lower reduction rate of 7.2 dB/halving of distance (hd), thus producing a change of echo rate at the ears of + 4 dB/hd. At the weaker target reaction distance was shorter (0.71 ± 0.24 m) and the reduction rate (9.1 dB/hd) was higher, producing a change of echo rate of-1.2 dB/hd. Independent of dish type, bats lowered the emission SPL by about 26 dB on average. In one bat where the echo SPL from both targets could be measured, the reduction of emission SPL was triggered when the echo SPL surpassed a similar threshold value around 41-42 dB. Echo SPL was not adjusted at a constant value indicating that Myotis myotis and most likely all other bats do not use a closed loop system for intensity compensation when approaching a target of interest. We propose that bats lower the emission SPL to adjust the SPL of the perceived pulse-echo-pairs to the optimal auditory range for the processing of range information and hypothesize that bats use flow field information not only to control the reduction of the approach speed to the target but also to control the reduction of emission SPL.

Internal combustion engine run on biogas is a potential solution to meet Indonesia emission target

NASA Astrophysics Data System (ADS)

Ambarita, Himsar

2017-09-01

Indonesia has released two different Greenhouse Gas (GHG) emissions reduction targets. The first target, released in 2009, is reduction GHG emissions 26% from Business-as-Usual (BAU) level using own budget and up 41% if supported international aids by 2020. The second target is reduction 29% and 41% from BAU by 2030 using own budget and with international support, respectively. In this paper, the BAU emissions and emissions reduction target of these two targets are elaborated. In addition, the characteristics of emissions from transportation sector are discussed. One of the potential mitigation actions is switching fuel in transportation sector. The results the most promising mitigation action in the transportation is switching oil fuel with biofuel. The Government of Indonesia (GoI) focuses on using biodiesel and bioethanol to run internal combustion engine in transportation sector and biogas is aimed to fuel power plant unit. However, there is very limited of success stories on using biogas in the power plant. The barriers and challenges will be discussed here. It is suggested to run internal combustion engine with biogas.

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

PubMed

Santangelo, K S; Bertone, A L

2011-12-01

To ascertain a viral vector-based short hairpin RNA (shRNA) capable of reducing the interleukin-1β (IL-1β) transcript in osteoarthritis (OA)-prone chondrocytes and detect corresponding changes in the expression patterns of several critical disease mediators. Cultured chondrocytes from 2-month-old Hartley guinea pigs were screened for reduction of the IL-1β transcript following plasmid-based delivery of U6-driven shRNA sequences. A successful plasmid/shRNA knockdown combination was identified and used to construct an adeno-associated virus serotype 5 (AAV5) vector for further evaluation. Relative real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify in vitro transcript changes of IL-1β and an additional nine genes following transduction with this targeting knockdown vector. To validate in vitro findings, this AAV5 vector was injected into one knee, while either an equivalent volume of saline vehicle (three animals) or non-targeting control vector (three animals) were injected into opposite knees. Fold differences and subsequent percent gene expression levels relative to control groups were calculated using the comparative CT (2(-ΔΔCT)) method. Statistically significant decreases in IL-1β expression were achieved by the targeting knockdown vector relative to both the mock-transduced control and non-targeting vector control groups in vitro. Transcript levels of anabolic transforming growth factor-β (TGF-β) were significantly increased by use of this targeting knockdown vector. Transduction with this targeting AAV5 vector also significantly decreased the transcript levels of key inflammatory cytokines [tumor necrosis factor-α (TNF-α), IL-2, IL-8, and IL-12] and catabolic agents [matrix metalloproteinase (MMP)13, MMP2, interferon-γ (IFN-γ), and inducible nitrous oxide synthase (iNOS)] relative to both mock-transduced and non-targeting vector control groups. In vivo application of this targeting knockdown vector resulted in a >50% reduction (P=0.0045) or >90% (P=0.0001) of the IL-1β transcript relative to vehicle-only or non-targeting vector control exposed cartilage, respectively. Successful reduction of the IL-1β transcript was achieved via RNA interference (RNAi) techniques. Importantly, this alteration significantly influenced the transcript levels of several major players involved in OA pathogenesis in the direction of disease modification. Investigations to characterize additional gene expression changes influenced by targeting knockdown AAV5 vector-based diminution of the IL-1β transcript in vivo are warranted. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effect of oxidation and catalytic reduction of trace organic contaminants on their activated carbon adsorption.

PubMed

Schoutteten, Klaas V K M; Hennebel, Tom; Dheere, Ellen; Bertelkamp, Cheryl; De Ridder, David J; Maes, Synthia; Chys, Michael; Van Hulle, Stijn W H; Vanden Bussche, Julie; Vanhaecke, Lynn; Verliefde, Arne R D

2016-12-01

The combination of ozonation and activated carbon (AC) adsorption is an established technology for removal of trace organic contaminants (TrOCs). In contrast to oxidation, reduction of TrOCs has recently gained attention as well, however less attention has gone to the combination of reduction with AC adsorption. In addition, no literature has compared the removal behavior of reduction vs. ozonation by-products by AC. In this study, the effect of pre-ozonation vs pre-catalytic reduction on the AC adsorption efficiency of five TrOCs and their by-products was compared. All compounds were susceptible to oxidation and reduction, however the catalytic reductive treatment proved to be a slower reaction than ozonation. New oxidation products were identified for dinoseb and new reduction products were identified for carbamazepine, bromoxynil and dinoseb. In terms of compatibility with AC adsorption, the influence of the oxidative and reductive pretreatments proved to be compound dependent. Oxidation products of bromoxynil and diatrizoic acid adsorbed better than their parent TrOCs, but oxidation products of atrazine, carbamazepine and dinoseb showed a decreased adsorption. The reductive pre-treatment showed an enhanced AC adsorption for dinoseb and a major enhancement for diatrizoic acid. For atrazine and bromoxynil, no clear influence on adsorption was noted, while for carbamazepine, the reductive pretreatment resulted in a decreased AC affinity. It may thus be concluded that when targeting mixtures of TrOCs, a trade-off will undoubtedly have to be made towards overall reactivity and removal of the different constituents, since no single treatment proves to be superior to the other. Copyright © 2016 Elsevier Ltd. All rights reserved.

Virtual Institute of Microbial Stress and Survival: Deduction of Stress Response Pathways in Metal and Radionuclide Reducing Microorganisms

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

None

2004-04-17

The projects application goals are to: (1) To understand bacterial stress-response to the unique stressors in metal/radionuclide contamination sites; (2) To turn this understanding into a quantitative, data-driven model for exploring policies for natural and biostimulatory bioremediation; (3) To implement proposed policies in the field and compare results to model predictions; and (4) Close the experimental/computation cycle by using discrepancies between models and predictions to drive new measurements and construction of new models. The projects science goals are to: (1) Compare physiological and molecular response of three target microorganisms to environmental perturbation; (2) Deduce the underlying regulatory pathways that controlmore » these responses through analysis of phenotype, functional genomic, and molecular interaction data; (3) Use differences in the cellular responses among the target organisms to understand niche specific adaptations of the stress and metal reduction pathways; (4) From this analysis derive an understanding of the mechanisms of pathway evolution in the environment; and (5) Ultimately, derive dynamical models for the control of these pathways to predict how natural stimulation can optimize growth and metal reduction efficiency at field sites.« less

A systematic review of economic evaluations of population-based sodium reduction interventions.

PubMed

Hope, Silvia F; Webster, Jacqui; Trieu, Kathy; Pillay, Arti; Ieremia, Merina; Bell, Colin; Snowdon, Wendy; Neal, Bruce; Moodie, Marj

2017-01-01

To summarise evidence describing the cost-effectiveness of population-based interventions targeting sodium reduction. A systematic search of published and grey literature databases and websites was conducted using specified key words. Characteristics of identified economic evaluations were recorded, and included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Twenty studies met the study inclusion criteria and received a full paper review. Fourteen studies were identified as full economic evaluations in that they included both costs and benefits associated with an intervention measured against a comparator. Most studies were modelling exercises based on scenarios for achieving salt reduction and assumed effects on health outcomes. All 14 studies concluded that their specified intervention(s) targeting reductions in population sodium consumption were cost-effective, and in the majority of cases, were cost saving. Just over half the studies (8/14) were assessed as being of 'excellent' reporting quality, five studies fell into the 'very good' quality category and one into the 'good' category. All of the identified evaluations were based on modelling, whereby inputs for all the key parameters including the effect size were either drawn from published datasets, existing literature or based on expert advice. Despite a clear increase in evaluations of salt reduction programs in recent years, this review identified relatively few economic evaluations of population salt reduction interventions. None of the studies were based on actual implementation of intervention(s) and the associated collection of new empirical data. The studies universally showed that population-based salt reduction strategies are likely to be cost effective or cost saving. However, given the reliance on modelling, there is a need for the effectiveness of new interventions to be evaluated in the field using strong study designs and parallel economic evaluations.

Reducing GHG emissions in the United States' transportation sector

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

Das, Sujit; Andress, David A; Nguyen, Tien

Reducing GHG emissions in the U.S. transportation sector requires both the use of highly efficient propulsion systems and low carbon fuels. This study compares reduction potentials that might be achieved in 2060 for several advanced options including biofuels, hybrid electric vehicles (HEV), plug-in hybrid electric vehicles (PHEV), and fuel cell electric vehicles (FCEV), assuming that technical and cost reduction targets are met and necessary fueling infrastructures are built. The study quantifies the extent of the reductions that can be achieved through increasing engine efficiency and transitioning to low-carbon fuels separately. Decarbonizing the fuels is essential for achieving large reductions inmore » GHG emissions, and the study quantifies the reductions that can be achieved over a range of fuel carbon intensities. Although renewables will play a vital role, some combination of coal gasification with carbon capture and sequestration, and/or nuclear energy will likely be needed to enable very large reductions in carbon intensities for hydrogen and electricity. Biomass supply constraints do not allow major carbon emission reductions from biofuels alone; the value of biomass is that it can be combined with other solutions to help achieve significant results. Compared with gasoline, natural gas provides 20% reduction in GHG emissions in internal combustion engines and up to 50% reduction when used as a feedstock for producing hydrogen or electricity, making it a good transition fuel for electric propulsion drive trains. The material in this paper can be useful information to many other countries, including developing countries because of a common factor: the difficulty of finding sustainable, low-carbon, cost-competitive substitutes for petroleum fuels.« less

Salt Reduction Initiatives around the World - A Systematic Review of Progress towards the Global Target.

PubMed

Trieu, Kathy; Neal, Bruce; Hawkes, Corinna; Dunford, Elizabeth; Campbell, Norm; Rodriguez-Fernandez, Rodrigo; Legetic, Branka; McLaren, Lindsay; Barberio, Amanda; Webster, Jacqui

2015-01-01

To quantify progress with the initiation of salt reduction strategies around the world in the context of the global target to reduce population salt intake by 30% by 2025. A systematic review of the published and grey literature was supplemented by questionnaires sent to country program leaders. Core characteristics of strategies were extracted and categorised according to a pre-defined framework. A total of 75 countries now have a national salt reduction strategy, more than double the number reported in a similar review done in 2010. The majority of programs are multifaceted and include industry engagement to reformulate products (n = 61), establishment of sodium content targets for foods (39), consumer education (71), front-of-pack labelling schemes (31), taxation on high-salt foods (3) and interventions in public institutions (54). Legislative action related to salt reduction such as mandatory targets, front of pack labelling, food procurement policies and taxation have been implemented in 33 countries. 12 countries have reported reductions in population salt intake, 19 reduced salt content in foods and 6 improvements in consumer knowledge, attitudes or behaviours relating to salt. The large and increasing number of countries with salt reduction strategies in place is encouraging although activity remains limited in low- and middle-income regions. The absence of a consistent approach to implementation highlights uncertainty about the elements most important to success. Rigorous evaluation of ongoing programs and initiation of salt reduction programs, particularly in low- and middle- income countries, will be vital to achieving the targeted 30% reduction in salt intake.

Salt Reduction Initiatives around the World – A Systematic Review of Progress towards the Global Target

PubMed Central

Trieu, Kathy; Neal, Bruce; Hawkes, Corinna; Dunford, Elizabeth; Campbell, Norm; Rodriguez-Fernandez, Rodrigo; Legetic, Branka; McLaren, Lindsay; Barberio, Amanda; Webster, Jacqui

2015-01-01

Objective To quantify progress with the initiation of salt reduction strategies around the world in the context of the global target to reduce population salt intake by 30% by 2025. Methods A systematic review of the published and grey literature was supplemented by questionnaires sent to country program leaders. Core characteristics of strategies were extracted and categorised according to a pre-defined framework. Results A total of 75 countries now have a national salt reduction strategy, more than double the number reported in a similar review done in 2010. The majority of programs are multifaceted and include industry engagement to reformulate products (n = 61), establishment of sodium content targets for foods (39), consumer education (71), front-of-pack labelling schemes (31), taxation on high-salt foods (3) and interventions in public institutions (54). Legislative action related to salt reduction such as mandatory targets, front of pack labelling, food procurement policies and taxation have been implemented in 33 countries. 12 countries have reported reductions in population salt intake, 19 reduced salt content in foods and 6 improvements in consumer knowledge, attitudes or behaviours relating to salt. Conclusion The large and increasing number of countries with salt reduction strategies in place is encouraging although activity remains limited in low- and middle-income regions. The absence of a consistent approach to implementation highlights uncertainty about the elements most important to success. Rigorous evaluation of ongoing programs and initiation of salt reduction programs, particularly in low- and middle- income countries, will be vital to achieving the targeted 30% reduction in salt intake. PMID:26201031

Motivating smokers to quit using computer-generated letters that target either reduction or cessation: A population-based randomized controlled trial among smokers who do not intend to quit.

PubMed

Meyer, Christian; Ulbricht, Sabina; Haug, Severin; Broda, Anja; Bischof, Gallus; Rumpf, Hans-Jürgen; John, Ulrich

2016-09-01

This study examined the long-term efficacy of individualized counseling letters that targeted either smoking abstinence or reducing the number of cigarettes smoked per day to promote future cessation. A nationwide random-digit-dialing telephone sample was used to identify smokers from the general adult population (participation proportion: 54.5%). In total, 1462 participants (48% female) who did not intend to quit within the next six months and who smoked ten or more cigarettes a day were randomized to one of two intervention groups or an assessment-only control condition. The interventions consisted of three tailored letters that were sent after baseline and follow-up assessments after three and six months. Follow-up data on smoking status were provided by 82% and 77% of the participants 12 and 24 months after study inclusion, respectively. Generalized estimation equation (GEE) models adjusted for potential baseline confounders and multiple imputation of missing follow-up data were used to estimate intervention effects. At 24-month follow-up prevalence of 7-day point abstinence was 8.4%, 12.9% and 14.7% in the control, abstinence intervention and reduction intervention condition, which corresponds to a number needed to treat of 22 (95%-CI: 11-707) and 16 (95%-CI: 9-53). Adjusted GEE analyses revealed that the smoking reduction intervention (ORadj=2.3, p<0.01) but not the abstinence intervention (ORadj=1.4, p=0.20) increased the odds of 6-month prolonged abstinence compared with the control condition. No significant differences appear when directly comparing both intervention groups. Smoking reduction should be considered as an alternative intervention goal for smokers who are unable or unwilling to quit. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

42 CFR 413.88 - Incentive payments under plans for voluntary reduction in number of medical residents.

Code of Federal Regulations, 2010 CFR

2010-10-01

... voluntary residency reduction plan. (5) Updates to annual and cumulative targets (i) Except as provided in... paragraphs (g)(2) and (g)(3) of this section. (ii) An entity may update annual reduction targets specified in... used for direct GME payments for the last residency training year in which a qualifying entity...

Beneficial effects of a woman-focused development programme on child survival: evidence from rural Bangladesh.

PubMed

Bhuiya, Abbas; Chowdhury, Mushtaque

2002-11-01

This paper reports results from a prospective study of the impact of a woman-focused development programme on child survival in Matlab, a rural area of Bangladesh. The programme was targeted to households owning less than 50 decimals of land and members selling more than 100 days of labour for living in a year. Programme components included formation of women's groups for saving and credit, training on skill development, functional literacy including legal and social awareness, and technical and marketing support to projects undertaken with the loan money from the organization. A total of 13,549 children born alive during 1988-97 in the study area were included in the study. Hazards of mortality during pre- and post-intervention periods were compared among the programme participants and non-participants controlling the effects of other relevant variables. There has been a substantial reduction in mortality during the post-intervention period; however, the reduction was much greater for infants whose mothers participated in the development programme compared to infants of non-participant mothers from similar socioeconomic background. In a relative sense, there has been a 52% reduction of the pre-intervention level hazard of death of children during infancy of participant mothers compared to 31% reduction for the infants of non-participant mothers from similar socioeconomic background. There had also been a substantial reduction in hazard of death during childhood (1-4 year age group), however, the reduction was statistically similar for all groups of children irrespective of their mothers' participation in the development programmes.

Biased normalized cuts for target detection in hyperspectral imagery

NASA Astrophysics Data System (ADS)

Zhang, Xuewen; Dorado-Munoz, Leidy P.; Messinger, David W.; Cahill, Nathan D.

2016-05-01

The Biased Normalized Cuts (BNC) algorithm is a useful technique for detecting targets or objects in RGB imagery. In this paper, we propose modifying BNC for the purpose of target detection in hyperspectral imagery. As opposed to other target detection algorithms that typically encode target information prior to dimensionality reduction, our proposed algorithm encodes target information after dimensionality reduction, enabling a user to detect different targets in interactive mode. To assess the proposed BNC algorithm, we utilize hyperspectral imagery (HSI) from the SHARE 2012 data campaign, and we explore the relationship between the number and the position of expert-provided target labels and the precision/recall of the remaining targets in the scene.

Contribution of gold nanoparticles to the catalytic DNA strand displacement in leakage reduction and signal amplification.

PubMed

Wang, Bei; Zhou, Xiang; Yao, Dongbao; Sun, Xianbao; He, Miao; Wang, Xiaojing; Yin, Xue; Liang, Haojun

2017-10-03

A new model using a gold nanoparticle (AuNP)-DNA system to constrain leakage and improve efficiency of catalytic toehold-mediated strand displacement reactions was outlined. A 10-bp spacer on AuNPs and fourfold amount of fuels were determined for good performance of this model with an optimized toehold strategy. After the reaction at 25 °C for 10 h, a 258 pM target could be identified, which is a remarkable improvement compared with the traditional AuNP-DNA system without fuel. Moreover, this model was also studied to differentiate specific single nucleotide polymorphism on target with superior selection factors. This model may help by introducing a proposition of target detection to guide further investigation.

Deep space target location with Hubble Space Telescope (HST) and Hipparcos data

NASA Technical Reports Server (NTRS)

Null, George W.

1988-01-01

Interplanetary spacecraft navigation requires accurate a priori knowledge of target positions. A concept is presented for attaining improved target ephemeris accuracy using two future Earth-orbiting optical observatories, the European Space Agency (ESA) Hipparcos observatory and the Nasa Hubble Space Telescope (HST). Assuming nominal observatory performance, the Hipparcos data reduction will provide an accurate global star catalog, and HST will provide a capability for accurate angular measurements of stars and solar system bodies. The target location concept employs HST to observe solar system bodies relative to Hipparcos catalog stars and to determine the orientation (frame tie) of these stars to compact extragalactic radio sources. The target location process is described, the major error sources discussed, the potential target ephemeris error predicted, and mission applications identified. Preliminary results indicate that ephemeris accuracy comparable to the errors in individual Hipparcos catalog stars may be possible with a more extensive HST observing program. Possible future ground and spacebased replacements for Hipparcos and HST astrometric capabilities are also discussed.

New subspace methods for ATR

NASA Astrophysics Data System (ADS)

Zhang, Peng; Peng, Jing; Sims, S. Richard F.

2005-05-01

In ATR applications, each feature is a convolution of an image with a filter. It is important to use most discriminant features to produce compact representations. We propose two novel subspace methods for dimension reduction to address limitations associated with Fukunaga-Koontz Transform (FKT). The first method, Scatter-FKT, assumes that target is more homogeneous, while clutter can be anything other than target and anywhere. Thus, instead of estimating a clutter covariance matrix, Scatter-FKT computes a clutter scatter matrix that measures the spread of clutter from the target mean. We choose dimensions along which the difference in variation between target and clutter is most pronounced. When the target follows a Gaussian distribution, Scatter-FKT can be viewed as a generalization of FKT. The second method, Optimal Bayesian Subspace, is derived from the optimal Bayesian classifier. It selects dimensions such that the minimum Bayes error rate can be achieved. When both target and clutter follow Gaussian distributions, OBS computes optimal subspace representations. We compare our methods against FKT using character image as well as IR data.

Synthesis and x-ray characterization of cobalt phosphide (Co₂P) nanorods for the oxygen reduction reaction

DOE PAGES

Doan-Nguyen, Vicky V.T.; Su, Dong; Zhang, Sen; ...

2015-07-14

Low temperature fuel cells are clean, effective alternative fuel conversion technology. Oxygen reduction reaction (ORR) at the fuel cell cathode has required Pt as the electrocatalyst for high activity and selectivity of the four-electron reaction pathway. Targeting a less expensive, earth abundant alternative, we have developed the synthesis of cobalt phosphide (Co₂P) nanorods for ORR. Characterization techniques that include total X-ray scattering and extended X-ray absorption fine structure revealed a deviation of the nanorods from bulk crystal structure with a contraction along the b orthorhombic lattice parameter. The carbon supported nanorods have comparable activity but are remarkably more stable thanmore » conventional Pt catalysts for the oxygen reduction reaction in alkaline environments.« less

Optimizing Eco-Efficiency Across the Procurement Portfolio.

PubMed

Pelton, Rylie E O; Li, Mo; Smith, Timothy M; Lyon, Thomas P

2016-06-07

Manufacturing organizations' environmental impacts are often attributable to processes in the firm's upstream supply chain. Environmentally preferable procurement (EPP) and the establishment of environmental purchasing criteria can potentially reduce these indirect impacts. Life-cycle assessment (LCA) can help identify the purchasing criteria that are most effective in reducing environmental impacts. However, the high costs of LCA and the problems associated with the comparability of results have limited efforts to integrate procurement performance with quantitative organizational environmental performance targets. Moreover, environmental purchasing criteria, when implemented, are often established on a product-by-product basis without consideration of other products in the procurement portfolio. We develop an approach that utilizes streamlined LCA methods, together with linear programming, to determine optimal portfolios of product impact-reduction opportunities under budget constraints. The approach is illustrated through a simulated breakfast cereal manufacturing firm procuring grain, containerboard boxes, plastic packaging, electricity, and industrial cleaning solutions. Results suggest that extending EPP decisions and resources to the portfolio level, recently made feasible through the methods illustrated herein, can provide substantially greater CO2e and water-depletion reductions per dollar spend than a product-by-product approach, creating opportunities for procurement organizations to participate in firm-wide environmental impact reduction targets.

Comparing estimates of child mortality reduction modelled in LiST with pregnancy history survey data for a community-based NGO project in Mozambique

PubMed Central

2011-01-01

Background There is a growing body of evidence that integrated packages of community-based interventions, a form of programming often implemented by NGOs, can have substantial child mortality impact. More countries may be able to meet Millennium Development Goal (MDG) 4 targets by leveraging such programming. Analysis of the mortality effect of this type of programming is hampered by the cost and complexity of direct mortality measurement. The Lives Saved Tool (LiST) produces an estimate of mortality reduction by modelling the mortality effect of changes in population coverage of individual child health interventions. However, few studies to date have compared the LiST estimates of mortality reduction with those produced by direct measurement. Methods Using results of a recent review of evidence for community-based child health programming, a search was conducted for NGO child health projects implementing community-based interventions that had independently verified child mortality reduction estimates, as well as population coverage data for modelling in LiST. One child survival project fit inclusion criteria. Subsequent searches of the USAID Development Experience Clearinghouse and Child Survival Grants databases and interviews of staff from NGOs identified no additional projects. Eight coverage indicators, covering all the project’s technical interventions were modelled in LiST, along with indicator values for most other non-project interventions in LiST, mainly from DHS data from 1997 and 2003. Results The project studied was implemented by World Relief from 1999 to 2003 in Gaza Province, Mozambique. An independent evaluation collecting pregnancy history data estimated that under-five mortality declined 37% and infant mortality 48%. Using project-collected coverage data, LiST produced estimates of 39% and 34% decline, respectively. Conclusions LiST gives reasonably accurate estimates of infant and child mortality decline in an area where a package of community-based interventions was implemented. This and other validation exercises support use of LiST as an aid for program planning to tailor packages of community-based interventions to the epidemiological context and for project evaluation. Such targeted planning and assessments will be useful to accelerate progress in reaching MDG4 targets. PMID:21501454

Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice

PubMed Central

Li, Weidong; Hua, Baojin; Saud, Shakir M.; Lin, Hongsheng; Hou, Wei; Matter, Matthias S.; Jia, Libin; Colburn, Nancy H.; Young, Matthew R.

2015-01-01

Colorectal cancer, a leading cause of cancer death, has been linked to inflammation and obesity. Berberine, an isoquinoline alkaloid, possesses anti-inflammatory, anti-diabetes and anti-tumor properties. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, berberine treated mice showed a 60% reduction in tumor number (P=0.009), a 48% reduction in tumors <2 mm, (P=0.05); 94% reduction in tumors 2-4 mm, (P=0.001) and 100% reduction in tumors >4 mm (P=0.02) compared to vehicle treated mice. Berberine also decreased AOM/DSS induced Ki-67 and COX-2 expression. In vitro analysis showed that in addition to its anti-proliferation activity, berberine also induced apoptosis in colorectal cancer cell lines. Berberine activated AMP-activated protein kinase (AMPK), a major regulator of metabolic pathways, and inhibited mammalian target of rapamycin (mTOR), a downstream target of AMPK. Furthermore, 4E-binding protein-1 and p70 ribosomal S6 kinases, downstream targets of mTOR, were down regulated by berberine treatment. Berberine did not affect Liver kinase B1 (LKB1) activity or the mitogen-activated protein kinase pathway. Berberine inhibited Nuclear Factor kappa-B (NF-κB) activity, reduced the expression of cyclin D1 and survivin, induced phosphorylation of p53 and increased caspase-3 cleavage in vitro. Berberine inhibition of mTOR activity and p53 phosphorylation was found to be AMPK dependent, while inhibition NF-κB was AMPK independent. In vivo, berberine also activated AMPK, inhibited mTOR and p65 phosphorylation and activated caspase-3 cleavage. Our data suggests that berberine suppresses colon epithelial proliferation and tumorigenesis via AMPK dependent inhibition of mTOR activity and AMPK independent inhibition of NF-κB. PMID:24838344

42 CFR 413.88 - Incentive payments under plans for voluntary reduction in number of medical residents.

Code of Federal Regulations, 2014 CFR

2014-10-01

... reduction plan. (5) Updates to annual and cumulative targets (i) Except as provided in paragraph (g)(5)(ii...)(2) and (g)(3) of this section. (ii) An entity may update annual reduction targets specified in its... used for direct GME payments for the last residency training year in which a qualifying entity...

SU-F-T-404: Dosimetric Advantages of Flattening Free Beams to Prone Accelerated Partial Breast Irradiation

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

Galavis, P; Barbee, D; Jozsef, G

2016-06-15

Purpose: Prone accelerated partial breast irradiation (APBI) results in dose reduction to the heart and lung. Flattening filter free beams (FFF) reduce out of field dose due to the reduced scatter from the removal of the flattening filter and reduce the buildup region. The aim of this work is to evaluate the dosimetric advantages of FFF beams to prone APBI target coverage and reduction in dose to organs at risk. Methods: Fifteen clinical prone APBI cases using flattened photon beams were retrospectively re-planned in Eclipse-TPS using FFF beams. FFF plans were designed to provide equivalent target coverage with similar hotspotsmore » using the same field arrangements, resulting in comparable target DVHs. Both plans were transferred to a prone breast phantom and delivered on Varian-Edge-Linac. GafChromic-film was placed in the coronal plane of the phantom, partially overlapping the treatment field and extending into OARs to compare dose profiles from both plans. Results: FFF plans were comparable to the clinical plans with maximum doses of (108.3±2.3)% and (109.2±2.4)% and mean doses of (104.5±1.0)% and (104.6±1.2)%, respectively. Similar mean dose doses to the heart and contralateral lungs were observed from both plans, whereas the mean dose to the contra-lateral breast was (2.79±1.18) cGy and (2.86±1.40) cGy for FFF and clinical plans respectively. However for both plans the error between calculated and measured doses at 4 cm from the field edge was 10%. Conclusion: The results showed that FFF beams in prone APBI provide dosimetrically equivalent target coverage and improved coverage in superficial target due to softer energy spectra. Film analysis showed that the TPS underestimates dose outside field edges for both cases. The FFF measured plans showed less dose outside the beam that might reduce the probability of secondary cancers in the contralateral breast.« less

A telephonic intervention for promoting occupational re-integration in work-disabled individuals with musculoskeletal pain.

PubMed

Sullivan, Michael J L; Simon, Gregory

2012-06-01

The purpose of the present research was to examine the feasibility of a telephonic occupational rehabilitation program. A sample of 23 individuals with chronic musculoskeletal pain was enrolled in the telephonic version of the Progressive Goal Attainment Program (PGAP-Tel). The PGAP-Tel is a risk-targeted intervention designed to reduce pain-related disability consequent to musculoskeletal injury. Treatment outcomes of PGAP-Tel were compared to a group of individuals with chronic musculoskeletal pain, who participated in the face-to-face format of the PGAP. Results showed that PGAP-Tel was acceptable to the majority of participants (76%) to whom it was offered. There were indications that engagement and adherence issues were more problematic in PGAP-Tel than in the face-to-face intervention. Both groups showed comparable reductions in pain, depression, fear of symptom exacerbation, and self-reported disability. Participants in the face-to-face intervention showed greater reduction in catastrophic thinking than participants in PGAP-Tel. Finally, 26% of participants in PGAP-Tel had resumed some form of employment at treatment termination compared to 56% of the participants in the face-to-face intervention. Given the low cost of the PGAP-Tel intervention and the accessibility advantages of a telephonic delivery, this type of intervention might be an important resource for targeting occupational disability in rural or remote communities when face-to-face services are not available.

Cross-sectional survey of salt content in cheese: a major contributor to salt intake in the UK.

PubMed

Hashem, Kawther M; He, Feng J; Jenner, Katharine H; MacGregor, Graham A

2014-07-18

To investigate the salt (sodium chloride) content in cheese sold in UK supermarkets. We carried out a cross-sectional survey in 2012, including 612 cheeses available in UK supermarkets. The salt content (g/100 g) was collected from product packaging and nutrient information panels of cheeses available in the top seven retailers. Salt content in cheese was high with a mean (±SD) of 1.7±0.58 g/100 g. There was a large variation in salt content between different types of cheeses and within the same type of cheese. On average, halloumi (2.71±0.34 g/100 g) and imported blue cheese (2.71±0.83 g/100 g) contained the highest amounts of salt and cottage cheese (0.55±0.14 g/100 g) contained the lowest amount of salt. Overall, among the 394 cheeses that had salt reduction targets, 84.5% have already met their respective Department of Health 2012 salt targets. Cheddar and cheddar-style cheese is the most popular/biggest selling cheese in the UK and has the highest number of products in the analysis (N=250). On average, salt level was higher in branded compared with supermarket own brand cheddar and cheddar-style products (1.78±0.13 vs 1.72±0.14 g/100 g, p<0.01). Ninety per cent of supermarket own brand products met the 2012 target for cheddar and cheddar-style cheese compared with 73% of branded products (p=0.001). Salt content in cheese in the UK is high. There is a wide variation in the salt content of different types of cheeses and even within the same type of cheese. Despite this, 84.5% of cheeses have already met their respective 2012 targets. These findings demonstrate that much larger reductions in the amount of salt added to cheese could be made and more challenging targets need to be set, so that the UK can continue to lead the world in salt reduction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Potential benefits of farm scale measures versus landscape measures for reducing nitrate loads in a Danish catchment.

PubMed

Hashemi, Fatemeh; Olesen, Jørgen E; Børgesen, Christen D; Tornbjerg, Henrik; Thodsen, Hans; Dalgaard, Tommy

2018-05-08

To comply with the EU Water Framework Directive, Denmark must further reduce the nitrate (N)-load to marine ecosystems from agricultural areas. Under the anticipated future spatially targeted regulation, the required N-load reductions will differ between catchments, and these are expected to be mitigated by a combination of land and water management measures. Here, we explored how the expected N-load reduction target of 38% for a Danish catchment (River Odense) could be achieved through a combination of farm and landscape measures. These include: (a) N-leaching reduction through changing the crop rotation and applying cover crops, (b) enhancing N-reduction through (re)establishment of wetlands, and (c) reducing N-leaching through spatially targeting of set-aside to high N-load areas. Changes in crop rotations were effective in reducing N-leaching by growing crops with a longer growing season and by allowing a higher use of cover crops. A combination of wetlands and changes in crop rotations were needed for reaching the N-load reduction target without use of set-aside. However, not all combinations of wetlands and crop rotation changes achieved the required N-load reduction, resulting in a need for targeted set-aside, implying a need for balancing measures at farm and landscape scale to maximize N load reduction while minimizing loss of productive land. The effectiveness of farm scale measures is affected by farm and soil types as well as by N-reduction in groundwater, while the possibilities for using wetlands for decreasing the N-load depends on landscape features, allowing the establishment of wetlands connected to streams and rivers. Copyright © 2018 Elsevier B.V. All rights reserved.

Can There Ever Be Enough to Impact Water Quality? Evaluating BMPs in Elliot Ditch, Indiana Using the LTHIA-LID Model

NASA Astrophysics Data System (ADS)

Rahman, M. S.; Hoover, F. A.; Bowling, L. C.

2017-12-01

Elliot Ditch is an urban/urbanizing watershed located in the city of Lafayette, IN, USA. The city continues to struggle with stormwater management and combined sewer overflow (CSO) events. Several best-management practices (BMP) such as rain gardens, green roofs, and bioswales have been implemented in the watershed, but the level of adoption needed to achieve meaningful impact is currently unknown. This study's goal is to determine what level of BMP coverage is needed to impact water quality, whether meaningful impact is determined by achieving water quality targets or statistical significance. A power analysis was performed using water quality data for total suspended solids (TSS), E.coli, total phosphorus (TP) and nitrate (NO3-N) from Elliot Ditch from 2011 to 2015. The minimum detectable difference (MDD) was calculated as the percent reduction in load needed to detect a significant change in the watershed. The water quality targets were proposed by stakeholders as part of a watershed management planning process. The water quality targets and the MDD percentages were then compared to simulated load reductions due to BMP implementation using the Long-term Hydrologic Impact Assessment-Low Impact Development (LTHIA-LID) model. Seven baseline model scenarios were simulated by implementing the maximum number of each of six types of BMPs (rain barrels, permeable patios, green roofs, grassed swale/bioswales, bioretention/rain gardens, and porous pavement), as well as all the practices combined in the watershed. These provide the baseline for targeted implementation scenarios designed to determine if statistically and physically meaningful load reductions can be achieved through BMP implementation alone.

The Efficacy of Web-Based and Print-Delivered Computer-Tailored Interventions to Reduce Fat Intake: Results of a Randomized, Controlled Trial

ERIC Educational Resources Information Center

Kroeze, Willemieke; Oenema, Anke; Campbell, Marci; Brug, Johannes

2008-01-01

Objective: To test and compare the efficacy of interactive- and print-delivered computer-tailored nutrition education targeting saturated fat intake reduction. Design: A 3-group randomized, controlled trial (2003-2005) with posttests at 1 and 6 months post-intervention. Setting: Worksites and 2 neighborhoods in the urban area of Rotterdam.…

Teens in the Twenty-First Century Still Prefer People over Machines: Importance of Intervention Delivery Style in Adolescent HIV/STD Prevention

ERIC Educational Resources Information Center

Pendleton, Sara M.; Stanton, Bonita; Cottrell, Lesley A.; Marshall, Sharon; Pack, Robert; Burns, James; Gibson, Catherine; Wu, Ying; Li, Xiaoming; Cole, Matthew

2007-01-01

Purpose: To assess and compare youth satisfaction with two delivery approaches to a HIV/STD risk reduction intervention targeting adolescents: an on-site, face-to-face (FTF) approach versus a long distance interactive televised (DIT) approach. Methods: A convenience sample of 571 rural adolescents ages 12-16 years who participated in an HIV/STD…

TH-AB-BRA-08: Simulated Tumor Tracking in An MRI Linac for Lung Tumor Lesions Using the Monaco Treatment Planning System

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

Al-Ward, S; Kim, A; McCann, C

2016-06-15

Purpose: To simulate tumor tracking in an Elekta MRI-linac (MRL) and to compare this tracking method with our current ITV approach in terms of OAR sparing for lung cancer patients. Methods: Five SABR-NSCLC patients with central lung tumors were selected for reasons of potential enhancement of tumor-tissue delineation using MRI. The Monaco TPS was used to compare the current clinical ITV approach to a simulated, novel tracking method which used a 7MV MRL beam in the presence of an orthogonal 1.5 T magnetic field (4D-MRL method). In the simulated tracking scenario, achieved using the virtual couch shift (VCS), the PTVmore » was defined using an isotropic 5mm margin applied to the GTV of each phase, as acquired from an 8-phase amplitude-binned 4DCT. These VCS plans were optimized and weighted on each phase. The dose weighting was performed using the patient-specific breathing traces. The doses were accumulated on the inhale phase. The two methods were compared by assessing the OAR DVHs. Results: The 4D-MRL method resulted in a reduced target volume (by an average of 29% over all patients). The benefits of using an MRL tracking system depended on the tumor motion amplitude and the relative OAR motion (ROM) to the target. The reduction in mean doses to parallel organs was up to 3 Gy for the heart and 2.1 Gy for the lung. The reductions in maximum doses to serial organs were up to 9.4 Gy, 5.6 Gy, and 8.7 Gy for the esophagus, spinal cord, and the trachea, respectively. Serial organs benefited from MRL tracking when the ROM was ≥ 0.3 cm despite small tumor motion amplitude in some cases. Conclusions: This work demonstrated the potential benefit for an MRL tracking system to spare OARs in SABR-NSCLC patients with central tumors. The benefits are embodied in the target volume reduction. This project was made possible with the financial support of Elekta.« less

Magnetized Target Fusion Driven by Plasma Liners

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Kirkpatrick, Ronald C.; Knapp, Charles E.; Rodgers, Stephen L. (Technical Monitor)

2002-01-01

Magnetized target fusion is an emerging, relatively unexplored approach to fusion for electrical power and propulsion application. The physical principles of the concept are founded upon both inertial confinement fusion (ICF) and magnetic confinement fusion (MCF). It attempts to combine the favorable attributes of both these orthogonal approaches to fusion, but at the same time, avoiding the extreme technical challenges of both by exploiting a fusion regime intermediate between them. It uses a material liner to compress, heat and contain the fusion reacting plasma (the target plasma) mentally. By doing so, the fusion burn could be made to occur at plasma densities as high as six orders of magnitude higher than conventional MCF such as tokamak, thus leading to an approximately three orders of magnitude reduction in the plasma energy required for ignition. It also uses a transient magnetic field, compressed to extremely high intensity (100's T to 1000T) in the target plasma, to slow down the heat transport to the liner and to increase the energy deposition of charged-particle fusion products. This has several compounding beneficial effects. It leads to longer energy confinement time compared with conventional ICF without magnetized target, and thus permits the use of much lower plasma density to produce reasonable burn-up fraction. The compounding effects of lower plasma density and the magneto-insulation of the target lead to greatly reduced compressional heating power on the target. The increased energy deposition rate of charged-particle fusion products also helps to lower the energy threshold required for ignition and increasing the burn-up fraction. The reduction in ignition energy and the compressional power compound to lead to reduced system size, mass and R&D cost. It is a fusion approach that has an affordable R&D pathway, and appears attractive for propulsion application in the nearer term.

Body hair counts during hair length reduction procedures: a comparative study between Computer Assisted Image Analysis after Manual Processing (CAIAMP) and Trichoscan(™).

PubMed

Van Neste, D J J

2015-08-01

To compare two measurement methods for body hair. Calibration of computer assisted image analysis after manual processing (CAIAMP) showed variation <4% for thickness and <2.3% for densities. Images from 6 body sites with 'good natural contrast between hair and skin' were taken before hair dye, after hair dye or after hair length reduction without hair extraction or destruction. Data in the same targets were compared with Trichoscan(™) quoted for 'unambiguous evaluation of the hair growth after shaving'. CAIAMP detected a total of 337 hair and showed no statistically significant differences with the three procedures confirming 'good natural contrast between hair and skin' and that reduction methods did not affect hair counts. While CAIAMP found a mean number of 19 thick hair (≥30 μm) before dye, 18 after dye and 20 after hair reduction, Trichoscan(™) found in the same sites respectively 44, 73 and 61. Trichoscan(™) generated counts differed statistically significantly from CAIAMP-data. Automated analyses were considered un-specifically influenced by hair medulla and natural or artificial skin background. Quality control including all steps of human intervention and measurement technology are mandatory for body hair measurements during experimental or clinical trials on body hair grooming, shaving or removal. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Investigation of E. coli and Virus Reductions Using Replicate, Bench-Scale Biosand Filter Columns and Two Filter Media

PubMed Central

Elliott, Mark; Stauber, Christine E.; DiGiano, Francis A.; Fabiszewski de Aceituno, Anna; Sobsey, Mark D.

2015-01-01

The biosand filter (BSF) is an intermittently operated, household-scale slow sand filter for which little data are available on the effect of sand composition on treatment performance. Therefore, bench-scale columns were prepared according to the then-current (2006–2007) guidance on BSF design and run in parallel to conduct two microbial challenge experiments of eight-week duration. Triplicate columns were loaded with Accusand silica or crushed granite to compare virus and E. coli reduction performance. Bench-scale experiments provided confirmation that increased schmutzdecke growth, as indicated by decline in filtration rate, is the primary factor causing increased E. coli reductions of up to 5-log10. However, reductions of challenge viruses improved only modestly with increased schmutzdecke growth. Filter media type (Accusand silica vs. crushed granite) did not influence reduction of E. coli bacteria. The granite media without backwashing yielded superior virus reductions when compared to Accusand. However, for columns in which the granite media was first backwashed (to yield a more consistent distribution of grains and remove the finest size fraction), virus reductions were not significantly greater than in columns with Accusand media. It was postulated that a decline in surface area with backwashing decreased the sites and surface area available for virus sorption and/or biofilm growth and thus decreased the extent of virus reduction. Additionally, backwashing caused preferential flow paths and deviation from plug flow; backwashing is not part of standard BSF field preparation and is not recommended for BSF column studies. Overall, virus reductions were modest and did not meet the 5- or 3-log10 World Health Organization performance targets. PMID:26308036

Assessment of the trade-offs and synergies between low-carbon power sector transition and land and water resources of the United Kingdom using the "ForeseerTM" approach

NASA Astrophysics Data System (ADS)

Konadu, D. D.; Sobral Mourao, Z.

2016-12-01

Transitioning to a low-carbon power system has been identified as one of the main strategies for achieving GHG emissions reduction targets stipulated in the UK Climate Change Act (2008). However, projected mix of technologies aimed at achieving the targeted level of decarbonisation have implications for sustainable level natural resource exploitation at different spatial and temporal scales. Critical among these are the impact on land use (food production) and water resources, which are usually not adequately analysed and accounted for in developing these long-term energy system transition strategies and scenarios. Given the importance of the UK power sector to meeting economy-wide emissions targets, the overall environmental consequence of the prescribed scenarios could significantly affect meeting long-term legislated GHG emission reduction targets. It is therefore imperative that synergies and trade-offs between the power systems and these resources are comprehensively analysed. The current study employs an integrated energy and resource use accounting methodology, called ForeseerTM, to assess the land and water requirement for the deployment of the power sector technologies of the UK Committee on Climate Change (CCC) Carbon Budget scenarios. This is analysed under different scenarios of energy crop yield and electricity infrastructure location. The outputs are then compared with sustainable limits of resource exploitation to establish the environmental tractability of the scenarios. The results show that even if stringent environmental and land use restrictions are applied, all the projected bioenergy and ground-mounted solar PV can be deployed within the UK with no significant impacts on land use and food production. However, inland water resources would be significantly affected if high Carbon Capture and Storage deployment, and without new nuclear capacity. Overall, the output highlights that contrary to the notion of the inevitability of CCS deployment in delivering emissions reduction targets, a future without CCS poses the least overall environmental impacts.

SU-G-BRC-02: A Novel Multi-Criteria Optimization Approach to Generate Deliverable Intensity-Modulated Radiation Therapy (IMRT) Treatment Plans

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

Kirlik, G; D’Souza, W; Zhang, H

2016-06-15

Purpose: To present a novel multi-criteria optimization (MCO) solution approach that generates treatment plans with deliverable apertures using column generation. Methods: We demonstrate our method with 10 locally advanced head-and-neck cancer cases retrospectively. In our MCO formulation, we defined an objective function for each structure in the treatment volume. This resulted in 9 objective functions, including 3 distinct objectives for primary target volume, high-risk and low-risk target volumes, 5 objectives for each of the organs-at-risk (OARs) (two parotid glands, spinal cord, brain stem and oral cavity), and one for the non-target non-OAR normal tissue. Conditional value-at-risk (CVaR) constraints were utilizedmore » to ensure at least certain fraction of the target volumes receiving the prescription doses. To directly generate deliverable plans, column generation algorithm was embedded within our MCO approach for aperture shape generation. Final dose distributions for all plans were generated using a Monte Carlo kernel-superposition dose calculation. We compared the MCO plans with the clinical plans, which were created by clinicians. Results: At least 95% target coverage was achieved by both MCO plans and clinical plans. However, the average conformity indices of clinical plans and the MCO plans were 1.95 and 1.35, respectively (31% reduction, p<0.01). Compared to the conventional clinical plan, the proposed MCO method achieved average reductions in left parotid mean dose of 5% (p=0.06), right parotid mean dose of 18% (p<0.01), oral cavity mean dose of 21% (p=0.03), spinal cord maximum dose of 20% (p<0.01), brain stem maximum dose of 61% (p<0.01), and normal tissue maximum dose of 5% (p<0.01), respectively. Conclusion: We demonstrated that the proposed MCO method was able to obtain deliverable IMRT treatment plans while achieving significant improvements in dosimetric plan quality.« less

A new functional method to choose the target lobe for lung volume reduction in emphysema - comparison with the conventional densitometric method.

PubMed

Hetzel, Juergen; Boeckeler, Michael; Horger, Marius; Ehab, Ahmed; Kloth, Christopher; Wagner, Robert; Freitag, Lutz; Slebos, Dirk-Jan; Lewis, Richard Alexander; Haentschel, Maik

2017-01-01

Lung volume reduction (LVR) improves breathing mechanics by reducing hyperinflation. Lobar selection usually focuses on choosing the most destroyed emphysematous lobes as seen on an inspiratory CT scan. However, it has never been shown to what extent these densitometric CT parameters predict the least deflation of an individual lobe during expiration. The addition of expiratory CT analysis allows measurement of the extent of lobar air trapping and could therefore provide additional functional information for choice of potential treatment targets. To determine lobar vital capacity/lobar total capacity (LVC/LTC) as a functional parameter for lobar air trapping using on an inspiratory and expiratory CT scan. To compare lobar selection by LVC/LTC with the established morphological CT density parameters. 36 patients referred for endoscopic LVR were studied. LVC/LTC, defined as delta volume over maximum volume of a lobe, was calculated using inspiratory and expiratory CT scans. The CT morphological parameters of mean lung density (MLD), low attenuation volume (LAV), and 15th percentile of Hounsfield units (15%P) were determined on an inspiratory CT scan for each lobe. We compared and correlated LVC/LTC with MLD, LAV, and 15%P. There was a weak correlation between the functional parameter LVC/LTC and all inspiratory densitometric parameters. Target lobe selection using lowest lobar deflation (lowest LVC/LTC) correlated with target lobe selection based on lowest MLD in 18 patients (50.0%), with the highest LAV in 13 patients (36.1%), and with the lowest 15%P in 12 patients (33.3%). CT-based measurement of deflation (LVC/LTC) as a functional parameter correlates weakly with all densitometric CT parameters on a lobar level. Therefore, morphological criteria based on inspiratory CT densitometry partially reflect the deflation of particular lung lobes, and may be of limited value as a sole predictor for target lobe selection in LVR.

Comparison of surgical conditions in 2 different anesthesia techniques of esmolol-induced controlled hypotension in breast reduction surgery

PubMed Central

Besir, Ahmet; Cekic, Bahanur; Kutanis, Dilek; Akdogan, Ali; Livaoglu, Murat

2017-01-01

Abstract Background: Breast reduction surgery is a common cosmetic surgery with a high incidence of blood loss and transfusion. In this surgery, the reduction of blood loss related to surgical manipulation and the volume of resected tissue is a target. In the present study, we compared the effects of esmolol-induced controlled hypotension on surgical visibility, surgical bleeding, and the duration of surgery in patients anesthetized with propofol/remifentanil (PR) or sevoflurane/remifentanil (SR). Methods: Patients in the American Society of Anesthesiologists I/II risk group undergoing breast reduction surgery were prospectively randomized into PR (n = 25) and SR (n = 25) groups. Controlled hypotension was induced with esmolol in both groups. During the intraoperative period, the heart rate (HR), mean arterial pressure (MAP), operation duration, volume of intraoperative blood loss, volume of blood received through postoperative drains, volume of resected tissues, and surgical area bleeding score were recorded. Results: The duration of operation in the incisional period was shorter in group PR compared to group SR (P = 0.04). The change in HR was lower in incision and hemostasis periods in the group PR compared to the group SR (P < 0.001). Total intraoperative intraoperative bleeding volume and volume of blood received through drains on postoperative postoperative day 1, day 2, and in total were found to be significantly lower in group PR compared to group SR. Surgical visibility scoring was more effective in group PR compared to SR. Conclusion: In the breast reduction surgery performed under esmolol-induced controlled hypotension, the effect of propofol + remifentanil anesthesia on the duration of incisional surgery, surgical visibility, and volume of surgical blood loss was more reliable and effective compared to that of sevoflurane + remifentanil, which seems to be an advantage. PMID:28272228

On the Efficacy and Mediation of a One-on-One HIV Risk-Reduction Intervention for African American Men Who Have Sex with Men: A Randomized Controlled Trial.

PubMed

Jemmott, John B; Jemmott, Loretta Sweet; O'Leary, Ann; Icard, Larry D; Rutledge, Scott E; Stevens, Robin; Hsu, Janet; Stephens, Alisa J

2015-07-01

We examined the efficacy and mediation of Being Responsible for Ourselves (BRO), an HIV/STI risk-reduction intervention for African American men who have sex with men (MSM), the population with the highest HIV-diagnosis rate in the US. We randomized African American MSM to one of two interventions: BRO HIV/STI risk-reduction, targeting condom use; or attention-matched control, targeting physical activity and healthy diet. The interventions were based on social cognitive theory, the reasoned-action approach, and qualitative research. Men reporting anal intercourse with other men in the past 90 days were eligible and completed pre-intervention, immediately post-intervention, and 6 and 12 months post-intervention surveys. Of 595 participants, 503 (85 %) completed the 12-month follow-up. Generalized-estimating-equations analysis indicated that, compared with the attention-matched control intervention, the BRO intervention did not increase consistent condom use averaged over the 6- and 12-month follow-ups, which was the primary outcome. Although BRO did not affect the proportion of condom-protected intercourse acts, unprotected sexual intercourse, multiple partners, or insertive anal intercourse, it did reduce receptive anal intercourse compared with the control, a behavior linked to incident HIV infection. Mediation analysis using the product-of-coefficients approach revealed that although BRO increased seven of nine theoretical constructs it was designed to affect, it increased only one of three theoretical constructs that predicted consistent condom use: condom-use impulse-control self-efficacy. Thus, BRO indirectly increased consistent condom use through condom-use impulse-control self-efficacy. In conclusion, although BRO increased several theoretical constructs, most of those constructs did not predict consistent condom use; hence, the intervention did not increase it. Theoretical constructs that interventions should target to increase African American MSM's condom use are discussed.

The likelihood of achieving quantified road safety targets: a binary logistic regression model for possible factors.

PubMed

Sze, N N; Wong, S C; Lee, C Y

2014-12-01

In past several decades, many countries have set quantified road safety targets to motivate transport authorities to develop systematic road safety strategies and measures and facilitate the achievement of continuous road safety improvement. Studies have been conducted to evaluate the association between the setting of quantified road safety targets and road fatality reduction, in both the short and long run, by comparing road fatalities before and after the implementation of a quantified road safety target. However, not much work has been done to evaluate whether the quantified road safety targets are actually achieved. In this study, we used a binary logistic regression model to examine the factors - including vehicle ownership, fatality rate, and national income, in addition to level of ambition and duration of target - that contribute to a target's success. We analyzed 55 quantified road safety targets set by 29 countries from 1981 to 2009, and the results indicate that targets that are in progress and with lower level of ambitions had a higher likelihood of eventually being achieved. Moreover, possible interaction effects on the association between level of ambition and the likelihood of success are also revealed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Epidemiological impact of achieving UNAIDS 90-90-90 targets for HIV care in India: a modelling study.

PubMed

Maddali, Manoj V; Gupta, Amita; Shah, Maunank

2016-07-07

Recent UNAIDS '90-90-90' targets propose that to end the HIV epidemic by 2030, 90% of persons living with HIV (PLWH) worldwide should know their diagnosis, 90% of diagnosed PLWH should be on antiretroviral therapy (ART) and 90% of PLWH on ART should be virally suppressed by 2020. We sought to quantify the epidemiological impact of achieving these targets in India. We constructed a dynamic-transmission model of the Indian HIV epidemic to project HIV infections and AIDS-related deaths that would occur in India over 15 years. We considered several scenarios: continuation of current care engagement (with early ART initiation), achieving 90-90-90 targets on time and delaying achievement by 5 or 10 years. In the base case, assuming continuation of current care engagement, we project 794 000 (95% uncertainty range (UR) 571 000-1 104 000) HIV infections and 689 000 (95% UR 468 000-976 000) AIDS-related deaths in India over 15 years. In this scenario, nearly half of PLWH diagnosed would fail to achieve viral suppression by 2030. With achievement of 90-90-90 targets, India could avert 392 000 (95% UR 248 000-559 000) transmissions (48% reduction) and 414 000 (95% UR 260 000-598 000) AIDS-related deaths (59% reduction) compared to the base-case scenario. Furthermore, fewer than 20 000 (95% UR 12 000-30 000) HIV infections would occur in 2030. Delaying achievement of targets resulted in a similar reduction in HIV incidence by 2030 but at the cost of excess overall infections and mortality. India can halve the epidemiological burden of HIV over 15 years with achievement of the UNAIDS 90-90-90 targets. Reaching the targets on time will require comprehensive healthcare strengthening, especially in early diagnosis and treatment, expanded access to second-line and third-line ART and long-term retention in care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Does the Police-Monitored CCTV Scheme Really Matter on Crime Reduction? A Quasi-Experimental Test in Taiwan's Taipei City.

PubMed

Lai, Yung-Lien; Sheu, Chuen-Jim; Lu, Yi-Fen

2018-06-01

Although numerous public closed-circuit television (CCTV) initiatives have been implemented at varying levels in Taiwan's cities and counties, systematic evaluations of these crime reduction efforts have been largely overlooked. To address this void, a quasi-experimental evaluation research project was designed to assess the effect of police-monitored CCTV on crime reduction in Taipei City for a period of 54 months, including data for both before and after camera installation dates. A total of 40 viewsheds within a 100-m (328 feet) radius were selected as research sites to observe variations in four types of crime incidents that became known to police during the January 2008 to June 2012 period. While crime incidents occurring in both the target and control sites were reduced in frequency after CCTV installation, results derived from time-series analysis indicated that the monitoring had no significant effect on the reduction of property crime incidents with the sole exception of robbery. With respect to the effects of comparing target and control sites, the average Crime Reduction Quotient (CRQ) was 0.36, suggesting that CCTV has an overall marginal yet noteworthy influence. Viewed broadly, however, the police-installed CCTV system in Taipei City did not appear to be as efficient as one would expect. Conversely, cameras installed in some observation sites proved to be significantly more effective than cameras in other sites. As a recommendation, future researchers should identify how particular micro-level attributes may lead to CCTV cameras working more effectively, thereby optimizing location choices where monitoring will prove to be most productive.

HIV testing and sexual risk reduction counseling in office-based buprenorphine/naloxone treatment.

PubMed

Edelman, E Jennifer; Moore, Brent A; Caffrey, Sarah; Sikkema, Kathleen J; Jones, Emlyn S; Schottenfeld, Richard S; Fiellin, David A; Fiellin, Lynn E

2013-01-01

We assessed the feasibility and preliminary efficacy of human immunodeficiency virus (HIV) testing with sexual risk reduction counseling for opioid-dependent patients initiating office-based buprenorphine/naloxone treatment. We conducted a 14-week randomized, controlled trial with 30 patients (original target of 114) assigned to receive buprenorphine/naloxone induction/stabilization and HIV testing with Brief Sexual Risk Management (BSRM) or Enhanced Sexual Risk Management (ESRM). We evaluated process measures and compared outcomes at baseline and during the 3-month follow-up. Similar proportions of patients receiving BSRM and ESRM underwent HIV testing (93% vs 80%; P = 0.28) and completed counseling sessions (80% vs 67%; P = 0.40). Brief Sexual Risk Management sessions were shorter than ESRM sessions (15.4 vs 23.4 minutes), with comparable manual adherence (P = 0.80). Outcomes did not vary by BSRM versus ESRM. Although the recruitment of opioid-dependent patients with sexual risk behaviors is challenging, HIV testing with sexual risk reduction counseling in office-based buprenorphine/naloxone treatment practice is feasible. Interventions to decrease sexual risk behaviors among a segment of this population are necessary.

Variability in climate change simulations affects needed long-term riverine nutrient reductions for the Baltic Sea.

PubMed

Bring, Arvid; Rogberg, Peter; Destouni, Georgia

2015-06-01

Changes to runoff due to climate change may influence management of nutrient loading to the sea. Assuming unchanged river nutrient concentrations, we evaluate the effects of changing runoff on commitments to nutrient reductions under the Baltic Sea Action Plan. For several countries, climate projections point to large variability in load changes in relation to reduction targets. These changes either increase loads, making the target more difficult to reach, or decrease them, leading instead to a full achievement of the target. The impact of variability in climate projections varies with the size of the reduction target and is larger for countries with more limited commitments. In the end, a number of focused actions are needed to manage the effects of climate change on nutrient loads: reducing uncertainty in climate projections, deciding on frameworks to identify best performing models with respect to land surface hydrology, and increasing efforts at sustained monitoring of water flow changes.

Variability in climate change simulations affects needed long-term riverine nutrient reductions for the Baltic Sea

DOE PAGES

Bring, Arvid; Rogberg, Peter; Destouni, Georgia

2015-05-28

Changes to runoff due to climate change may influence management of nutrient loading to the sea. Assuming unchanged river nutrient concentrations, we evaluate the effects of changing runoff on commitments to nutrient reductions under the Baltic Sea Action Plan. For several countries, climate projections point to large variability in load changes in relation to reduction targets. These changes either increase loads, making the target more difficult to reach, or decrease them, leading instead to a full achievement of the target. The impact of variability in climate projections varies with the size of the reduction target and is larger for countriesmore » with more limited commitments. Finally, in the end, a number of focused actions are needed to manage the effects of climate change on nutrient loads: reducing uncertainty in climate projections, deciding on frameworks to identify best performing models with respect to land surface hydrology, and increasing efforts at sustained monitoring of water flow changes.« less

Variability in climate change simulations affects needed long-term riverine nutrient reductions for the Baltic Sea

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

Bring, Arvid; Rogberg, Peter; Destouni, Georgia

Changes to runoff due to climate change may influence management of nutrient loading to the sea. Assuming unchanged river nutrient concentrations, we evaluate the effects of changing runoff on commitments to nutrient reductions under the Baltic Sea Action Plan. For several countries, climate projections point to large variability in load changes in relation to reduction targets. These changes either increase loads, making the target more difficult to reach, or decrease them, leading instead to a full achievement of the target. The impact of variability in climate projections varies with the size of the reduction target and is larger for countriesmore » with more limited commitments. Finally, in the end, a number of focused actions are needed to manage the effects of climate change on nutrient loads: reducing uncertainty in climate projections, deciding on frameworks to identify best performing models with respect to land surface hydrology, and increasing efforts at sustained monitoring of water flow changes.« less

Development of a 350ppm community carbon budget in Eugene, Oregon

NASA Astrophysics Data System (ADS)

Rice, A. L.; McRae, M.

2016-12-01

In the absence of national greenhouse gas emissions regulations, cities and county agencies across the United States have pursued a patchwork of emissions reduction targets and approaches to achieve those targeted goals. Some regions currently aim to meet efforts in mitigation with ambitious reduction targets that go beyond those pursued at national or international levels (e.g., UNFCCC, Paris, 2015). In 2014 The City of Eugene (Oregon, USA) City Council passed the Climate Recovery Ordinance which, in addition to outlining City emissions targets for 2020 and 2030, requested a proposal to adopt a community greenhouse gas reduction target consistent with achieving a global atmospheric carbon dioxide concentration of 350ppm by the year 2100. A 350ppm 2100 target, if achieved, could keep global average temperature rise to within 1°C by century-end but would necessarily limit cumulative fossil fuel carbon emissions to 500GtC (currently 375GtC). In contrast to historically-based approaches to greenhouse gas mitigation targets typically established by cities, the request of a community target based on a 350ppm target required the development of new methods by the City of Eugene. Collaborating with a Thriving Earth Exchange (TEX) scientist and working with a peer review team of regional analysts, the City of Eugene City Manager's Office produced a report which described a methodology for establishing a 350ppm community carbon budget and led a multi-session dialog with Eugene City Council members on possible action towards this goal. Here, we describe the methods developed and the collaborative effort which made it possible. The work led to the recent Eugene City Council adoption of an ambitious community-wide greenhouse gas emission reduction goal of 7.6% per year, consistent with global emissions reductions needed to achieve an atmospheric carbon dioxide concentration 350ppm by 2100.

Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT.

PubMed

Murthy, Kk; Shukeili, Ka; Kumar, Ss; Davis, Ca; Chandran, Rr; Namrata, S

2010-01-01

To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT) planning in postoperative adjuvant radiotherapy for patients with gastric carcinoma. In a retrospective study, for plan comparison, dose distribution was recalculated in 15 patients treated with 3D-CRT on the contoured structures of same CT images using an IMRT technique. 3D-conformal plans with three fields and four-fields were compared with seven-field dynamic IMRT plans. The different plans were compared by analyzing the dose coverage of planning target volume using TV(95), D(mean), uniformity index, conformity index and homogeneity index parameters. To assess critical organ sparing, D(mean), D(max), dose to one-third and two-third volumes of the OARs and percentage of volumes receiving more than their tolerance doses were compared. The average dose coverage values of PTV with 3F-CRT and 4F-CRT plans were comparable, where as IMRT plans achieved better target coverage(p<0.001) with higher conformity index value of 0.81±0.07 compared to both the 3D-CRT plans. The doses to the liver and bowel reduced significantly (p<0.001) with IMRT plans compared to other 3D-CRT plans. For all OARs the percentage of volumes receiving more than their tolerance doses were reduced with the IMRT plans. This study showed that a better target coverage and significant dose reduction to OARs could be achieved with the IMRT plans. The IMRT can be preferred with caution for organ motion. The authors are currently studying organ motion in the upper abdomen to use IMRT for patient treatment.

Observation of shadowing of neutrino- and antineutrino-nucleus interactions and comparison with PCAC predictions

NASA Astrophysics Data System (ADS)

Allport, P. P.; Erriquez, O.; Guy, J.; Venus, W.; Aderholz, M.; Berggren, M.; Bullock, F. W.; Calicchio, M.; Coghen, T.; Cooper-Sarkar, A. M.; Jones, G. T.; Marage, P.; Mobayyen, M.; Morrison, D. R. O.; Neveu, M.; Parker, M. A.; Radojicic, D.; Sansum, R. A.; Saitta, B.; Schmitz, N.; Simopoulou, E.; O'neale, S.; Van Apeldoorn, G.; Varvell, K.; Vayaki, A.; Wachsmuth, H.; Wittek, W.; BEBC WA59 Collaboration

1989-12-01

Comparing the kinematical distributions of events obtained on neon and deuterium targets in similar experimental conditions reveals a reduction of the neutrino and antineutrino charged current cross section per nucleon in neon at low Q2. The effect, interpreted as due to geometric shadowing of the weak propagator in interactions of neutrinos and antineutrinos with nuclei, agrees well with predictions derived from PCAC.

Simultaneous treatment to attain blood pressure and lipid goals and reduced CV risk burden using amlodipine/atorvastatin single-pill therapy in treated hypertensive participants in a randomized controlled trial

PubMed Central

Grimm, Richard; Malik, Mobin; Yunis, Carla; Sutradhar, Santosh; Kursun, Attila

2010-01-01

TOGETHER investigated whether targeting multiple cardiovascular (CV) risk factors using single-pill amlodipine/atorvastatin (AML/ATO) and therapeutic lifestyle changes (TLC) results in greater blood pressure (BP)/lipid control and additional reduction in estimated cardiovascular disease (CVD) risk compared with blood pressure intervention only using amlodipine (AML) + TLC. TOGETHER was a 6-week, randomized, double-blind, double-dummy trial using hypertensive participants with additional CV risk factors without CVD/diabetes. Participants were randomized to either AML/ATO (5 to 10/20 mg) + TLC or AML (5 to 10 mg) + TLC. The primary end point was the difference in proportion of participants attaining both BP (<140/90 mm Hg) and low-density lipoprotein cholesterol (LDL-C) (<100 mg/dL) goals at week 6. At week 6, 67.8% of participants receiving AML/ATO + TLC attained the combined BP/LDL-C goal versus 9.6% with AML + TLC (RD [A–B]: 58.2; 95% CI [48.1 to 68.4] P < 0.001; OR: 19.0; 95% CI 9.1 to 39.6; P < 0.001). Significant reductions from baseline in LDL-C, total cholesterol and triglycerides and estimated 10-year Framingham risk were also observed. Treatment with AML/ATO was well tolerated. In conclusion, a multifactorial CV management approach is more effective in achieving combined BP/LDL-C targets as well as CV risk reduction compared with BP intervention only in this patient population. PMID:20479948

The impact of PET/CT scanning on the size of target volumes, radiation exposure of organs at risk, TCP and NTCP, in the radiotherapy planning of non-small cell lung cancer.

PubMed

Vojtíšek, Radovan; Mužík, Jan; Slampa, Pavel; Budíková, Marie; Hejsek, Jaroslav; Smolák, Petr; Ferda, Jiří; Fínek, Jindřich

2014-05-01

To compare radiotherapy plans made according to CT and PET/CT and to investigate the impact of changes in target volumes on tumour control probability (TCP), normal tissue complication probability (NTCP) and the impact of PET/CT on the staging and treatment strategy. Contemporary studies have proven that PET/CT attains higher sensitivity and specificity in the diagnosis of lung cancer and also leads to higher accuracy than CT alone in the process of target volume delineation in NSCLC. Between October 2009 and March 2012, 31 patients with locally advanced NSCLC, who had been referred to radical radiotherapy were involved in our study. They all underwent planning PET/CT examination. Then we carried out two separate delineations of target volumes and two radiotherapy plans and we compared the following parameters of those plans: staging, treatment purpose, the size of GTV and PTV and the exposure of organs at risk (OAR). TCP and NTCP were also compared. PET/CT information led to a significant decrease in the sizes of target volumes, which had the impact on the radiation exposure of OARs. The reduction of target volume sizes was not reflected in the significant increase of the TCP value. We found that there is a very strong direct linear relationship between all evaluated dosimetric parameters and NTCP values of all evaluated OARs. Our study found that the use of planning PET/CT in the radiotherapy planning of NSCLC has a crucial impact on the precise determination of target volumes, more precise staging of the disease and thus also on possible changes of treatment strategy.

Evolving Concepts in Posterior Subthalamic Area Deep Brain Stimulation for Treatment of Tremor: Surgical Neuroanatomy and Practical Considerations.

PubMed

Ramirez-Zamora, Adolfo; Smith, Heather; Kumar, Vignessh; Prusik, Julia; Phookan, Sujoy; Pilitsis, Julie G

2016-01-01

Although thalamic deep brain stimulation (DBS) has been established as an effective therapy for refractory tremor in Parkinson's disease and essential tremor, reports investigating the efficacy of posterior subthalamic area (PSA) DBS for severe, debilitating tremors continue to emerge. However, questions regarding the optimal anatomical target, surgical approach, programming paradigms and effectiveness compared to other targets remain. In this report, we aimed to review the current literature to assess different stereotactic techniques, anatomical considerations, adverse effects and stimulation settings in PSA DBS. A comprehensive literature review was performed searching for articles discussing tremors and PSA stimulation. We performed a quantitative analysis comparing different DBS tremor targets. Tremor improvement is consistently documented in most reports with an average reduction in tremor of 79% depending on the specific tremor syndrome. Tremor benefit in patients with multiple sclerosis (MS) tremor was significantly higher than for other stimulation targets. Transient paresthesias, imbalance, dizziness and dysarthria are the most common side effects with PSA DBS. PSA DBS is an effective and safe treatment for tremor control and should be considered in patients with refractory tremors with associated cerebellar or dystonic features, proximal tremors and MS tremor. © 2016 S. Karger AG, Basel.

An analysis of the potential for achieving the fourth millennium development goal in SSA with domestic resources.

PubMed

O'Hare, Bernadette; Makuta, Innocent

2015-02-25

The importance of good health is reflected in the fact that more than half of the eight Millennium Development Goals (MDGs) are aimed at improving health status. Goal 4 (MDG4) aims to reduce child mortality. The progress indicator for goal 4 is the under-five mortality rate (U5M), with a targeted reduction of two thirds by 2015 from 1990 levels. This paper seeks to compare the time (in years) Sub Saharan African (SSA) countries will take to reach their MDG4 target at the current rate of decline, and the time it could have taken to reach their target if domestic resources had not been lost through illicit financial flows, corruption and servicing of debt since 2000. We estimate the amount by which the Gross Domestic Product (GDP) per capita would increase (in percentage terms) if losses of resource through illicit financial flows, corruption and debt servicing, were reduced. Using the income elasticity of U5M, a metric which reports the percentage change in U5M for a one percent change in GDP per capita, we estimate the potential gains in the annual reduction of the under-five mortality if these resource losses were reduced. At the current rate of reduction in U5M, nine countries out of this sample of 36 SSA countries (25%) will achieve their MDG4 target by 2015. In the absence of the leakages (IFF, corruption and debt service) 30 out of 36 (83%) would reach their MDG4 target by 2015 and all except one country, Zimbabwe would have achieved their MDG4 by 2017 (97%). In view of the uncertainty of the legitimacy of African debts we have also provided results where we excluded debt repayment from our analysis. Most countries would have met MDG4 target by curtailing these outflows. In order to release latent resources in SSA for development, action will be needed both by African countries and internationally. We consider that stemming these outflows, and thereby reducing the need for aid, can be achieved with a more transparent global financial system.

Spray drift and off-target loss reduction with a precision air-assisted sprayer

USDA-ARS?s Scientific Manuscript database

Spray drift and off-target losses are inherent problems of conventional air-assisted sprayers. Their low efficiencies cause environmental pollutions resulting in public anxieties. A new drift reduction technology incorporating laser scanning capabilities with a variable-rate air-assisted sprayer w...

Antisense oligonucleotide inhibition of cholesteryl ester transfer protein enhances RCT in hyperlipidemic, CETP transgenic, LDLr-/- mice.

PubMed

Bell, Thomas A; Graham, Mark J; Lee, Richard G; Mullick, Adam E; Fu, Wuxia; Norris, Dan; Crooke, Rosanne M

2013-10-01

Due to their ability to promote positive effects across all of the lipoprotein classes, cholesteryl ester transfer protein (CETP) inhibitors are currently being developed as therapeutic agents for cardiovascular disease. In these studies, we compared an antisense oligonucleotide (ASO) inhibitor of CETP to the CETP small molecule inhibitor anacetrapib. In hyperlipidemic CETP transgenic (tg) mice, both drugs provided comparable reductions in total plasma cholesterol, decreases in CETP activity, and increases in HDL cholesterol. However, only mice treated with the antisense inhibitor showed an enhanced effect on macrophage reverse cholesterol transport, presumably due to differences in HDL apolipoprotein composition and decreases in plasma triglyceride. Additionally, the ASO-mediated reductions in CETP mRNA were associated with less accumulation of aortic cholesterol. These preliminary findings suggest that CETP ASOs may represent an alternative means to inhibit that target and to support their continued development as a treatment for cardiovascular disease in man.

What does the 2°C target imply for a global climate agreement in 2020? The limits study on Durban Platform scenarios

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

KRIEGLER, ELMAR; TAVONI, MASSIMO; ABOUMAHBOUB, TINO

This paper provides a novel and comprehensive model-based assessment of possible outcomes of the Durban Platform negotiations with a focus on emissions reduction requirements, the consistency with the 2°C target and global economic impacts. The Durban Platform scenarios investigated in the LIMITS study — all assuming the implementation of comprehensive global emission reductions after 2020, but assuming different 2020 emission reduction levels as well as different long-term concentration targets — exhibit a probability of exceeding the 2°C limit of 22–41% when reaching 450 (450–480) ppm CO 2e, and 35–59% when reaching 500 (480–520) ppm CO 2e in 2100. Forcing andmore » temperature show a peak and decline pattern for both targets. Consistency of the resulting temperature trajectory with the 2°C target is a societal choice, and may be based on the maximum exceedance probability at the time of the peak and the long run exceedance probability, e.g., in the year 2100. The challenges of implementing a long-term target after a period of fragmented near-term climate policy can be significant as reflected in steep reductions of emissions intensity and transitional and long-term economic impacts. In particular, the challenges of adopting the target are significantly higher in 2030 than in 2020, both in terms of required emissions intensity decline rates and economic impacts. Finally, we conclude that an agreement on comprehensive emissions reductions to be implemented from 2020 onwards has particular significance for meeting long-term climate policy objectives.« less

Model assessment of atmospheric pollution control schemes for critical emission regions

NASA Astrophysics Data System (ADS)

Zhai, Shixian; An, Xingqin; Liu, Zhao; Sun, Zhaobin; Hou, Qing

2016-01-01

In recent years, the atmospheric environment in portions of China has become significantly degraded and the need for emission controls has become urgent. Because more international events are being planned, it is important to implement air quality assurance targeted at significant events held over specific periods of time. This study sets Yanqihu (YQH), Beijing, the location of the 2014 Beijing APEC (Asia-Pacific Economic Cooperation) summit, as the target region. By using the atmospheric inversion model FLEXPART, we determined the sensitive source zones that had the greatest impact on the air quality of the YQH region in November 2012. We then used the air-quality model Models-3/CMAQ and a high-resolution emissions inventory of the Beijing-Tianjian-Hebei region to establish emission reduction tests for the entire source area and for specific sensitive source zones. This was achieved by initiating emission reduction schemes at different ratios and different times. The results showed that initiating a moderate reduction of emissions days prior to a potential event is more beneficial to the air quality of Beijing than initiating a high-strength reduction campaign on the day of the event. The sensitive source zone of Beijing (BJ-Sens) accounts for 54.2% of the total source area of Beijing (BJ), but its reduction effect reaches 89%-100% of the total area, with a reduction efficiency 1.6-1.9 times greater than that of the entire area. The sensitive source zone of Huabei (HuaB-Sens.) only represents 17.6% of the total area of Huabei (HuaB), but its emission reduction effect reaches 59%-97% of the entire area, with a reduction efficiency 4.2-5.5 times greater than that of the total area. The earlier that emission reduction measures are implemented, the greater the effect they have on preventing the transmission of pollutants. In addition, expanding the controlling areas to sensitive provinces and cities around Beijing (HuaB-sens) can significantly accelerate the reduction effects compared to controlling measures only in the Beijing sensitive source zone (BJ-Sens). Therefore, when enacting emission reduction schemes, cooperating with surrounding provinces and cities, as well as narrowing the reduction scope to specific sensitive source zones prior to unfavorable meteorological conditions, can help reduce emissions control costs and improve the efficiency and maneuverability of emission reduction schemes.

Models for the Economics of Resilience

PubMed Central

Gilbert, Stanley; Ayyub, Bilal M.

2016-01-01

Estimating the economic burden of disasters requires appropriate models that account for key characteristics and decision making needs. Natural disasters in 2011 resulted in $366 billion in direct damages and 29,782 fatalities worldwide. Average annual losses in the US amount to about $55 billion. Enhancing community and system resilience could lead to significant savings through risk reduction and expeditious recovery. The management of such reduction and recovery is facilitated by an appropriate definition of resilience and associated metrics with models for examining the economics of resilience. This paper provides such microeconomic models, compares them, examines their sensitivities to key parameters, and illustrates their uses. Such models enable improving the resiliency of systems to meet target levels. PMID:28133626

A novel approach to Hough Transform for implementation in fast triggers

NASA Astrophysics Data System (ADS)

Pozzobon, Nicola; Montecassiano, Fabio; Zotto, Pierluigi

2016-10-01

Telescopes of position sensitive detectors are common layouts in charged particles tracking, and programmable logic devices, such as FPGAs, represent a viable choice for the real-time reconstruction of track segments in such detector arrays. A compact implementation of the Hough Transform for fast triggers in High Energy Physics, exploiting a parameter reduction method, is proposed, targeting the reduction of the needed storage or computing resources in current, or next future, state-of-the-art FPGA devices, while retaining high resolution over a wide range of track parameters. The proposed approach is compared to a Standard Hough Transform with particular emphasis on their application to muon detectors. In both cases, an original readout implementation is modeled.

Models for the Economics of Resilience.

PubMed

Gilbert, Stanley; Ayyub, Bilal M

2016-12-01

Estimating the economic burden of disasters requires appropriate models that account for key characteristics and decision making needs. Natural disasters in 2011 resulted in $366 billion in direct damages and 29,782 fatalities worldwide. Average annual losses in the US amount to about $55 billion. Enhancing community and system resilience could lead to significant savings through risk reduction and expeditious recovery. The management of such reduction and recovery is facilitated by an appropriate definition of resilience and associated metrics with models for examining the economics of resilience. This paper provides such microeconomic models, compares them, examines their sensitivities to key parameters, and illustrates their uses. Such models enable improving the resiliency of systems to meet target levels.

Supervised non-negative tensor factorization for automatic hyperspectral feature extraction and target discrimination

NASA Astrophysics Data System (ADS)

Anderson, Dylan; Bapst, Aleksander; Coon, Joshua; Pung, Aaron; Kudenov, Michael

2017-05-01

Hyperspectral imaging provides a highly discriminative and powerful signature for target detection and discrimination. Recent literature has shown that considering additional target characteristics, such as spatial or temporal profiles, simultaneously with spectral content can greatly increase classifier performance. Considering these additional characteristics in a traditional discriminative algorithm requires a feature extraction step be performed first. An example of such a pipeline is computing a filter bank response to extract spatial features followed by a support vector machine (SVM) to discriminate between targets. This decoupling between feature extraction and target discrimination yields features that are suboptimal for discrimination, reducing performance. This performance reduction is especially pronounced when the number of features or available data is limited. In this paper, we propose the use of Supervised Nonnegative Tensor Factorization (SNTF) to jointly perform feature extraction and target discrimination over hyperspectral data products. SNTF learns a tensor factorization and a classification boundary from labeled training data simultaneously. This ensures that the features learned via tensor factorization are optimal for both summarizing the input data and separating the targets of interest. Practical considerations for applying SNTF to hyperspectral data are presented, and results from this framework are compared to decoupled feature extraction/target discrimination pipelines.

Report of the River Master of the Delaware River for the period of December 1, 1980 to November 30, 1981

USGS Publications Warehouse

Schaefer, Francis T.; Fish, Robert E.

1982-01-01

Water supply conditions at the beginning of the year were marginal in marked contrast to those for the preceeding nine years. Discharge of the Delaware River at Montague, New Jersey, was only 72% of median as compared to 68% in excess of median the previous year. In December, with reservoir storage again declining, further reductions in both diversions and releases were imposed. With consent of all the parties, reductions were effected on December 20 limiting New York City diversions to 560 mgd, New Jersey to 65 mgd, and the required discharge at Montague was targeted at 1550 cfs. To conserve supplies, additional reductions were imposed in January when the Delaware River basin Commission formally declared a drought. New York City 's limitations was set at 520 mgd and that for New Jersey at 62 mgd. Montague flows were targeted between 1100 cfs, depending upon the location of the salt front in the estuary. Water quality of the Delaware River and Estuary was monitored on a continuous basis at eight sites for most of the year and on a monthly basis at ten sites to accurately locate the salt front. Highest concentrations observed at the Benjamin Franklin Bridge site was 133 mg/l (milligram per liter) on February 2. (USGS)

Life cycle environmental impacts of three products derived from wild-caught Antarctic krill (Euphausia superba).

PubMed

Parker, Robert W R; Tyedmers, Peter H

2012-05-01

Concern has been voiced in recent years regarding the environmental implications of the Antarctic krill fishery. Attention has focused primarily on ecological concerns, whereas other environmental aspects, including potentially globally problematic emissions and material and energy demands, have not been examined in detail. Here we apply life cycle assessment to measure the contributions of krill meal, oil, and omega-3 capsules to global warming, ozone depletion, acidification, eutrophication, energy use, and biotic resource use. Supply chains of one krill fishing and processing company, Aker BioMarine of Norway, were assessed. Impacts of krill products were found to be driven primarily by the combustion of fossil fuels onboard the fishing vessel and a transport/resupply vessel. Approximately 190 L of fuel are burned per tonne of raw krill landed, markedly higher than fuel inputs to reduction fisheries targeting other species. In contrast, the biotic resource use associated with extracting krill is relatively low compared to that of other reduction fisheries. Results of this study provide insight into the broader environmental implications of the krill fishery, comparisons between products derived from krill and other species targeted for reduction, opportunities for improving the fishery's performance, and a baseline against which to measure future performance. © 2012 American Chemical Society

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials

PubMed Central

Ha, Vanessa; Sievenpiper, John L.; de Souza, Russell J.; Jayalath, Viranda H.; Mirrahimi, Arash; Agarwal, Arnav; Chiavaroli, Laura; Mejia, Sonia Blanco; Sacks, Frank M.; Di Buono, Marco; Bernstein, Adam M.; Leiter, Lawrence A.; Kris-Etherton, Penny M.; Vuksan, Vladimir; Bazinet, Richard P.; Josse, Robert G.; Beyene, Joseph; Kendall, Cyril W.C.; Jenkins, David J.A.

2014-01-01

Background: Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. Methods: We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks’ duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non–high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. Results: We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference −0.17 mmol/L, 95% confidence interval −0.25 to −0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. Interpretation: Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. Trial registration: ClinicalTrials.gov, no. NCT01594567. PMID:24710915

Assessing a change mechanism in a randomized home-visiting trial: Reducing disrupted maternal communication decreases infant disorganization.

PubMed

Tereno, Susana; Madigan, Sheri; Lyons-Ruth, Karlen; Plamondon, Andre; Atkinson, Leslie; Guedeney, Nicole; Greacen, Tim; Dugravier, Romain; Saias, Thomas; Guedeney, Antoine

2017-05-01

Although randomized interventions trials have been shown to reduce the incidence of disorganized attachment, no studies to date have identified the mechanisms of change responsible for such reductions. Maternal sensitivity has been assessed in various studies and shown to change with intervention, but in the only study to formally assess mediation, changes in maternal sensitivity did not mediate changes in infant security of attachment (Cicchetti, Rogosch, & Toth, 2006). Primary aims of the current randomized controlled intervention trial in a high-risk population were to fill gaps in the literature by assessing whether the intervention (a) reduced disorganization, (b) reduced disrupted maternal communication, and (c) whether reductions in disrupted maternal communication mediated changes in infant disorganization. The results indicated that, compared to controls (n = 52), both infant disorganization and disrupted maternal communication were significantly reduced in the intervention group (n = 65) that received regular home-visiting during pregnancy and the first year of life. Furthermore, reductions in disrupted maternal communication partially accounted for the observed reductions in infant disorganization compared to randomized controls. The results are discussed in relation to the societal cost effectiveness of early attachment-informed interventions for mothers and infants, as well as the importance of formally assessing underlying mechanisms of change in order to improve and appropriately target preventive interventions.

Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

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

Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp; Yokokawa, Takumi; Endo, Yuriko

2013-10-11

Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modestmore » hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via decreased glucose uptake and lipogenic protein expression and increased basal lipolysis. Such an hypoxia-induced decrease in lipogenesis may be an attractive therapeutic target against lipid-associated metabolic diseases.« less

Changing Conspiracy Beliefs through Rationality and Ridiculing.

PubMed

Orosz, Gábor; Krekó, Péter; Paskuj, Benedek; Tóth-Király, István; Bőthe, Beáta; Roland-Lévy, Christine

2016-01-01

Conspiracy theory (CT) beliefs can be harmful. How is it possible to reduce them effectively? Three reduction strategies were tested in an online experiment using general and well-known CT beliefs on a comprehensive randomly assigned Hungarian sample ( N = 813): exposing rational counter CT arguments, ridiculing those who hold CT beliefs, and empathizing with the targets of CT beliefs. Several relevant individual differences were measured. Rational and ridiculing arguments were effective in reducing CT, whereas empathizing with the targets of CTs had no effect. Individual differences played no role in CT reduction, but the perceived intelligence and competence of the individual who conveyed the CT belief-reduction information contributed to the success of the CT belief reduction. Rational arguments targeting the link between the object of belief and its characteristics appear to be an effective tool in fighting conspiracy theory beliefs.

The Effects of HSP27 on Gemcitabine-Resistant Pancreatic Cancer Cell Line Through Snail.

PubMed

Zhang, Song; Zhang, Xiao-qi; Huang, Shu-ling; Chen, Min; Shen, Shan-shan; Ding, Xi-wei; Lv, Ying; Zou, Xiao-ping

2015-10-01

To evaluate the regulation mechanism of heat shock protein 27 (HSP27) on gemcitabine (GEM) resistance of pancreatic cancer cell. The expression vectors pEGFP-C1-HSP27 and the vectors of MicroRNA targeting Snail were introduced into GEM-sensitive pancreatic cancer SW1990 cells, and the vectors of small hairpin RNA targeting HSP27 were transfected into SW1990 and GEM-resistant SW1990/GEM cells. The expressions of HSP27, p-HSP27 (Ser82), Snail, ERCC1, and E-cadherin were evaluated by Western blotting. The sensitivity of transfected cells to GEM was detected by CCK-8 assay and Annexin V-FITC apoptosis assay. As compared to SW1990, SW1990/GEM showed significantly increased expressions of HSP27, p-HSP27, Snail and ERCC1 with decreased expression of E-cadherin. By increasing HSP27 expression, we found increase of Snail and ERCC1 with reduction of E-cadherin expressions, while reduction of HSP27 expression caused reduction of Snail and ERCC1 but increase of E-cadherin expressions. Downregulation of Snail resulted in the reduction of ERCC1 expression and increase of E-cadherin. Furthermore, downregulation of HSP27 or snail caused increased GEM sensitivity of pancreatic cancer cells, and upregulation of HSP27 showed the opposite results. There is an inverse correlation between HSP27 expression and GEM sensitivity of SW1990 cells, which might be realized by regulating E-cadherin and ERCC1 expressions through Snail.

A longitudinal study on deep brain stimulation of the medial forebrain bundle for treatment-resistant depression.

PubMed

Fenoy, Albert J; Schulz, Paul E; Selvaraj, Sudhakar; Burrows, Christina L; Zunta-Soares, Giovanna; Durkin, Kathryn; Zanotti-Fregonara, Paolo; Quevedo, Joao; Soares, Jair C

2018-06-04

Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to lead to rapid antidepressant effects. In this longitudinal study, we expand upon the initial results we reported at 26 weeks (Fenoy et al., 2016), showing sustained antidepressant effects of MFB DBS on six patients with treatment-resistant depression (TRD) over 1 year. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary assessment tool. Deterministic fiber tracking was used to individually map the target area; analysis was performed to compare modulated fiber tracts between patients. Intraoperatively, upon stimulation at target, responders reported immediate increases in energy and motivation. An insertional effect was seen during the 4-week sham stimulation phase from baseline (28% mean MADRS reduction, p = 0.02). However, after 1 week of initiating stimulation, three of six patients had a > 50% decrease in MADRS scores relative to baseline (43% mean MADRS reduction, p = 0.005). One patient withdrew from study participation. At 52 weeks, four of remaining five patients have > 70% decrease in MADRS scores relative to baseline (73% mean MADRS reduction, p = 0.007). Evaluation of modulated fiber tracts reveals significant common orbitofrontal connectivity to the target region in all responders. Neuropsychological testing and 18 F-fluoro-deoxyglucose-positron emission tomography cerebral metabolism evaluations performed at baseline and at 52 weeks showed minimal changes and verified safety. This longitudinal evaluation of MFB DBS demonstrated rapid antidepressant effects, as initially reported by Schlaepfer et al. (2013), and supports the use of DBS for TRD.

A systematic review of economic evaluations of population-based sodium reduction interventions

PubMed Central

Hope, Silvia F.; Webster, Jacqui; Trieu, Kathy; Pillay, Arti; Ieremia, Merina; Bell, Colin; Snowdon, Wendy; Neal, Bruce; Moodie, Marj

2017-01-01

Objective To summarise evidence describing the cost-effectiveness of population-based interventions targeting sodium reduction. Methods A systematic search of published and grey literature databases and websites was conducted using specified key words. Characteristics of identified economic evaluations were recorded, and included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results Twenty studies met the study inclusion criteria and received a full paper review. Fourteen studies were identified as full economic evaluations in that they included both costs and benefits associated with an intervention measured against a comparator. Most studies were modelling exercises based on scenarios for achieving salt reduction and assumed effects on health outcomes. All 14 studies concluded that their specified intervention(s) targeting reductions in population sodium consumption were cost-effective, and in the majority of cases, were cost saving. Just over half the studies (8/14) were assessed as being of ‘excellent’ reporting quality, five studies fell into the ‘very good’ quality category and one into the ‘good’ category. All of the identified evaluations were based on modelling, whereby inputs for all the key parameters including the effect size were either drawn from published datasets, existing literature or based on expert advice. Conclusion Despite a clear increase in evaluations of salt reduction programs in recent years, this review identified relatively few economic evaluations of population salt reduction interventions. None of the studies were based on actual implementation of intervention(s) and the associated collection of new empirical data. The studies universally showed that population-based salt reduction strategies are likely to be cost effective or cost saving. However, given the reliance on modelling, there is a need for the effectiveness of new interventions to be evaluated in the field using strong study designs and parallel economic evaluations. PMID:28355231

Sodium Reduction in Processed Foods in Brazil: Analysis of Food Categories and Voluntary Targets from 2011 to 2017

PubMed Central

Silva, Sara A.; L’Abbé, Mary; Jaime, Patricia C.

2017-01-01

Non-communicable diseases, including cardiovascular diseases, are responsible for over 70% of deaths in Brazil. Currently, over 25% of Brazilian adults are diagnosed as hypertensive; overall, current dietary sodium intake in Brazil (4700 mg/person) is over twice the international recommendations, and 70–90% of adolescents and adults consume excessive sodium. National sodium reduction strategies consider the main dietary sources of sodium to be added salt to foods, foods consumed outside of the household, and sodium in processed foods. The national voluntary strategy for sodium reduction in priority food categories has been continuously monitored over a 6-year period (2011–2017) and there was a significant 8–34% reduction in the average sodium content of over half food categories. Different food categories have undergone differing reductions in sodium over time, aiding gradual biannual targets to allow industries to develop new technologies and consumers to adapt to foods with less salt. By 2017, most products of all food categories had met the regional targets proposed by the Pan American Health Organization, showing that voluntary sodium reduction strategies can potentially contribute to food reformulation. Nevertheless, regulatory approaches may still be necessary in the future in order to reach all food producers and to allow stronger enforcement to meet more stringent regional targets. PMID:28704932

Implications of Sustainability for the United States Light-Duty Transportation Sector

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

Gearhart, Chris

Climate change is a problem that must be solved. The primary cause of this problem is burning of fossil fuels to generate energy. A dramatic reduction in carbon emissions must happen soon, and a significant fraction of this reduction must come from the transportation sector. This paper reviews existing literature to assess the consensus of the scientific and engineering communities concerning the potential for the United States' light-duty transportation sector to meet a goal of 80 percent reduction in vehicle emissions and examine what it will take to meet this target. It is unlikely that reducing energy consumption in justmore » vehicles with gasoline-based internal combustion drivetrains will be sufficient to meet GHG emission-reduction targets. This paper explores what additional benefits are possible through the adoption of alternative energy sources, looking at three possible on-vehicle energy carriers: carbon-based fuels, hydrogen, and batteries. potential for the United States' light-duty transportation sector to meet a goal of 80 percent reduction in vehicle emissions and examine what it will take to meet this target. It is unlikely that reducing energy consumption in just vehicles with gasoline-based internal combustion drivetrains will be sufficient to meet GHG emission-reduction targets. This paper explores what additional benefits are possible through the adoption of alternative energy sources, looking at three possible on-vehicle energy carriers: carbon-based fuels, hydrogen, and batteries.« less

Targeting hepatic cancer cells with pegylated dendrimers displaying N-acetylgalactosamine and SP94 peptide ligands.

PubMed

Medina, Scott H; Tiruchinapally, Gopinath; Chevliakov, Maxim V; Durmaz, Yasemin Yuksel; Stender, Rachell N; Ensminger, William D; Shewach, Donna S; Elsayed, Mohamed E H

2013-10-01

Poly(amidoamine) (PAMAM) dendrimers are branched water-soluble polymers defined by consecutive generation numbers (Gn) indicating a parallel increase in size, molecular weight, and number of surface groups available for conjugation of bioactive agents. In this article, we compare the biodistribution of N-acetylgalactosamine (NAcGal)-targeted [(14) C]1 -G5-(NH2 )5 -(Ac)108 -(NAcGal)14 particles to non-targeted [(14) C]1 -G5-(NH2 )127 and PEGylated [(14) C]1 -G5-(NH2 )44 -(Ac)73 -(PEG)10 particles in a mouse hepatic cancer model. Results show that both NAcGal-targeted and non-targeted particles are rapidly cleared from the systemic circulation with high distribution to the liver. However, NAcGal-targeted particles exhibited 2.5-fold higher accumulation in tumor tissue compared to non-targeted ones. In comparison, PEGylated particles showed a 16-fold increase in plasma residence time and a 5-fold reduction in liver accumulation. These results motivated us to engineer new PEGylated G5 particles with PEG chains anchored to the G5 surface via acid-labile cis-aconityl linkages where the free PEG tips are functionalized with NAcGal or SP94 peptide to investigate their potential as targeting ligands for hepatic cancer cells as a function of sugar conformation (α versus β), ligand concentration (100-4000 nM), and incubation time (2 and 24 hours) compared to fluorescently (Fl)-labeled and non-targeted G5-(Fl)6 -(NH2 )122 and G5-(Fl)6 -(Ac)107 -(cPEG)15 particles. Results show G5-(Fl)6 -(Ac)107 -(cPEG[NAcGalβ ])14 particles achieve faster uptake and higher intracellular concentrations in HepG2 cancer cells compared to other G5 particles while escaping the non-specific adsorption of serum protein and phagocytosis by Kupffer cells, which make these particles the ideal carrier for selective drug delivery into hepatic cancer cells. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model.

PubMed

Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Schneider, Ronen; Hoogstraten, Charlotte A; Ullmann, Jeremy F P; Schapiro, David; Majmundar, Amar J; Kolb, Amy; Eddy, Kaitlyn; Shril, Shirlee; Braun, Daniela A; Poduri, Annapurna; Hildebrandt, Friedhelm

2018-01-01

Until recently, morpholino oligonucleotides have been widely employed in zebrafish as an acute and efficient loss-of-function assay. However, off-target effects and reproducibility issues when compared to stable knockout lines have compromised their further use. Here we employed an acute CRISPR/Cas approach using multiple single guide RNAs targeting simultaneously different positions in two exemplar genes (osgep or tprkb) to increase the likelihood of generating mutations on both alleles in the injected F0 generation and to achieve a similar effect as morpholinos but with the reproducibility of stable lines. This multi single guide RNA approach resulted in median likelihoods for at least one mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated the microcephaly phenotype and reduction in survival that we observed previously in stable knockout lines, though milder in the acute multi-sgRNA knockout. Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a mathematical model to quantitate the chance for a biallelic loss-of-function mutation. Our findings can be generalized to acute and stable CRISPR/Cas targeting for any zebrafish gene of interest.

Reversal of Vascular Calcification and Aneurysms in a Rat Model Using Dual Targeted Therapy with EDTA- and PGG-Loaded Nanoparticles

PubMed Central

Nosoudi, Nasim; Chowdhury, Aniqa; Siclari, Steven; Karamched, Saketh; Parasaram, Vaideesh; Parrish, Joe; Gerard, Patrick; Vyavahare, Narendra

2016-01-01

Degeneration of elastic lamina and vascular calcification are common features of vascular pathology such as aortic aneurysms. We tested whether dual therapy with targeted nanoparticles (NPs) can remove mineral deposits (by delivery of a chelating agent, ethylene diamine tetraacetic acid (EDTA)) and restore elastic lamina (by delivery of a polyphenol, pentagalloyl glucose (PGG)) to reverse moderate aneurysm development. EDTA followed by PGG NP delivery led to reduction in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin degradation and calcification in the aorta as compared to delivery of control blank NPs. Such dual therapy restored vascular elastic lamina and improved vascular function as observed by improvement in circumferential strain. Therefore, dual targeted therapy may be an attractive option to remove mineral deposits and restore healthy arterial structures in moderately developed aneurysms. PMID:27698934

Adolescent Weight Control: An Intervention Targeting Parent Communication and Modeling Compared With Minimal Parental Involvement

PubMed Central

Hadley, Wendy; Sato, Amy; Kuhl, Elizabeth; Rancourt, Diana; Oster, Danielle; Lloyd-Richardson, Elizabeth

2015-01-01

Objective Adolescent weight control interventions demonstrate variable findings, with inconsistent data regarding the appropriate role for parents. The current study examined the efficacy of a standard adolescent behavioral weight control (BWC) intervention that also targeted parent–adolescent communication and parental modeling of healthy behaviors (Standard Behavioral Treatment + Enhanced Parenting; SBT + EP) compared with a standard BWC intervention (SBT). Methods 49 obese adolescents (M age = 15.10; SD = 1.33; 76% female; 67.3% non-Hispanic White) and a caregiver were randomly assigned to SBT or SBT + EP. Adolescent and caregiver weight and height, parental modeling, and weight-related communication were obtained at baseline and end of the 16-week intervention. Results Significant decreases in adolescent weight and increases in parental self-monitoring were observed across both conditions. Analyses of covariance revealed a trend for greater reduction in weight and negative maternal commentary among SBT condition participants. Conclusions Contrary to hypotheses, targeting parent–adolescent communication and parental modeling did not lead to better outcomes in adolescent weight control. PMID:25294840

Environmental implications of carbon limits on market ...

EPA Pesticide Factsheets

Combined heat and power (CHP) is promoted as an economical, energy-efficient option for combating climate change. To fully examine the viability of CHP as a clean-technology solution, its market potential and impacts need to be analyzed as part of scenarios of the future energy system, particularly those with policies limiting greenhouse gas (GHG) emissions. This paper develops and analyzes scenarios using a bottom-up, technology rich optimization model of the U.S. energy system. Two distinct carbon reduction goals were set up for analysis. In Target 1, carbon emission reduction goals were only included for the electric sector. In Target 2, carbon emission reduction goals were set across the entire energy system with the target patterned after the U.S.’s commitment to reducing GHG emissions as part of the Paris Agreement reached at the COP21 summit. From a system-wide carbon reduction standpoint, Target 2 is significantly more stringent. In addition, these scenarios examine the implications of various CHP capacity expansion and contraction assumptions and energy prices. The largest CHP capacity expansion are observed in scenarios that included Target 1, but investments were scaled back in scenarios that incorporated Target 2. The latter scenario spurred rapid development of zero-emissions technologies within the electric sector, and purchased electricity increased dramatically in many end-use sectors. The results suggest that CHP may play a role in a carbon-c

SU-F-J-145: MRI-Guided Interventional Boost Radiotherapy for Rectal Cancer: Investigating the Feasibility of Adapting the Anatomy

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

Kleijnen, J J E; Couwenberg, A M; Asselen, B van

Purpose: The recent development of an MRI-linac allows adaptation of treatments to the anatomy of the moment. This anatomy, in turn, could be altered into a more favorable situation for radiotherapy purposes. The purpose of this study is to investigate the potential dosimetric benefits of manipulating rectal anatomy in MRI-guided interventional external-beam radiotherapy for rectal cancer. Methods: For this retrospective analysis, four patients (1M/3F) diagnosed with rectal cancer were included. These underwent MR-imaging using sonography transmission gel as endorectal contrast at time of diagnosis and standard, non-contrast, MR-imaging prior to radiotherapy planning. In the contrast scan, the rectum is inflatedmore » by the inserted contrast gel, thereby potentially increasing the distance between tumor and the organs-at-risk (OAR). Both anatomies were delineated and 7- beam IMRT-plans were calculated for both situations (RT-standard and RT-inflated), using in-house developed treatment planning software. Each plan was aimed to deliver 15Gy to the planning target volume (PTV; tumor+3mm margin) with a D99>95% and Dmax<120% of the planned dose. The D2cc dose to the OAR were then compared for both situations. Results: At equal (or better) target coverage, we found a mean reduction in D2cc of 4.1Gy/237% [range 2.6Gy–6.3Gy/70%–621%] for the bladder and of 2.0Gy/145% [range −0.7Gy–7.9Gy/−73%–442%] for the small-bowel, for the RT-inflated compared to the RT-standard plans. For the three female patients, a reduction in D2cc of 5.2Gy/191% [range 3.2Gy–9.2Gy/44%–475%] for the gynecological organs was found. We found all D2cc doses to be better for the RT-inflated plans, except for one patient for whom the bladder D2cc dose was slightly increased. Conclusion: Reduction of OAR dose by manipulation of anatomy is feasible. Inflation of the rectum results in more distance between OAR and PTV. This leads to a substantial reduction in dose to OAR at equal or better target coverage.« less

Risk-based enteric pathogen reduction targets for non-potable and direct potable use of roof runoff, stormwater, and greywater

EPA Science Inventory

This paper presents risk-based enteric pathogen log reduction targets for non-potable and potable uses of a variety of alternative source waters (i.e., locally-collected greywater, roof runoff, and stormwater). A probabilistic Quantitative Microbial Risk Assessment (QMRA) was use...

Blood pressure targets for the treatment of people with hypertension and cardiovascular disease.

PubMed

Saiz, Luis Carlos; Gorricho, Javier; Garjón, Javier; Celaya, Mª Concepción; Muruzábal, Lourdes; Malón, Mª Del Mar; Montoya, Rodolfo; López, Antonio

2017-10-11

Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown. To determine if 'lower' blood pressure targets (≤ 135/85 mmHg) are associated with reduction in mortality and morbidity as compared with 'standard' blood pressure targets (≤ 140 to 160/ 90 to 100 mmHg) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease). The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to February 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the Latin American and Caribbean Health Science Literature Database (from 1982) and contacted authors of relevant papers regarding further published and unpublished work. There were no language restrictions. We included randomized controlled trials (RCTs) with more than 50 participants per group and at least six months follow-up. Trial reports needed to present data for at least one primary outcome (total mortality, serious adverse events, total cardiovascular events, cardiovascular mortality). Eligible interventions were lower target for systolic/diastolic blood pressure (≤ 135/85 mmHg) compared with standard target for blood pressure (≤ 140 to 160/90 to 100 mmHg).Participants were adults with documented hypertension or who were receiving treatment for hypertension and cardiovascular history for myocardial infarction, stroke, chronic peripheral vascular occlusive disease or angina pectoris. Two review authors independently assessed search results and extracted data using standard methodological procedures expected by The Cochrane Collaboration. We included six RCTs that involved a total of 9795 participants. Mean follow-up was 3.7 years (range 1.0 to 4.7 years). Five RCTs provided individual patient data for 6775 participants.We found no change in total mortality (RR 1.05, 95% CI 0.90 to 1.22) or cardiovascular mortality (RR 0.96, 95% CI 0.77 to 1.21; moderate-quality evidence). Similarly, no differences were found in serious adverse events (RR 1.02, 95% CI 0.95 to 1.11; low-quality evidence). There was a reduction in fatal and non fatal cardiovascular events (including myocardial infarction, stroke, sudden death, hospitalization or death from congestive heart failure) with the lower target (RR 0.87, 95% CI 0.78 to 0.98; ARR 1.6% over 3.7 years; low-quality evidence). There were more participant withdrawals due to adverse effects in the lower target arm (RR 8.16, 95% CI 2.06 to 32.28; very low-quality evidence). Blood pressures were lower in the lower' target group by 9.5/4.9 mmHg. More drugs were needed in the lower target group but blood pressure targets were achieved more frequently in the standard target group. No evidence of a difference in total mortality and serious adverse events was found between treating to a lower or to a standard blood pressure target in people with hypertension and cardiovascular disease. This suggests no net health benefit from a lower systolic blood pressure target despite the small absolute reduction in total cardiovascular serious adverse events. There was very limited evidence on adverse events, which lead to high uncertainty. At present there is insufficient evidence to justify lower blood pressure targets (≤ 135/85 mmHg) in people with hypertension and established cardiovascular disease. More trials are needed to answer this question.

Animals Do Not Induce or Reduce Attentional Blinking, But They Are Reported More Accurately in a Rapid Serial Visual Presentation Task

PubMed Central

2017-01-01

Evolutionary psychologists have suggested that modern humans have evolved to automatically direct their attention toward animal stimuli. Although this suggestion has found support in several attentional paradigms, it is not without controversy. Recently, a study employing methods customary to studying the attentional blink has shown inconclusive support for the prioritization of animals in attention. This showed an advantage for reporting animals as second targets within the typical window of the attentional blink, but it remained unclear whether this advantage was really due to a reduction of the attentional blink. We reassessed for the presence of a reduced attentional blink for animals compared with artifacts by using three disparate stimuli sets. A general advantage for animals was found but no indication of a reduction of the attentional blink for animals. There was no support for the prediction that animal distractors should lead to spontaneous inductions of attentional blinks when presented as critical distractors before single targets. Another experiment with single targets still showed that animals were reported more accurately than artifacts. A final experiment showed that when animals were first target, they did not generate stronger attentional blinks. In summary, we did find a general advantage for animal images in the rapid serial visual presentation task, but animal images did not either induce or reduce attentional blinks. This set of results is in line with conclusions from previous research showing no evidence for a special role of animals in attention. PMID:29085619

Enhanced lysis by bispecific oncolytic measles viruses simultaneously using HER2/neu or EpCAM as target receptors

PubMed Central

Hanauer, Jan RH; Gottschlich, Lisa; Riehl, Dennis; Rusch, Tillmann; Koch, Vivian; Friedrich, Katrin; Hutzler, Stefan; Prüfer, Steffen; Friedel, Thorsten; Hanschmann, Kay-Martin; Münch, Robert C; Jost, Christian; Plückthun, Andreas; Cichutek, Klaus; Buchholz, Christian J; Mühlebach, Michael D

2016-01-01

To target oncolytic measles viruses (MV) to tumors, we exploit the binding specificity of designed ankyrin repeat proteins (DARPins). These DARPin-MVs have high tumor selectivity while maintaining excellent oncolytic potency. Stability, small size, and efficacy of DARPins allowed the generation of MVs simultaneously targeted to tumor marker HER2/neu and cancer stem cell (CSC) marker EpCAM. For optimization, the linker connecting both DARPins was varied in flexibility and length. Flexibility had no impact on fusion helper activity whereas length had. MVs with bispecific MV-H are genetically stable and revealed the desired double-target specificity. In vitro, the cytolytic activity of bispecific MVs was superior or comparable to mono-targeted viruses depending on the target cells. In vivo, therapeutic efficacy of the bispecific viruses was validated in an orthotopic ovarian carcinoma model revealing an effective reduction of tumor mass. Finally, the power of bispecific targeting was demonstrated on cocultures of different tumor cells thereby mimicking tumor heterogeneity in vitro, more closely reflecting real tumors. Here, bispecific excelled monospecific viruses in efficacy. DARPin-based targeting domains thus allow the generation of efficacious oncolytic viruses with double specificity, with the potential to handle intratumoral variation of antigen expression and to simultaneously target CSCs and the bulk tumor mass. PMID:27119117

An active target for the accelerator-based transmutation system

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

Grebyonkin, K.F.

1995-10-01

Consideration is given to the possibility of radical reduction in power requirements to the proton accelerator of the electronuclear reactor due to neutron multiplication both in the blanket and the target of an active material. The target is supposed to have the fast-neutron spectrum, and the blanket-the thermal one. The blanket and the target are separated by the thermal neutrons absorber, which is responsible for the neutron decoupling of the active target and blanket. Also made are preliminary estimations which illustrate that the realization of the idea under consideration can lead to significant reduction in power requirements to the protonmore » beam and, hence considerably improve economic characteristics of the electronuclear reactor.« less

Monte Carlo isotopic inventory analysis for complex nuclear systems

NASA Astrophysics Data System (ADS)

Phruksarojanakun, Phiphat

Monte Carlo Inventory Simulation Engine (MCise) is a newly developed method for calculating isotopic inventory of materials. It offers the promise of modeling materials with complex processes and irradiation histories, which pose challenges for current, deterministic tools, and has strong analogies to Monte Carlo (MC) neutral particle transport. The analog method, including considerations for simple, complex and loop flows, is fully developed. In addition, six variance reduction tools provide unique capabilities of MCise to improve statistical precision of MC simulations. Forced Reaction forces an atom to undergo a desired number of reactions in a given irradiation environment. Biased Reaction Branching primarily focuses on improving statistical results of the isotopes that are produced from rare reaction pathways. Biased Source Sampling aims at increasing frequencies of sampling rare initial isotopes as the starting particles. Reaction Path Splitting increases the population by splitting the atom at each reaction point, creating one new atom for each decay or transmutation product. Delta Tracking is recommended for high-frequency pulsing to reduce the computing time. Lastly, Weight Window is introduced as a strategy to decrease large deviations of weight due to the uses of variance reduction techniques. A figure of merit is necessary to compare the efficiency of different variance reduction techniques. A number of possibilities for figure of merit are explored, two of which are robust and subsequently used. One is based on the relative error of a known target isotope (1/R 2T) and the other on the overall detection limit corrected by the relative error (1/DkR 2T). An automated Adaptive Variance-reduction Adjustment (AVA) tool is developed to iteratively define parameters for some variance reduction techniques in a problem with a target isotope. Sample problems demonstrate that AVA improves both precision and accuracy of a target result in an efficient manner. Potential applications of MCise include molten salt fueled reactors and liquid breeders in fusion blankets. As an example, the inventory analysis of a liquid actinide fuel in the In-Zinerator, a sub-critical power reactor driven by a fusion source, is examined. The result reassures MCise as a reliable tool for inventory analysis of complex nuclear systems.

SU-F-T-36: Dosimetric Comparison of Point Based Vs. Target Based Prescription for Intracavitary Brachytherapy in Cancer of the Cervix

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

Ashenafi, M; McDonald, D; Peng, J

Purpose: Improved patient imaging used for planning the treatment of cervical cancer with Tandem and Ovoid (T&O) Intracavitary high-dose-rate brachytherapy (HDR) now allows for 3D delineation of target volumes and organs-at-risk. However, historical data relies on the conventional point A-based planning technique. A comparative dosimetric study was performed by generating both target-based (TBP) and point-based (PBP) plans for ten clinical patients. Methods: Treatment plans created using Elekta Oncentra v. 4.3 for ten consecutive cervical cancer patients were analyzed. All patients were treated with HDR using the Utrecht T&O applicator. Both CT and MRI imaging modalities were utilized to delineate clinicalmore » target volume (CTV) and organs-at-risk (rectum, sigmoid, bladder, and small bowel). Point A (left and right), vaginal mucosa, and ICRU rectum and bladder points were defined on CT. Two plans were generated for each patient using two prescription methods (PBP and TBP). 7Gy was prescribed to each point A for each PBP plan and to the target D90% for each TBP plan. Target V90%, V100%, and V200% were evaluated. In addition, D0.1cc and D2cc were analyzed for each organ-at-risk. Differences were assessed for statistical significance (p<0.05) by use of Student’s t-test. Results: Target coverage was comparable for both planning methods, with each method providing adequate target coverage. TBP showed lower absolute dose to the target volume than PBP (D90% = 7.0Gy vs. 7.4Gy, p=0.028), (V200% = 10.9cc vs. 12.8cc, p=0.014), (ALeft = 6.4Gy vs. 7Gy, p=0.009), and (ARight = 6.4Gy vs. 7Gy, p=0.013). TBP also showed a statistically significant reduction in bladder, rectum, small bowel, and sigmoid doses compared to PBP. There was no statistically significant difference in vaginal mucosa or ICRU-defined rectum and bladder dose. Conclusion: Target based prescription resulted in substantially lower dose to delineated organs-at-risk compared to point based prescription, while maintaining similar target coverage.« less

Curcumin inhibits hepatitis B virus infection by down-regulating cccDNA-bound histone acetylation.

PubMed

Wei, Zhi-Qiang; Zhang, Yong-Hong; Ke, Chang-Zheng; Chen, Hong-Xia; Ren, Pan; He, Yu-Lin; Hu, Pei; Ma, De-Qiang; Luo, Jie; Meng, Zhong-Ji

2017-09-14

To investigate the potential effect of curcumin on hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and the underlying mechanism. A HepG2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen (HBsAg) and e antigen (HBeAg) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and cccDNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound cccDNA was detected by chromatin immunoprecipitation (ChIP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs (siRNAs) targeting HBV were tested along with curcumin. Curcumin treatment led to time- and dose-dependent reductions in HBsAg and HBeAg expression and significant reductions in intracellular HBV DNA replication intermediates and HBV cccDNA. After treatment with 20 μmol/L curcumin for 2 d, HBsAg and cccDNA levels in HepG2.2.15 cells were reduced by up to 57.7% ( P < 0.01) and 75.5% ( P < 0.01), respectively, compared with levels in non-treated cells. Meanwhile, time- and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3- and H4-bound cccDNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of siRNAs targeting HBV enhanced the inhibitory effects of curcumin. Curcumin inhibits HBV gene replication via down-regulation of cccDNA-bound histone acetylation and has the potential to be developed as a cccDNA-targeting antiviral agent for hepatitis B.

Therapeutic targeting of cancer cell metabolism

PubMed Central

Hamaker, Max; Sun, Peng; Le, Anne; Gao, Ping

2012-01-01

In 1927, Otto Warburg and coworkers reported the increased uptake of glucose and production of lactate by tumors in vivo as compared with normal tissues. This phenomenon, now known as the Warburg effect, was recapitulated in vitro with cancer tissue slices exhibiting excessive lactate production even with adequate oxygen. Warburg's in vivo studies of tumors further suggest that the dependency of tumors in vivo on glucose could be exploited for therapy, because reduction of arterial glucose by half resulted in a four-fold reduction in tumor fermentation. Recent work in cancer metabolism indicates that the Warburg effect or aerobic glycolysis contributes to redox balance and lipid synthesis, but glycolysis is insufficient to sustain a growing and dividing cancer cell. In this regard, glutamine, which contributes its carbons to the tricarboxylic acid (TCA) cycle, has been re-discovered as an essential bioenergetic and anabolic substrate for many cancer cell types. Could alterations in cancer metabolism be exploited for therapy? Here, we address this question by reviewing current concepts of normal metabolism and altered metabolism in cancer cells with specific emphasis on molecular targets involved directly in glycolysis or glutamine metabolism. PMID:21301795

Modeling nitrate-nitrogen load reduction strategies for the des moines river, iowa using SWAT

USGS Publications Warehouse

Schilling, K.E.; Wolter, C.F.

2009-01-01

The Des Moines River that drains a watershed of 16,175 km2 in portions of Iowa and Minnesota is impaired for nitrate-nitrogen (nitrate) due to concentrations that exceed regulatory limits for public water supplies. The Soil Water Assessment Tool (SWAT) model was used to model streamflow and nitrate loads and evaluate a suite of basin-wide changes and targeting configurations to potentially reduce nitrate loads in the river. The SWAT model comprised 173 subbasins and 2,516 hydrologic response units and included point and nonpoint nitrogen sources. The model was calibrated for an 11-year period and three basin-wide and four targeting strategies were evaluated. Results indicated that nonpoint sources accounted for 95% of the total nitrate export. Reduction in fertilizer applications from 170 to 50 kg/ha achieved the 38% reduction in nitrate loads, exceeding the 34% reduction required. In terms of targeting, the most efficient load reductions occurred when fertilizer applications were reduced in subbasins nearest the watershed outlet. The greatest load reduction for the area of land treated was associated with reducing loads from 55 subbasins with the highest nitrate loads, achieving a 14% reduction in nitrate loads achieved by reducing applications on 30% of the land area. SWAT model results provide much needed guidance on how to begin implementing load reduction strategies most efficiently in the Des Moines River watershed. ?? 2009 Springer Science+Business Media, LLC.

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 Placement to Guide Cardiac Resynchronization Therapy [TARGET] study); ISRCTN19717943). Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

A method for deriving a 4D-interpolated balanced planning target for mobile tumor radiotherapy.

PubMed

Roland, Teboh; Hales, Russell; McNutt, Todd; Wong, John; Simari, Patricio; Tryggestad, Erik

2012-01-01

Tumor control and normal tissue toxicity are strongly correlated to the tumor and normal tissue volumes receiving high prescribed dose levels in the course of radiotherapy. Planning target definition is, therefore, crucial to ensure favorable clinical outcomes. This is especially important for stereotactic body radiation therapy of lung cancers, characterized by high fractional doses and steep dose gradients. The shift in recent years from population-based to patient-specific treatment margins, as facilitated by the emergence of 4D medical imaging capabilities, is a major improvement. The commonly used motion-encompassing, or internal-target volume (ITV), target definition approach provides a high likelihood of coverage for the mobile tumor but inevitably exposes healthy tissue to high prescribed dose levels. The goal of this work was to generate an interpolated balanced planning target that takes into account both tumor coverage and normal tissue sparing from high prescribed dose levels, thereby improving on the ITV approach. For each 4DCT dataset, 4D deformable image registration was used to derive two bounding targets, namely, a 4D-intersection and a 4D-composite target which minimized normal tissue exposure to high prescribed dose levels and maximized tumor coverage, respectively. Through definition of an "effective overlap volume histogram" the authors derived an "interpolated balanced planning target" intended to balance normal tissue sparing from prescribed doses with tumor coverage. To demonstrate the dosimetric efficacy of the interpolated balanced planning target, the authors performed 4D treatment planning based on deformable image registration of 4D-CT data for five previously treated lung cancer patients. Two 4D plans were generated per patient, one based on the interpolated balanced planning target and the other based on the conventional ITV target. Plans were compared for tumor coverage and the degree of normal tissue sparing resulting from the new approach was quantified. Analysis of the 4D dose distributions from all five patients showed that while achieving tumor coverage comparable to the ITV approach, the new planning target definition resulted in reductions of lung V(10), V(20), and V(30) of 6.3% ± 1.7%, 10.6% ± 3.9%, and 12.9% ± 5.5%, respectively, as well as reductions in mean lung dose, mean dose to the GTV-ring and mean heart dose of 8.8% ± 2.5%, 7.2% ± 2.5%, and 10.6% ± 3.6%, respectively. The authors have developed a simple and systematic approach to generate a 4D-interpolated balanced planning target volume that implicitly incorporates the dynamics of respiratory-organ motion without requiring 4D-dose computation or optimization. Preliminary results based on 4D-CT data of five previously treated lung patients showed that this new planning target approach may improve normal tissue sparing without sacrificing tumor coverage.

Volumetric modulated arc radiotherapy for esophageal cancer.

PubMed

Vivekanandan, Nagarajan; Sriram, Padmanaban; Kumar, S A Syam; Bhuvaneswari, Narayanan; Saranya, Kamalakannan

2012-01-01

A treatment planning study was performed to evaluate the performance of volumetric arc modulation with RapidArc (RA) against 3D conformal radiation therapy (3D-CRT) and conventional intensity-modulated radiation therapy (IMRT) techniques for esophageal cancer. Computed tomgraphy scans of 10 patients were included in the study. 3D-CRT, 4-field IMRT, and single-arc and double-arc RA plans were generated with the aim to spare organs at risk (OAR) and healthy tissue while enforcing highly conformal target coverage. The planning objective was to deliver 54 Gy to the planning target volume (PTV) in 30 fractions. Plans were evaluated based on target conformity and dose-volume histograms of organs at risk (lung, spinal cord, and heart). The monitor unit (MU) and treatment delivery time were also evaluated to measure the treatment efficiency. The IMRT plan improves target conformity and spares OAR when compared with 3D-CRT. Target conformity improved with RA plans compared with IMRT. The mean lung dose was similar in all techniques. However, RA plans showed a reduction in the volume of the lung irradiated at V(₂₀Gy) and V(₃₀Gy) dose levels (range, 4.62-17.98%) compared with IMRT plans. The mean dose and D(₃₅%) of heart for the RA plans were better than the IMRT by 0.5-5.8%. Mean V(₁₀Gy) and integral dose to healthy tissue were almost similar in all techniques. But RA plans resulted in a reduced low-level dose bath (15-20 Gy) in the range of 14-16% compared with IMRT plans. The average MU needed to deliver the prescribed dose by RA technique was reduced by 20-25% compared with IMRT technique. The preliminary study on RA for esophageal cancers showed improvements in sparing OAR and healthy tissue with reduced beam-on time, whereas only double-arc RA offered improved target coverage compared with IMRT and 3D-CRT plans. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

The Influence on Population Weight Gain and Obesity of the Macronutrient Composition and Energy Density of the Food Supply.

PubMed

Crino, Michelle; Sacks, Gary; Vandevijvere, Stefanie; Swinburn, Boyd; Neal, Bruce

2015-03-01

Rates of overweight and obesity have increased dramatically in all regions of the world over the last few decades. Almost all of the world's population now has ubiquitous access to low-cost, but highly-processed, energy-dense, nutrient-poor food products. These changes in the food supply, rather than decreases in physical activity, are most likely the primary driver of population weight gain and obesity. To-date, the majority of prevention efforts focus on personalised approaches targeting individuals. Population-wide food supply interventions addressing sodium and trans fat reduction have proven highly effective and comparable efforts are now required to target obesity. The evidence suggests that strategies focusing upon reducing the energy density and portion size of foods will be more effective than those targeting specific macronutrients. Government leadership, clearly specified targets, accountability and transparency will be the key to achieving the food supply changes required to address the global obesity epidemic.

Characterizing the influence of transportation infrastructure on Emergency Medical Services (EMS) in urban area-A case study of Seoul, South Korea.

PubMed

Cho, Jungwoo; You, Myoungsoon; Yoon, Yoonjin

2017-01-01

In highly urbanized area where traffic condition fluctuates constantly, transportation infrastructure is one of the major contributing factors to Emergency Medical Service (EMS) availability and patient outcome. In this paper, we assess the impact of traffic fluctuation to the EMS first response availability in urban area, by evaluating the k-minute coverage under 21 traffic scenarios. The set of traffic scenarios represents the time-of-day and day-of-week effects, and is generated by combining road link speed information from multiple historical speed databases. In addition to the k-minute area coverage calculation, the k-minute population coverage is also evaluated for every 100m by 100m grid that partitions the case study area of Seoul, South Korea. In the baseline case of traveling at the speed limit, both the area and population coverage reached nearly 100% when compared to the five-minute travel time national target. Employing the proposed LoST (Loss of Serviceability due to Traffic) index, which measures coverage reduction in percentage compared to the baseline case, we find that the citywide average LoST for area and population coverage are similar at 34.2% and 33.8%. However, district-wise analysis reveals that such reduction varies significantly by district, and the magnitude of area and population coverage reduction is not always proportional. We conclude that the effect of traffic variation is significant to successful urban EMS first response performance, and regional variation is evident among local districts. Complexity in the urban environment requires a more adaptive approach in public health resource management and EMS performance target determination.

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-Troglitazone-induced Apoptosis in Prostate Cancer Cells Involve AMP-activated Protein Kinase*

PubMed Central

Santha, Sreevidya; Viswakarma, Navin; Das, Subhasis; Rana, Ajay; Rana, Basabi

2015-01-01

Prostate cancer (PCa) is one of the most frequently diagnosed cancers in men with limited treatment options for the hormone-resistant forms. Development of novel therapeutic options is critically needed to target advanced forms. Here we demonstrate that combinatorial treatment with the thiazolidinedione troglitazone (TZD) and TNF-related apoptosis-inducing ligand (TRAIL) can induce significant apoptosis in various PCa cells independent of androgen receptor status. Because TZD is known to activate AMP-activated protein kinase (AMPK), we determined whether AMPK is a molecular target mediating this apoptotic cascade by utilizing PCa cell lines stably overexpressing AMPKα1 dominant negative (C4-2-DN) or empty vector (C4-2-EV). Our results indicated a significantly higher degree of apoptosis with TRAIL-TZD combination in C4-2-EV cells compared with C4-2-DN cells. Similarly, results from a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed a larger reduction of viability of C4-2-EV cells compared with C4-2-DN cells when treated with TRAIL-TZD, thus suggesting that C4-2-DN cells were more apoptosis-resistant. Additionally, siRNA-mediated knockdown of endogenous AMPKα1 expression showed a reduction of TRAIL-TZD-induced apoptosis, further confirming the participation of AMPK in mediating this apoptosis. Apoptosis induction by this combinatorial treatment was also associated with a cleavage of β-catenin that was inhibited in both C4-2-DN cells and those cells in which AMPKα1 was knocked down. In addition, time course studies showed an increase in pACCS79 (AMPK target) levels coinciding with the time of apoptosis. These studies indicate the involvement of AMPK in TRAIL-TZD-mediated apoptosis and β-catenin cleavage and suggest the possibility of utilizing AMPK as a therapeutic target in apoptosis-resistant prostate cancer. PMID:26198640

Developing Strategies for Waste Reduction by Means of Tailored Interventions in Santiago De Cuba

ERIC Educational Resources Information Center

Tobias, Robert; Brugger, Adrian; Mosler, Hans-Joachim

2009-01-01

This article introduces an approach to tailoring behavior-change campaigns to target populations using the example of solid waste reduction in Santiago de Cuba. Tailoring is performed in the following steps: (1) Psychological constructs are selected to detect problems in performing the target behavior, and data are gathered on these constructs.…

Two-Plasmon Decay Mitigation in Direct-Drive Inertial-Confinement-Fusion Experiments Using Multilayer Targets.

PubMed

Follett, R K; Delettrez, J A; Edgell, D H; Goncharov, V N; Henchen, R J; Katz, J; Michel, D T; Myatt, J F; Shaw, J; Solodov, A A; Stoeckl, C; Yaakobi, B; Froula, D H

2016-04-15

Multilayer direct-drive inertial-confinement-fusion targets are shown to significantly reduce two-plasmon decay (TPD) driven hot-electron production while maintaining high hydrodynamic efficiency. Implosion experiments on the OMEGA laser used targets with silicon layered between an inner beryllium and outer silicon-doped plastic ablator. A factor-of-5 reduction in hot-electron generation (>50  keV) was observed in the multilayer targets relative to pure CH targets. Three-dimensional simulations of the TPD-driven hot-electron production using a laser-plasma interaction code (lpse) that includes nonlinear and kinetic effects show good agreement with the measurements. The simulations suggest that the reduction in hot-electron production observed in the multilayer targets is primarily caused by increased electron-ion collisional damping.

Association of Intensive Blood Pressure Control and Kidney Disease Progression in Nondiabetic Patients With Chronic Kidney Disease

PubMed Central

Tsai, Wan-Chuan; Peng, Yu-Sen; Yang, Ju-Yeh; Chen, Hung-Yuan; Chiu, Yen-Ling; Hsu, Shih-Ping; Ko, Mei-Ju; Pai, Mei-Fen; Tu, Yu-Kang; Hung, Kuan-Yu; Chien, Kuo-Liong

2017-01-01

Importance The optimal blood pressure (BP) target remains debated in nondiabetic patients with chronic kidney disease (CKD). Objective To compare intensive BP control (<130/80 mm Hg) with standard BP control (<140/90 mm Hg) on major renal outcomes in patients with CKD without diabetes. Data Sources Searches of PubMed, MEDLINE, Embase, and Cochrane Library for publications up to March 24, 2016. Study Selection Randomized clinical trials that compared an intensive vs a standard BP target in nondiabetic adults with CKD, reporting changes in glomerular filtration rate (GFR), doubling of serum creatinine level, 50% reduction in GFR, end-stage renal disease (ESRD), or all-cause mortality. Data Extraction and Synthesis Random-effects meta-analyses for pooling effect measures. Meta-regression and subgroup analyses for exploring heterogeneity. Main Outcomes and Measures Differences in annual rate of change in GFR were expressed as mean differences with 95% CIs. Differences in doubling of serum creatinine or 50% reduction in GFR, ESRD, composite renal outcome, and all-cause mortality were expressed as risk ratios (RRs) with 95% CIs. Results We identified 9 trials with 8127 patients and a median follow-up of 3.3 years. Compared with standard BP control, intensive BP control did not show a significant difference on the annual rate of change in GFR (mean difference, 0.07; 95% CI, −0.16 to 0.29 mL/min/1.73 m2/y), doubling of serum creatinine level or 50% reduction in GFR (RR, 0.99; 95% CI, 0.76-1.29), ESRD (RR, 0.96; 95% CI, 0.78-1.18), composite renal outcome (RR, 0.99; 95% CI, 0.81-1.21), or all-cause mortality (RR, 0.81; 95% CI, 0.64-1.02). Intensive BP control reduced mortality (RR, 0.78; 95% CI, 0.61-0.99) in sensitivity analysis when the study populations were strictly restricted to those without diabetes. Nonblacks and patients with higher levels of proteinuria showed a trend of lower risk of kidney disease progression with intensive BP control. Conclusions and Relevance Targeting BP below the current standard did not provide additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes. However, nonblack patients or those with higher levels of proteinuria might benefit from the intensive BP-lowering treatments. PMID:28288249

Influence of jaw tracking in intensity-modulated and volumetric-modulated arc radiotherapy for head and neck cancers: a dosimetric study.

PubMed

Mani, Karthick Raj; Upadhayay, Sagar; Das, K J Maria

2017-03-01

To Study the dosimetric advantage of the Jaw tracking technique in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for Head and Neck Cancers. We retrospectively selected 10 previously treated head and neck cancer patients stage (T1/T2, N1, M0) in this study. All the patients were planned for IMRT and VMAT with simultaneous integrated boost technique. IMRT and VMAT plans were performed with jaw tracking (JT) and with static jaw (SJ) technique by keeping the same constraints and priorities for a particular patient. Target conformity, dose to the critical structures and low dose volumes were recorded and analyzed for IMRT and VMAT plans with and without JT for all the patients. The conformity index average of all patients followed by standard deviation ([Formula: see text] ± [Formula: see text]) of the JT-IMRT, SJ-IMRT, JT-VMAT, and SJ-VMAT were 1.72 ± 0.56, 1.67 ± 0.57, 1.83 ± 0.65, and 1.85 ± 0.64, and homogeneity index were 0.059 ± 0.05, 0.064 ± 0.05, 0.064 ± 0.04, and 0.064 ± 0.05. JT-IMRT shows significant mean reduction in right parotid and left parotid shows of 7.64% (p < 0.001) and 7.45% (p < 0.001) compare to SJ-IMRT. JT-IMRT plans also shows considerable dose reduction to thyroid, inferior constrictors, spinal cord and brainstem compared to the SJ-IMRT plans. Significant dose reductions were observed for critical structure in the JT-IMRT compared to SJ-IMRT technique. In JT-VMAT plans dose reduction to the critical structure were not significant compared to the SJ-IMRT due to relatively lesser monitor units.

Efficacy of patient-specific bolus created using three-dimensional printing technique in photon radiotherapy.

PubMed

Fujimoto, Koya; Shiinoki, Takehiro; Yuasa, Yuki; Hanazawa, Hideki; Shibuya, Keiko

2017-06-01

A commercially available bolus ("commercial-bolus") does not make complete contact with the irregularly shaped patient skin. This study aims to customise a patient-specific three-dimensional (3D) bolus using a 3D printing technique ("3D-bolus") and to evaluate its clinical feasibility for photon radiotherapy. The 3D-bolus was designed using a treatment planning system (TPS) in Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format, and converted to stereolithographic format for printing. To evaluate its physical characteristics, treatment plans were created for water-equivalent phantoms that were bolus-free, or had a flat-form printed 3D-bolus, a TPS-designed bolus ("virtual-bolus"), or a commercial-bolus. These plans were compared based on the percentage depth dose (PDD) and target-volume dose volume histogram (DVH) measurements. To evaluate the clinical feasibility, treatment plans were created for head phantoms that were bolus-free or had a 3D-bolus, a virtual-bolus, or a commercial-bolus. These plans were compared based on the target volume DVH. In the physical evaluation, the 3D-bolus provided effective dose coverage in the build-up region, which was equivalent to the commercial-bolus. With regard to the clinical feasibility, the air gaps were lesser with the 3D-bolus when compared to the commercial-bolus. Furthermore, the prescription dose could be delivered appropriately to the target volume. The 3D-bolus has potential use for air-gap reduction compared to the commercial-bolus and facilitates target-volume dose coverage and homogeneity improvement. A 3D-bolus produced using a 3D printing technique is comparable to a commercial-bolus applied to an irregular-shaped skin surface. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

The Role of 3T Magnetic Resonance Imaging for Targeting the Human Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease.

PubMed

Longhi, Michele; Ricciardi, Giuseppe; Tommasi, Giorgio; Nicolato, Antonio; Foroni, Roberto; Bertolasi, Laura; Beltramello, Alberto; Moretto, Giuseppe; Tinazzi, Michele; Gerosa, Massimo

2015-05-01

Chronic stimulation of the human subthalamic nucleus (STN) is gradually becoming accepted as a long-term therapeutic option for patients with advanced Parkinson disease (PD). 3Tesla (T) magnetic resonance imaging (MRI) improves contrast resolution in basal ganglia nuclei containing high levels of iron, because of magnetic susceptibility effects that increase significantly as the magnetic field gets higher. This phenomenon can be used for better visualization of the STN and may reduce the time necessary for detailed microrecording (MER) mapping, increasing surgery efficacy and lowering morbidity. The objective of this retrospective study is to analyze a population of 20 deep brain stimulation (DBS) electrode implanted patients with PD divided into two groups in which different targeting methods were used. Mean age was 56 years (range 37 to 69 years). Mean disease duration was 11.6 years. Mean follow-up was 12 months (range 6 to 36 months). Patients were divided into two groups: Group A contained 6 patients who underwent STN targeting using 1T stereotactic (T1w + T2w) MRI plus STN indirect atlas derived targeting. Group B consisted of 14 patients who underwent STN targeting using 3T nonstereotactic (T2w) MRI fused with 1T T1w stereotactic MRI and STN direct targeting. For statistical analysis, we compared (five different parameters in both (matched) groups: Unified Parkinson's disease rating scale (UPDRS) score reduction (medication off before surgery against stimulation on/medication off after surgery), postoperative drug reduction, duration of surgery, the "central preoperative track" chosen as final implantation track during surgery, and correspondence between the targeted STN and the intraoperative neurophysiologic data. Mean UPDRS III score reduction (medication off/stimulation on versus preoperative medication off) was 69% in Group A and 74% in Group B (p = 0.015, log-rank test) respectively. Postoperatively, antiparkinsonian treatment was reduced by 66% in Group A and 75% in Group B (p = 0.006, log-rank test). The preoperative "central" track (which corresponds to ideal STN targeting) proved to be the most clinically effective in 2/12 leads for Group A versus 21/28 for Group B (p < 0.001).Neurophysiologic data confirmed these results; the hypothetical target was confirmed by MER data in 76% of tracks in Group A, and in 75% of tracks in Group B (p < 0.001, univariate and multivariate analysis). 3T MRI appears to be a useful tool in STN-DBS preoperative targeting. Neurophysiologic testing remains fundamental to determine lead deepness (and prevent clinical side effects. Georg Thieme Verlag KG Stuttgart · New York.

The cost-effectiveness of harm reduction.

PubMed

Wilson, David P; Donald, Braedon; Shattock, Andrew J; Wilson, David; Fraser-Hurt, Nicole

2015-02-01

HIV prevalence worldwide among people who inject drugs (PWID) is around 19%. Harm reduction for PWID includes needle-syringe programs (NSPs) and opioid substitution therapy (OST) but often coupled with antiretroviral therapy (ART) for people living with HIV. Numerous studies have examined the effectiveness of each harm reduction strategy. This commentary discusses the evidence of effectiveness of the packages of harm reduction services and their cost-effectiveness with respect to HIV-related outcomes as well as estimate resources required to meet global and regional coverage targets. NSPs have been shown to be safe and very effective in reducing HIV transmission in diverse settings; there are many historical and very recent examples in diverse settings where the absence of, or reduction in, NSPs have resulted in exploding HIV epidemics compared to controlled epidemics with NSP implementation. NSPs are relatively inexpensive to implement and highly cost-effective according to commonly used willingness-to-pay thresholds. There is strong evidence that substitution therapy is effective, reducing the risk of HIV acquisition by 54% on average among PWID. OST is relatively expensive to implement when only HIV outcomes are considered; other societal benefits substantially improve the cost-effectiveness ratios to be highly favourable. Many studies have shown that ART is cost-effective for keeping people alive but there is only weak supportive, but growing evidence, of the additional effectiveness and cost-effectiveness of ART as prevention among PWID. Packages of combined harm reduction approaches are highly likely to be more effective and cost-effective than partial approaches. The coverage of harm reduction programs remains extremely low across the world. The total annual costs of scaling up each of the harm reduction strategies from current coverage levels, by region, to meet WHO guideline coverage targets are high with ART greatest, followed by OST and then NSPs. But scale-up of all three approaches is essential. These interventions can be cost-effective by most thresholds in the short-term and cost-saving in the long-term. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

WE-G-BRD-08: Motion Analysis for Rectal Cancer: Implications for Adaptive Radiotherapy On the MR-Linac

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

Kleijnen, J; Asselen, B van; Burbach, M

2015-06-15

Purpose: Purpose of this study is to find the optimal trade-off between adaptation interval and margin reduction and to define the implications of motion for rectal cancer boost radiotherapy on a MR-linac. Methods: Daily MRI scans were acquired of 16 patients, diagnosed with rectal cancer, prior to each radiotherapy fraction in one week (N=76). Each scan session consisted of T2-weighted and three 2D sagittal cine-MRI, at begin (t=0 min), middle (t=9:30 min) and end (t=18:00 min) of scan session, for 1 minute at 2 Hz temporal resolution. Tumor and clinical target volume (CTV) were delineated on each T2-weighted scan andmore » transferred to each cine-MRI. The start frame of the begin scan was used as reference and registered to frames at time-points 15, 30 and 60 seconds, 9:30 and 18:00 minutes and 1, 2, 3 and 4 days later. Per time-point, motion of delineated voxels was evaluated using the deformation vector fields of the registrations and the 95th percentile distance (dist95%) was calculated as measure of motion. Per time-point, the distance that includes 90% of all cases was taken as estimate of required planning target volume (PTV)-margin. Results: Highest motion reduction is observed going from 9:30 minutes to 60 seconds. We observe a reduction in margin estimates from 10.6 to 2.7 mm and 16.1 to 4.6 mm for tumor and CTV, respectively, when adapting every 60 seconds compared to not adapting treatment. A 75% and 71% reduction, respectively. Further reduction in adaptation time-interval yields only marginal motion reduction. For adaptation intervals longer than 18:00 minutes only small motion reductions are observed. Conclusion: The optimal adaptation interval for adaptive rectal cancer (boost) treatments on a MR-linac is 60 seconds. This results in substantial smaller PTV-margin estimates. Adaptation intervals of 18:00 minutes and higher, show little improvement in motion reduction.« less

Comparative statistical component analysis of transgenic, cyanophycin-producing potatoes in greenhouse and field trials.

PubMed

Schmidt, Kerstin; Schmidtke, Jörg; Mast, Yvonne; Waldvogel, Eva; Wohlleben, Wolfgang; Klemke, Friederike; Lockau, Wolfgang; Hausmann, Tina; Hühns, Maja; Broer, Inge

2017-08-01

Potatoes are a promising system for industrial production of the biopolymer cyanophycin as a second compound in addition to starch. To assess the efficiency in the field, we analysed the stability of the system, specifically its sensitivity to environmental factors. Field and greenhouse trials with transgenic potatoes (two independent events) were carried out for three years. The influence of environmental factors was measured and target compounds in the transgenic plants (cyanophycin, amino acids) were analysed for differences to control plants. Furthermore, non-target parameters (starch content, number, weight and size of tubers) were analysed for equivalence with control plants. The huge amount of data received was handled using modern statistical approaches to model the correlation between influencing environmental factors (year of cultivation, nitrogen fertilization, origin of plants, greenhouse or field cultivation) and key components (starch, amino acids, cyanophycin) and agronomic characteristics. General linear models were used for modelling, and standard effect sizes were applied to compare conventional and genetically modified plants. Altogether, the field trials prove that significant cyanophycin production is possible without reduction of starch content. Non-target compound composition seems to be equivalent under varying environmental conditions. Additionally, a quick test to measure cyanophycin content gives similar results compared to the extensive enzymatic test. This work facilitates the commercial cultivation of cyanophycin potatoes.

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.

PubMed

Li, Chang-Jun; Cheng, Peng; Liang, Meng-Ke; Chen, Yu-Si; Lu, Qiong; Wang, Jin-Yu; Xia, Zhu-Ying; Zhou, Hou-De; Cao, Xu; Xie, Hui; Liao, Er-Yuan; Luo, Xiang-Hang

2015-04-01

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss.

Plasma confinement at JET

NASA Astrophysics Data System (ADS)

Nunes, I.; JET Contributors

2016-01-01

Operation with a Be/W wall at JET (JET-ILW) has an impact on scenario development and energy confinement with respect to the carbon wall (JET-C). The main differences observed were (1) strong accumulation of W in the plasma core and (2) the need to mitigate the divertor target temperature to avoid W sputtering by Be and other low Z impurities and (3) a decrease of plasma energy confinement. A major difference is observed on the pedestal pressure, namely a reduction of the pedestal temperature which, due to profile stiffness the plasma core temperature is also reduced leading to a degradation of the global confinement. This effect is more pronounced in low β N scenarios. At high β N, the impact of the wall on the plasma energy confinement is mitigated by the weaker plasma energy degradation with power relative to the IPB98(y, 2) scaling calculated empirically for a CFC first wall. The smaller tolerable impurity concentration for tungsten (<10-5) compared to that of carbon requires the use of electron heating methods to prevent W accumulation in the plasma core region as well as gas puffing to avoid W entering the plasma core by ELM flushing and reduction of the W source by decreasing the target temperature. W source and the target temperature can also be controlled by impurity seeding. Nitrogen and Neon have been used and with both gases the reduction of the W source and the target temperature is observed. Whilst more experiments with Neon are necessary to assess its impact on energy confinement, a partial increase of plasma energy confinement is observed with Nitrogen, through the increase of edge temperature. The challenge for scenario development at JET is to extend the pulse length curtailed by its transient behavior (W accumulation or MHD), but more importantly by the divertor target temperature limits. Re-optimisation of the scenarios to mitigate the effect of the change of wall materials maintaining high global energy confinement similar to JET-C is underway and JET has successfully achieved H 98(y,2)  =  1 for plasma currents up to 2.5 MA at moderate β N.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2015-06-01

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

Active/Passive Control of Sound Radiation from Panels using Constrained Layer Damping

NASA Technical Reports Server (NTRS)

Gibbs, Gary P.; Cabell, Randolph H.

2003-01-01

A hybrid passive/active noise control system utilizing constrained layer damping and model predictive feedback control is presented. This system is used to control the sound radiation of panels due to broadband disturbances. To facilitate the hybrid system design, a methodology for placement of constrained layer damping which targets selected modes based on their relative radiated sound power is developed. The placement methodology is utilized to determine two constrained layer damping configurations for experimental evaluation of a hybrid system. The first configuration targets the (4,1) panel mode which is not controllable by the piezoelectric control actuator, and the (2,3) and (5,2) panel modes. The second configuration targets the (1,1) and (3,1) modes. The experimental results demonstrate the improved reduction of radiated sound power using the hybrid passive/active control system as compared to the active control system alone.

Synthesis and evaluation of hetero- and homo-dimers of ribosome-targeting antibiotics: Antimicrobial activity, in vitro inhibition of translation, and drug resistance

PubMed Central

Berkov-Zrihen, Yifat; Green, Keith D.; Labby, Kristin J.; Feldman, Mark; Garneau-Tsodikova, Sylvie; Fridman, Micha

2013-01-01

In this study, we describe the synthesis of a full set of homo- and hetero-dimers of three intact structures of different ribosome-targeting antibiotics: tobramycin, clindamycin, and chloramphenicol. Several aspects of the biological activity of the dimeric structures were evaluated including antimicrobial activity, inhibition of in vitro bacterial protein translation, and the effect of dimerization on the action of several bacterial resistance mechanisms that deactivate tobramycin and chloramphenicol. This study demonstrates that covalently linking two identical or different ribosome-targeting antibiotics may lead to (i) a broader spectrum of antimicrobial activity, (ii) improved inhibition of bacterial translation properties compared to that of the parent antibiotics, and (iii) reduction in the efficacy of some drug-modifying enzymes that confer high levels of resistance to the parent antibiotics from which the dimers were derived. PMID:23786357

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 generated for MTS, the model developed should be revisited and cost-effectiveness re-estimated under different testing scenarios to further understand the value of precision medicine and its potential impact on the overall health budget. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The air quality and health co-benefits of alternative post-2020 pathways for achieving peak carbon targets in Jiangsu, China

NASA Astrophysics Data System (ADS)

Liu, M.; Bi, J.; Huang, Y.; Kinney, P. L.

2016-12-01

Jiangsu, which has three national low-carbon pilot cities, is set to be a model province in China for achieving peak carbon targets before 2030. However, according to local planning of responding to climate change, carbon emissions are projected to keep going up before 2020 even the strictest measures are implemented. In other words, innovative measures must be in action after 2020. This work aimed at assessing the air quality and health co-benefits of alternative post-2020 measures to help remove barriers of policy implementation through tying it to local incentives for air quality improvement. To achieve the aim, we select 2010 as baseline year and develop Bussiness As Usual (BAU) and Traditional Carbon Reduction (TCR) scenarios before 2020. Under BAU, only existing climate and air pollution control policies are considered; under TCR, potential climate policies in local planning and existing air pollution control policies are considered. After 2020, integrated gasification combined cycle (IGCC) plant with carbon capture and storage (CCS) technology and large-scale substitution of renewable energy seem to be two promising pathways for achieving peak carbon targets. Therefore, two additional scenarios (TCR-IGCC and TCR-SRE) are set after 2020. Based on the projections of future energy balances and industrial productions, we estimate the pollutant emissions and simulate PM2.5 and ozone concentrations by 2017, 2020, 2030 and 2050 using CMAQ. Then using health impact assessment approach, the premature deaths are estimated and monetized. Results show that the carbon peak in Jiangsu will be achieved before 2030 only under TCR-IGCC and TCR-SRE scenarios. Under three policy scenarios, Jiangsu's carbon emission control targets would have substantial effects on primary air pollutant emissions far beyond those we estimate would be needed to meet the PM2.5 concentration targets in 2017. Compared with IGCC with CCS, large-scale substitutions of renewable energy bring comparable pollutant emission reductions but more health benefits because it reduces more emissions from traffic sources which are more harmful to health. However, large-scale substitution of renewable energy posed challenges on energy supply capacity, which need to be seriously considered in future policy decision.

A high-resolution photon-counting breast CT system with tensor-framelet based iterative image reconstruction for radiation dose reduction

NASA Astrophysics Data System (ADS)

Ding, Huanjun; Gao, Hao; Zhao, Bo; Cho, Hyo-Min; Molloi, Sabee

2014-10-01

Both computer simulations and experimental phantom studies were carried out to investigate the radiation dose reduction with tensor framelet based iterative image reconstruction (TFIR) for a dedicated high-resolution spectral breast computed tomography (CT) based on a silicon strip photon-counting detector. The simulation was performed with a 10 cm-diameter water phantom including three contrast materials (polyethylene, 8 mg ml-1 iodine and B-100 bone-equivalent plastic). In the experimental study, the data were acquired with a 1.3 cm-diameter polymethylmethacrylate (PMMA) phantom containing iodine in three concentrations (8, 16 and 32 mg ml-1) at various radiation doses (1.2, 2.4 and 3.6 mGy) and then CT images were reconstructed using the filtered-back-projection (FBP) technique and the TFIR technique, respectively. The image quality between these two techniques was evaluated by the quantitative analysis on contrast-to-noise ratio (CNR) and spatial resolution that was evaluated using the task-based modulation transfer function (MTF). Both the simulation and experimental results indicated that the task-based MTF obtained from TFIR reconstruction with one-third of the radiation dose was comparable to that from the FBP reconstruction for low contrast target. For high contrast target, the TFIR was substantially superior to the FBP reconstruction in terms of spatial resolution. In addition, TFIR was able to achieve a factor of 1.6-1.8 increase in CNR, depending on the target contrast level. This study demonstrates that the TFIR can reduce the required radiation dose by a factor of two-thirds for a CT image reconstruction compared to the FBP technique. It achieves much better CNR and spatial resolution for high contrast target in addition to retaining similar spatial resolution for low contrast target. This TFIR technique has been implemented with a graphic processing unit system and it takes approximately 10 s to reconstruct a single-slice CT image, which can potentially be used in a future multi-slit multi-slice spiral CT system.

Non-traditional Serum Lipid Variables and Recurrent Stroke Risk

PubMed Central

Park, Jong-Ho; Lee, Juneyoung; Ovbiagele, Bruce

2014-01-01

Background and Purpose Expert consensus guidelines recommend low-density lipoprotein cholesterol (LDL-C) as the primary serum lipid target for recurrent stroke risk reduction. However, mounting evidence suggests that other lipid parameters might be additional therapeutic targets or at least also predict cardiovascular risk. Little is known about the effects of non-traditional lipid variables on recurrent stroke risk. Methods We analyzed the Vitamin Intervention for Stroke Prevention study database comprising 3680 recent (<120 days) ischemic stroke patients followed up for 2 years. Independent associations of baseline serum lipid variables with recurrent ischemic stroke (primary outcome) and the composite endpoint of ischemic stroke/coronary heart disease (CHD)/vascular death (secondary outcomes) were assessed. Results Of all variables evaluated, only triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio was consistently and independently related to both outcomes: compared with the lowest quintile, the highest TG/HDL-C ratio quintile was associated with stroke (adjusted hazard ratio, 1.56; 95% CI, 1.05−2.32) and stroke/CHD/vascular death (1.39; 1.05−1.83), including adjustment for lipid modifier use. Compared with the lowest quintile, the highest total cholesterol/HDL-C ratio quintile was associated with stroke/CHD/vascular death (1.45; 1.03−2.03). LDL-C/HDL-C ratio, non-HDL-C, elevated TG alone, and low HDL-C alone were not independently linked to either outcome. Conclusions Of various non-traditional lipid variables, elevated baseline TG/HDL-C and TC/HDL-C ratios predict future vascular risk after a stroke, but only elevated TG/HDL-C ratio is related to risk of recurrent stroke. Future studies should assess the role of TG/HDL as a potential therapeutic target for global vascular risk reduction after stroke. PMID:25236873

Polo-like kinase 1, a new therapeutic target in hepatocellular carcinoma

PubMed Central

Mok, Wei Chuen; Wasser, Shanthi; Tan, Theresa; Lim, Seng Gee

2012-01-01

AIM: To investigate the role of polo-like kinase 1 (PLK1) as a therapeutic target for hepatocellular carcinoma (HCC). METHODS: PLK1 gene expression was evaluated in HCC tissue and HCC cell lines. Gene knockdown with short-interfering RNA (siRNA) was used to study PLK1 gene and protein expression using real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, and cell proliferation using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4-sulfophenyl)-2H-tetrazolium (MTS) and bromodeoxyuridine (BrdU) assays. Apoptosis was evaluated using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and caspase-inhibition assay. Huh-7 cells were transplanted into nude mice and co-cultured with PLK1 siRNA or control siRNA, and tumor progression was compared with controls. RESULTS: RT-PCR showed that PLK1 was overexpressed 12-fold in tumor samples compared with controls, and also was overexpressed in Huh-7 cells. siRNA against PLK1 showed a reduction in PLK1 gene and protein expression of up to 96% in Huh-7 cells, and a reduction in cell proliferation by 68% and 92% in MTS and BrdU cell proliferation assays, respectively. There was a 3-fold increase in apoptosis events, and TUNEL staining and caspase-3 assays suggested that this was caspase-independent. The pan-caspase inhibitor Z-VAD-FMK was unable to rescue the apoptotic cells. Immnofluorescence co-localized endonuclease-G to fragmented chromosomes, implicating it in apoptosis. Huh-7 cells transplanted subcutaneously into nude mice showed tumor regression in siPLK1-treated mice, but not in controls. CONCLUSION: Knockdown of PLK1 overexpression in HCC was shown to be a potential therapeutic target, leading to apoptosis through the endonuclease-G pathway. PMID:22826617

Electrostatic application of antimicrobial sprays to sanitize food handling and processing surfaces for enhanced food safety

NASA Astrophysics Data System (ADS)

Lyons, Shawn M.; Harrison, Mark A.; Law, S. Edward

2011-06-01

Human illnesses and deaths caused by foodborne pathogens (e.g., Salmonella enterica, Listeria monocytogenes, Escherichia coli O157:H7, etc.) are of increasing concern globally in maintaining safe food supplies. At various stages of the food production, processing and supply chain antimicrobial agents are required to sanitize contact surfaces. Additionally, during outbreaks of contagious pathogenic microorganisms (e.g., H1N1 influenza), public health requires timely decontamination of extensive surfaces within public schools, mass transit systems, etc. Prior publications verify effectiveness of air-assisted, induction-charged (AAIC) electrostatic spraying of various chemical and biological agents to protect on-farm production of food crops...typically doubling droplet deposition efficiency with concomitant increases in biological control efficacy. Within a biosafety facility this present work evaluated the AAIC electrostatic-spraying process for application of antimicrobial liquids onto various pathogen-inoculated food processing and handling surfaces as a food safety intervention strategy. Fluoroanalysis of AAIC electrostatic sprays (-7.2 mC/kg charge-to-mass ratio) showed significantly greater (p<0.05) mass of tracer active ingredient (A.I.) deposited onto target surfaces at various orientations as compared both to a similar uncharged spray nozzle (0 mC/kg) and to a conventional hydraulic-atomizing nozzle. Per unit mass of A.I. dispensed toward targets, for example, A.I. mass deposited by AAIC electrostatic sprays onto difficult to coat backsides was 6.1-times greater than for similar uncharged sprays and 29.0-times greater than for conventional hydraulic-nozzle sprays. Even at the 56% reduction in peracetic acid sanitizer A.I. dispensed by AAIC electrostatic spray applications, they achieved equal or greater CFU population reductions of Salmonella on most target orientations and materials as compared to uncharged sprays and conventional full-rate hydraulic-nozzle sprays.

A planning study investigating dual-gated volumetric arc stereotactic treatment of primary renal cell carcinoma

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

Devereux, Thomas, E-mail: thomas.devereux@petermac.org; Pham, Daniel; Kron, Tomas

2015-04-01

This is a planning study investigating the dosimetric advantages of gated volumetric-modulated arc therapy (VMAT) to the end-exhale and end-inhale breathing phases for patients undergoing stereotactic treatment of primary renal cell carcinoma. VMAT plans were developed from the end-inhale (VMATinh) and the end-exhale (VMATexh) phases of the breathing cycle as well as a VMAT plan and 3-dimensional conformal radiation therapy plan based on an internal target volume (ITV) (VMATitv). An additional VMAT plan was created by giving the respective gated VMAT plan a 50% weighting and summing the inhale and exhale plans together to create a summed gated plan. Dosemore » to organs at risk (OARs) as well as comparison of intermediate and low-dose conformity was evaluated. There was no difference in the volume of healthy tissue receiving the prescribed dose for the planned target volume (PTV) (CI100%) for all the VMAT plans; however, the mean volume of healthy tissue receiving 50% of the prescribed dose for the PTV (CI50%) values were 4.7 (± 0.2), 4.6 (± 0.2), and 4.7 (± 0.6) for the VMATitv, VMATinh, and VMATexh plans, respectively. The VMAT plans based on the exhale and inhale breathing phases showed a 4.8% and 2.4% reduction in dose to 30 cm{sup 3} of the small bowel, respectively, compared with that of the ITV-based VMAT plan. The summed gated VMAT plans showed a 6.2% reduction in dose to 30 cm{sup 3} of the small bowel compared with that of the VMAT plans based on the ITV. Additionally, when compared with the inhale and the exhale VMAT plans, a 4% and 1.5%, respectively, reduction was observed. Gating VMAT was able to reduce the amount of prescribed, intermediate, and integral dose to healthy tissue when compared with VMAT plans based on an ITV. When summing the inhale and exhale plans together, dose to healthy tissue and OARs was optimized. However, gating VMAT plans would take longer to treat and is a factor that needs to be considered.« less

Challenges for the geosciences after the Paris agreement

NASA Astrophysics Data System (ADS)

Knutti, R.; Sedlacek, J.; Rogelj, J.; Fischer, E. M.

2016-12-01

The world's governments agreed to limit global mean temperature change to below 2 °C or 1.5°C compared with pre-industrial levels in Paris. These warming targets are often perceived by the public as a universally accepted goal, identified by scientists as a safe limit that avoids dangerous climate change. This perception is incorrect: no scientific assessment has clearly justified or defended 2°C as a safe level of warming, and indeed, this is not a problem that science alone can address. We argue that global temperature is the best climate target quantity, but it is unclear what level can be considered safe. However, irrespective of the target, the concept of cumulative carbon implies that substantial and sustained emission reductions are required to limit climate change to temperature levels that are currently being considered safe. The Paris agreement poses many open questions to the geoscience community: the impacts of a temperature overshoot, the limits of negative emissions, and the role of radiative forcings other than carbon dioxide need to be better understood. Treating uncertainties, incorporating risk, and linking local impacts and development objectives to global climate goals also remain major open issues that need to be tackled in a continued dialogue with science communities. The negotiations up to Paris and the 2 °C target have been useful for anchoring discussions, but ineffective in triggering the required emission reductions; the debates on considering different targets are strongly at odds with the current real-world level of action. These debates are moot, however, as the decisions that need to be taken now to limit warming to 1.5 or 2 °C are very similar. We need to agree how to start, not where to end mitigation.

Potential dosimetric benefits of adaptive tumor tracking over the internal target volume concept for stereotactic body radiation therapy of pancreatic cancer.

PubMed

Karava, Konstantina; Ehrbar, Stefanie; Riesterer, Oliver; Roesch, Johannes; Glatz, Stefan; Klöck, Stephan; Guckenberger, Matthias; Tanadini-Lang, Stephanie

2017-11-09

Radiotherapy for pancreatic cancer has two major challenges: (I) the tumor is adjacent to several critical organs and, (II) the mobility of both, the tumor and its surrounding organs at risk (OARs). A treatment planning study simulating stereotactic body radiation therapy (SBRT) for pancreatic tumors with both the internal target volume (ITV) concept and the tumor tracking approach was performed. The two respiratory motion-management techniques were compared in terms of doses to the target volume and organs at risk. Two volumetric-modulated arc therapy (VMAT) treatment plans (5 × 5 Gy) were created for each of the 12 previously treated pancreatic cancer patients, one using the ITV concept and one the tumor tracking approach. To better evaluate the overall dose delivered to the moving tumor volume, 4D dose calculations were performed on four-dimensional computed tomography (4DCT) scans. The resulting planning target volume (PTV) size for each technique was analyzed. Target and OAR dose parameters were reported and analyzed for both 3D and 4D dose calculation. Tumor motion ranged from 1.3 to 11.2 mm. Tracking led to a reduction of PTV size (max. 39.2%) accompanied with significant better tumor coverage (p<0.05, paired Wilcoxon signed rank test) both in 3D and 4D dose calculations and improved organ at risk sparing. Especially for duodenum, stomach and liver, the mean dose was significantly reduced (p<0.05) with tracking for 3D and 4D dose calculations. By using an adaptive tumor tracking approach for respiratory-induced pancreatic motion management, a significant reduction in PTV size can be achieved, which subsequently facilitates treatment planning, and improves organ dose sparing. The dosimetric benefit of tumor tracking is organ and patient-specific.

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.

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

PubMed

Zanchetti, Alberto; Liu, Lisheng; Mancia, Giuseppe; Parati, Gianfranco; Grassi, Guido; Stramba-Badiale, Marco; Silani, Vincenzo; Bilo, Grzegorz; Corrao, Giovanni; Zambon, Antonella; Scotti, Lorenza; Zhang, Xinhua; Wang, HayYan; Zhang, Yuqing; Zhang, Xuezhong; Guan, Ting Rui; Berge, Eivind; Redon, Josep; Narkiewicz, Krzysztof; Dominiczak, Anna; Nilsson, Peter; Viigimaa, Margus; Laurent, Stéphane; Agabiti-Rosei, Enrico; Wu, Zhaosu; Zhu, Dingliang; Rodicio, José Luis; Ruilope, Luis Miguel; Martell-Claros, Nieves; Pinto, Fernando; Schmieder, Roland E; Burnier, Michel; Banach, Maciej; Cifkova, Renata; Farsang, Csaba; Konradi, Alexandra; Lazareva, Irina; Sirenko, Yuriy; Dorobantu, Maria; Postadzhiyan, Arman; Accetto, Rok; Jelakovic, Bojan; Lovic, Dragan; Manolis, Athanasios J; Stylianou, Philippos; Erdine, Serap; Dicker, Dror; Wei, Gangzhi; Xu, Chengbin; Xie, Hengge; Coca, Antonio; O'Brien, John; Ford, Gary

2014-09-01

The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125  mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8  mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.

ACE2 Therapy Using Adeno-associated Viral Vector Inhibits Liver Fibrosis in Mice

PubMed Central

Mak, Kai Y; Chin, Ruth; Cunningham, Sharon C; Habib, Miriam R; Torresi, Joseph; Sharland, Alexandra F; Alexander, Ian E; Angus, Peter W; Herath, Chandana B

2015-01-01

Angiotensin converting enzyme 2 (ACE2) which breaks down profibrotic peptide angiotensin II to antifibrotic peptide angiotensin-(1–7) is a potential therapeutic target in liver fibrosis. We therefore investigated the long-term therapeutic effect of recombinant ACE2 using a liver-specific adeno-associated viral genome 2 serotype 8 vector (rAAV2/8-ACE2) with a liver-specific promoter in three murine models of chronic liver disease, including carbon tetrachloride-induced toxic injury, bile duct ligation-induced cholestatic injury, and methionine- and choline-deficient diet-induced steatotic injury. A single injection of rAAV2/8-ACE2 was administered after liver disease has established. Hepatic fibrosis, gene and protein expression, and the mechanisms that rAAV2/8-ACE2 therapy associated reduction in liver fibrosis were analyzed. Compared with control group, rAAV2/8-ACE2 therapy produced rapid and sustained upregulation of hepatic ACE2, resulting in a profound reduction in fibrosis and profibrotic markers in all diseased models. These changes were accompanied by reduction in hepatic angiotensin II levels with concomitant increases in hepatic angiotensin-(1–7) levels, resulting in significant reductions of NADPH oxidase assembly, oxidative stress and ERK1/2 and p38 phosphorylation. Moreover, rAAV2/8-ACE2 therapy normalized increased intrahepatic vascular tone in fibrotic livers. We conclude that rAAV2/8-ACE2 is an effective liver-targeted, long-term therapy for liver fibrosis and its complications without producing unwanted systemic effects. PMID:25997428

Biochemical Characterization and Vaccine Potential of a Heme-Binding Glutathione Transferase from the Adult Hookworm Ancylostoma caninum

PubMed Central

Zhan, Bin; Liu, Sen; Perally, Samirah; Xue, Jian; Fujiwara, Ricardo; Brophy, Peter; Xiao, Shuhua; Liu, Yueyuan; Feng, Jianjun; Williamson, Angela; Wang, Yan; Bueno, Lilian L.; Mendez, Susana; Goud, Gaddam; Bethony, Jeffrey M.; Hawdon, John M.; Loukas, Alex; Jones, Karen; Hotez, Peter J.

2005-01-01

We report the cloning and expression of Ac-GST-1, a novel glutathione S-transferase from the adult hookworm Ancylostoma caninum, and its possible role in parasite blood feeding and as a vaccine target. The predicted Ac-GST-1 open reading frame contains 207 amino acids (mass, 24 kDa) and exhibited up to 65% amino acid identity with other nematode GSTs. mRNA encoding Ac-GST-1 was detected in adults, eggs, and larval stages, but the protein was detected only in adult hookworm somatic extracts and excretory/secretory products. Using antiserum to the recombinant protein, Ac-GST-1 was immunolocalized to the parasite hypodermis and muscle tissue and weakly to the intestine. Recombinant Ac-GST-1 was enzymatically active, as determined by conjugation of glutathione to a model substrate, and exhibited a novel high-affinity binding site for hematin. The possible role of Ac-GST-1 in parasite heme detoxification during hemoglobin digestion or heme uptake prompted interest in evaluating it as a potential vaccine antigen. Vaccination of dogs with Ac-GST-1 resulted in a 39.4% reduction in the mean worm burden and 32.3% reduction in egg counts compared to control dogs following larval challenge, although the reductions were not statistically significant. However, hamsters vaccinated with Ac-GST-1 exhibited statistically significant worm reduction (53.7%) following challenge with heterologous Necator americanus larvae. These studies suggest that Ac-GST-1 is a possible drug and vaccine target for hookworm infection. PMID:16177370

Residual Viral and Bacterial Contamination of Surfaces after Cleaning and Disinfection

PubMed Central

Tuladhar, Era; Hazeleger, Wilma C.; Koopmans, Marion; Zwietering, Marcel H.; Beumer, Rijkelt R.

2012-01-01

Environmental surfaces contaminated with pathogens can be sources of indirect transmission, and cleaning and disinfection are common interventions focused on reducing contamination levels. We determined the efficacy of cleaning and disinfection procedures for reducing contamination by noroviruses, rotavirus, poliovirus, parechovirus, adenovirus, influenza virus, Staphylococcus aureus, and Salmonella enterica from artificially contaminated stainless steel surfaces. After a single wipe with water, liquid soap, or 250-ppm free chlorine solution, the numbers of infective viruses and bacteria were reduced by 1 log10 for poliovirus and close to 4 log10 for influenza virus. There was no significant difference in residual contamination levels after wiping with water, liquid soap, or 250-ppm chlorine solution. When a single wipe with liquid soap was followed by a second wipe using 250- or 1,000-ppm chlorine, an extra 1- to 3-log10 reduction was achieved, and except for rotavirus and norovirus genogroup I, no significant additional effect of 1,000 ppm compared to 250 ppm was found. A reduced correlation between reduction in PCR units (PCRU) and reduction in infectious particles suggests that at least part of the reduction achieved in the second step is due to inactivation instead of removal alone. We used data on infectious doses and transfer efficiencies to estimate a target level to which the residual contamination should be reduced and found that a single wipe with liquid soap followed by a wipe with 250-ppm free chlorine solution was sufficient to reduce the residual contamination to below the target level for most of the pathogens tested. PMID:22941071

Residual viral and bacterial contamination of surfaces after cleaning and disinfection.

PubMed

Tuladhar, Era; Hazeleger, Wilma C; Koopmans, Marion; Zwietering, Marcel H; Beumer, Rijkelt R; Duizer, Erwin

2012-11-01

Environmental surfaces contaminated with pathogens can be sources of indirect transmission, and cleaning and disinfection are common interventions focused on reducing contamination levels. We determined the efficacy of cleaning and disinfection procedures for reducing contamination by noroviruses, rotavirus, poliovirus, parechovirus, adenovirus, influenza virus, Staphylococcus aureus, and Salmonella enterica from artificially contaminated stainless steel surfaces. After a single wipe with water, liquid soap, or 250-ppm free chlorine solution, the numbers of infective viruses and bacteria were reduced by 1 log(10) for poliovirus and close to 4 log(10) for influenza virus. There was no significant difference in residual contamination levels after wiping with water, liquid soap, or 250-ppm chlorine solution. When a single wipe with liquid soap was followed by a second wipe using 250- or 1,000-ppm chlorine, an extra 1- to 3-log(10) reduction was achieved, and except for rotavirus and norovirus genogroup I, no significant additional effect of 1,000 ppm compared to 250 ppm was found. A reduced correlation between reduction in PCR units (PCRU) and reduction in infectious particles suggests that at least part of the reduction achieved in the second step is due to inactivation instead of removal alone. We used data on infectious doses and transfer efficiencies to estimate a target level to which the residual contamination should be reduced and found that a single wipe with liquid soap followed by a wipe with 250-ppm free chlorine solution was sufficient to reduce the residual contamination to below the target level for most of the pathogens tested.

A modeling comparison of deep greenhouse gas emissions reduction scenarios by 2030 in California

DOE PAGES

Yeh, Sonia; Yang, Christopher; Gibbs, Michael; ...

2016-10-21

California aims to reduce greenhouse gas (GHG) emissions to 40% below 1990 levels by 2030. We compare six energy models that have played various roles in informing the state policymakers in setting climate policy goals and targets. These models adopt a range of modeling structures, including stock-turnover back-casting models, a least-cost optimization model, macroeconomic/macro-econometric models, and an electricity dispatch model. Results from these models provide useful insights in terms of the transformations in the energy system required, including efficiency improvements in cars, trucks, and buildings, electrification of end-uses, low- or zero-carbon electricity and fuels, aggressive adoptions of zero-emission vehicles (ZEVs),more » demand reduction, and large reductions of non-energy GHG emissions. Some of these studies also suggest that the direct economic costs can be fairly modest or even generate net savings, while the indirect macroeconomic benefits are large, as shifts in employment and capital investments could have higher economic returns than conventional energy expenditures. These models, however, often assume perfect markets, perfect competition, and zero transaction costs. They also do not provide specific policy guidance on how these transformative changes can be achieved. Greater emphasis on modeling uncertainty, consumer behaviors, heterogeneity of impacts, and spatial modeling would further enhance policymakers' ability to design more effective and targeted policies. Here, this paper presents an example of how policymakers, energy system modelers and stakeholders interact and work together to develop and evaluate long-term state climate policy targets. Lastly, even though this paper focuses on California, the process of dialogue and interactions, modeling results, and lessons learned can be generally adopted across different regions and scales.« less

A simulation model for designing effective interventions in early childhood caries.

PubMed

Hirsch, Gary B; Edelstein, Burton L; Frosh, Marcy; Anselmo, Theresa

2012-01-01

Early childhood caries (ECC)--tooth decay among children younger than 6 years--is prevalent and consequential, affecting nearly half of US 5-year-olds, despite being highly preventable. Various interventions have been explored to limit caries activity leading to cavities, but little is known about the long-term effects and costs of these interventions. We developed a system dynamics model to determine which interventions, singly and in combination, could have the greatest effect in reducing caries experience and cost in a population of children aged birth to 5 years. System dynamics is a computer simulation technique useful to policy makers in choosing the most appropriate interventions for their populations. This study of Colorado preschool children models 6 categories of ECC intervention--applying fluorides, limiting cariogenic bacterial transmission from mothers to children, using xylitol directly with children, clinical treatment, motivational interviewing, and combinations of these--to compare their relative effect and cost. The model projects 10-year intervention costs ranging from $6 million to $245 million and relative reductions in cavity prevalence ranging from none to 79.1% from the baseline. Interventions targeting the youngest children take 2 to 4 years longer to affect the entire population of preschool-age children but ultimately exert a greater benefit in reducing ECC; interventions targeting the highest-risk children provide the greatest return on investment, and combined interventions that target ECC at several stages of its natural history have the greatest potential for cavity reduction. Some interventions save more in dental repair than their cost; all produce substantial reductions in repair cost. By using data relevant to any geographic area, this system model can provide policy makers with information to maximize the return on public health and clinical care investments.

Strategy to reduce E. coli bacteraemia based on cohort data from a London teaching hospital.

PubMed

Hsu, Desmond; Melzer, Mark

2018-04-01

In 2017, National Health Service Improvement set a 10% reduction target for Escherichia coli bacteraemia by 2018, followed by a 50% reduction in healthcare-associated Gram-negative bacteraemias by 2022. We analysed consecutive cases of E. coli bacteraemia and devised a strategy to achieve these targets. From December 2012 to November 2013, demographic, clinical and microbiological data were prospectively collected on all patients with bacteraemia at the Royal London Hospital in East London, UK. There were 594 significant bacteraemic episodes and 207 (34.8%) were E. coli . Twenty-four (11.6%) of the E. coli isolates were extended spectrum beta-lactamase producers, 22 (10.6%) gentamicin resistant and 2 (1.0%) amikacin resistant. The three most common sites of infection were pyelonephritis 105 (56.7%), catheter-associated urinary tract infection 22 (10.6%), and other medical devices and procedures that cause bacteraemia 32 (15.5%). In the pyelonephritis group, trimethoprim resistance in urinary isolates was 16/47 (34.0%) compared with 3/47 (6.4%) for nitrofurantoin. Twelve months postbacteraemia, recurrent bacteraemia rates were 10/105 (9.5%). There were 44 medical device-associated E. coli bacteraemias, and 22 (50%) were urinary catheter associated. There were 10 patients with E. coli bacteraemia caused by procedures, seven genitourinary or biliary tract instrumentation and three postgastrointestinal surgery. E. coli bacteraemias related to urosepsis could have been prevented by better empirical treatment and targeted prophylaxis. Urinary catheter quality improvement programmes should contribute to a further reduction. For patients undergoing high-risk urinary or biliary tract procedures or device manipulation, we advocate single-dose amikacin prophylaxis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Non-Hardware ("Soft") Cost-Reduction Roadmap for Residential and Small Commercial Solar Photovoltaics, 2013-2020

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

Ardani, K.; Seif, D.; Margolis, R.

2013-08-01

The objective of this analysis is to roadmap the cost reductions and innovations necessary to achieve the U.S. Department of Energy (DOE) SunShot Initiative's total soft-cost targets by 2020. The roadmap focuses on advances in four soft-cost areas: (1) customer acquisition; (2) permitting, inspection, and interconnection (PII); (3) installation labor; and (4) financing. Financing cost reductions are in terms of the weighted average cost of capital (WACC) for financing PV system installations, with real-percent targets of 3.0% (residential) and 3.4% (commercial).

Targeting the impact of agri-environmental policy - Future scenarios in two less favoured areas in Portugal.

PubMed

Jones, Nadia; Fleskens, Luuk; Stroosnijder, Leo

2016-10-01

Targeting agri-environmental measures (AEM) improves their effectiveness in the delivery of public goods, provided the necessary coordination with other incentives. In less favoured areas (LFA) measures focusing on the conservation of extensive farming contribute to sustainable land management in these areas. In this paper we investigate the implementation of a possible AEM supporting the improvement of permanent pastures coordinated with the extensive livestock and single farm payments actually in place. Through applying a spatially-explicit mixed integer optimisation model we simulate future land use scenarios for two less favoured areas in Portugal (Centro and Alentejo) considering two policy scenarios: a 'targeted AEM', and a 'non-targeted AEM'. We then compare the results with a 'basic policy' option (reflecting a situation without AEM). This is done with regard to landscape-scale effects on the reduction of fire hazard and erosion risk, as well as effects on farm income. The results show that an AEM for permanent pastures would be more cost-effective for erosion and fire hazard mitigation if implemented within a spatially targeted framework. However when cost-effectiveness is assessed with other indicators (e.g. net farm income and share of grazing livestock) 'non-targeted AEM' implementation delivers the best outcome in Alentejo. In Centro the implementation of an AEM involves important losses of income compared to the 'basic policy'. 'Targeted AEM' tends to favour farms in very marginal conditions, i.e. targeting is demonstrated to perform best in landscapes where spatial heterogeneity is higher. The results also show the risk of farm abandonment in the two studied less favoured areas: in all three scenarios more than 30% of arable land is deemed to be abandoned. Copyright © 2016 Elsevier Ltd. All rights reserved.

What Can China Do? China's Best Alternative Outcome for Energy Efficiency and CO2 Emissions

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

G. Fridley, David; Zheng, Nina; T. Aden, Nathaniel

After rapid growth in economic development and energy demand over the last three decades, China has undertaken energy efficiency improvement efforts to reduce its energy intensity under the 11th Five Year Plan (FYP). Since becoming the world's largest annual CO{sub 2} emitter in 2007, China has set reduction targets for energy and carbon intensities and committed to meeting 15% of its total 2020 energy demand with non-fossil fuel. Despite having achieved important savings in 11th FYP efficiency programs, rising per capita income and the continued economic importance of trade will drive demand for transport activity and fuel use. At themore » same time, an increasingly 'electrified' economy will drive rapid power demand growth. Greater analysis is therefore needed to understand the underlying drivers, possible trajectories and mitigation potential in the growing industrial, transport and power sectors. This study uses scenario analysis to understand the likely trajectory of China's energy and carbon emissions to 2030 in light of the current and planned portfolio of programs, policies and technology development and ongoing urbanization and demographic trends. It evaluates the potential impacts of alternative transportation and power sector development using two key scenarios, Continued Improvement Scenario (CIS) and Accelerated Improvement Scenario (AIS). CIS represents the most likely path of growth based on continuation of current policies and meeting announced targets and goals, including meeting planned appliance efficiency standard revisions, fuel economy standards, and industrial targets and moderate phase-out of subcritical coal-fired generation with additional non-fossil generation. AIS represents a more aggressive trajectory of accelerated improvement in energy intensity and decarbonized power and transport sectors. A range of sensitivity analysis and power technology scenarios are tested to evaluate the impact of additional actions such as carbon capture and sequestration (CCS) and integrated mine-mouth generation. The CIS and AIS results are also contextualized and compared to model scenarios in other published studies. The results of this study show that China's energy and CO{sub 2} emissions will not likely peak before 2030, although growth is expected to slow after 2020. Moreover, China will be able to meet its 2020 carbon intensity reduction target of 40 to 45% under both CIS and AIS, but only meet its 15% non-fossil fuel target by 2020 under AIS. Under both scenarios, efficiency remains a key resource and has the same, if not greater, mitigation potential as new technologies in transport and power sectors. In the transport sector, electrification will be closely linked the degree of decarbonization in the power sector and EV deployment has little or no impact on China's crude oil import demand. Rather, power generation improvements have the largest sector potential for overall emission mitigation while mine-mouth power generation and CCS have limited mitigation potential compared to fuel switching and efficiency improvements. Comparisons of this study's results with other published studies reveal that CIS and AIS are within the range of other national energy projections but alternative studies rely much more heavily on CCS for carbon reduction. The McKinsey study, in particular, has more optimistic assumptions for reductions in crude oil imports and coal demand in its abatement scenario and has much higher gasoline reduction potential for the same level of EV deployment. Despite these differences, this study's scenario analysis of both transport and power sectors illustrate the necessity for continued efficiency improvements and aggressive power sector decarbonization in flattening China's CO{sub 2} emissions.« less

Cancer targeting potential of folate targeted nanocarrier under comparative influence of tretinoin and dexamethasone.

PubMed

Dhakad, Raghvendra Singh; Tekade, Rakesh Kumar; Jain, Narendra Kumar

2013-08-01

The objective of this investigation was aimed to explore the cancer targeting potential of folate conjugated dendrimer (polypropylene imine, PPI) under strategic influence of folate receptor up-regulators (all trans Retinoic acid, ATRA and Dexamethasone, DEXA). The folate conjugated dendrimer nanoconjugate (FPPI) was synthesized and characterized by FTIR, and (1)H-NMR spectroscopy. The cell line studies investigations were performed on MCF-7 cells. ATRA and DEXA caused 2.17 and 1.65 folds selective up-regulation of folate receptor respectively, when compared with untreated control, after 48 h of pretreatment. ATRA caused 50.47±2.11% more up regulation of folate receptor, than DEXA treated cell. Both up regulators showed a lag phase of 12 h in up-regulating the folate receptors. After 48 h, the IC50 values of naked docetaxel (DTX) and DTX loaded dendrimer (PPI-DTX) were found to be 678.93±11.99 nM and 663.51±15.23 nM, respectively, while DTX loaded folate-anchored dendrimer (FPPI-DTX) showed a selectively lowered IC50 value of 468.56±20.86 nM. FPPI-DTX further showed a significant reduction in IC50 value in ATRA and DEXA pretreated cells, wherein IC50 values of 184.21 nM and 290.40±14.05 nM, respectively were observed. The study also concludes ATRA to be a superior receptor up-regulator as well as promoter of folate based targeting compared to DEXA.

Uptake and impact of vaccinating school age children against influenza during a season with circulation of drifted influenza A and B strains, England, 2014/15.

PubMed

Pebody, Richard G; Green, Helen K; Andrews, Nick; Boddington, Nicola L; Zhao, Hongxin; Yonova, Ivelina; Ellis, Joanna; Steinberger, Sophia; Donati, Matthew; Elliot, Alex J; Hughes, Helen E; Pathirannehelage, Sameera; Mullett, David; Smith, Gillian E; de Lusignan, Simon; Zambon, Maria

2015-01-01

The 2014/15 influenza season was the second season of roll-out of a live attenuated influenza vaccine (LAIV) programme for healthy children in England. During this season, besides offering LAIV to all two to four year olds, several areas piloted vaccination of primary (4-11 years) and secondary (11-13 years) age children. Influenza A(H3N2) circulated, with strains genetically and antigenically distinct from the 2014/15 A(H3N2) vaccine strain, followed by a drifted B strain. We assessed the overall and indirect impact of vaccinating school age children, comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot to non-pilot areas. Uptake levels were 56.8% and 49.8% in primary and secondary school pilot areas respectively. In primary school age pilot areas, cumulative primary care influenza-like consultation, emergency department respiratory attendance, respiratory swab positivity, hospitalisation and excess respiratory mortality were consistently lower in targeted and non-targeted age groups, though less for adults and more severe end-points, compared with non-pilot areas. There was no significant reduction for excess all-cause mortality. Little impact was seen in secondary school age pilot only areas compared with non-pilot areas. Vaccination of healthy primary school age children resulted in population-level impact despite circulation of drifted A and B influenza strains.

A novel albumin nanocomplex containing both small interfering RNA and gold nanorods for synergetic anticancer therapy

NASA Astrophysics Data System (ADS)

Choi, Jin-Ha; Hwang, Hai-Jin; Shin, Seung Won; Choi, Jeong-Woo; Um, Soong Ho; Oh, Byung-Keun

2015-05-01

Therapeutic nanocomplexes have been extensively developed for the effective treatment of aggressive cancers because of their outstanding versatility, easy manipulation, and low cytotoxicity. In this study, we describe the synthesis of a novel bovine serum albumin (BSA)-based nanocomplex harboring both Bcl-2-specific small interfering RNA (siRNA) and gold (Au) nanorods (siRNA and rods encapsulated in BSA; SREB) with the aim of developing a targeted breast cancer therapeutic. The SREB complexes contained 2 × 105 siRNA molecules and eight Au nanorods per BSA complex and were successively functionalized with polyethylene glycol (PEG) and anti-ErbB-2 antibodies to facilitate active targeting. The synergetic therapeutic activity originating from the two components effectively induced cell death (~80% reduction in viability compared with control cells) in target breast cancer cells after a single dose of laser irradiation. Intracellular SREB nanocomplex decomposition by proteolytic enzymes resulted in simultaneous RNA interference and thermal ablation, thus leading to apoptosis in the targeted cancer cells. Moreover, these therapeutic effects were sustained for approximately 72 hours. The intrinsic biocompatibility, multifunctionality, and potent in vitro anticancer properties of these SREB nanocomplexes indicate that they have great therapeutic potential for in vivo targeted cancer therapy, in addition to other areas of nanomedicine.Therapeutic nanocomplexes have been extensively developed for the effective treatment of aggressive cancers because of their outstanding versatility, easy manipulation, and low cytotoxicity. In this study, we describe the synthesis of a novel bovine serum albumin (BSA)-based nanocomplex harboring both Bcl-2-specific small interfering RNA (siRNA) and gold (Au) nanorods (siRNA and rods encapsulated in BSA; SREB) with the aim of developing a targeted breast cancer therapeutic. The SREB complexes contained 2 × 105 siRNA molecules and eight Au nanorods per BSA complex and were successively functionalized with polyethylene glycol (PEG) and anti-ErbB-2 antibodies to facilitate active targeting. The synergetic therapeutic activity originating from the two components effectively induced cell death (~80% reduction in viability compared with control cells) in target breast cancer cells after a single dose of laser irradiation. Intracellular SREB nanocomplex decomposition by proteolytic enzymes resulted in simultaneous RNA interference and thermal ablation, thus leading to apoptosis in the targeted cancer cells. Moreover, these therapeutic effects were sustained for approximately 72 hours. The intrinsic biocompatibility, multifunctionality, and potent in vitro anticancer properties of these SREB nanocomplexes indicate that they have great therapeutic potential for in vivo targeted cancer therapy, in addition to other areas of nanomedicine. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00211g

Assessment of air quality and climate co-benefits of decarbonisation of the UK energy system using remote sensing and model simulations - the case for prioritizing end uses in urban areas

NASA Astrophysics Data System (ADS)

Sobral Mourao, Zenaida; Konadu, Daniel Dennis; Damoah, Richard; Li, Pei-hao

2017-04-01

The UK has a binding obligation to reduce GHG emission by 80% (based on 1990 levels) by 2050. Meeting this target requires extensive decarbonisation of the UK energy system. Different pathways that achieve this target at the lowest system costs are being explored at different levels of policy and decisions on future energy infrastructure. Whilst benefits of decarbonisation are mainly focused on the impacts on climate change, there are other potential environmental and health impacts such as air-quality. In particular, a decrease in fossil fuel use by directly substituting current systems with low-carbon technologies could lead to significant reductions in the concentrations of SO2, NOX, CO and other atmospheric pollutants. So far, the proposed decarbonisation pathways tend to target the electricity sector first, followed by a transition in transport and heating technologies and use. However, the spatial dimension of where short term changes in the energy sector occur in relation to high density population areas is not taken into account when defining the energy transition strategies. This may lead to limited short-term improvements in air quality within urban areas, where use of fossil fuels for heating and transport is the main contribution to overall atmospheric pollutant levels. It is therefore imperative to explore decarbonisation strategies that prioritise transition in sectors of the energy system that produce immediate improvements in air quality in key regions of the UK. This study aims to use a combination of Remote Sensing observations and atmospheric chemistry/transport modelling approaches to estimate and map the impact on NOx of the traditional approach of decarbonising electricity first compared to a slower transition in the electricity sector, but faster change in the transport sector. This is done by generating a set of alternative energy system pathways with a higher share of zero emissions vehicles in 2030 than the energy system optimization model would choose if the only goal was the 80% GHG emissions reduction. Our overarching goal is to provide an additional standard to compare future energy system pathways beyond the traditional metrics of cost and GHG emissions reductions.

Pregnancy at early age is associated with a reduction of progesterone-responsive cells and epithelial Wnt signaling in human breast tissue.

PubMed

Muenst, Simone; Mechera, Robert; Däster, Silvio; Piscuoglio, Salvatore; Ng, Charlotte K Y; Meier-Abt, Fabienne; Weber, Walter P; Soysal, Savas D

2017-04-04

Pregnancy at early age is the most significant modifiable factor which consistently decreases lifetime breast cancer risk. However, the underlying mechanisms haven't been conclusively identified. Studies in mice suggest a reduction in progesterone-receptor (PR) sensitive epithelial cells as well as a downregulation of the Wnt signaling pathway as being one of the main mechanisms for the protective effect of early pregnancy. The aim of our study was to validate these findings in humans. We collected benign breast tissue of 125 women who had been stratified according to age at first pregnancy and the occurrence of subsequent breast cancer, and performed immunohistochemistry for PR, Wnt4 and the Wnt-target Versican. The number of PR positive epithelial cells was significantly lower in the group of women with early pregnancy and no subsequent breast cancer compared to the group of nulliparous women with subsequent invasive breast cancer (p = 0.0135). In women with early pregnancy, expression of Versican and Wnt4 was significantly lower compared to nulliparous women (p = 0.0036 and p = 0.0241 respectively), and Versican expression was also significant lower compared to women with late pregnancy (p < 0.0001). Our results confirm prior observations in mice and suggest a role of downregulation of epithelial Wnt signaling in the protective effect of early pregnancy in humans. This results in a decreased proliferation of stem/progenitor cells; therefore, the Wnt signaling pathway may represent a potential target for breast cancer prevention in humans.

40 CFR Table 4 of Subpart Bbbbbbb... - Continuous Compliance Demonstration Methods With the Emission Reduction and PM Concentration...

Code of Federal Regulations, 2012 CFR

2012-07-01

... compliance by * * * 1. Requirement to route all process vent streams from equipment in target HAP service to a PM control device with a PM percent reduction efficiency of 95 percent (98 percent for new sources... chemical preparations operation was in target HAP service. The control device monitoring data are averaged...

40 CFR Table 4 of Subpart Bbbbbbb... - Continuous Compliance Demonstration Methods With the Emission Reduction and PM Concentration...

Code of Federal Regulations, 2013 CFR

2013-07-01

... compliance by * * * 1. Requirement to route all process vent streams from equipment in target HAP service to a PM control device with a PM percent reduction efficiency of 95 percent (98 percent for new sources... chemical preparations operation was in target HAP service. The control device monitoring data are averaged...

40 CFR Table 4 of Subpart Bbbbbbb... - Continuous Compliance Demonstration Methods With the Emission Reduction and PM Concentration...

Code of Federal Regulations, 2014 CFR

2014-07-01

... compliance by * * * 1. Requirement to route all process vent streams from equipment in target HAP service to a PM control device with a PM percent reduction efficiency of 95 percent (98 percent for new sources... chemical preparations operation was in target HAP service. The control device monitoring data are averaged...

40 CFR Table 4 of Subpart Bbbbbbb... - Continuous Compliance Demonstration Methods With the Emission Reduction and PM Concentration...

Code of Federal Regulations, 2011 CFR

2011-07-01

... compliance by * * * 1. Requirement to route all process vent streams from equipment in target HAP service to a PM control device with a PM percent reduction efficiency of 95 percent (98 percent for new sources... chemical preparations operation was in target HAP service. The control device monitoring data are averaged...

Melanoma-targeted delivery system (part 1): design, synthesis and evaluation of releasable disulfide drug by glutathione.

PubMed

El Aissi, Radhia; Chezal, Jean-Michel; Tarrit, Sébastien; Chavignon, Olivier; Moreau, Emmanuel

2015-08-28

Here we describe the design and synthesis of a prodrug developed for pigmented melanoma therapy, consisting of a Melanin-Targeting Probe (MTP) conjugated to 5-iodo-2'-deoxyuridine (IUdR) with a reduction-sensitive pre-determined breaking point. Compared with the non-cleavable conjugate (17b), prodrug (17a) bearing a self-immolative disulfide linker achieved complete release of IUdR within 20 min in the presence of reducing agents such as DTT or glutathione. Analytical results also showed that prodrug (17a) was more sensitive than parent non-cleavable conjugate (17b) for a concentration range of glutathione similar to that found in the intracellular compartment of tumours. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Analysis of esophageal-sparing treatment plans for patients with high-grade esophagitis.

PubMed

Niedzielski, Joshua; Bluett, Jaques B; Williamson, Ryan T; Liao, Zhongxing; Gomez, Daniel R; Court, Laurence E

2013-07-08

We retrospectively generated IMRT plans for 14 NSCLC patients who had experienced grade 2 or 3 esophagitis (CTCAE version 3.0). We generated 11-beam and reduced esophagus dose plan types to compare changes in the volume and length of esophagus receiving doses of 50, 55, 60, 65, and 70 Gy. Changes in planning target volume (PTV) dose coverage were also compared. If necessary, plans were renormalized to restore 95% PTV coverage. The critical organ doses examined were mean lung dose, mean heart dose, and volume of spinal cord receiving 50 Gy. The effect of interfractional motion was determined by applying a three-dimensional rigid shift to the dose grid. For the esophagus plan, the mean reduction in esophagus V50, V55, V60, V65, and V70 Gy was 2.8, 4.1, 5.9, 7.3, and 9.5 cm(3), respectively, compared with the clinical plan. The mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 2.0, 3.0, 3.8, 4.0, and 4.6 cm, respectively. The mean heart and lung dose decreased 3.0 Gy and 2.4 Gy, respectively. The mean decreases in 90% and 95% PTV coverage were 1.7 Gy and 2.8 Gy, respectively. The normalized plans' mean reduction of esophagus V50, V55, V60, V65, and V70 Gy were 1.6, 2.0, 2.9, 3.9, and 5.5 cm(3), respectively, compared with the clinical plans. The normalized plans' mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 4.9, 5.2, 5.4, 4.9, and 4.8 cm, respectively. The mean reduction in maximum esophagus dose with simulated interfractional motion was 3.0 Gy and 1.4 Gy for the clinical plan type and the esophagus plan type, respectively. In many cases, the esophagus dose can be greatly reduced while maintaining critical structure dose constraints. PTV coverage can be restored by increasing beam output, while still obtaining a dose reduction to the esophagus and maintaining dose constraints.

Analysis of esophageal‐sparing treatment plans for patients with high‐grade esophagitis

PubMed Central

Bluett, Jaques B.; Williamson, Ryan T.; Liao, Zhongxing; Gomez, Daniel R.; Court, Laurence E.

2013-01-01

We retrospectively generated IMRT plans for 14 NSCLC patients who had experienced grade 2 or 3 esophagitis (CTCAE version 3.0). We generated 11‐beam and reduced esophagus dose plan types to compare changes in the volume and length of esophagus receiving doses of 50, 55, 60, 65, and 70 Gy. Changes in planning target volume (PTV) dose coverage were also compared. If necessary, plans were renormalized to restore 95% PTV coverage. The critical organ doses examined were mean lung dose, mean heart dose, and volume of spinal cord receiving 50 Gy. The effect of interfractional motion was determined by applying a three‐dimensional rigid shift to the dose grid. For the esophagus plan, the mean reduction in esophagus V50, V55, V60, V65, and V70 Gy was 2.8, 4.1, 5.9, 7.3, and 9.5 cm3, respectively, compared with the clinical plan. The mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 2.0, 3.0, 3.8, 4.0, and 4.6 cm, respectively. The mean heart and lung dose decreased 3.0 Gy and 2.4 Gy, respectively. The mean decreases in 90% and 95% PTV coverage were 1.7 Gy and 2.8 Gy, respectively. The normalized plans’ mean reduction of esophagus V50, V55, V60, V65, and V70 Gy were 1.6, 2.0, 2.9, 3.9, and 5.5 cm3, respectively, compared with the clinical plans. The normalized plans’ mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 4.9, 5.2, 5.4, 4.9, and 4.8 cm, respectively. The mean reduction in maximum esophagus dose with simulated interfractional motion was 3.0 Gy and 1.4 Gy for the clinical plan type and the esophagus plan type, respectively. In many cases, the esophagus dose can be greatly reduced while maintaining critical structure dose constraints. PTV coverage can be restored by increasing beam output, while still obtaining a dose reduction to the esophagus and maintaining dose constraints. PACS number: 87.53 Tf PMID:23835390

Two-plasmon decay mitigation in direct-drive inertial-confinement-fusion experiments using multilayer targets

DOE PAGES

Follett, R. K.; Delettrez, J. A.; Edgell, D. H.; ...

2016-04-15

Multilayer direct-drive inertial-confinement-fusion (ICF) targets are shown to significantly reduce two-plasmon-decay (TPD) driven hot-electron production while maintaining high hydrodynamic efficiency. Implosion experiments on the OMEGA Laser used targets with silicon layered between an inner beryllium and outer silicon-doped plastic ablator. A factor of five reduction in hot-electron generation (> 50 keV) was observed in the multilayer targets relative to pure CH targets. Three-dimensional simulations of the TPD driven hot-electron production using a laser-plasma interaction code (LPSE) that includes nonlinear and kinetic effects show excellent agreement with the measurements. As a result, the simulations suggest that the reduction in hot-electron productionmore » observed in the multilayer targets is primarily due to increased electron-ion collisional damping.« less

Telephone based cognitive behavioral therapy targeting major depression among urban dwelling, low income people living with HIV/AIDS: results of a randomized controlled trial.

PubMed

Himelhoch, Seth; Medoff, Deborah; Maxfield, Jennifer; Dihmes, Sarah; Dixon, Lisa; Robinson, Charles; Potts, Wendy; Mohr, David C

2013-10-01

This pilot randomized controlled trial evaluated a previously developed manualized telephone based cognitive behavioral therapy (T-CBT) intervention compared to face-to-face (f2f) therapy among low-income, urban dwelling HIV infected depressed individuals. The primary outcome was the reduction of depressive symptoms as measured by the Hamliton rating scale for depression scale. The secondary outcome was adherence to HAART as measured by random telephone based pill counts. Outcome measures were collected by trained research assistants masked to treatment allocation. Analysis was based on intention-to-treat. Thirty-four participants met eligibility criteria and were randomly assigned to receive T-CBT (n = 16) or f2f (n = 18). There was no statistically significant difference in depression treatment outcomes comparing f2f to T-CBT. Within group evaluation demonstrated that both the T-CBT and the f2f psychotherapy groups resulted in significant reductions in depressive symptoms. Those who received the T-CBT were significantly more likely to maintain their adherence to antiretroviral medication compared to the f2f treatment. None of the participants discontinued treatment due to adverse events. T-CBT can be delivered to low-income, urban dwelling HIV infected depressed individuals resulting in significant reductions in depression symptoms and improved adherence to antiretroviral medication. Clinical Trial.gov identifier: NCT01055158.

Blue and Black Cloth Targets: Effects of Size, Shape, and Color on Stable Fly (Diptera: Muscidae) Attraction.

PubMed

Hogsette, Jerome A; Foil, Lane D

2018-04-02

Stable fly management is challenging because of the fly's dispersal behavior and its tendency to remain on the host only while feeding. Optically attractive traps have been used to survey and sometimes reduce adult populations. Insecticide-treated blue and black cloth targets developed for tsetse fly management in Africa were found to be attractive to stable flies in the United States, and various evaluations were conducted in Louisiana and Florida. Tests using untreated targets were designed to answer questions about configuration, size, and color relative to efficacy and stability in high winds. Studies with electric grid targets and with targets paired with Olson traps showed cloth target color attraction in the following decreasing order: black > blue-black > blue. A solid black target is easier to make than a blue-black target because no sewing is involved. Attraction was not affected when flat 1-m2 targets were formed into cylinders, despite the limited view of the blue and black colors together. There was no reduction in attraction when the 1-m2 cylindrical targets were compared with smaller (63 × 30 cm high) cylindrical targets. In addition, there was no difference in attraction between the small blue-black, blue, and black targets. Significance of findings and implications of potential uses for treated targets are discussed. Target attraction was indicated by the numbers of stable flies captured on an Olson sticky trap placed 30 cm from the target. Although this system is adequate for field research, it greatly underestimates the actual numbers of stable flies attracted to treated targets.

[Effects of bilateral deep brain stimulation in the subthalamic nucleus using two methods of target structure verification].

PubMed

Goubareva, N N; Fedorova, N V; Bril', E V; Tomskiy, A A; Gamaleya, A A; Poddubskaya, A A; Shabalov, V A; Omarova, S M

To evaluate the efficacy of deep brain stimulation in the subthalamic nucleus (DBS STN) in patients with Parkinson's disease (PD) using different methods of targeting according to the dynamics of motor symptoms of PD. The study involved 90 patients treated with DBS STN. In 30 cases intraoperative microelectrode recording (MER) was used. MER was not performed in 30 patients of the comparison group. The control group consisted of 30 patients with PD who received conservative treatment. Hoehn and Yahr scale, Tinetti Balance and Mobility Scale (TBMS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Quality of Life-39 Scoring System (РDQ-39), Schwab & England ADL Scale were used. Levodopa equivalent daily dose (LEDD, 2010) was calculated for each patient. The effect of DBS STN using intraoperative microelectrode recording on the main motor symptoms, motor complications, walking as well as indicators of quality of life and daily activities was shown. In both DBS STN groups, there was a significant reduction in the LEDD and marked improvement of the control of motor symptoms of PD. A significant reduction in the severity of motor fluctuations (50%) and drug-induced dyskinesia (51%) was observed. Quality of life and daily activity in off-medication condition were significantly improved in both DBS STN groups of patients, irrespective of the method of target planning (75-100%), compared with the control group.

Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model

PubMed Central

Schneider, Ronen; Hoogstraten, Charlotte A.; Schapiro, David; Majmundar, Amar J.; Kolb, Amy; Eddy, Kaitlyn; Shril, Shirlee; Braun, Daniela A.; Poduri, Annapurna

2018-01-01

Until recently, morpholino oligonucleotides have been widely employed in zebrafish as an acute and efficient loss-of-function assay. However, off-target effects and reproducibility issues when compared to stable knockout lines have compromised their further use. Here we employed an acute CRISPR/Cas approach using multiple single guide RNAs targeting simultaneously different positions in two exemplar genes (osgep or tprkb) to increase the likelihood of generating mutations on both alleles in the injected F0 generation and to achieve a similar effect as morpholinos but with the reproducibility of stable lines. This multi single guide RNA approach resulted in median likelihoods for at least one mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated the microcephaly phenotype and reduction in survival that we observed previously in stable knockout lines, though milder in the acute multi-sgRNA knockout. Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a mathematical model to quantitate the chance for a biallelic loss-of-function mutation. Our findings can be generalized to acute and stable CRISPR/Cas targeting for any zebrafish gene of interest. PMID:29346415

Optimization of Craniospinal Irradiation for Pediatric Medulloblastoma Using VMAT and IMRT.

PubMed

Al-Wassia, Rolina K; Ghassal, Noor M; Naga, Adly; Awad, Nesreen A; Bahadur, Yasir A; Constantinescu, Camelia

2015-10-01

Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) provide highly conformal target radiation doses, but also expose large volumes of healthy tissue to low-dose radiation. With improving survival, more children with medulloblastoma (MB) are at risk of late adverse effects of radiotherapy, including secondary cancers. We evaluated the characteristics of IMRT and VMAT craniospinal irradiation treatment plans in children with standard-risk MB to compare radiation dose delivery to target organs and organs at risk (OAR). Each of 10 children with standard-risk MB underwent both IMRT and VMAT treatment planning. Dose calculations used inverse planning optimization with a craniospinal dose of 23.4 Gy followed by a posterior fossa boost to 55.8 Gy. Clinical and planning target volumes were demarcated on axial computed tomography images. Dose distributions to target organs and OAR for each planning technique were measured and compared with published dose-volume toxicity data for pediatric patients. All patients completed treatment planning for both techniques. Analyses and comparisons of dose distributions and dose-volume histograms for the planned target volumes, and dose delivery to the OAR for each technique demonstrated the following: (1) VMAT had a modest, but significantly better, planning target volume-dose coverage and homogeneity compared with IMRT; (2) there were different OAR dose-sparing profiles for IMRT versus VMAT; and (3) neither IMRT nor VMAT demonstrated dose reductions to the published pediatric dose limits for the eyes, the lens, the cochlea, the pituitary, and the brain. The use of both IMRT and VMAT provides good target tissue coverage and sparing of the adjacent tissue for MB. Both techniques resulted in OAR dose delivery within published pediatric dose guidelines, except those mentioned above. Pediatric patients with standard-risk MB remain at risk for late endocrinologic, sensory (auditory and visual), and brain functional impairments.

SU-G-BRA-17: Tracking Multiple Targets with Independent Motion in Real-Time Using a Multi-Leaf Collimator

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

Ge, Y; Keall, P; Poulsen, P

Purpose: Multiple targets with large intrafraction independent motion are often involved in advanced prostate, lung, abdominal, and head and neck cancer radiotherapy. Current standard of care treats these with the originally planned fields, jeopardizing the treatment outcomes. A real-time multi-leaf collimator (MLC) tracking method has been developed to address this problem for the first time. This study evaluates the geometric uncertainty of the multi-target tracking method. Methods: Four treatment scenarios are simulated based on a prostate IMAT plan to treat a moving prostate target and static pelvic node target: 1) real-time multi-target MLC tracking; 2) real-time prostate-only MLC tracking; 3)more » correcting for prostate interfraction motion at setup only; and 4) no motion correction. The geometric uncertainty of the treatment is assessed by the sum of the erroneously underexposed target area and overexposed healthy tissue areas for each individual target. Two patient-measured prostate trajectories of average 2 and 5 mm motion magnitude are used for simulations. Results: Real-time multi-target tracking accumulates the least uncertainty overall. As expected, it covers the static nodes similarly well as no motion correction treatment and covers the moving prostate similarly well as the real-time prostate-only tracking. Multi-target tracking reduces >90% of uncertainty for the static nodal target compared to the real-time prostate-only tracking or interfraction motion correction. For prostate target, depending on the motion trajectory which affects the uncertainty due to leaf-fitting, multi-target tracking may or may not perform better than correcting for interfraction prostate motion by shifting patient at setup, but it reduces ∼50% of uncertainty compared to no motion correction. Conclusion: The developed real-time multi-target MLC tracking can adapt for the independently moving targets better than other available treatment adaptations. This will enable PTV margin reduction to minimize health tissue toxicity while remain tumor coverage when treating advanced disease with independently moving targets involved. The authors acknowledge funding support from the Australian NHMRC Australia Fellowship and NHMRC Project Grant No. APP1042375.« less

Comparing extraction rates of fossil fuel producers against global climate goals

NASA Astrophysics Data System (ADS)

Rekker, Saphira A. C.; O'Brien, Katherine R.; Humphrey, Jacquelyn E.; Pascale, Andrew C.

2018-06-01

Meeting global and national climate goals requires action and cooperation from a multitude of actors1,2. Current methods to define greenhouse gas emission targets for companies fail to acknowledge the unique influence of fossil fuel producers: combustion of reported fossil fuel reserves has the potential to push global warming above 2 °C by 2050, regardless of other efforts to mitigate climate change3. Here, we introduce a method to compare the extraction rates of individual fossil fuel producers against global climate targets, using two different approaches to quantify a burnable fossil fuel allowance (BFFA). BFFAs are calculated and compared with cumulative extraction since 2010 for the world's ten largest investor-owned companies and ten largest state-owned entities (SOEs), for oil and for gas, which together account for the majority of global oil and gas reserves and production. The results are strongly influenced by how BFFAs are quantified; allocating based on reserves favours SOEs over investor-owned companies, while allocating based on production would require most reduction to come from SOEs. Future research could refine the BFFA to account for equity, cost-effectiveness and emissions intensity.

Quasi-steady state reduction of molecular motor-based models of directed intermittent search.

PubMed

Newby, Jay M; Bressloff, Paul C

2010-10-01

We present a quasi-steady state reduction of a linear reaction-hyperbolic master equation describing the directed intermittent search for a hidden target by a motor-driven particle moving on a one-dimensional filament track. The particle is injected at one end of the track and randomly switches between stationary search phases and mobile nonsearch phases that are biased in the anterograde direction. There is a finite possibility that the particle fails to find the target due to an absorbing boundary at the other end of the track. Such a scenario is exemplified by the motor-driven transport of vesicular cargo to synaptic targets located on the axon or dendrites of a neuron. The reduced model is described by a scalar Fokker-Planck (FP) equation, which has an additional inhomogeneous decay term that takes into account absorption by the target. The FP equation is used to compute the probability of finding the hidden target (hitting probability) and the corresponding conditional mean first passage time (MFPT) in terms of the effective drift velocity V, diffusivity D, and target absorption rate λ of the random search. The quasi-steady state reduction determines V, D, and λ in terms of the various biophysical parameters of the underlying motor transport model. We first apply our analysis to a simple 3-state model and show that our quasi-steady state reduction yields results that are in excellent agreement with Monte Carlo simulations of the full system under physiologically reasonable conditions. We then consider a more complex multiple motor model of bidirectional transport, in which opposing motors compete in a "tug-of-war", and use this to explore how ATP concentration might regulate the delivery of cargo to synaptic targets.

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

Aznar, Alexandra; Day, Megan; Doris, Elizabeth

The report analyzes and presents information learned from a sample of 20 cities across the United States, from New York City to Park City, Utah, including a diverse sample of population size, utility type, region, annual greenhouse gas reduction targets, vehicle use, and median household income. The report compares climate, sustainability, and energy plans to better understand where cities are taking energy-related actions and how they are measuring impacts. Some common energy-related goals focus on reducing city-wide carbon emissions, improving energy efficiency across sectors, increasing renewable energy, and increasing biking and walking.

New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

DTIC Science & Technology

2013-05-01

resistance to enter status epilepticus in contrast to colonies established at Dr. Stanton’s laboratories based in animals originally provided by Dr...of SV2A proteins by Western Blotting at 10 days following status epilepticus (Fig. 8C). At 1 month after status epilepticus , SV2A protein levels were... status epilepticus . Reduction of SV2A transcripts in qPCR was not as dramatic when compared to changes in protein expression (Fig. 8D) but this may

Impact of an antimicrobial stewardship intervention on appropriateness of prescribing for community-acquired pneumonia in an Australian regional hospital.

PubMed

Bond, Stuart E; Boutlis, Craig S; Yeo, Wilfred W; Miyakis, Spiros

2017-05-01

Community-acquired pneumonia (CAP) is the second commonest indication for antibiotic use in Australian hospitals and is therefore a frequent target for antimicrobial stewardship. A single-centre prospective study was conducted in a regional referral hospital comparing management of adult patients with CAP before and after an educational intervention. We demonstrated a reduction in duration of therapy and reduced inappropriate use of ceftriaxone-based regimens for non-severe CAP. © 2017 Royal Australasian College of Physicians.

Variance Reduction Factor of Nuclear Data for Integral Neutronics Parameters

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

Chiba, G., E-mail: go_chiba@eng.hokudai.ac.jp; Tsuji, M.; Narabayashi, T.

We propose a new quantity, a variance reduction factor, to identify nuclear data for which further improvements are required to reduce uncertainties of target integral neutronics parameters. Important energy ranges can be also identified with this variance reduction factor. Variance reduction factors are calculated for several integral neutronics parameters. The usefulness of the variance reduction factors is demonstrated.

Restoration of chemosensitivity in cancer cells with MDR phenotype by deoxyribozyme, compared with ribozyme.

PubMed

Xing, Ai-Yan; Shi, Duan-bo; Liu, Wei; Chen, Xu; Sun, Yan-Lin; Wang, Xiao; Zhang, Jian-ping; Gao, Peng

2013-06-01

One of the main mechanisms for multidrug resistance (MDR) involves multidrug resistance gene 1 (MDR1) which encodes P-glycoprotein (Pgp). Pgp acts as a drug efflux pump and exports chemotherapeutic agents from cancer cells. Specific inhibition of Pgp expression by gene therapy is considered a well-respective strategy having less innate toxicities. At present, the investigation of DRz in reversal MDR is scarce. In the study, phosphorothioate DRz that targets to the translation initiation codon AUG was synthesized and transfected into breast cancer cells and leukemia cells with MDR phenotype. ASODN (antisense oligonucleotide) and ribozyme targets to the same region were also synthesized for comparison analysis. Alterations in MDR1 mRNA and Pgp were determined by RT-PCR, Northern blot, flow cytometry and Rh123 retention tests. Chemosensitivity of the treated cells was determined by MTT assay. The results showed that DRz could significantly suppress expression of MDR1 mRNA and inhibit synthesis of Pgp. The efflux activity of Pgp was inhibited accordingly. Chemosensitivity assay showed that a 21-fold reduction in drug resistance for Adriamycin and a 45-fold reduction in drug resistance for Vinblastine were found in the treated cells 36h after transfection. These data suggest that DRz targeted to the translation initiation codon AUG can reverse MDR phenotype in cancer cells and restore their chemosensitivity. Moreover, the reversal efficiency of DRz is better than that of ribozyme and ASODN targets to the same region of MDR1 mRNA. Copyright © 2013 Elsevier Inc. All rights reserved.

Reduction of angular divergence of laser-driven ion beams during their acceleration and transport

NASA Astrophysics Data System (ADS)

Zakova, M.; Pšikal, Jan; Margarone, Daniele; Maggiore, Mario; Korn, G.

2015-05-01

Laser plasma physics is a field of big interest because of its implications in basic science, fast ignition, medicine (i.e. hadrontherapy), astrophysics, material science, particle acceleration etc. 100-MeV class protons accelerated from the interaction of a short laser pulse with a thin target have been demonstrated. With continuing development of laser technology, greater and greater energies are expected, therefore projects focusing on various applications are being formed, e.g. ELIMAIA (ELI Multidisciplinary Applications of laser-Ion Acceleration). One of the main characteristic and crucial disadvantage of ion beams accelerated by ultra-short intense laser pulses is their large divergence, not suitable for the most of applications. In this paper two ways how to decrease beam divergence are proposed. Firstly, impact of different design of targets on beam divergence is studied by using 2D Particlein-cell simulations (PIC). Namely, various types of targets include at foils, curved foil and foils with diverse microstructures. Obtained results show that well-designed microstructures, i.e. a hole in the center of the target, can produce proton beam with the lowest divergence. Moreover, the particle beam accelerated from a curved foil has lower divergence compared to the beam from a flat foil. Secondly, another proposed method for the divergence reduction is using of a magnetic solenoid. The trajectories of the laser accelerated particles passing through the solenoid are modeled in a simple Matlab program. Results from PIC simulations are used as input in the program. The divergence is controlled by optimizing the magnetic field inside the solenoid and installing an aperture in front of the device.

Clinical benefit of drugs targeting mitochondrial function as an adjunct to reperfusion in ST-segment elevation myocardial infarction: A meta-analysis of randomized clinical trials.

PubMed

Campo, Gianluca; Pavasini, Rita; Morciano, Giampaolo; Lincoff, A Michael; Gibson, C Michael; Kitakaze, Masafumi; Lonborg, Jacob; Ahluwalia, Amrita; Ishii, Hideki; Frenneaux, Michael; Ovize, Michel; Galvani, Marcello; Atar, Dan; Ibanez, Borja; Cerisano, Giampaolo; Biscaglia, Simone; Neil, Brandon J; Asakura, Masanori; Engstrom, Thomas; Jones, Daniel A; Dawson, Dana; Ferrari, Roberto; Pinton, Paolo; Ottani, Filippo

2017-10-01

To perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing the effectiveness of drugs targeting mitochondrial function vs. placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical coronary reperfusion. Inclusion criteria: RCTs enrolling STEMI patients treated with primary percutaneous coronary intervention (PCI) and comparing drugs targeting mitochondrial function vs. placebo. Odds ratios (OR) were computed from individual studies and pooled with random-effect meta-analysis. Fifteen studies were identified involving 5680 patients. When compared with placebo, drugs targeting mitochondrial component/pathway were not associated with significant reduction of cardiovascular and all-cause mortality (OR 0.9, 95% CI 0.7-1.17 and OR 0.92, 95% CI 0.69-1.23, respectively). However, these agents significantly reduced hospital admission for heart failure (HF) (OR 0.64; 95% CI 0.45-0.92) and increased left ventricular ejection fraction (LVEF) (OR 1.44; 95% CI 1.15-1.82). After analysis for subgroups according to the mechanism of action, drugs with direct/selective action did not reduce any outcome. Conversely, those with indirect/unspecific action showed a significant effect on cardiovascular mortality (0.65, 95% CI 0.46-0.92), all-cause mortality (OR 0.69, 95% CI 0.52-0.92), hospital readmission for HF (OR 0.41, 95% CI 0.28-0.6) and LVEF (OR 1.49, 95% CI 1.09-2.05). Administration of drugs targeting mitochondrial function in STEMI patients undergoing primary PCI appear to have no effect on mortality, but may reduce hospital readmission for HF. The drugs with a broad-spectrum mechanism of action seem to be more effective in reducing adverse events. Copyright © 2017 Elsevier B.V. All rights reserved.

Strategic Accident Reduction in an Energy Company and Its Resulting Financial Benefits.

PubMed

Reiman, Arto; Räisänen, Tuomo; Väyrynen, Seppo; Autio, Tommi

2018-04-10

This study provides a case example of an energy company that prioritised occupational safety and health and accident reduction as long-term, strategic development targets. Furthermore, this study describes the monetary benefits of this strategic decision. Company-specific accident indicators and monetary costs and benefits are evaluated. During the observation period (2010-2016), strategic investments in occupational safety and health cost the company EUR 0.8 million. However, EUR 1.8 million were saved in the same period, resulting in a 2.20 cost-benefit ratio. The trend in cost savings is strongly positive. Annual accident costs were EUR 0.4 million lower in 2016 compared to costs in 2010. This study demonstrates that long-term, strategic commitment to occupational safety and health provides monetary value.

Control of Aedes albopictus with attractive toxic sugar baits (ATSB) and potential impact on non-target organisms in St. Augustine, Florida

PubMed Central

Revay, Edita E.; Müller, Gunter C.; Qualls, Whitney A.; Kline, Daniel; Naranjo, Diana P.; Arheart, Kristopher L.; Kravchenko, Vasiliy D.; Yfremova, Zoya; Hausmann, Axel; Beier, John C.; Schlein, Yosef; Xue, Rui-De

2013-01-01

The purpose of this study was to test the efficacy of bait stations and foliar applications containing attractive toxic sugar baits (ATSB) and eugenol to control Aedes albopictus. At the same time the potential impact of these control methods was evaluated on non-target organisms. The study was conducted at five tire sites in St. Augustine, Florida. Aedes albopictus populations were significantly reduced with ATSB-eugenol applications applied directly to non-flowering vegetation and as bait stations compared with non-attractive sugar baits and control. The application of ATSB made to non-flowering vegetation resulted in more significant reductions of mosquito populations compared to the application of ATSB presented in a bait station. Over 5.5% of the non-targets were stained in the flowering vegetation application site. However, when the attractive sugar bait application was made to non-flowering vegetation or presented in bait stations the impact on non-target insects was very low for all non-target orders as only 0.6% of the individual insects were stained with the dye from the sugar solutions, respectively. There were no significant differences between the staining of mosquitoes collected in flowering vegetation (206/1000) or non-flowering vegetation (242/1000) sites during the non-target evaluation. Our field studies support the use of eugenol as an active ingredient for controlling the dengue vector Ae. albopictus when used as an ATSB toxin and demonstrates potential use in sub-tropical and tropical environments for dengue control. PMID:24122115

A Multi-institutional Clinical Trial of Rectal Dose Reduction via Injected Polyethylene-Glycol Hydrogel During Intensity Modulated Radiation Therapy for Prostate Cancer: Analysis of Dosimetric Outcomes

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

Song, Danny Y., E-mail: dsong2@jhmi.edu; Herfarth, Klaus K.; Uhl, Matthias

2013-09-01

Purpose: To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction. Methods and Materials: Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥25%. Multiple regression analysis was performed tomore » evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry. Results: Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection (P=.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity (P=.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. Conclusions: Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results.« less

Silica-gold nanoparticles for atheroprotective management of plaques: results of the NANOM-FIM trial

NASA Astrophysics Data System (ADS)

Kharlamov, Alexander N.; Tyurnina, Anastasiya E.; Veselova, Vera S.; Kovtun, Olga P.; Shur, Vladimir Y.; Gabinsky, Jan L.

2015-04-01

Background: Atheroregression becomes an attractive target for cardiovascular treatment. Some clinical trials have demonstrated that intensive therapy with rosuvastatin or recombinant ApoA-I Milano can partially reduce the total atheroma volume (TAV) up to 6.38 mm3 or 14.1 mm3 respectively. Our previous bench studies of selected nanotechnologies documented TAV reduction up to an unprecedented 79.4 mm3. Methods: The completed observational three arms (n = 180) first-in-man trial (the NANOM FIM trial) assessed (NCT01270139) the safety and feasibility of two delivery techniques for nanoparticles (NP), and plasmonic photothermal therapy (PPTT). Patients were assigned to receive either (1) nano-intervention with delivery of silica-gold NP in a bioengineered on-artery patch (n = 60), or (2) nano-intervention with delivery of silica-gold iron-bearing NP with targeted micro-bubbles and stem cells using a magnetic navigation system (n = 60) versus (3) stent implantation (n = 60). The primary outcome was TAV at 12 months. Results: The mean TAV reduction at 12 months in the Nano group was 60.3 mm3 (SD 39.5; min 41.9 mm3, max 94.2 mm3; p < 0.05) up to mean 37.8% (95% CI: 31.1%, 51.7%; p < 0.05) plaque burden. The analysis of the event free survival of the ongoing clinical follow-up shows the significantly lower risk of cardiovascular death in the Nano group when compared with others (91.7% vs. 81.7% and 80% respectively; p < 0.05) with no cases of the target lesion-related complications. Conclusions: PPTT using silica-gold NP associated with significant regression of coronary atherosclerosis.Background: Atheroregression becomes an attractive target for cardiovascular treatment. Some clinical trials have demonstrated that intensive therapy with rosuvastatin or recombinant ApoA-I Milano can partially reduce the total atheroma volume (TAV) up to 6.38 mm3 or 14.1 mm3 respectively. Our previous bench studies of selected nanotechnologies documented TAV reduction up to an unprecedented 79.4 mm3. Methods: The completed observational three arms (n = 180) first-in-man trial (the NANOM FIM trial) assessed (NCT01270139) the safety and feasibility of two delivery techniques for nanoparticles (NP), and plasmonic photothermal therapy (PPTT). Patients were assigned to receive either (1) nano-intervention with delivery of silica-gold NP in a bioengineered on-artery patch (n = 60), or (2) nano-intervention with delivery of silica-gold iron-bearing NP with targeted micro-bubbles and stem cells using a magnetic navigation system (n = 60) versus (3) stent implantation (n = 60). The primary outcome was TAV at 12 months. Results: The mean TAV reduction at 12 months in the Nano group was 60.3 mm3 (SD 39.5; min 41.9 mm3, max 94.2 mm3; p < 0.05) up to mean 37.8% (95% CI: 31.1%, 51.7%; p < 0.05) plaque burden. The analysis of the event free survival of the ongoing clinical follow-up shows the significantly lower risk of cardiovascular death in the Nano group when compared with others (91.7% vs. 81.7% and 80% respectively; p < 0.05) with no cases of the target lesion-related complications. Conclusions: PPTT using silica-gold NP associated with significant regression of coronary atherosclerosis. On behalf of the team of the NANOM FIM study.

Determination of Flood Reduction Alternatives for Climate Change Adaptation in Gyeongancheon basin

NASA Astrophysics Data System (ADS)

Han, D.; Joo, H. J.; Jung, J.; Kim, H. S.

2017-12-01

Recently, the frequency of extreme rainfall event has increased due to the climate change and the impermeable area in an urban watershed has also increased due to the rapid urbanization. Therefore, the flood risk is increasing and we ought to prepare countermeasures for flood damage reduction. For the determination of appropriate measures or alternatives, firstly, this study estimated the frequency based rainfall considering the climate change according to the each target period(reference : 1971˜2010, Target period Ⅰ : 2011˜2040, Target period Ⅱ : 2041˜2070, Target period Ⅲ : 2071˜2100). Then the future flood discharge was computed by using HEC-HMS model. We set 5 sizes of drainage pumps and detention ponds respectively as the flood reduction alternatives and the flood level in the river was obtained by each alternative through HEC-RAS model. The flood inundation map was constructed using topographical data and flood water level in the river and the economic analysis was conducted for the flood damage reduction studies using Multi Dimensional Flood Damage Analysis (MD-FDA) tool. As a result of the effectiveness analysis of the flood reduction alternatives, the flood level by drainage pump was reduced by 0.06m up to 0.44m while it was reduced by 0.01m up to 1.86m in the case of the detention pond. The flooded area was shrunk by up to 32.64% from 0.3% and inundation depth was also dropped. As a result of a comparison of the Benefit/Cost ratio estimated by the economic analysis, a detention pond E in the target period Ⅰ and the pump D in the periods Ⅱ and Ⅲ were considered as the appropriate alternatives for the flood damage reduction under the climate change. AcknowledgementsThis research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning(2017R1A2B3005695)

A Practical Platform for Blood Biomarker Study by Using Global Gene Expression Profiling of Peripheral Whole Blood

PubMed Central

Schmid, Patrick; Yao, Hui; Galdzicki, Michal; Berger, Bonnie; Wu, Erxi; Kohane, Isaac S.

2009-01-01

Background Although microarray technology has become the most common method for studying global gene expression, a plethora of technical factors across the experiment contribute to the variable of genome gene expression profiling using peripheral whole blood. A practical platform needs to be established in order to obtain reliable and reproducible data to meet clinical requirements for biomarker study. Methods and Findings We applied peripheral whole blood samples with globin reduction and performed genome-wide transcriptome analysis using Illumina BeadChips. Real-time PCR was subsequently used to evaluate the quality of array data and elucidate the mode in which hemoglobin interferes in gene expression profiling. We demonstrated that, when applied in the context of standard microarray processing procedures, globin reduction results in a consistent and significant increase in the quality of beadarray data. When compared to their pre-globin reduction counterparts, post-globin reduction samples show improved detection statistics, lowered variance and increased sensitivity. More importantly, gender gene separation is remarkably clearer in post-globin reduction samples than in pre-globin reduction samples. Our study suggests that the poor data obtained from pre-globin reduction samples is the result of the high concentration of hemoglobin derived from red blood cells either interfering with target mRNA binding or giving the pseudo binding background signal. Conclusion We therefore recommend the combination of performing globin mRNA reduction in peripheral whole blood samples and hybridizing on Illumina BeadChips as the practical approach for biomarker study. PMID:19381341

Implications of sustainability for the United States light-duty transportation sector

DOE PAGES

Gearhart, Chris

2016-08-08

This article reviews existing literature to assess the consensus of the scientific and engineering communities concerning the potential for the United States’ light-duty transportation sector to meet a goal of 80% reduction in vehicle emissions and examine what it will take to meet this target. Climate change is a problem that must be solved. The primary cause of this problem is burning of fossil fuels to generate energy. A dramatic reduction in carbon emissions must happen soon, and a significant fraction of this reduction must come from the transportation sector. This paper reviews existing literature to assess the consensus ofmore » the scientific and engineering communities concerning the potential for the United States' light-duty transportation sector to meet a goal of 80% reduction in vehicle emissions and examine what it will take to meet this target. It is unlikely that reducing energy consumption in just vehicles with gasoline-based internal combustion drivetrains will be sufficient to meet GHG emission-reduction targets. This paper explores what additional benefits are possible through the adoption of alternative energy sources, looking at three possible on-vehicle energy carriers: carbon-based fuels, hydrogen, and batteries.« less

Modelling the elimination of hepatitis C as a public health threat in Iceland: A goal attainable by 2020.

PubMed

Scott, Nick; Ólafsson, Sigurður; Gottfreðsson, Magnús; Tyrfingsson, Thorarinn; Rúnarsdóttir, Valgerdur; Hansdottir, Ingunn; Hernandez, Ubaldo Benitez; Sigmundsdóttir, Guðrún; Hellard, Margaret

2018-05-01

In Iceland a nationwide program has been launched offering direct-acting antiviral (DAA) treatment for everyone living with hepatitis C virus (HCV). We estimate (i) the time and treatment scale-up required to achieve the World Health Organization's HCV elimination target of an 80% reduction in incidence; and (ii) the ongoing frequency of HCV testing and harm reduction coverage among people who inject drugs (PWID) required to minimize the likelihood of future HCV outbreaks occurring. We used a dynamic compartmental model of HCV transmission, liver disease progression and the HCV cascade of care, calibrated to reproduce the epidemic of HCV in Iceland. The model was stratified according to injecting drug use status, age and stage of engagement. Four scenarios were considered for the projections. The model estimated that an 80% reduction in domestic HCV incidence was achievable by 2030, 2025 or 2020 if a minimum of 55/1,000, 75/1,000 and 188/1,000 PWID were treated per year, respectively (a total of 22, 30 and 75 of the estimated 400 PWID in Iceland per year, respectively). Regardless of time frame, this required an increased number of PWID to be diagnosed to generate enough treatment demand, or a 20% scale-up of harm reduction services to complement treatment-as-prevention incidence reductions. When DAA scale-up was combined with annual antibody testing of PWID, the incidence reduction target was reached by 2024. Treatment scale-up with no other changes to current testing and harm reduction services reduced the basic reproduction number of HCV from 1.08 to 0.59, indicating that future outbreaks would be unlikely. HCV elimination in Iceland is achievable by 2020 with some additional screening of PWID. Maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that outbreaks are unlikely to occur once elimination targets have been reached. In Iceland, a nationwide program has been launched offering treatment for the entire population living with hepatitis C virus (HCV). A mathematical model was used to estimate the additional health system requirements to achieve the HCV elimination targets of the World Health Organization (WHO), as well as the year that this could occur. With some additional screening of people who inject drugs, Iceland could reach the WHO targets by 2020, becoming one of the first countries to achieve HCV elimination. The model estimated that once elimination targets were reached, maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that future HCV outbreaks are unlikely to occur. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Quantification of Functionalised Gold Nanoparticle-Targeted Knockdown of Gene Expression in HeLa Cells

PubMed Central

Jiwaji, Meesbah; Sandison, Mairi E.; Reboud, Julien; Stevenson, Ross; Daly, Rónán; Barkess, Gráinne; Faulds, Karen; Kolch, Walter; Graham, Duncan; Girolami, Mark A.; Cooper, Jonathan M.; Pitt, Andrew R.

2014-01-01

Introduction Gene therapy continues to grow as an important area of research, primarily because of its potential in the treatment of disease. One significant area where there is a need for better understanding is in improving the efficiency of oligonucleotide delivery to the cell and indeed, following delivery, the characterization of the effects on the cell. Methods In this report, we compare different transfection reagents as delivery vehicles for gold nanoparticles functionalized with DNA oligonucleotides, and quantify their relative transfection efficiencies. The inhibitory properties of small interfering RNA (siRNA), single-stranded RNA (ssRNA) and single-stranded DNA (ssDNA) sequences targeted to human metallothionein hMT-IIa are also quantified in HeLa cells. Techniques used in this study include fluorescence and confocal microscopy, qPCR and Western analysis. Findings We show that the use of transfection reagents does significantly increase nanoparticle transfection efficiencies. Furthermore, siRNA, ssRNA and ssDNA sequences all have comparable inhibitory properties to ssDNA sequences immobilized onto gold nanoparticles. We also show that functionalized gold nanoparticles can co-localize with autophagosomes and illustrate other factors that can affect data collection and interpretation when performing studies with functionalized nanoparticles. Conclusions The desired outcome for biological knockdown studies is the efficient reduction of a specific target; which we demonstrate by using ssDNA inhibitory sequences targeted to human metallothionein IIa gene transcripts that result in the knockdown of both the mRNA transcript and the target protein. PMID:24926959

siRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

PubMed

Vickers, Timothy A; Crooke, Stanley T

2012-07-01

While most siRNAs induce sequence-specific target mRNA cleavage and degradation in a process mediated by Ago2/RNA-induced silencing complex (RISC), certain siRNAs have also been demonstrated to direct target RNA reduction through deadenylation and subsequent degradation of target transcripts in a process which involves Ago1/RISC and P-bodies. In the current study, we present data suggesting that a third class of siRNA exist, which are capable of promoting target RNA reduction that is independent of both Ago and RISC. These siRNAs bind the target messenger RNA at the polyA signal and are capable of redirecting a small amount of polyadenylation to downstream polyA sites when present, however, the majority of the activity appears to be due to inhibition of polyadenylation or deadenylation of the transcript, followed by exosomal degradation of the immature mRNA.

Microenterprise Development Interventions for Sexual Risk Reduction: A Systematic Review

PubMed Central

Lee, Ramon; Thirumurthy, Harsha; Muessig, Kathryn E.; Tucker, Joseph D.

2013-01-01

Comprehensive interventions that address both individual and structural determinants associated with HIV/STI risk are gaining increasing attention over the past decade. Microenterprise development offers an appealing model for HIV prevention by addressing poverty and gender equality. This study systematically reviewed the effects of microenterprise development interventions on HIV/STI incidence and sexual risk behaviors. Microenterprise development was defined as developing small business capacity among individuals to alleviate poverty. Seven eligible research studies representing five interventions were identified and included in this review. All of the studies targeted women, and three focused on sex workers. None measured biomarker outcomes. All three sex worker studies showed significant reduction in sexual risk behaviors when compared to the control group. Non-sex worker studies showed limited changes in sexual risk behavior. This review indicates the potential utility of microenterprise development in HIV risk reduction programs. More research is needed to determine how microenterprise development can be effectively incorporated in comprehensive HIV control strategies. PMID:23963497

Microenterprise development interventions for sexual risk reduction: a systematic review.

PubMed

Cui, Rosa R; Lee, Ramon; Thirumurthy, Harsha; Muessig, Kathryn E; Tucker, Joseph D

2013-11-01

Comprehensive interventions that address both individual and structural determinants associated with HIV/STI risk are gaining increasing attention over the past decade. Microenterprise development offers an appealing model for HIV prevention by addressing poverty and gender equality. This study systematically reviewed the effects of microenterprise development interventions on HIV/STI incidence and sexual risk behaviors. Microenterprise development was defined as developing small business capacity among individuals to alleviate poverty. Seven eligible research studies representing five interventions were identified and included in this review. All of the studies targeted women, and three focused on sex workers. None measured biomarker outcomes. All three sex worker studies showed significant reduction in sexual risk behaviors when compared to the control group. Non-sex worker studies showed limited changes in sexual risk behavior. This review indicates the potential utility of microenterprise development in HIV risk reduction programs. More research is needed to determine how microenterprise development can be effectively incorporated in comprehensive HIV control strategies.

The Girlfriends Project: Results of a pilot study assessing feasibility of an HIV testing and risk reduction intervention developed, implemented, and evaluated in community settings.

PubMed

Hawk, Mary

2013-12-01

African American women in the United States experience significant HIV health disparities. The majority of evidence-based risk reduction interventions do not incorporate HIV testing, and most are targeted only to narrow segments of the population such as women who are pregnant or seen in STI clinics. This pilot study assessed the feasibility and efficacy of The Girlfriends Project (TGP), a community developed and community evaluated HIV risk reduction and testing intervention. A group randomized wait-list design was used to recruit 149 women and to compare findings for intervention group versus control group participants. Women in the intervention group demonstrated statistically-significant increases in HIV knowledge scores and in condom use during vaginal sex. Eighty-seven percent of participants accessed HIV testing with a 100% return rate for results. Study findings suggest that TGP has the potential to be an effective intervention and to increase number of African American women who access HIV testing.

Diffraction-limited lucky imaging with a 12" commercial telescope

NASA Astrophysics Data System (ADS)

Baptista, Brian J.

2014-08-01

Here we demonstrate a novel lucky imaging camera which is designed to produce diffraction-limited imaging using small telescopes similar to ones used by many academic institutions for outreach and/or student training. We present a design that uses a Meade 12" SCT paired with an Andor iXon fast readout EMCCD. The PSF of the telescope is matched to the pixel size of the EMCCD by adding a simple, custom-fabricated, intervening optical system. We demonstrate performance of the system by observing both astronomical and terrestrial targets. The astronomical application requires simpler data reconstruction techniques as compared to the terrestrial case. We compare different lucky imaging registration and reconstruction algorithms for use with this imager for both astronomical and terrestrial targets. We also demonstrate how this type of instrument would be useful for both undergraduate and graduate student training. As an instructional aide, the instrument can provide a hands-on approach for teaching instrument design, standard data reduction techniques, lucky imaging data processing, and high resolution imaging concepts.

SU-E-T-495: Influence of Reduced Target-To-Nozzle Distance On Secondary Neutron Dose Equivalent in Proton and Carbon Ion Radiotherapy

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

Sheng, Y; Shahnazi, K; Wang, W

Purpose: Ion beams have an unavoidable lateral spread due to nuclear interactions interacting with the air and monitoring systems. To minimize this spread, the distance between the nozzle and the patient should be kept as small as possible.The purpose of this work was to determine the impact of the target-to-nozzle distance reduction on the secondary neutron dose equivalent in proton and carbon ion radiotherapy. Methods: In this study, abdominal and head phantoms were scanned with our CT scanner. Cubical targets with side lengths of 3 cm to 10 cm and 1 cm to 5 cm were drawn in the abdominalmore » and head phantoms respectively. Two intensity-modulated plans were made for each phantom and ion. The first of these plans placed the target at the isocenter while the other shifted the phantom 30 cm towards the nozzle. The plans at both phantom locations were optimized to provide identical dose coverage to the PTVs.Secondary neutron dose equivalent at 50 cm lateral to the center of target. Results: The neutron dose equivalent was higher for the larger field size from 0.25µSv per Gy (RBE) to 72µSv per Gy (RBE). The neutron dose equivalent was smaller when the phantom was placed at the upstream target location versus at the isocenter location by 8.9% to 10.4% and 11.0% to 22.1% for proton plans of the abdominal and head phantoms respectively. Differences for carbon plans with different target-to-nozzle locations were less than 3% for both phantoms. Conclusion: A reduction of target-to-nozzle distance can lead to benefits for proton radiotherapy. In this study, a reduction of secondary neutron dose equivalent was found for proton plans with a smaller target-to-nozzle distance. A greater impact was found for a head phantom with a smaller field size; however, a reduction of the target-to-nozzle distance had little effect for carbon therapy.« less

Radiomics based targeted radiotherapy planning (Rad-TRaP): a computational framework for prostate cancer treatment planning with MRI.

PubMed

Shiradkar, Rakesh; Podder, Tarun K; Algohary, Ahmad; Viswanath, Satish; Ellis, Rodney J; Madabhushi, Anant

2016-11-10

Radiomics or computer - extracted texture features have been shown to achieve superior performance than multiparametric MRI (mpMRI) signal intensities alone in targeting prostate cancer (PCa) lesions. Radiomics along with deformable co-registration tools can be used to develop a framework to generate targeted focal radiotherapy treatment plans. The Rad-TRaP framework comprises three distinct modules. Firstly, a module for radiomics based detection of PCa lesions on mpMRI via a feature enabled machine learning classifier. The second module comprises a multi-modal deformable co-registration scheme to map tissue, organ, and delineated target volumes from MRI onto CT. Finally, the third module involves generation of a radiomics based dose plan on MRI for brachytherapy and on CT for EBRT using the target delineations transferred from the MRI to the CT. Rad-TRaP framework was evaluated using a retrospective cohort of 23 patient studies from two different institutions. 11 patients from the first institution were used to train a radiomics classifier, which was used to detect tumor regions in 12 patients from the second institution. The ground truth cancer delineations for training the machine learning classifier were made by an experienced radiation oncologist using mpMRI, knowledge of biopsy location and radiology reports. The detected tumor regions were used to generate treatment plans for brachytherapy using mpMRI, and tumor regions mapped from MRI to CT to generate corresponding treatment plans for EBRT. For each of EBRT and brachytherapy, 3 dose plans were generated - whole gland homogeneous ([Formula: see text]) which is the current clinical standard, radiomics based focal ([Formula: see text]), and whole gland with a radiomics based focal boost ([Formula: see text]). Comparison of [Formula: see text] against conventional [Formula: see text] revealed that targeted focal brachytherapy would result in a marked reduction in dosage to the OARs while ensuring that the prescribed dose is delivered to the lesions. [Formula: see text] resulted in only a marginal increase in dosage to the OARs compared to [Formula: see text]. A similar trend was observed in case of EBRT with [Formula: see text] and [Formula: see text] compared to [Formula: see text]. A radiotherapy planning framework to generate targeted focal treatment plans has been presented. The focal treatment plans generated using the framework showed reduction in dosage to the organs at risk and a boosted dose delivered to the cancerous lesions.

Volumetric modulated arc therapy of head-and-neck cancer on a fast-rotating O-ring linac: Plan quality and delivery time comparison with a C-arm linac.

PubMed

Michiels, Steven; Poels, Kenneth; Crijns, Wouter; Delombaerde, Laurence; De Roover, Robin; Vanstraelen, Bianca; Haustermans, Karin; Nuyts, Sandra; Depuydt, Tom

2018-05-05

Linac improvements in gantry speed, leaf speed and dose rate may increase the time-efficiency of volumetric modulated arc therapy (VMAT) delivery. The plan quality achievable with faster VMAT however remains to be investigated. In this study, a fast-rotating O-ring linac with fast-moving leaves is compared with a C-arm linac in terms of plan quality and delivery time for VMAT of head-and-neck cancer (HNC). For 30 patients with HNC, treatment planning was performed using dual-arc (HA2) and triple-arc (HA3) VMAT on a Halcyon fast-rotating O-ring linac and using dual-arc VMAT on a TrueBeam C-arm linac (TB2). Target coverage metrics and complication probabilities were compared. Plan delivery was verified using 3%/3 mm gamma-index analysis of helical diode array measurements. Volumetric image acquisition and plan delivery times were compared. All studied VMAT-techniques fulfilled the target coverage objectives. D 2% to the boost volume was higher for HA2 (median 103.7%, 1st-3rd quartile [103.5%;104.0%]) and HA3 (103.2% [103.0%;103.7%)] than for TB2 (102.6% [102.3%;103.0%)], resulting in an increased boost target dose heterogeneity for HA2 and HA3. Complication probabilities were comparable between HA2 and TB2, while HA3 showed a xerostomia probability reduction (0.8% [0.2%;1.8%]) and dysphagia probability reduction (1.0% [0.2%;1.8%]) compared with TB2. Gamma-index agreement scores were never below 93.0% for HA2, HA3 and TB2. Volumetric imaging and plan delivery time was shorter for HA2 (1 m 24 s ± 1 s) and HA3 (1 m 54 s ± 1 s) than for TB2 (2 m 47 s ± 1 s). For VMAT of HNC, the fast-rotating O-ring linac at least maintains the plan quality of two arcs on a C-arm linac while reducing the image acquisition and plan delivery time. Copyright © 2018 Elsevier B.V. All rights reserved.

Glyphosate decreases mycorrhizal colonization and affects plant-soil feedback.

PubMed

Helander, Marjo; Saloniemi, Irma; Omacini, Marina; Druille, Magdalena; Salminen, Juha-Pekka; Saikkonen, Kari

2018-06-11

Our aim was to study the effects of glyphosate, tilling practice and cultivation history on mycorrhizal colonization and growth of target (weeds) and non-target (crops) plants. Glyphosate, the world's most widely used pesticide, inhibits an enzyme found in plants but also in microbes. We examined the effects of glyphosate treatment applied in the preceding fall on growth of a perennial weed, Elymus repens (target plant) and a forage grass, Festuca pratensis (non-target plant) and their arbuscular mycorrhizal fungal (AMF) root colonization in a field pot experiment. Non-target plants were sown in the following spring. Furthermore, we tested if glyphosate effects depend on tillage or soil properties modulated by long cultivation history of endophyte symbiotic grass (E+ grass). AMF root colonization, plant establishment and growth, glyphosate residues in plants, and soil chemistry were measured. Glyphosate reduced the mycorrhizal colonization and growth of both target and non-target grasses. The magnitude of reduction depended on tillage and soil properties due to cultivation history of E+ grass. We detected glyphosate residues in weeds and crop plants in the growing season following the glyphosate treatment. Residues were higher in plants growing in no-till pots compared to conspecifics in tilled pots. These results demonstrate negative effects of glyphosate on non-target organisms in agricultural environments and grassland ecosystems. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Automating data analysis for two-dimensional gas chromatography/time-of-flight mass spectrometry non-targeted analysis of comparative samples.

PubMed

Titaley, Ivan A; Ogba, O Maduka; Chibwe, Leah; Hoh, Eunha; Cheong, Paul H-Y; Simonich, Staci L Massey

2018-03-16

Non-targeted analysis of environmental samples, using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC/ToF-MS), poses significant data analysis challenges due to the large number of possible analytes. Non-targeted data analysis of complex mixtures is prone to human bias and is laborious, particularly for comparative environmental samples such as contaminated soil pre- and post-bioremediation. To address this research bottleneck, we developed OCTpy, a Python™ script that acts as a data reduction filter to automate GC × GC/ToF-MS data analysis from LECO ® ChromaTOF ® software and facilitates selection of analytes of interest based on peak area comparison between comparative samples. We used data from polycyclic aromatic hydrocarbon (PAH) contaminated soil, pre- and post-bioremediation, to assess the effectiveness of OCTpy in facilitating the selection of analytes that have formed or degraded following treatment. Using datasets from the soil extracts pre- and post-bioremediation, OCTpy selected, on average, 18% of the initial suggested analytes generated by the LECO ® ChromaTOF ® software Statistical Compare feature. Based on this list, 63-100% of the candidate analytes identified by a highly trained individual were also selected by OCTpy. This process was accomplished in several minutes per sample, whereas manual data analysis took several hours per sample. OCTpy automates the analysis of complex mixtures of comparative samples, reduces the potential for human error during heavy data handling and decreases data analysis time by at least tenfold. Copyright © 2018 Elsevier B.V. All rights reserved.

Higher levels of depression are associated with reduced global bias in visual processing.

PubMed

de Fockert, Jan W; Cooper, Andrew

2014-04-01

Negative moods have been associated with a tendency to prioritise local details in visual processing. The current study investigated the relation between depression and visual processing using the Navon task, a standard task of local and global processing. In the Navon task, global stimuli are presented that are made up of many local parts, and the participants are instructed to report the identity of either a global or a local target shape. Participants with a low self-reported level of depression showed evidence of the expected global processing bias, and were significantly faster at responding to the global, compared with the local level. By contrast, no such difference was observed in participants with high levels of depression. The reduction of the global bias associated with high levels of depression was only observed in the overall speed of responses to global (versus local) targets, and not in the level of interference produced by the global (versus local) distractors. These results are in line with recent findings of a dissociation between local/global processing bias and interference from local/global distractors, and support the claim that depression is associated with a reduction in the tendency to prioritise global-level processing.

Vehicle emissions of short-lived and long-lived climate forcers: trends and tradeoffs.

PubMed

Edwards, Morgan R; Klemun, Magdalena M; Kim, Hyung Chul; Wallington, Timothy J; Winkler, Sandra L; Tamor, Michael A; Trancik, Jessika E

2017-08-24

Evaluating technology options to mitigate the climate impacts of road transportation can be challenging, particularly when they involve a tradeoff between long-lived emissions (e.g., carbon dioxide) and short-lived emissions (e.g., methane or black carbon). Here we present trends in short- and long-lived emissions for light- and heavy-duty transport globally and in the U.S., EU, and China over the period 2000-2030, and we discuss past and future changes to vehicle technologies to reduce these emissions. We model the tradeoffs between short- and long-lived emission reductions across a range of technology options, life cycle emission intensities, and equivalency metrics. While short-lived vehicle emissions have decreased globally over the past two decades, significant reductions in CO 2 will be required by mid-century to meet climate change mitigation targets. This is true regardless of the time horizon used to compare long- and short-lived emissions. The short-lived emission intensities of some low-CO 2 technologies are higher than others, and thus their suitability for meeting climate targets depends sensitively on the evaluation time horizon. Other technologies offer low intensities of both short-lived emissions and CO 2 .

Economic Benefits of Achieving Realistic Smoking Cessation Targets in Australia

PubMed Central

Cadilhac, Dominique; Sheppard, Lauren; Cumming, Toby; Pearce, Dora; Carter, Rob

2011-01-01

Objectives. We estimated the economic impact of reductions in the prevalence of tobacco smoking on health, production, and leisure in the 2008 Australian population. Methods. We selected a prevalence target of 15%. Cohort lifetime health benefits were modeled as fewer incident cases of tobacco-related diseases, deaths, and disability-adjusted life-years. We estimated production gains by comparing surveyed participation and absenteeism rates of adult smokers and ex-smokers valued according to the human capital and friction cost approaches. We estimated household production and leisure gains from time use surveys and valued these gains with the appropriate proxy. Results. In the 2008 Australian population, an absolute reduction in smoking prevalence of 8% would result in 158 000 fewer incident cases of disease, 5000 fewer deaths, 2.2 million fewer lost working days, and 3000 fewer early retirements and would reduce health sector costs by AUD 491 million. The gain in workforce production was AUD 415 million (friction cost) or AUD 863 million (human capital), along with gains of 373 000 days of household production and 23 000 days of leisure time. Conclusions. Lowering smoking prevalence rates can lead to substantial economic savings and health benefits. PMID:21164092

Radio-Frequency-Controlled Urea Dosing for NH₃-SCR Catalysts: NH₃ Storage Influence to Catalyst Performance under Transient Conditions.

PubMed

Dietrich, Markus; Hagen, Gunter; Reitmeier, Willibald; Burger, Katharina; Hien, Markus; Grass, Philippe; Kubinski, David; Visser, Jaco; Moos, Ralf

2017-11-28

Current developments in exhaust gas aftertreatment led to a huge mistrust in diesel driven passenger cars due to their NO x emissions being too high. The selective catalytic reduction (SCR) with ammonia (NH₃) as reducing agent is the only approach today with the capability to meet upcoming emission limits. Therefore, the radio-frequency-based (RF) catalyst state determination to monitor the NH₃ loading on SCR catalysts has a huge potential in emission reduction. Recent work on this topic proved the basic capability of this technique under realistic conditions on an engine test bench. In these studies, an RF system calibration for the serial type SCR catalyst Cu-SSZ-13 was developed and different approaches for a temperature dependent NH₃ storage were determined. This paper continues this work and uses a fully calibrated RF-SCR system under transient conditions to compare different directly measured and controlled NH₃ storage levels, and NH₃ target curves. It could be clearly demonstrated that the right NH₃ target curve, together with a direct control on the desired level by the RF system, is able to operate the SCR system with the maximum possible NO x conversion efficiency and without NH₃ slip.

Comparison of the pharmacological profiles of murine antisense oligonucleotides targeting apolipoprotein B and microsomal triglyceride transfer protein

PubMed Central

Lee, Richard G.; Fu, Wuxia; Graham, Mark J.; Mullick, Adam E.; Sipe, Donna; Gattis, Danielle; Bell, Thomas A.; Booten, Sheri; Crooke, Rosanne M.

2013-01-01

Therapeutic agents that suppress apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) levels/activity are being developed in the clinic to benefit patients who are unable to reach target LDL-C levels with maximally tolerated lipid-lowering drugs. To compare and contrast the metabolic consequences of reducing these targets, murine-specific apoB or MTP antisense oligonucleotides (ASOs) were administered to chow-fed and high fat-fed C57BL/6 or to chow-fed and Western diet-fed LDLr−/− mice for periods ranging from 2 to 12 weeks, and detailed analyses of various factors affecting fatty acid metabolism were performed. Administration of these drugs significantly reduced target hepatic mRNA and protein, leading to similar reductions in hepatic VLDL/triglyceride secretion. MTP ASO treatment consistently led to increases in hepatic triglyceride accumulation and biomarkers of hepatotoxicity relative to apoB ASO due in part to enhanced expression of peroxisome proliferator activated receptor γ target genes and the inability to reduce hepatic fatty acid synthesis. Thus, although both drugs effectively lowered LDL-C levels in mice, the apoB ASO produced a more positive liver safety profile. PMID:23220583

Discovery of Boolean metabolic networks: integer linear programming based approach.

PubMed

Qiu, Yushan; Jiang, Hao; Ching, Wai-Ki; Cheng, Xiaoqing

2018-04-11

Traditional drug discovery methods focused on the efficacy of drugs rather than their toxicity. However, toxicity and/or lack of efficacy are produced when unintended targets are affected in metabolic networks. Thus, identification of biological targets which can be manipulated to produce the desired effect with minimum side-effects has become an important and challenging topic. Efficient computational methods are required to identify the drug targets while incurring minimal side-effects. In this paper, we propose a graph-based computational damage model that summarizes the impact of enzymes on compounds in metabolic networks. An efficient method based on Integer Linear Programming formalism is then developed to identify the optimal enzyme-combination so as to minimize the side-effects. The identified target enzymes for known successful drugs are then verified by comparing the results with those in the existing literature. Side-effects reduction plays a crucial role in the study of drug development. A graph-based computational damage model is proposed and the theoretical analysis states the captured problem is NP-completeness. The proposed approaches can therefore contribute to the discovery of drug targets. Our developed software is available at " http://hkumath.hku.hk/~wkc/APBC2018-metabolic-network.zip ".

Using injectable hydrogel markers to assess resimulation for boost target volume definition in a patient undergoing whole-breast radiotherapy

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

Patel, Henal; Goyal, Sharad; Kim, Leonard, E-mail: kimlh@rutgers.edu

Several publications have recommended that patients undergoing whole-breast radiotherapy be resimulated for boost planning. The rationale for this is that the seroma may be smaller when compared with the initial simulation. However, the decision remains whether to use the earlier or later images to define an appropriate boost target volume. A patient undergoing whole-breast radiotherapy had new, injectable, temporary hydrogel fiducial markers placed 1 to 3 cm from the seroma at the time of initial simulation. The patient was resimulated 4.5 weeks later for conformal photon boost planning. Computed tomography (CT) scans acquired at the beginning and the end ofmore » whole-breast radiotherapy showed that shrinkage of the lumpectomy cavity was not matched by a corresponding reduction in the surrounding tissue volume, as demarcated by hydrogel markers. This observation called into question the usual interpretation of cavity shrinkage for boost target definition. For this patient, it was decided to define the boost target volume on the initial planning CT instead of the new CT.« less

Stereotypical rapid source level regulation in the harbour porpoise biosonar

NASA Astrophysics Data System (ADS)

Linnenschmidt, Meike; Kloepper, Laura N.; Wahlberg, Magnus; Nachtigall, Paul E.

2012-09-01

Some odontocetes and bats vary both click intensity and receiver sensitivity during echolocation, depending on target range. It is not known how this so-called automatic gain control is regulated by the animal. The source level of consecutive echolocation clicks from a harbour porpoise was measured with a hydrophone array while the animal detected an aluminium cylinder at 2, 4 or 8 m distance in a go/no-go paradigm. On-axis clicks had source levels of 145-174 dB re 1 μPa peak-to-peak. During target-present trials the click trains reached comparable source levels independent of the range to the target after three clicks. After an additional click, the source level was reduced for the 2 and 4 m trials until it equalled the one-way transmission loss. During target-absent trials, the source level remained high throughout the entire click train. Given typical values of harbour porpoise inter-click intervals, the source level reduction commenced within a few 100 ms from the first click in the click train. This may indicate a sub-cortically regulated source level regulation in the harbour porpoise.

Analysis of direct-drive capsule compression experiments on the Iskra-5 laser facility

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

Gus'kov, S. Yu.; Demchenko, N. N.; Zhidkov, N. V.

2010-09-15

We have analyzed and numerically simulated our experiments on the compression of DT-gas-filled glass capsules under irradiation by a small number of beams on the Iskra-5 facility (12 beams) at the second harmonic of an iodine laser ({lambda} = 0.66 {mu}m) for a laser pulse energy of 2 kJ and duration of 0.5 ns in the case of asymmetric irradiation and compression. Our simulations include the construction of a target illumination map and a histogram of the target surface illumination distribution; 1D capsule compression simulations based on the DIANA code corresponding to various target surface regions; and 2D compression simulationsmore » based on the NUTCY code corresponding to the illumination conditions. We have succeeded in reproducing the shape of the compressed region at the time of maximum compression and the reduction in neutron yield (compared to the 1D simulations) to the experimentally observed values. For the Iskra-5 conditions, we have considered targets that can provide a more symmetric compression and a higher neutron yield.« less

Unraveling the role of hypoxia-inducible factor (HIF)-1α and HIF-2α in the adaption process of human microvascular endothelial cells (HMEC-1) to hypoxia: Redundant HIF-dependent regulation of macrophage migration inhibitory factor.

PubMed

Hahne, Martin; Schumann, Peggy; Mursell, Mathias; Strehl, Cindy; Hoff, Paula; Buttgereit, Frank; Gaber, Timo

2018-03-01

Hypoxia driven angiogenesis is a prominent feature of tissue regeneration, inflammation and tumor growth and is regulated by hypoxia-inducible factor (HIF)-1 and -2. The distinct functions of HIFs in the hypoxia-induced angiogenesis and metabolic switch of endothelial cells are still unknown and therefore aim of this study. We investigated the role of HIF-1 and -2 in the adaptation of immortalized human microvascular endothelial cells (HMEC-1) to hypoxic conditions (1% O 2 ) in terms of angiogenesis, cytokine secretion, gene expression and ATP/ADP-ratio using shRNA-mediated reduction of the oxygen sensitive α-subunits of either HIF-1 or HIF-2 or the combination of both. Reduction of HIF-1α diminished cellular energy, hypoxia-induced glycolytic gene expression, and angiogenesis not altering pro-angiogenic factors. Reduction of HIF-2α diminished hypoxia-induced pro-angiogenic factors, enhanced anti-angiogenic factors and attenuated angiogenesis not altering glycolytic gene expression. Reduction of both HIFs reduced cell survival, gene expression of glycolytic enzymes and pro-angiogenic factors as compared to the corresponding control. Finally, we identified the macrophage migration inhibitory factor (MIF) to be redundantly regulated by HIF-1 and HIF-2 and to be essential in the process of hypoxia-driven angiogenesis. Our results demonstrate a major impact of HIF-1 and HIF-2 on hypoxia-induced angiogenesis indicating distinct but also overlapping functions of HIF-1 and HIF-2. These findings open new possibilities for therapeutic approaches by specifically targeting the HIF-1 and HIF-2 or their target MIF. Copyright © 2017 Elsevier Inc. All rights reserved.

The ABCs of diabetes: diabetes self-management education program for African Americans affects A1C, lipid-lowering agent prescriptions, and emergency department visits.

PubMed

Magee, Michelle; Bowling, Andrea; Copeland, James; Fokar, Ali; Pasquale, Patricia; Youssef, Gretchen

2011-01-01

The purpose of the study was to examine the feasibility and impact of a concise community-based program on diabetes self-management education (DSME), according to frequency of emergency department visits and knowledge of, prescriptions for, and control of A1C, blood pressure, and low-density lipoprotein (LDL) cholesterol. A free community-based DSME program was placed in a public library. Adults with diabetes (N, 360) consented to participate in this prospective nonrandomized cohort study with preintervention-postintervention design. The small-group interactive DSME (two 2.5-hour classes) focused on improving cardiovascular disease risk factors and facilitating communication with the primary care physician. An increase in knowledge of American Diabetes Association-recommended targets for A1C, blood pressure, and LDL cholesterol from baseline to postintervention was seen among participants. Significant clinical outcomes included reduction in self-reported emergency department visits and reduction in mean A1C. However, despite an increase in prescriptions written for lipid-lowering drugs, blood pressure and LDL cholesterol did not change. Participants who started on insulin were more likely to achieve or maintain A1C < 7% compared to those who either did not take or stopped taking insulin during the study. Offering DSME classes for African Americans at a public library was feasible and significantly affected 6-month clinical outcomes, including a reduction in A1C, an increased likelihood of attaining a target A1C of < 7% if insulin was started during the study period, and a two-thirds reduction in emergency department visits for uncontrolled diabetes. Observed results suggest that partnering with community-based organizations such as public libraries offers an accessible and well-received location for offering DSME programs.

Influence of different treatment techniques on radiation dose to the LAD coronary artery

PubMed Central

Nieder, Carsten; Schill, Sabine; Kneschaurek, Peter; Molls, Michael

2007-01-01

Background The purpose of this proof-of-principle study was to test the ability of an intensity-modulated radiotherapy (IMRT) technique to reduce the radiation dose to the heart plus the left ventricle and a coronary artery. Radiation-induced heart disease might be a serious complication in long-term cancer survivors. Methods Planning CT scans from 6 female patients were available. They were part of a previous study of mediastinal IMRT for target volumes used in lymphoma treatment that included 8 patients and represent all cases where the left anterior descending coronary artery (LAD) could be contoured. We compared 6 MV AP/PA opposed fields to a 3D conformal 4-field technique and an optimised 7-field step-and-shoot IMRT technique and evaluated DVH's for several structures. The planning system was BrainSCAN 5.21 (BrainLAB, Heimstetten, Germany). Results IMRT maintained target volume coverage but resulted in better dose reduction to the heart, left ventricle and LAD than the other techniques. Selective dose reduction could be accomplished, although not to the degree initially attempted. The median LAD dose was approximately 50% lower with IMRT. In 5 out of 6 patients, IMRT was the best technique with regard to heart sparing. Conclusion IMRT techniques are able to reduce the radiation dose to the heart. In addition to dose reduction to whole heart, individualised dose distributions can be created, which spare, e.g., one ventricle plus one of the coronary arteries. Certain patients with well-defined vessel pathology might profit from an approach of general heart sparing with further selective dose reduction, accounting for the individual aspects of pre-existing damage. PMID:17547777

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation

PubMed Central

Li, Chang-Jun; Cheng, Peng; Liang, Meng-Ke; Chen, Yu-Si; Lu, Qiong; Wang, Jin-Yu; Xia, Zhu-Ying; Zhou, Hou-De; Cao, Xu; Xie, Hui; Liao, Er-Yuan; Luo, Xiang-Hang

2015-01-01

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra–bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss. PMID:25751060

Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria.

PubMed

Liu, Cindy M; Hungate, Bruce A; Tobian, Aaron A R; Serwadda, David; Ravel, Jacques; Lester, Richard; Kigozi, Godfrey; Aziz, Maliha; Galiwango, Ronald M; Nalugoda, Fred; Contente-Cuomo, Tania L; Wawer, Maria J; Keim, Paul; Gray, Ronald H; Price, Lance B

2013-04-16

Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable.

Online dimensionality reduction using competitive learning and Radial Basis Function network.

PubMed

Tomenko, Vladimir

2011-06-01

The general purpose dimensionality reduction method should preserve data interrelations at all scales. Additional desired features include online projection of new data, processing nonlinearly embedded manifolds and large amounts of data. The proposed method, called RBF-NDR, combines these features. RBF-NDR is comprised of two modules. The first module learns manifolds by utilizing modified topology representing networks and geodesic distance in data space and approximates sampled or streaming data with a finite set of reference patterns, thus achieving scalability. Using input from the first module, the dimensionality reduction module constructs mappings between observation and target spaces. Introduction of specific loss function and synthesis of the training algorithm for Radial Basis Function network results in global preservation of data structures and online processing of new patterns. The RBF-NDR was applied for feature extraction and visualization and compared with Principal Component Analysis (PCA), neural network for Sammon's projection (SAMANN) and Isomap. With respect to feature extraction, the method outperformed PCA and yielded increased performance of the model describing wastewater treatment process. As for visualization, RBF-NDR produced superior results compared to PCA and SAMANN and matched Isomap. For the Topic Detection and Tracking corpus, the method successfully separated semantically different topics. Copyright © 2011 Elsevier Ltd. All rights reserved.

Model-based analyses to compare health and economic outcomes of cancer control: inclusion of disparities.

PubMed

Goldie, Sue J; Daniels, Norman

2011-09-21

Disease simulation models of the health and economic consequences of different prevention and treatment strategies can guide policy decisions about cancer control. However, models that also consider health disparities can identify strategies that improve both population health and its equitable distribution. We devised a typology of cancer disparities that considers types of inequalities among black, white, and Hispanic populations across different cancers and characteristics important for near-term policy discussions. We illustrated the typology in the specific example of cervical cancer using an existing disease simulation model calibrated to clinical, epidemiological, and cost data for the United States. We calculated average reduction in cancer incidence overall and for black, white, and Hispanic women under five different prevention strategies (Strategies A1, A2, A3, B, and C) and estimated average costs and life expectancy per woman, and the cost-effectiveness ratio for each strategy. Strategies that may provide greater aggregate health benefit than existing options may also exacerbate disparities. Combining human papillomavirus vaccination (Strategy A2) with current cervical cancer screening patterns (Strategy A1) resulted in an average reduction of 69% in cancer incidence overall but a 71.6% reduction for white women, 68.3% for black women, and 63.9% for Hispanic women. Other strategies targeting risk-based screening to racial and ethnic minorities reduced disparities among racial subgroups and resulted in more equitable distribution of benefits among subgroups (reduction in cervical cancer incidence, white vs. Hispanic women, 69.7% vs. 70.1%). Strategies that employ targeted risk-based screening and new screening algorithms, with or without vaccination (Strategies B and C), provide excellent value. The most effective strategy (Strategy C) had a cost-effectiveness ratio of $28,200 per year of life saved when compared with the same strategy without vaccination. We identify screening strategies for cervical cancer that provide greater aggregate health benefit than existing options, offer excellent cost-effectiveness, and have the biggest positive impact in worst-off groups. The typology proposed here may also be useful in research and policy decisions when trade-offs between fairness and cost-effectiveness are unavoidable.

Model-Based Analyses to Compare Health and Economic Outcomes of Cancer Control: Inclusion of Disparities

PubMed Central

Daniels, Norman

2011-01-01

Background Disease simulation models of the health and economic consequences of different prevention and treatment strategies can guide policy decisions about cancer control. However, models that also consider health disparities can identify strategies that improve both population health and its equitable distribution. Methods We devised a typology of cancer disparities that considers types of inequalities among black, white, and Hispanic populations across different cancers and characteristics important for near-term policy discussions. We illustrated the typology in the specific example of cervical cancer using an existing disease simulation model calibrated to clinical, epidemiological, and cost data for the United States. We calculated average reduction in cancer incidence overall and for black, white, and Hispanic women under five different prevention strategies (Strategies A1, A2, A3, B, and C) and estimated average costs and life expectancy per woman, and the cost-effectiveness ratio for each strategy. Results Strategies that may provide greater aggregate health benefit than existing options may also exacerbate disparities. Combining human papillomavirus vaccination (Strategy A2) with current cervical cancer screening patterns (Strategy A1) resulted in an average reduction of 69% in cancer incidence overall but a 71.6% reduction for white women, 68.3% for black women, and 63.9% for Hispanic women. Other strategies targeting risk-based screening to racial and ethnic minorities reduced disparities among racial subgroups and resulted in more equitable distribution of benefits among subgroups (reduction in cervical cancer incidence, white vs Hispanic women, 69.7% vs 70.1%). Strategies that employ targeted risk-based screening and new screening algorithms, with or without vaccination (Strategies B and C), provide excellent value. The most effective strategy (Strategy C) had a cost-effectiveness ratio of $28 200 per year of life saved when compared with the same strategy without vaccination. Conclusions We identify screening strategies for cervical cancer that provide greater aggregate health benefit than existing options, offer excellent cost-effectiveness, and have the biggest positive impact in worst-off groups. The typology proposed here may also be useful in research and policy decisions when trade-offs between fairness and cost-effectiveness are unavoidable. PMID:21900120

Evapotranspiration management based on the application of SWAT for balancing water consumption: A case study in Guantao, China

NASA Astrophysics Data System (ADS)

Liu, Bin; Gan, Hong

2018-06-01

Rapid social and economic development results in increased demand for water resources. This can lead to the unsustainable development and exploitation of water resources which in turn causes significant environmental problems. Conventional water resource management approaches, such as supply and demand management strategies, frequently fail to restore regional water balance. This paper introduces the concept of water consumption balance, the balance between actual evapotranspiration (ET) and target ET, and establishes a framework to realize regional water balance. The framework consists of three stages: (1) determination of target ET and actual ET; (2) quantification of the water-saving requirements for the region; and (3) reduction of actual ET by implementing various water saving management strategies. Using this framework, a case study was conducted for Guantao County, China. The SWAT model was utilized to aid in the selection of the best water saving management strategy by comparing the ET of different irrigation methods and crop pattern adjustments. Simulation results revealed that determination of SWAT model parameters using remote sensing ET is feasible and that the model is a valuable tool for ET management. Irrigation was found to have a greater influence on the ET of winter wheat as compared to that of maize, indicating that reduction in winter wheat cultivation is the most effective way to reduce regional ET. However, the effect of water-saving irrigation methods on the reduction of ET was not obvious. This indicates that it would be difficult to achieve regional ET reduction using water-saving irrigation methods only. Furthermore, selecting the best water saving management strategy by relying solely on the amount of reduced ET was insufficient, because it ignored the impact of water conservation measures on the livelihood of the agricultural community. Incorporating these considerations with our findings, we recommend changing the current irrigation method to sprinkler irrigation and replacing 20% of the winter wheat-maize cultivated area with cotton, as the best strategy to achieve water balance in the study area.

Continuous Positive Airway Pressure for Motion Management in Stereotactic Body Radiation Therapy to the Lung: A Controlled Pilot Study

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

Goldstein, Jeffrey D.; Lawrence, Yaacov R.; Sackler School of Medicine, Tel Aviv University, Tel Aviv

Objective: To determine the effect of continuous positive airway pressure (CPAP) on tumor motion, lung volume, and dose to critical organs in patients receiving stereotactic body radiation therapy (SBRT) for lung tumors. Methods and Materials: After institutional review board approval in December 2013, patients with primary or secondary lung tumors referred for SBRT underwent 4-dimensional computed tomographic simulation twice: with free breathing and with CPAP. Tumor excursion was calculated by subtracting the vector of the greatest dimension of the gross tumor volume (GTV) from the internal target volume (ITV). Volumetric and dosimetric determinations were compared with the Wilcoxon signed-rank test.more » CPAP was used during treatment if judged beneficial. Results: CPAP was tolerated well in 10 of the 11 patients enrolled. Ten patients with 18 lesions were evaluated. The use of CPAP decreased tumor excursion by 0.5 ± 0.8 cm, 0.4 ± 0.7 cm, and 0.6 ± 0.8 cm in the superior–inferior, right–left, and anterior–posterior planes, respectively (P≤.02). Relative to free breathing, the mean ITV reduction was 27% (95% confidence interval [CI] 16%-39%, P<.001). CPAP significantly augmented lung volume, with a mean absolute increase of 915 ± 432 cm{sup 3} and a relative increase of 32% (95% CI 21%-42%, P=.003), contributing to a 22% relative reduction (95% CI 13%-32%, P=.001) in mean lung dose. The use of CPAP was also associated with a relative reduction in mean heart dose by 29% (95% CI 23%-36%, P=.001). Conclusion: In this pilot study, CPAP significantly reduced lung tumor motion compared with free breathing. The smaller ITV, the planning target volume (PTV), and the increase in total lung volume associated with CPAP contributed to a reduction in lung and heart dose. CPAP was well tolerated, reproducible, and simple to implement in the treatment room and should be evaluated further as a novel strategy for motion management in radiation therapy.« less

Feasibility of a Miniature Esophageal Heat Exchange Device for Rapid Therapeutic Cooling in Newborns: Preliminary Investigations in a Piglet Model.

PubMed

Dingley, John; Okano, Satomi; Planas, Silvia; Chakkarapani, Elavazhagan

2018-03-01

Therapeutic hypothermia (TH) after neonatal encephalopathy, commonly provided by 72 hours of whole-body cooling using a wrap, limits parents' physical contact with their infants affecting bonding and may not be suitable for encephalopathic preterm infants with fragile skin. Alternative cooling methods are unavailable for this population. We investigated in a neonatal pig model the feasibility of achieving a 3.5°C reduction in rectal temperature (T rectal ) similar to clinical TH protocols from 38.5°C (normothermia for pigs) to a target of 35°C ± 0.2°C, using a novel neonatal esophageal heat exchanger (NEHE), compared its efficacy to passive cooling, and investigated its ability to maintain target T rectal . Ventilated and anesthetized Landrace/Large white newborn pigs had the NEHE inserted. Water at adjustable temperatures and rates flowed down a central tube, returning up a surrounding distensible blind ending latex tube in a continuous loop. An initial experiment guided four subsequent cycles of passive cooling (30 minutes), rewarming to 38.5°C, active esophageal cooling to 35°C ± 0.2°C, active maintenance of target T rectal (30 minutes), and rewarming. We compared surface, rectal temperature, and hemodynamic changes among passive, active, and maintenance phases, and esophageal histopathology against control. Compared with passive cooling, esophageal cooling achieved target T rectal significantly earlier (71.3 minutes vs. 17.25 minutes, p = 0.003) with significantly greater rates of reduction in rectal (p = 0.0002) and surface (p = 0.005) temperatures and heart rate (p = 0.04). A water temperature of 39.1°C-40.2°C at a flow of 108-120 mL/min maintained T rectal around 35°C ± 0.2°C. The higher peak heart rate and blood pressure within 8 minutes of the maintenance phase (p = 0.04) subsequently stabilized. Histopathology showed congestion, edema, and neutrophil infiltration with increasing cycles. Esophageal cooling is feasible and effective in achieving rapid cooling in newborns. Subsequent maintenance at this temperature required continued circulation of warm water. Esophageal histopathology needs further evaluation after 72 hours servo-control cooling with a narrower range of water temperatures in a larger group of animals.

Alcohol harm reduction advertisements: a content analysis of topic, objective, emotional tone, execution and target audience.

PubMed

Dunstone, Kimberley; Brennan, Emily; Slater, Michael D; Dixon, Helen G; Durkin, Sarah J; Pettigrew, Simone; Wakefield, Melanie A

2017-04-11

Public health mass media campaigns may contribute to reducing the health and social burden attributed to alcohol consumption, but little is known about which advertising characteristics have been used, or have been effective, in alcohol harm reduction campaigns to date. As a first step towards encouraging further research to identify the impact of various advertising characteristics, this study aimed to systematically identify and examine the content of alcohol harm reduction advertisements (ads). Ads were identified through an exhaustive internet search of Google, YouTube, Vimeo, and relevant government and health agency websites. Eligible ads were: English language, produced between 2006 and 2014, not primarily focused on drink-driving or alcohol in pregnancy, and not alcohol industry funded. Systematic content analysis of all ads was performed; each ad was double-coded. In total, 110 individual ads from 72 different alcohol harm reduction campaigns were identified, with the main source countries being Australia (40%) and the United Kingdom (26%). The dominant topic for 52% of ads was short-term harms, while 10% addressed long-term harms, 18% addressed underage drinking, 17% communicated a how-to-change message, and 3% advocated for policy change. The behavioural objective of most ads was to motivate audiences to reduce their alcohol consumption (38%) or to behave responsibly and/or not get drunk when drinking (33%). Only 10% of all ads mentioned low-risk drinking guidelines. Eighty-seven percent of ads used a dramatisation execution style and 74% had a negative emotional tone. Ninety percent of ads contained messages or content that appeared to target adults, and 36% specifically targeted young adults. Some message attributes have been employed more frequently than others, suggesting several promising avenues for future audience or population-based research to compare the relative effectiveness of different characteristics of alcohol harm reduction ads. Given most alcohol-attributable harm is due to long-term disease, these findings suggest future campaigns may fill a potentially important gap if they were to focus on long-term harms. There is scope for such long-term harm campaigns to place greater emphasis on encouraging reduced personal consumption of alcohol, potentially through more frequent communication of low-risk drinking guidelines.

Targeted Assessment for Prevention of Healthcare-Associated Infections: A New Prioritization Metric.

PubMed

Soe, Minn M; Gould, Carolyn V; Pollock, Daniel; Edwards, Jonathan

2015-12-01

To develop a method for calculating the number of healthcare-associated infections (HAIs) that must be prevented to reach a HAI reduction goal and identifying and prioritizing healthcare facilities where the largest reductions can be achieved. Acute care hospitals that report HAI data to the Centers for Disease Control and Prevention's National Healthcare Safety Network. METHODS :The cumulative attributable difference (CAD) is calculated by subtracting a numerical prevention target from an observed number of HAIs. The prevention target is the product of the predicted number of HAIs and a standardized infection ratio goal, which represents a HAI reduction goal. The CAD is a numeric value that if positive is the number of infections to prevent to reach the HAI reduction goal. We calculated the CAD for catheter-associated urinary tract infections for each of the 3,639 hospitals that reported such data to National Healthcare Safety Network in 2013 and ranked the hospitals by their CAD values in descending order. Of 1,578 hospitals with positive CAD values, preventing 10,040 catheter-associated urinary tract infections at 293 hospitals (19%) with the highest CAD would enable achievement of the national 25% catheter-associated urinary tract infection reduction goal. The CAD is a new metric that facilitates ranking of facilities, and locations within facilities, to prioritize HAI prevention efforts where the greatest impact can be achieved toward a HAI reduction goal.

PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates.

PubMed

Lindholm, Marie W; Elmén, Joacim; Fisker, Niels; Hansen, Henrik F; Persson, Robert; Møller, Marianne R; Rosenbohm, Christoph; Ørum, Henrik; Straarup, Ellen M; Koch, Troels

2012-02-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for the reduction of low-density lipoprotein cholesterol (LDL-C). PCSK9 increases the degradation of the LDL receptor, resulting in high LDL-C in individuals with high PCSK9 activity. Here, we show that two locked nucleic acid (LNA) antisense oligonucleotides targeting PCSK9 produce sustained reduction of LDL-C in nonhuman primates after a loading dose (20 mg/kg) and four weekly maintenance doses (5 mg/kg). PCSK9 messenger RNA (mRNA) and serum PCSK9 protein were reduced by 85% which resulted in a 50% reduction in circulating LDL-C. Serum total cholesterol (TC) levels were reduced to the same extent as LDL-C with no reduction in high-density lipoprotein levels, demonstrating a specific pharmacological effect on LDL-C. The reduction in hepatic PCSK9 mRNA correlated with liver LNA oligonucleotide content. This verified that anti-PCSK9 LNA oligonucleotides regulated LDL-C through an antisense mechanism. The compounds were well tolerated with no observed effects on toxicological parameters (liver and kidney histology, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine). The pharmacologic evidence and initial safety profile of the compounds used in this study indicate that LNA antisense oligonucleotides targeting PCSK9 provide a viable therapeutic strategy and are potential complements to statins in managing high LDL-C.

Fusion yield rate recovery by escaping hot-spot fast ions in the neighboring fuel layer

NASA Astrophysics Data System (ADS)

Tang, Xian-Zhu; McDevitt, C. J.; Guo, Zehua; Berk, H. L.

2014-02-01

Free-streaming loss by fast ions can deplete the tail population in the hot spot of an inertial confinement fusion (ICF) target. Escaping fast ions in the neighboring fuel layer of a cryogenic target can produce a surplus of fast ions locally. In contrast to the Knudsen layer effect that reduces hot-spot fusion reactivity due to tail ion depletion, the inverse Knudsen layer effect increases fusion reactivity in the neighboring fuel layer. In the case of a burning ICF target in the presence of significant hydrodynamic mix which aggravates the Knudsen layer effect, the yield recovery largely compensates for the yield reduction. For mix-dominated sub-ignition targets, the yield reduction is the dominant process.

Investigation of Cost and Energy Optimization of Drinking Water Distribution Systems.

PubMed

Cherchi, Carla; Badruzzaman, Mohammad; Gordon, Matthew; Bunn, Simon; Jacangelo, Joseph G

2015-11-17

Holistic management of water and energy resources through energy and water quality management systems (EWQMSs) have traditionally aimed at energy cost reduction with limited or no emphasis on energy efficiency or greenhouse gas minimization. This study expanded the existing EWQMS framework and determined the impact of different management strategies for energy cost and energy consumption (e.g., carbon footprint) reduction on system performance at two drinking water utilities in California (United States). The results showed that optimizing for cost led to cost reductions of 4% (Utility B, summer) to 48% (Utility A, winter). The energy optimization strategy was successfully able to find the lowest energy use operation and achieved energy usage reductions of 3% (Utility B, summer) to 10% (Utility A, winter). The findings of this study revealed that there may be a trade-off between cost optimization (dollars) and energy use (kilowatt-hours), particularly in the summer, when optimizing the system for the reduction of energy use to a minimum incurred cost increases of 64% and 184% compared with the cost optimization scenario. Water age simulations through hydraulic modeling did not reveal any adverse effects on the water quality in the distribution system or in tanks from pump schedule optimization targeting either cost or energy minimization.

Efficiency of an emissions payment system for nitrogen in sewage treatment plants - a case study.

PubMed

Malmaeus, J Mikael; Ek, Mats; Åmand, Linda; Roth, Susanna; Baresel, Christian; Olshammar, Mikael

2015-05-01

An emissions payment system for nitrogen in Swedish sewage treatment plants (STPs) was evaluated using a semi-empirical approach. The system was based on a tariff levied on each unit of nitrogen emitted by STPs, and profitable measures to reduce nitrogen emissions were identified for twenty municipal STPs. This was done through direct involvement with the plant personnel and the results were scaled up to cover all treatment plants larger than 2000 person equivalents in the Swedish tributary areas of the Kattegat and the Baltic Proper. The sum of costs and nitrogen reductions were compared with an assumed command-and-control regulation requiring all STPs to obtain 80% total nitrogen reduction in their effluents. Costs for the latter case were estimated using a database containing standard estimates for reduction costs by six specified measures. For both cases a total reduction target of 3000 tonnes of nitrogen was set. We did not find that the emissions payment system was more efficient in terms of total reduction costs, although some practical and administrative advantages could be identified. Our results emphasize the need to evaluate the performance of policy instruments on a case-by-case basis since the theoretical efficiency is not always reflected in practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Projecting effects of improvements in passive safety of the New Zealand light vehicle fleet.

PubMed

Keall, Michael; Newstead, Stuart; Jones, Wayne

2007-09-01

In the year 2000, as part of the process for setting New Zealand road safety targets, a projection was made for a reduction in social cost of 15.5 percent associated with improvements in crashworthiness, which is a measure of the occupant protection of the light passenger vehicle fleet. Since that document was produced, new estimates of crashworthiness have become available, allowing for a more accurate projection. The objective of this paper is to describe a methodology for projecting changes in casualty rates associated with passive safety features and to apply this methodology to produce a new prediction. The shape of the age distribution of the New Zealand light passenger vehicle fleet was projected to 2010. Projected improvements in crashworthiness and associated reductions in social cost were also modeled based on historical trends. These projections of changes in the vehicle fleet age distribution and of improvements in crashworthiness together provided a basis for estimating the future performance of the fleet in terms of secondary safety. A large social cost reduction of about 22 percent for 2010 compared to the year 2000 was predicted due to the expected huge impact of improvements in passive vehicle features on road trauma in New Zealand. Countries experiencing improvements in their vehicle fleets can also expect significant reductions in road injury compared to a less crashworthy passenger fleet. Such road safety gains can be analyzed using some of the methodology described here.

Effect of coagulation on treatment of municipal wastewater reverse osmosis concentrate by UVC/H2O2.

PubMed

Umar, Muhammad; Roddick, Felicity; Fan, Linhua

2014-02-15

Disposal of reverse osmosis concentrate (ROC) is a growing concern due to potential health and ecological risks. Alum coagulation was investigated as pre-treatment for the UVC/H2O2 treatment of two high salinity ROC samples (ROC A and B) of comparable organic and inorganic content. Coagulation removed a greater fraction of the organic content for ROC B (29%) than ROC A (16%) which correlated well with the reductions of colour and A254. Although the total reductions after 60 min UVC/H2O2 treatment with and without coagulation were comparable, large differences in the trends of reduction were observed which were attributed to the different nature of the organic content (humic-like) of the samples as indicated by the LC-OCD analyses and different initial (5% and 16%) biodegradability. Coagulation and UVC/H2O2 treatment preferentially removed humic-like compounds which resulted in low reaction rates after UVC/H2O2 treatment of the coagulated samples. The improvement in biodegradability was greater (2-3-fold) during UVC/H2O2 treatment of the pre-treated samples than without pre-treatment. The target DOC residual (≤ 15 mg/L) was obtained after 30 and 20 min irradiation of pre-treated ROC A and ROC B with downstream biological treatment, corresponding to reductions of 55% and 62%, respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

PubMed

Woodford, Katrina; Panettieri, Vanessa; Ruben, Jeremy D; Senthi, Sashendra

2016-05-01

Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

Cardiac Dose Reduction with Deep-Inspiratory Breath Hold Technique of Radiotherapy for Left-Sided Breast Cancer.

PubMed

Sripathi, Lalitha Kameshwari; Ahlawat, Parveen; Simson, David K; Khadanga, Chira Ranjan; Kamarsu, Lakshmipathi; Surana, Shital Kumar; Arasu, Kavi; Singh, Harpreet

2017-01-01

Different techniques of radiation therapy have been studied to reduce the cardiac dose in left breast cancer. In this prospective dosimetric study, the doses to heart as well as other organs at risk (OAR) were compared between free-breathing (FB) and deep inspiratory breath hold (DIBH) techniques in intensity modulated radiotherapy (IMRT) and opposed-tangent three-dimensional radiotherapy (3DCRT) plans. Fifteen patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Radiotherapy plans were generated with 3DCRT and IMRT techniques in FB and DIBH images in each patient. Target coverage, conformity index, homogeneity index, and mean dose to heart (Heart D mean ), left lung, left anterior descending artery (LAD) and right breast were compared between the four plans using the Wilcoxon signed rank test. Target coverage was adequate with both 3DCRT and IMRT plans, but IMRT plans showed better conformity and homogeneity. A statistically significant dose reduction of all OARs was found with DIBH. 3DCRT DIBH decreased the Heart D mean by 53.5% (7.1 vs. 3.3 Gy) and mean dose to LAD by 28% compared to 3DCRT FB . IMRT further lowered mean LAD dose by 18%. Heart D mean was lower with 3DCRT DIBH over IMRT DIBH (3.3 vs. 10.2 Gy). Mean dose to the contralateral breast was also lower with 3DCRT over IMRT (0.32 vs. 3.35 Gy). Mean dose and the V 20 of ipsilateral lung were lower with 3DCRT DIBH over IMRT DIBH (13.78 vs. 18.9 Gy) and (25.16 vs. 32.95%), respectively. 3DCRT DIBH provided excellent dosimetric results in patients with left-sided breast cancer without the need for IMRT.

Cardiac Dose Reduction with Deep-Inspiratory Breath Hold Technique of Radiotherapy for Left-Sided Breast Cancer

PubMed Central

Sripathi, Lalitha Kameshwari; Ahlawat, Parveen; Simson, David K; Khadanga, Chira Ranjan; Kamarsu, Lakshmipathi; Surana, Shital Kumar; Arasu, Kavi; Singh, Harpreet

2017-01-01

Introduction: Different techniques of radiation therapy have been studied to reduce the cardiac dose in left breast cancer. Aim: In this prospective dosimetric study, the doses to heart as well as other organs at risk (OAR) were compared between free-breathing (FB) and deep inspiratory breath hold (DIBH) techniques in intensity modulated radiotherapy (IMRT) and opposed-tangent three-dimensional radiotherapy (3DCRT) plans. Materials and Methods: Fifteen patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Radiotherapy plans were generated with 3DCRT and IMRT techniques in FB and DIBH images in each patient. Target coverage, conformity index, homogeneity index, and mean dose to heart (Heart Dmean), left lung, left anterior descending artery (LAD) and right breast were compared between the four plans using the Wilcoxon signed rank test. Results: Target coverage was adequate with both 3DCRT and IMRT plans, but IMRT plans showed better conformity and homogeneity. A statistically significant dose reduction of all OARs was found with DIBH. 3DCRTDIBH decreased the Heart Dmean by 53.5% (7.1 vs. 3.3 Gy) and mean dose to LAD by 28% compared to 3DCRTFB. IMRT further lowered mean LAD dose by 18%. Heart Dmean was lower with 3DCRTDIBH over IMRTDIBH (3.3 vs. 10.2 Gy). Mean dose to the contralateral breast was also lower with 3DCRT over IMRT (0.32 vs. 3.35 Gy). Mean dose and the V20 of ipsilateral lung were lower with 3DCRTDIBH over IMRTDIBH (13.78 vs. 18.9 Gy) and (25.16 vs. 32.95%), respectively. Conclusions: 3DCRTDIBH provided excellent dosimetric results in patients with left-sided breast cancer without the need for IMRT. PMID:28974856

Prenatal Mechanistic Target of Rapamycin Complex 1 (m TORC1) Inhibition by Rapamycin Treatment of Pregnant Mice Causes Intrauterine Growth Restriction and Alters Postnatal Cardiac Growth, Morphology, and Function.

PubMed

Hennig, Maria; Fiedler, Saskia; Jux, Christian; Thierfelder, Ludwig; Drenckhahn, Jörg-Detlef

2017-08-04

Fetal growth impacts cardiovascular health throughout postnatal life in humans. Various animal models of intrauterine growth restriction exhibit reduced heart size at birth, which negatively influences cardiac function in adulthood. The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and growth factor availability with cell growth, thereby regulating organ size. This study aimed at elucidating a possible involvement of mTORC1 in intrauterine growth restriction and prenatal heart growth. We inhibited mTORC1 in fetal mice by rapamycin treatment of pregnant dams in late gestation. Prenatal rapamycin treatment reduces mTORC1 activity in various organs at birth, which is fully restored by postnatal day 3. Rapamycin-treated neonates exhibit a 16% reduction in body weight compared with vehicle-treated controls. Heart weight decreases by 35%, resulting in a significantly reduced heart weight/body weight ratio, smaller left ventricular dimensions, and reduced cardiac output in rapamycin- versus vehicle-treated mice at birth. Although proliferation rates in neonatal rapamycin-treated hearts are unaffected, cardiomyocyte size is reduced, and apoptosis increased compared with vehicle-treated neonates. Rapamycin-treated mice exhibit postnatal catch-up growth, but body weight and left ventricular mass remain reduced in adulthood. Prenatal mTORC1 inhibition causes a reduction in cardiomyocyte number in adult hearts compared with controls, which is partially compensated for by an increased cardiomyocyte volume, resulting in normal cardiac function without maladaptive left ventricular remodeling. Prenatal rapamycin treatment of pregnant dams represents a new mouse model of intrauterine growth restriction and identifies an important role of mTORC1 in perinatal cardiac growth. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Region-specific role of growth differentiation factor-5 in the establishment of sympathetic innervation.

PubMed

O'Keeffe, Gerard W; Gutierrez, Humberto; Howard, Laura; Laurie, Christopher W; Osorio, Catarina; Gavaldà, Núria; Wyatt, Sean L; Davies, Alun M

2016-02-15

Nerve growth factor (NGF) is the prototypical target-derived neurotrophic factor required for sympathetic neuron survival and for the growth and ramification of sympathetic axons within most but not all sympathetic targets. This implies the operation of additional target-derived factors for regulating terminal sympathetic axon growth and branching. Here report that growth differentiation factor 5 (GDF5), a widely expressed member of the transforming growth factor beta (TGFβ) superfamily required for limb development, promoted axon growth from mouse superior cervical ganglion (SCG) neurons independently of NGF and enhanced axon growth in combination with NGF. GDF5 had no effect on neuronal survival and influenced axon growth during a narrow window of postnatal development when sympathetic axons are ramifying extensively in their targets in vivo. SCG neurons expressed all receptors capable of participating in GDF5 signaling at this stage of development. Using compartment cultures, we demonstrated that GDF5 exerted its growth promoting effect by acting directly on axons and by initiating retrograde canonical Smad signalling to the nucleus. GDF5 is synthesized in sympathetic targets, and examination of several anatomically circumscribed tissues in Gdf5 null mice revealed regional deficits in sympathetic innervation. There was a marked, highly significant reduction in the sympathetic innervation density of the iris, a smaller though significant reduction in the trachea, but no reduction in the submandibular salivary gland. There was no reduction in the number of neurons in the SCG. These findings show that GDF5 is a novel target-derived factor that promotes sympathetic axon growth and branching and makes a distinctive regional contribution to the establishment of sympathetic innervation, but unlike NGF, plays no role in regulating sympathetic neuron survival.

Cholesterol-lowering Action of BNA-based Antisense Oligonucleotides Targeting PCSK9 in Atherogenic Diet-induced Hypercholesterolemic Mice.

PubMed

Yamamoto, Tsuyoshi; Harada-Shiba, Mariko; Nakatani, Moeka; Wada, Shunsuke; Yasuhara, Hidenori; Narukawa, Keisuke; Sasaki, Kiyomi; Shibata, Masa-Aki; Torigoe, Hidetaka; Yamaoka, Tetsuji; Imanishi, Takeshi; Obika, Satoshi

2012-05-15

Recent findings in molecular biology implicate the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in low-density lipoprotein receptor (LDLR) protein regulation. The cholesterol-lowering potential of anti-PCSK9 antisense oligonucleotides (AONs) modified with bridged nucleic acids (BNA-AONs) including 2',4'-BNA (also called as locked nucleic acid (LNA)) and 2',4'-BNA(NC) chemistries were demonstrated both in vitro and in vivo. An in vitro transfection study revealed that all of the BNA-AONs induce dose-dependent reductions in PCSK9 messenger RNA (mRNA) levels concomitantly with increases in LDLR protein levels. BNA-AONs were administered to atherogenic diet-fed C57BL/6J mice twice weekly for 6 weeks; 2',4'-BNA-AON that targeted murine PCSK9 induced a dose-dependent reduction in hepatic PCSK9 mRNA and LDL cholesterol (LDL-C); the 43% reduction of serum LDL-C was achieved at a dose of 20 mg/kg/injection with only moderate increases in toxicological indicators. In addition, the serum high-density lipoprotein cholesterol (HDL-C) levels increased. These results support antisense inhibition of PCSK9 as a potential therapeutic approach. When compared with 2',4'-BNA-AON, 2',4'-BNA(NC)-AON showed an earlier LDL-C-lowering effect and was more tolerable in mice. Our results validate the optimization of 2',4'-BNA(NC)-based anti-PCSK9 antisense molecules to produce a promising therapeutic agent for the treatment of hypercholesterolemia.

Abolishing inequity, a necessity for poverty reduction and the realisation of child mortality targets.

PubMed

Målqvist, Mats

2015-02-01

The first Millennium Development Goal (MDG 1) due in 2015 concerns poverty reduction. It has been claimed to be fulfilled on a global level, but still more than 1 billion people are living in abject poverty. There is a strong link between the economy and child survival, and only a minority of countries will have reached the MDG target for child mortality reduction by 2015. This paper discusses the relationship between poverty and child survival. It argues that a focus on equity is necessary to further reduce child mortality, through poverty reduction in absolute terms and also through targeting interventions for increased child survival to disadvantaged populations. The political will to actually achieve real change for those in greatest need is crucial but not to be taken for granted, and the distribution rather than the generation of wealth needs to be made a priority in the post-MDG era. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial.

PubMed

Amparo, Francisco; Dastjerdi, Mohammad H; Okanobo, Andre; Ferrari, Giulio; Smaga, Leila; Hamrah, Pedram; Jurkunas, Ula; Schaumberg, Debra A; Dana, Reza

2013-06-01

The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy. To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction. Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial. Seventy-five patients with refractory DED. Participants were randomized to receive treatment with topical anakinra, 2.5% (n = 30), anakinra, 5% (n = 15), or vehicle (1% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks. Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality. Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P = .12 compared with vehicle and P < .001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2 of 29 patients (7%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P = .02 and P = .01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms. Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00681109.

Recoil distance method lifetime measurements at TRIUMF-ISAC using the TIGRESS Integrated Plunger

NASA Astrophysics Data System (ADS)

Chester, A.; Ball, G. C.; Bernier, N.; Cross, D. S.; Domingo, T.; Drake, T. E.; Evitts, L. J.; Garcia, F. H.; Garnsworthy, A. B.; Hackman, G.; Hallam, S.; Henderson, J.; Henderson, R.; Krücken, R.; MacConnachie, E.; Moukaddam, M.; Padilla-Rodal, E.; Paetkau, O.; Pore, J. L.; Rizwan, U.; Ruotsalainen, P.; Shoults, J.; Smallcombe, J.; Smith, J. K.; Starosta, K.; Svensson, C. E.; Van Wieren, K.; Williams, J.; Williams, M.

2018-02-01

The TIGRESS Integrated Plunger device (TIP) has been developed for recoil distance method (RDM) lifetime measurements using the TIGRESS array of HPGe γ-ray detectors at TRIUMF's ISAC-II facility. A commissioning experiment was conducted utilizing a 250 MeV 84Kr beam at ≈ 2 × 108 particles per second. The 84Kr beam was Coulomb excited to the 21+ state on a movable 27Al target. A thin Cu foil fixed downstream from the target was used as a degrader. Excited nuclei emerged from the target and decayed by γ-ray emission at a distance determined by their velocity and the lifetime of the 21+ state. The ratio of decays which occur between the target and degrader to those occurring after traversing the degrader changes as a function of the target-degrader separation distance. Gamma-ray spectra at 13 target-degrader separation distances were measured and compared to simulated lineshapes to extract the lifetime. The result of τ = 5 . 541 ± 0 . 013(stat.) ± 0 . 063(sys.) ps is shorter than the literature value of 5 . 84 ± 0 . 18 ps with a reduction in uncertainty by a factor of approximately two. The TIP plunger device, experimental technique, analysis tools, and result are discussed.

[Synergistic emission reduction of chief air pollutants and greenhouse gases-based on scenario simulations of energy consumptions in Beijing].

PubMed

Xie, Yuan-bo; Li, Wei

2013-05-01

It is one of the common targets and important tasks for energy management and environmental control of Beijing to improve urban air quality while reducing the emissions of greenhouse gases (GHG). Here, based on the interim and long term developmental planning and energy structure of the city, three energy consumption scenarios in low, moderate and high restrictions were designed by taking the potential energy saving policies and environmental targets into account. The long-range energy alternatives planning (LEAP) model was employed to predict and evaluate reduction effects of the chief air pollutants and GHG during 2010 to 2020 under the three given scenarios. The results showed that if urban energy consumption system was optimized or adjusted by exercising energy saving and emission reduction and pollution control measures, the predicted energy uses will be reduced by 10 to 30 million tons of coal equivalents by 2020. Under the two energy scenarios with moderate and high restrictions, the anticipated emissions of SO2, NOx, PM10, PM2.5, VOC and GHG will be respectively reduced to 71 to 100.2, 159.2 to 218.7, 89.8 to 133.8, 51.4 to 96.0, 56.4 to 74.8 and 148 200 to 164 700 thousand tons. Correspondingly, when compared with the low-restriction scenario, the reducing rate will be 53% to 67% , 50% to 64% , 33% to 55% , 25% to 60% , 41% to 55% and 26% to 34% respectively. Furthermore, based on a study of synergistic emission reduction of the air pollutants and GHG, it was proposed that the adjustment and control of energy consumptions shall be intensively developed in the three sectors of industry, transportation and services. In this way the synergistic reduction of the emissions of chief air pollutants and GHG will be achieved; meanwhile the pressures of energy demands may be deliberately relieved.

Modelling the impact of vector control interventions on Anopheles gambiae population dynamics

PubMed Central

2011-01-01

Background Intensive anti-malaria campaigns targeting the Anopheles population have demonstrated substantial reductions in adult mosquito density. Understanding the population dynamics of Anopheles mosquitoes throughout their whole lifecycle is important to assess the likely impact of vector control interventions alone and in combination as well as to aid the design of novel interventions. Methods An ecological model of Anopheles gambiae sensu lato populations incorporating a rainfall-dependent carrying capacity and density-dependent regulation of mosquito larvae in breeding sites is developed. The model is fitted to adult mosquito catch and rainfall data from 8 villages in the Garki District of Nigeria (the 'Garki Project') using Bayesian Markov Chain Monte Carlo methods and prior estimates of parameters derived from the literature. The model is used to compare the impact of vector control interventions directed against adult mosquito stages - long-lasting insecticide treated nets (LLIN), indoor residual spraying (IRS) - and directed against aquatic mosquito stages, alone and in combination on adult mosquito density. Results A model in which density-dependent regulation occurs in the larval stages via a linear association between larval density and larval death rates provided a good fit to seasonal adult mosquito catches. The effective mosquito reproduction number in the presence of density-dependent regulation is dependent on seasonal rainfall patterns and peaks at the start of the rainy season. In addition to killing adult mosquitoes during the extrinsic incubation period, LLINs and IRS also result in less eggs being oviposited in breeding sites leading to further reductions in adult mosquito density. Combining interventions such as the application of larvicidal or pupacidal agents that target the aquatic stages of the mosquito lifecycle with LLINs or IRS can lead to substantial reductions in adult mosquito density. Conclusions Density-dependent regulation of anopheline larvae in breeding sites ensures robust, stable mosquito populations that can persist in the face of intensive vector control interventions. Selecting combinations of interventions that target different stages in the vector's lifecycle will result in maximum reductions in mosquito density. PMID:21798055

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 yield greater reductions in HbA1c with improved diabetes outcomes and meaningful hospital-based cost savings. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

AKSZ construction from reduction data

NASA Astrophysics Data System (ADS)

Bonechi, Francesco; Cabrera, Alejandro; Zabzine, Maxim

2012-07-01

We discuss a general procedure to encode the reduction of the target space geometry into AKSZ sigma models. This is done by considering the AKSZ construction with target the BFV model for constrained graded symplectic manifolds. We investigate the relation between this sigma model and the one with the reduced structure. We also discuss several examples in dimension two and three when the symmetries come from Lie group actions and systematically recover models already proposed in the literature.

Prospective Evaluation of Prior Image Constrained Compressed Sensing (PICCS) Algorithm in Abdominal CT: A comparison of reduced dose with standard dose imaging

PubMed Central

Lubner, Meghan G.; Pickhardt, Perry J.; Kim, David H.; Tang, Jie; Munoz del Rio, Alejandro; Chen, Guang-Hong

2014-01-01

Purpose To prospectively study CT dose reduction using the “prior image constrained compressed sensing” (PICCS) reconstruction technique. Methods Immediately following routine standard dose (SD) abdominal MDCT, 50 patients (mean age, 57.7 years; mean BMI, 28.8) underwent a second reduced-dose (RD) scan (targeted dose reduction, 70-90%). DLP, CTDIvol and SSDE were compared. Several reconstruction algorithms (FBP, ASIR, and PICCS) were applied to the RD series. SD images with FBP served as reference standard. Two blinded readers evaluated each series for subjective image quality and focal lesion detection. Results Mean DLP, CTDIvol, and SSDE for RD series was 140.3 mGy*cm (median 79.4), 3.7 mGy (median 1.8), and 4.2 mGy (median 2.3) compared with 493.7 mGy*cm (median 345.8), 12.9 mGy (median 7.9 mGy) and 14.6 mGy (median 10.1) for SD series, respectively. Mean effective patient diameter was 30.1 cm (median 30), which translates to a mean SSDE reduction of 72% (p<0.001). RD-PICCS image quality score was 2.8±0.5, improved over the RD-FBP (1.7±0.7) and RD-ASIR(1.9±0.8)(p<0.001), but lower than SD (3.5±0.5)(p<0.001). Readers detected 81% (184/228) of focal lesions on RD-PICCS series, versus 67% (153/228) and 65% (149/228) for RD-FBP and RD-ASIR, respectively. Mean image noise was significantly reduced on RD-PICCS series (13.9 HU) compared with RD-FBP (57.2) and RD-ASIR (44.1) (p<0.001). Conclusion PICCS allows for marked dose reduction at abdominal CT with improved image quality and diagnostic performance over reduced-dose FBP and ASIR. Further study is needed to determine indication-specific dose reduction levels that preserve acceptable diagnostic accuracy relative to higher-dose protocols. PMID:24943136

Variation of ambient non-methane hydrocarbons in Beijing city in summer 2008

NASA Astrophysics Data System (ADS)

Wang, B.; Shao, M.; Lu, S. H.; Yuan, B.; Zhao, Y.; Wang, M.; Zhang, S. Q.; Wu, D.

2010-02-01

In conjunction with hosting the 2008 Beijing Olympics, the municipal government implemented a series of stringent air quality control measures. To assess the impacts on variation of ambient non-methane hydrocarbons (NMHCs), the whole air was sampled by canisters at one urban site and two suburban sites in Beijing, and 55 NMHC species were quantified by gas chromatography equipped with a quadrupole mass spectrometer and a flame ionization detector (GC/MSD/FID) as parts of the field Campaign for the Beijing Olympic Games Air Quality program (CareBeijing). According to the control measures, the data were presented according to four periods: 18-30 June, 8-19 July, 15-24 August (during the Olympic Games), and 6-15 September (during the Paralympic Games). Compared with the levels in June, the mixing ratios of NMHCs obtained in the Olympic and Paralympic Games periods were reduced by 35% and 25%, respectively. Source contributions were calculated using a chemical mass balance model (CMB 8.2). After implementing the control measures, emissions from target sources were obviously reduced, and reductions in vehicle exhaust could explain 48-82% of the reductions of ambient NMHCs. Reductions in emissions from gasoline evaporation, paint and solvent use, and the chemical industry contributed 9-40%, 3-24%, and 1-5%, respectively, to reductions of ambient NMHCs. Sources of liquefied petroleum gas (LPG) and biogenic emissions were not controlled, and contributions from these sources from July to September were stable or even higher than in June. Ozone formation potentials (OFPs) were calculated for the measured NMHCs. The total OFPs during the Olympic and Paralympic Games were reduced by 48% and 32%, respectively, compared with values in June. Reductions in the OFPs of alkenes and aromatics explained 77-92% of total OFP reductions. The alkenes and aromatics were mainly from vehicle exhausts, and reductions of vehicle exhaust gases explained 67-87% of reductions in alkenes and 38-80% of reductions in aromatics. These findings demonstrate the effectiveness of the air quality control measures enacted for the 2008 Olympics and indicate that controlling vehicular emissions could be the most important measure to improve air quality in Beijing.

Variation of ambient non-methane hydrocarbons in Beijing city in summer 2008

NASA Astrophysics Data System (ADS)

Wang, B.; Shao, M.; Lu, S. H.; Yuan, B.; Zhao, Y.; Wang, M.; Zhang, S. Q.; Wu, D.

2010-07-01

In conjunction with hosting the 2008 Beijing Olympics, the municipal government implemented a series of stringent air quality control measures. To assess the impacts on variation of ambient non-methane hydrocarbons (NMHCs), the whole air was sampled by canisters at one urban site and two suburban sites in Beijing, and 55 NMHC species were quantified by gas chromatography equipped with a quadrupole mass spectrometer and a flame ionization detector (GC/MSD/FID) as parts of the field Campaign for the Beijing Olympic Games Air Quality program (CareBeijing). According to the control measures, the data were presented according to four periods: 18-30 June, 8-19 July, 15-24 August (during the Olympic Games), and 6-15 September (during the Paralympic Games). Compared with the levels in June, the mixing ratios of NMHCs obtained in the Olympic and Paralympic Games periods were reduced by 35% and 25%, respectively. Source contributions were calculated using a chemical mass balance model (CMB 8.2). After implementing the control measures, emissions from target sources were obviously reduced, and reductions in vehicle exhaust could explain 48-82% of the reductions of ambient NMHCs. Reductions in emissions from gasoline evaporation, paint and solvent use, and the chemical industry contributed 9-40%, 3-24%, and 1-5%, respectively, to reductions of ambient NMHCs. Sources of liquefied petroleum gas (LPG) and biogenic emissions were not controlled, and contributions from these sources from July to September were stable or even higher than in June. Ozone formation potentials (OFPs) were calculated for the measured NMHCs. The total OFPs during the Olympic and Paralympic Games were reduced by 48% and 32%, respectively, compared with values in June. Reductions in the OFPs of alkenes and aromatics explained 77-92% of total OFP reductions. The alkenes and aromatics were mainly from vehicle exhausts, and reductions of vehicle exhaust gases explained 67-87% of reductions in alkenes and 38-80% of reductions in aromatics. These findings demonstrate the effectiveness of the air quality control measures enacted for the 2008 Olympics and indicate that controlling vehicular emissions could be the most important measure to improve air quality in Beijing.

Patient geometry-driven information retrieval for IMRT treatment plan quality control

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

Wu Binbin; Ricchetti, Francesco; Sanguineti, Giuseppe

Purpose: Intensity modulated radiation therapy (IMRT) treatment plan quality depends on the planner's level of experience and the amount of time the planner invests in developing the plan. Planners often unwittingly accept plans when further sparing of the organs at risk (OARs) is possible. The authors propose a method of IMRT treatment plan quality control that helps planners to evaluate the doses of the OARs upon completion of a new plan. Methods: It is achieved by comparing the geometric configurations of the OARs and targets of a new patient with those of prior patients, whose plans are maintained in amore » database. They introduce the concept of a shape relationship descriptor and, specifically, the overlap volume histogram (OVH) to describe the spatial configuration of an OAR with respect to a target. The OVH provides a way to infer the likely DVHs of the OARs by comparing the relative spatial configurations between patients. A database of prior patients is built to serve as an external reference. At the conclusion of a new plan, planners search through the database and identify related patients by comparing the OAR-target geometric relationships of the new patient with those of prior patients. The treatment plans of these related patients are retrieved from the database and guide planners in determining whether lower doses delivered to the OARs in the new plan are feasible. Results: Preliminary evaluation is promising. In this evaluation, they applied the analysis to the parotid DVHs of 32 prior head-and-neck patients, whose plans are maintained in a database. Each parotid was queried against the other 63 parotids to determine whether a lower dose was possible. The 17 parotids that promised the greatest reduction in D{sub 50} (DVH dose at 50% volume) were flagged. These 17 parotids came from 13 patients. The method also indicated that the doses of the other nine parotids of the 13 patients could not be reduced, so they were included in the replanning process as controls. Replanning with an effort to reduce D{sub 50} was conducted on these 26 parotids. After replanning, the average reductions for D{sub 50} of the 17 flagged parotids and nine unflagged parotids were 6.6 and 1.9 Gy, respectively. These results demonstrate that the quality control method has accurately identified not only the parotids that require dose reductions but also those for which dose reductions are marginal. Originally, 11 of out the 17 flagged parotids did not meet the Radiation Therapy Oncology Group sparing goal of V(30 Gy)<50%. Replanning reduced them to three. Additionally, PTV coverage and OAR sparing of the original plans were compared to those of the replans by using pairwise Wilcoxon p test. The statistical comparisons show that replanning compromised neither PTV coverage nor OAR sparing. Conclusions: This method provides an effective quality control mechanism for evaluating the DVHs of the OARs. Adoption of such a method will advance the quality of current IMRT planning, providing better treatment plan consistency.« less

Adoption of Robotic vs Fluoroscopic Guidance in Total Hip Arthroplasty: Is Acetabular Positioning Improved in the Learning Curve?

PubMed

Kamara, Eli; Robinson, Jonathon; Bas, Marcel A; Rodriguez, Jose A; Hepinstall, Matthew S

2017-01-01

Acetabulum positioning affects dislocation rates, component impingement, bearing surface wear rates, and need for revision surgery. Novel techniques purport to improve the accuracy and precision of acetabular component position, but may have a significant learning curve. Our aim was to assess whether adopting robotic or fluoroscopic techniques improve acetabulum positioning compared to manual total hip arthroplasty (THA) during the learning curve. Three types of THAs were compared in this retrospective cohort: (1) the first 100 fluoroscopically guided direct anterior THAs (fluoroscopic anterior [FA]) done by a surgeon learning the anterior approach, (2) the first 100 robotic-assisted posterior THAs done by a surgeon learning robotic-assisted surgery (robotic posterior [RP]), and (3) the last 100 manual posterior (MP) THAs done by each surgeon (200 THAs) before adoption of novel techniques. Component position was measured on plain radiographs. Radiographic measurements were taken by 2 blinded observers. The percentage of hips within the surgeons' "target zone" (inclination, 30°-50°; anteversion, 10°-30°) was calculated, along with the percentage within the "safe zone" of Lewinnek (inclination, 30°-50°; anteversion, 5°-25°) and Callanan (inclination, 30°-45°; anteversion, 5°-25°). Relative risk (RR) and absolute risk reduction (ARR) were calculated. Variances (square of the standard deviations) were used to describe the variability of cup position. Seventy-six percentage of MP THAs were within the surgeons' target zone compared with 84% of FA THAs and 97% of RP THAs. This difference was statistically significant, associated with a RR reduction of 87% (RR, 0.13 [0.04-0.40]; P < .01; ARR, 21%; number needed to treat, 5) for RP compared to MP THAs. Compared to FA THAs, RP THAs were associated with a RR reduction of 81% (RR, 0.19 [0.06-0.62]; P < .01; ARR, 13%; number needed to treat, 8). Variances were lower for acetabulum inclination and anteversion in RP THAs (14.0 and 19.5) as compared to the MP (37.5 and 56.3) and FA (24.5 and 54.6) groups. These differences were statistically significant (P < .01). Adoption of robotic techniques delivers significant and immediate improvement in the precision of acetabular component positioning during the learning curve. While fluoroscopy has been shown to be beneficial with experience, a learning curve exists before precision improves significantly. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessing Screening Policies for Childhood Obesity

PubMed Central

Wein, Lawrence M.; Yang, Yan; Goldhaber-Fiebert, Jeremy D.

2014-01-01

To address growing concerns over childhood obesity, the United States Preventive Services Task Force (USPSTF) recently recommended that children undergo obesity screening beginning at age 6 [1]. An Expert Committee recommends starting at age 2 [2]. Analysis is needed to assess these recommendations and investigate whether there are better alternatives. We model the age- and sex-specific population-wide distribution of body mass index (BMI) through age 18 using National Longitudinal Survey of Youth data [3]. The impact of treatment on BMI is estimated using the targeted systematic review performed to aid the USPSTF [4]. The prevalence of hypertension and diabetes at age 40 are estimated from the Panel Study of Income Dynamics [5]. We fix the screening interval at 2 years, and derive the age- and sex-dependent BMI thresholds that minimize adult disease prevalence, subject to referring a specified percentage of children for treatment yearly. We compare this optimal biennial policy to biennial versions of the USPSTF and Expert Committee recommendations. Compared to the USPSTF recommendation, the optimal policy reduces adult disease prevalence by 3% in relative terms (the absolute reductions are < 1%) at the same treatment referral rate, or achieves the same disease prevalence at a 28% reduction in treatment referral rate. If compared to the Expert Committee recommendation, the reductions change to 6% and 40%, respectively. The optimal policy treats mostly 16 year olds and few children under age 14. Our results suggest that adult disease is minimized by focusing childhood obesity screening and treatment on older adolescents. PMID:22240724

A hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy.

PubMed

Lei, Yu; Wu, Qiuwen

2010-04-21

Offline adaptive radiotherapy (ART) has been used to effectively correct and compensate for prostate motion and reduce the required margin. The efficacy depends on the characteristics of the patient setup error and interfraction motion through the whole treatment; specifically, systematic errors are corrected and random errors are compensated for through the margins. In online image-guided radiation therapy (IGRT) of prostate cancer, the translational setup error and inter-fractional prostate motion are corrected through pre-treatment imaging and couch correction at each fraction. However, the rotation and deformation of the target are not corrected and only accounted for with margins in treatment planning. The purpose of this study was to investigate whether the offline ART strategy is necessary for an online IGRT protocol and to evaluate the benefit of the hybrid strategy. First, to investigate the rationale of the hybrid strategy, 592 cone-beam-computed tomography (CBCT) images taken before and after each fraction for an online IGRT protocol from 16 patients were analyzed. Specifically, the characteristics of prostate rotation were analyzed. It was found that there exist systematic inter-fractional prostate rotations, and they are patient specific. These rotations, if not corrected, are persistent through the treatment fraction, and rotations detected in early fractions are representative of those in later fractions. These findings suggest that the offline adaptive replanning strategy is beneficial to the online IGRT protocol with further margin reductions. Second, to quantitatively evaluate the benefit of the hybrid strategy, 412 repeated helical CT scans from 25 patients during the course of treatment were included in the replanning study. Both low-risk patients (LRP, clinical target volume, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles) were included in the simulation. The contours of prostate and seminal vesicles were delineated on each CT. The benefit of margin reduction to compensate for both rotation and deformation in the hybrid strategy was evaluated geometrically. With the hybrid strategy, the planning margins can be reduced by 1.4 mm for LRP, and 2.0 mm for IRP, compared with the standard online IGRT only, to maintain the same 99% target volume coverage. The average relative reduction in planning target volume (PTV) based on the internal target volume (ITV) from PTV based on CTV is 19% for LRP, and 27% for IRP.

Co-control of urban air pollutants and greenhouse gases in Mexico City.

PubMed

West, J Jason; Osnaya, Patricia; Laguna, Israel; Martínez, Julia; Fernández, Adrián

2004-07-01

This study addresses the synergies of mitigation measures to control urban air pollutant and greenhouse gas (GHG) emissions, in developing integrated "co-control" strategies for Mexico City. First, existing studies of emissions reduction measures--PROAIRE (the air quality plan for Mexico City) and separate GHG studies--are used to construct a harmonized database of options. Second, linear programming (LP) is developed and applied as a decision-support tool to analyze least-cost strategies for meeting co-control targets for multiple pollutants. We estimate that implementing PROAIRE measures as planned will reduce 3.1% of the 2010 metropolitan CO2 emissions, in addition to substantial local air pollutant reductions. Applying the LP, PROAIRE emissions reductions can be met at a 20% lower cost, using only the PROAIRE measures, by adjusting investments toward the more cost-effective measures; lower net costs are possible by including cost-saving GHG mitigation measures, but with increased investment. When CO2 emission reduction targets are added to PROAIRE targets, the most cost-effective solutions use PROAIRE measures for the majority of local pollutant reductions, and GHG measures for additional CO2 control. Because of synergies, the integrated planning of urban-global co-control can be beneficial, but we estimate that for Mexico City these benefits are often small.

Potential for Electrified Vehicles to Contribute to U.S. Petroleum and Climate Goals and Implications for Advanced Biofuels.

PubMed

Meier, Paul J; Cronin, Keith R; Frost, Ethan A; Runge, Troy M; Dale, Bruce E; Reinemann, Douglas J; Detlor, Jennifer

2015-07-21

To examine the national fuel and emissions impacts from increasingly electrified light-duty transportation, we reconstructed the vehicle technology portfolios from two national vehicle studies. Using these vehicle portfolios, we normalized assumptions and examined sensitivity around the rates of electrified vehicle penetration, travel demand growth, and electricity decarbonization. We further examined the impact of substituting low-carbon advanced cellulosic biofuels in place of petroleum. Twenty-seven scenarios were benchmarked against a 50% petroleum-reduction target and an 80% GHG-reduction target. We found that with high rates of electrification (40% of miles traveled) the petroleum-reduction benchmark could be satisfied, even with high travel demand growth. The same highly electrified scenarios, however, could not satisfy 80% GHG-reduction targets, even assuming 80% decarbonized electricity and no growth in travel demand. Regardless of precise consumer vehicle preferences, emissions are a function of the total reliance on electricity versus liquid fuels and the corresponding greenhouse gas intensities of both. We found that at a relatively high rate of electrification (40% of miles and 26% by fuel), an 80% GHG reduction could only be achieved with significant quantities of low-carbon liquid fuel in cases with low or moderate travel demand growth.

Co-control of local air pollutants and CO2 in the Chinese iron and steel industry.

PubMed

Mao, Xianqiang; Zeng, An; Hu, Tao; Zhou, Ji; Xing, Youkai; Liu, Shengqiang

2013-01-01

The present study proposes an integrated multipollutant cocontrol strategy framework in the context of the Chinese iron and steel industry. The unit cost of pollutant reduction (UCPR) was used to examine the cost-effectiveness of each emission reduction measure. The marginal abatement cost (MAC) curves for SO2, NOx, PM2.5, and CO2 were drawn based on the UCPR and the abatement potential. Air pollutant equivalence (APeq) captures the nature of the damage value-weights of various air pollutants and acts as uniformization multiple air pollutants index. Single pollutant abatement routes designed in accordance with the corresponding reduction targets revealed that the cocontrol strategy has promising potential. Moreover, with the same reduction cost limitations as the single pollutant abatement routes, the multipollutant cocontrol routes are able to obtain more desirable pollution reduction and health benefits. Co-control strategy generally shows cost-effective advantage over single-pollutant abatement strategy. The results are robust to changing parameters according to sensitivity analysis. Co-control strategy would be an important step to achieve energy/carbon intensity targets and pollution control targets in China. Though cocontrol strategy has got some traction in policy debates, there are barriers to integrate it into policy making in the near future in China.

Behavior analysis in consumer affairs: Retail and consumer response to publicizing food price information

PubMed Central

Greene, Brandon F.; Rouse, Mark; Green, Richard B.; Clay, Connie

1984-01-01

A popular program among consumer action groups involves publicizing comparative food price information (CFPI) gathered from retail stores. Its significance is based on the assumption that publishing CFPI maximizes retail competition (i.e., moderates price levels or price increases) and occasions more frugal store selections among consumers. We tested these assumptions during a 2-year analysis. Specifically, we monitored the prices of two distinct market baskets in the supermarkets of two midwestern cities (target and contrast cities). Following a lengthy baseline, we published the prices of only one of the market baskets at stores in the target city in the local newspaper on five different occasions. The results suggested that reductions in price inflation occurred for both market baskets at the independently operated target stores. The corporate chain stores were not similarly affected. In addition, surveys indicated that many consumers used the CFPI as a basis for store selection. Finally, the analysis included a discussion of the politics, economics, and future of CFPI programs. PMID:16795672

Electrophysiology of Memory-Updating Differs with Age

PubMed Central

Steiner, Genevieve Z.; Gonsalvez, Craig J.; De Blasio, Frances M.; Barry, Robert J.

2016-01-01

In oddball tasks, the P3 component of the event-related potential systematically varies with the time between target stimuli—the target-to-target interval (TTI). Longer TTIs result in larger P3 amplitudes and shorter latencies, and this pattern of results has been linked with working memory-updating processes. Given that working memory and the P3 have both been shown to diminish with age, the current study aimed to determine whether the linear relationship between P3 and TTI is compromised in healthy aging by comparing TTI effects on P3 amplitudes and latencies, and reaction time (RT), in young and older adults. Older adults were found to have an overall reduction in P3 amplitudes, longer latencies, an anterior shift in topography, a trend toward slower RTs, and a flatter linear relationship between P3 and TTI than young adults. Results suggest that the ability to maintain templates in working memory required for stimulus categorization decreases with age, and that as a result, neural compensatory mechanisms are employed. PMID:27378908

Simulation of neutron production using MCNPX+MCUNED.

PubMed

Erhard, M; Sauvan, P; Nolte, R

2014-10-01

In standard MCNPX, the production of neutrons by ions cannot be modelled efficiently. The MCUNED patch applied to MCNPX 2.7.0 allows to model the production of neutrons by light ions down to energies of a few kiloelectron volts. This is crucial for the simulation of neutron reference fields. The influence of target properties, such as the diffusion of reactive isotopes into the target backing or the effect of energy and angular straggling, can be studied efficiently. In this work, MCNPX/MCUNED calculations are compared with results obtained with the TARGET code for simulating neutron production. Furthermore, MCUNED incorporates more effective variance reduction techniques and a coincidence counting tally. This allows the simulation of a TCAP experiment being developed at PTB. In this experiment, 14.7-MeV neutrons will be produced by the reaction T(d,n)(4)He. The neutron fluence is determined by counting alpha particles, independently of the reaction cross section. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Electrophysiology of Memory-Updating Differs with Age.

PubMed

Steiner, Genevieve Z; Gonsalvez, Craig J; De Blasio, Frances M; Barry, Robert J

2016-01-01

In oddball tasks, the P3 component of the event-related potential systematically varies with the time between target stimuli-the target-to-target interval (TTI). Longer TTIs result in larger P3 amplitudes and shorter latencies, and this pattern of results has been linked with working memory-updating processes. Given that working memory and the P3 have both been shown to diminish with age, the current study aimed to determine whether the linear relationship between P3 and TTI is compromised in healthy aging by comparing TTI effects on P3 amplitudes and latencies, and reaction time (RT), in young and older adults. Older adults were found to have an overall reduction in P3 amplitudes, longer latencies, an anterior shift in topography, a trend toward slower RTs, and a flatter linear relationship between P3 and TTI than young adults. Results suggest that the ability to maintain templates in working memory required for stimulus categorization decreases with age, and that as a result, neural compensatory mechanisms are employed.

Body distributioin of RGD-mediated liposome in brain-targeting drug delivery.

PubMed

Qin, Jing; Chen, DaWei; Hu, Haiyang; Qiao, MingXi; Zhao, XiuLi; Chen, Baoyu

2007-09-01

RGD conjugation liposomes (RGD-liposomes) were evaluated for brain-targeting drug delivery. The flow cytometric in vitro study demonstrated that RGD-liposomes could bind to monocytes and neutrophils effectively. Ferulic acid (4-hydroxy-3-methoxycinnamic, FA) was loaded into liposomes. Rats were subjected to intrastriatal microinjections of 100 units of human recombinant IL-1beta to produce brain inflammation and caudal vein injection of three formulations (FA solution, FA liposome and RGD-coated FA liposome). Animals were sacrificed 15, 30, 60 and 120 min after administration to study the body distribution of the FA in the three formulations. HPLC was used to determine the concentration of FA in vivo with salicylic acid as internal standard. The results of body distribution indicated that RGD-coated liposomes could be mediated into the brain with a 6-fold FA concentration compared to FA solution and 3-fold in comparison to uncoated liposome. Brain targeted delivery was achieved and a reduction in dosage might be allowed.

Attentional adjustment to conflict strength: evidence from the effects of manipulating flanker-target SOA on response times and prestimulus pupil size.

PubMed

Wendt, Mike; Kiesel, Andrea; Geringswald, Franziska; Purmann, Sascha; Fischer, Rico

2014-01-01

Current models of cognitive control assume gradual adjustment of processing selectivity to the strength of conflict evoked by distractor stimuli. Using a flanker task, we varied conflict strength by manipulating target and distractor onset. Replicating previous findings, flanker interference effects were larger on trials associated with advance presentation of the flankers compared to simultaneous presentation. Controlling for stimulus and response sequence effects by excluding trials with feature repetitions from stimulus administration (Experiment 1) or from the statistical analyses (Experiment 2), we found a reduction of the flanker interference effect after high-conflict predecessor trials (i.e., trials associated with advance presentation of the flankers) but not after low-conflict predecessor trials (i.e., trials associated with simultaneous presentation of target and flankers). This result supports the assumption of conflict-strength-dependent adjustment of visual attention. The selective adaptation effect after high-conflict trials was associated with an increase in prestimulus pupil diameter, possibly reflecting increased cognitive effort of focusing attention.

Evaluation of the maximum-likelihood adaptive neural system (MLANS) applications to noncooperative IFF

NASA Astrophysics Data System (ADS)

Chernick, Julian A.; Perlovsky, Leonid I.; Tye, David M.

1994-06-01

This paper describes applications of maximum likelihood adaptive neural system (MLANS) to the characterization of clutter in IR images and to the identification of targets. The characterization of image clutter is needed to improve target detection and to enhance the ability to compare performance of different algorithms using diverse imagery data. Enhanced unambiguous IFF is important for fratricide reduction while automatic cueing and targeting is becoming an ever increasing part of operations. We utilized MLANS which is a parametric neural network that combines optimal statistical techniques with a model-based approach. This paper shows that MLANS outperforms classical classifiers, the quadratic classifier and the nearest neighbor classifier, because on the one hand it is not limited to the usual Gaussian distribution assumption and can adapt in real time to the image clutter distribution; on the other hand MLANS learns from fewer samples and is more robust than the nearest neighbor classifiers. Future research will address uncooperative IFF using fused IR and MMW data.

Cost-Reduction Roadmap for Residential Solar Photovoltaics (PV),

Science.gov Websites

2017-2030 | Solar Research | NREL Cost-Reduction Roadmap for Residential Solar Photovoltaics (PV), 2017-2030 Cost-Reduction Roadmap for Residential Solar Photovoltaics (PV), 2017-2030 This report Office (SETO) residential 2030 photovoltaics (PV) cost target of $0.05 per kilowatt-hour by identifying

Decreased echolocation performance following high-frequency hearing loss in the false killer whale (Pseudorca crassidens).

PubMed

Kloepper, L N; Nachtigall, P E; Gisiner, R; Breese, M

2010-11-01

Toothed whales and dolphins possess a hypertrophied auditory system that allows for the production and hearing of ultrasonic signals. Although the fossil record provides information on the evolution of the auditory structures found in extant odontocetes, it cannot provide information on the evolutionary pressures leading to the hypertrophied auditory system. Investigating the effect of hearing loss may provide evidence for the reason for the development of high-frequency hearing in echolocating animals by demonstrating how high-frequency hearing assists in the functioning echolocation system. The discrimination abilities of a false killer whale (Pseudorca crassidens) were measured prior to and after documented high-frequency hearing loss. In 1992, the subject had good hearing and could hear at frequencies up to 100 kHz. In 2008, the subject had lost hearing at frequencies above 40 kHz. First in 1992, and then again in 2008, the subject performed an identical echolocation task, discriminating between machined hollow aluminum cylinder targets of differing wall thickness. Performances were recorded for individual target differences and compared between both experimental years. Performances on individual targets dropped between 1992 and 2008, with a maximum performance reduction of 36.1%. These data indicate that, with a loss in high-frequency hearing, there was a concomitant reduction in echolocation discrimination ability, and suggest that the development of a hypertrophied auditory system capable of hearing at ultrasonic frequencies evolved in response to pressures for fine-scale echolocation discrimination.

Biotin Decorated Gold Nanoparticles for Targeted Delivery of a Smart-Linked Anticancer Active Copper Complex: In Vitro and In Vivo Studies.

PubMed

Pramanik, Anup K; Siddikuzzaman; Palanimuthu, Duraippandi; Somasundaram, Kumaravel; Samuelson, Ashoka G

2016-12-21

The synthesis and anticancer activity of a copper(II) diacetyl-bis(N4-methylthiosemicarbazone) complex and its nanoconjugates are reported. The copper(II) complex is connected to a carboxylic acid group through a cleavable disulfide link to enable smart delivery. The copper complex is tethered to highly water-soluble 20 nm gold nanoparticles (AuNPs), stabilized by amine terminated lipoic acid-polyethylene glycol (PEG). The gold nanoparticle carrier was further decorated with biotin to achieve targeted action. The copper complex and the conjugates with and without biotin, were tested against HeLa and HaCaT cells. They show very good anticancer activity against HeLa cells, a cell line derived from cervical cancer and are less active against HaCaT cells. Slow and sustained release of the complex from conjugates is demonstrated through cleavage of disulfide linker in the presence of glutathione (GSH), a reducing agent intrinsically present in high concentrations within cancer cells. Biotin appended conjugates do not show greater activity than conjugates without biotin against HeLa cells. This is consistent with drug uptake studies, which suggests similar uptake profiles for both conjugates in vitro. However, in vivo studies using a HeLa cell xenograft tumor model shows 3.8-fold reduction in tumor volume for the biotin conjugated nanoparticle compared to the control whereas the conjugate without biotin shows only 2.3-fold reduction in the tumor volume suggesting significant targeting.

Differential effects of subcutaneous electrical stimulation (SQS) and transcutaneous electrical nerve stimulation (TENS) in rodent models of chronic neuropathic or inflammatory pain.

PubMed

Vera-Portocarrero, Louis P; Cordero, Toni; Billstrom, Tina; Swearingen, Kim; Wacnik, Paul W; Johanek, Lisa M

2013-01-01

Electrical stimulation has been used for many years for the treatment of pain. Present-day research demonstrates that stimulation targets and parameters impact the induction of specific pain-modulating mechanisms. New targets are increasingly being investigated clinically, but the scientific rationale for a particular target is often not well established. This present study compares the behavioral effects of targeting peripheral axons by electrode placement in the subcutaneous space vs. electrode placement on the surface of the skin in a rodent model. Rodent models of inflammatory and neuropathic pain were used to investigate subcutaneous electrical stimulation (SQS) vs. transcutaneous electrical nerve stimulation (TENS). Electrical parameters and relative location of the leads were held constant under each condition. SQS had cumulative antihypersensitivity effects in both inflammatory and neuropathic pain rodent models, with significant inhibition of mechanical hypersensitivity observed on days 3-4 of treatment. In contrast, reduction of thermal hyperalgesia in the inflammatory model was observed during the first four days of treatment with SQS, and reduction of cold allodynia in the neuropathic pain model was seen only on the first day with SQS. TENS was effective in the inflammation model, and in agreement with previous studies, tolerance developed to the antihypersensitivity effects of TENS. With the exception of a reversal of cold hypersensitivity on day 1 of testing, TENS did not reveal significant analgesic effects in the neuropathic pain rodent model. The results presented show that TENS and SQS have different effects that could point to unique biologic mechanisms underlying the analgesic effect of each therapy. Furthermore, this study is the first to demonstrate in an animal model that SQS attenuates neuropathic and inflammatory-induced pain behaviors. © 2013 Medtronic, Inc.

The tick biocontrol agent Metarhizium brunneum (= M. anisopliae) (strain F52) does not reduce non-target arthropods

PubMed Central

Keesing, Felicia; Ostfeld, Richard S.

2017-01-01

Previous studies have found that Met52®, which contains the entomopathogenic fungus Metarhizium brunneum, is effective in reducing the abundance of Ixodes scapularis, the tick vector for the bacterium causing Lyme disease and for other tick-borne pathogens. Given widespread interest in effective, safe methods for controlling ticks, Met52 has the potential to be used at increasing scales. The non-target impacts of Met52, as applied for tick control, have not yet been assessed. A Before-After-Control-Impact experiment was conducted to assess the effects of Met52 on non-target arthropods in lawn and forest habitats typical of residential yards. Ground-dwelling arthropods were collected using bulk sampling of soil and litter, and pitfall sampling. Arthropods were sampled once before and twice after treatment of plots with either Met52 or water (control). Multivariate general linear models were used to jointly model the abundance of arthropod orders. For each sampling method and post-spray sampling occasion, Akaike Information Criterion values were used to compare the fits of two alternative models: one that included effects of period (before vs. after spray), habitat (lawn vs. forest), and treatment (Met52 vs. control), versus a nested null model that included effects of period, and habitat, but no treatment effect. The null model was consistently better supported by the data. Significant effects were found of period and habitat but not treatment. Retrospective power analysis indicated the study had 80% power to detect a 50% reduction in arthropod abundance, as measured by bulk samples taken before versus one week after treatment. The deployment of Met52 in suburban settings is unlikely to cause meaningful reductions in the abundance of non-target arthropods. PMID:29155838

Hypertension management: rationale for triple therapy based on mechanisms of action.

PubMed

Neutel, Joel M; Smith, David H G

2013-10-01

An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill, fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control. © 2012 John Wiley & Sons Ltd.

Understanding the contribution of non-carbon dioxide gases in deep mitigation scenarios

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

Gernaat, David; Calvin, Katherine V.; Lucas, Paul

2015-07-01

The combined 2010 emissions of methane (CH4), nitrous oxide (N2O) and the fluorinated gasses (F-gas) account for about 20-30% of total emissions and about 30% of radiative forcing. At the moment, most studies looking at reaching ambitious climate targets project the emission of carbon dioxide (CO2) to be reduced to zero (or less) by the end of the century. As for non-CO2 gases, the mitigation potential seem to be more constrained, we find that by the end of the century in the current deep mitigation scenarios non-CO2 emissions could form the lion’s share of remaining greenhouse gas emissions. In ordermore » to support effective climate policy strategies, in this paper we provide a more in-depth look at the role of non-CO2¬ emission sources (CH4, N2O and F-gases) in achieving deep mitigation targets (radiative forcing target of 2.8 W/m2 in 2100). Specifically, we look at the sectorial mitigation potential and the remaining non-CO2 emissions. By including a set of different models, we provide some insights into the associated uncertainty. Most of the remaining methane emissions in 2100 in the climate mitigation scenario come from the livestock sector. Strong reductions are seen in the energy supply sector across all models. For N2O, less reduction potential is seen compared to methane and the sectoral differences are larger between the models. The paper shows that the assumptions on remaining non-CO2 emissions are critical for the feasibility of reaching ambitious climate targets and the associated costs.« less

Introduction of a computer-based method for automated planning of reduction paths under consideration of simulated muscular forces.

PubMed

Buschbaum, Jan; Fremd, Rainer; Pohlemann, Tim; Kristen, Alexander

2017-08-01

Reduction is a crucial step in the surgical treatment of bone fractures. Finding an optimal path for restoring anatomical alignment is considered technically demanding because collisions as well as high forces caused by surrounding soft tissues can avoid desired reduction movements. The repetition of reduction movements leads to a trial-and-error process which causes a prolonged duration of surgery. By planning an appropriate reduction path-an optimal sequence of target-directed movements-these problems should be overcome. For this purpose, a computer-based method has been developed. Using the example of simple femoral shaft fractures, 3D models are generated out of CT images. A reposition algorithm aligns both fragments by reconstructing their broken edges. According to the criteria of a deduced planning strategy, a modified A*-algorithm searches collision-free route of minimal force from the dislocated into the computed target position. Muscular forces are considered using a musculoskeletal reduction model (OpenSim model), and bone collisions are detected by an appropriate method. Five femoral SYNBONE models were broken into different fracture classification types and were automatically reduced from ten randomly selected displaced positions. Highest mean translational and rotational error for achieving target alignment is [Formula: see text] and [Formula: see text]. Mean value and standard deviation of occurring forces are [Formula: see text] for M. tensor fasciae latae and [Formula: see text] for M. semitendinosus over all trials. These pathways are precise, collision-free, required forces are minimized, and thus regarded as optimal paths. A novel method for planning reduction paths under consideration of collisions and muscular forces is introduced. The results deliver additional knowledge for an appropriate tactical reduction procedure and can provide a basis for further navigated or robotic-assisted developments.

The numerical solution of ordinary differential equations by the Taylor series method

NASA Technical Reports Server (NTRS)

Silver, A. H.; Sullivan, E.

1973-01-01

A programming implementation of the Taylor series method is presented for solving ordinary differential equations. The compiler is written in PL/1, and the target language is FORTRAN IV. The reduction of a differential system to rational form is described along with the procedures required for automatic numerical integration. The Taylor method is compared with two other methods for a number of differential equations. Algorithms using the Taylor method to find the zeroes of a given differential equation and to evaluate partial derivatives are presented. An annotated listing of the PL/1 program which performs the reduction and code generation is given. Listings of the FORTRAN routines used by the Taylor series method are included along with a compilation of all the recurrence formulas used to generate the Taylor coefficients for non-rational functions.

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

Sakanaka, Katsuyuki; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Hiraoka, Masahiro

Purpose: To investigate the dosimetric advantage of intensity-modulated radiotherapy (IMRT) for whole ventricles (WV) in patients with a localized intracranial germinoma receiving induction chemotherapy. Methods and Materials: Data from 12 consecutive patients with localized intracranial germinomas who received induction chemotherapy and radiotherapy were used. Four-field coplanar three-dimensional conformal radiotherapy (3D-CRT) and seven-field coplanar IMRT plans were created. In both plans, 24 Gy was prescribed in 12 fractions for the planning target volume (PTV) involving WV and tumor bed. In IMRT planning, optimization was conducted to reduce the doses to the organs at risk (OARs) as much as possible, keeping themore » minimum dose equivalent to that of 3D-CRT. The 3D-CRT and IMRT plans were compared in terms of the dose-volume statistics for target coverage and the OARs. Results: IMRT significantly increased the percentage volume of the PTV receiving 24 Gy compared with 3D-CRT (93.5% vs. 84.8%; p = 0.007), while keeping target homogeneity equivalent to 3D-CRT (p = 0.869). The absolute percentage reduction in the irradiated volume of the normal brain receiving 100%, 75%, 50%, and 25% of 24 Gy ranged from 0.7% to 16.0% in IMRT compared with 3D-CRT (p < 0.001). No significant difference was observed in the volume of the normal brain receiving 10% and 5% of 24 Gy between IMRT and 3D-CRT. Conformation number was significantly improved in IMRT (p < 0.001). For other OARs, the mean dose to the cochlea was reduced significantly in IMRT by 22.3% of 24 Gy compared with 3D-CRT (p < 0.001). Conclusions: Compared with 3D-CRT, IMRT for WV improved the target coverage and reduced the irradiated volume of the normal brain in patients with intracranial germinomas receiving induction chemotherapy. IMRT for WV with induction chemotherapy could reduce the late side effects from cranial irradiation without compromising control of the tumor.« less

SU-F-T-198: Dosimetric Comparison of Carbon and Proton Radiotherapy for Recurrent Nasopharynx Carcinoma

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

Sheng, Y; Zhao, J; Wang, W

2016-06-15

Purpose: Various radiotherapy planning methods for locally recurrent nasopharynx carcinoma (R-NPC) have been proposed. The purpose of this study was to compare carbon and proton therapy for the treatment of R-NPC in terms of dose coverage for target volume and sparing for organs at risk (OARs). Methods: Six patients who were suffering from R-NPC and treated using carbon therapy were selected for this study. Treatment plans with a total dose of 57.5Gy (RBE) in 23 fractions were made using SIEMENS Syngo V11. An intensity-modulated radiotherapy optimization method was chosen for carbon plans (IMCT) while for proton plans both intensity-modulated radiotherapymore » (IMPT) and single beam optimization (proton-SBO) methods were chosen. Dose distributions, dose volume parameters, and selected dosimetric indices for target volumes and OARs were compared for all treatment plans. Results: All plans provided comparable PTV coverage. The volume covered by 95% of the prescribed dose was comparable for all three plans. The average values were 96.11%, 96.24% and 96.11% for IMCT, IMPT, and proton-SBO respectively. A significant reduction of the 80% and 50% dose volumes were observed for the IMCT plans compared to the IMPT and proton-SBO plans. Critical organs lateral to the target such as brain stem and spinal cord were better spared by IMPT than by proton-SBO, while IMCT spared those organs best. For organs in the beam path, such as parotid glands, the mean dose results were similar for all three plans. Conclusion: Carbon plans yielded better dose conformity than proton plans. They provided similar or better target coverage while significantly lowering the dose for normal tissues. Dose sparing for critical organs in IMPT plans was better than proton-SBO, however, IMPT is known to be more sensitive to range uncertainties. For proton plans it is essential to find a balance between the two optimization methods.« less

Essays on alternative energy policies affecting the US transportation sector

NASA Astrophysics Data System (ADS)

O'Rear, Eric G.

This dissertation encompasses three essays evaluating the impacts of different policies targeting the greenhouse gas (GHG) emissions, fuel demands, etc. of the transportation sector. Though there are some similarities across the three chapters, each essay stands alone as an independent work. The 2010 US EPA MARKAL model is used in each essay to evaluate policy effects. Essay 1 focuses on the recent increases in Corporate Average Fuel Economy (CAFE) standards, and the implications of a "rebound effect." These increases are compared to a carbon tax generating similar reductions in system-wide emissions. As anticipated, the largest reductions in fuel use by light-duty vehicles (LDV) and emissions are achieved under CAFE. Consideration of the rebound effect does little to distort CAFE benefits. Our work validates many economists' belief that a carbon tax is a more efficient approach. However, because the tax takes advantage of cheaper abatement opportunities in other sectors, reductions in transportation emissions will be much lower than what we observe with CAFE. Essay 2 compares CAFE increases with what some economists suggest would be a much more "efficient" alternative -- a system-wide oil tax internalizing some environmental externalities. Because oil taxes are likely to be implemented in addition to CAFE standards, we consider a combined policy case reflecting this. Our supplementary analysis approximates the appropriate tax rates to produce similar reductions in oil demands as CAFE (CAFE-equivalent tax rates). We discover that taxes result in greater and more cost-effective reductions in system-wide emissions and net oil imports than CAFE. The current fuel tax system is compared to three versions of a national vehicle miles traveled (VMT) tax charged to all LDVs in Essay 3. VMT taxes directly charge motorists for each mile driven and help to correct the problem of eroding tax revenues given the failure of today's fuel taxes to adjust with inflation. Results suggest that VMT taxes generate more revenue than our existing fuel tax structure, but do so at the expense of the LDV fleet becoming less fuel-inefficient. If stringent enough, VMT taxes can lead to some rather noticeable reductions in miles driven, fuel use, and emissions.

Improving management of type 2 diabetes in South Asian patients: a systematic review of intervention studies

PubMed Central

Bhurji, N; Javer, J; Gasevic, D; Khan, N A

2016-01-01

Objectives Optimal control of type 2 diabetes is challenging in many patient populations including in South Asian patients. We systematically reviewed studies on the effect of diabetes management interventions targeted at South Asian patients with type 2 diabetes on glycaemic control. Design Systematic review of MEDLINE, EMBASE and CINAHL databases for randomised controlled trials (RCTs) and pre-post-test studies (January 1990 to February 2014). Studies were stratified by where interventions were conducted (South Asia vs Western countries). Participants Patients originating from Pakistan, Bangladesh or India with type 2 diabetes. Primary outcome Change in glycated haemoglobin (HbA1c). Secondary end points included change in blood pressure, lipid levels, anthropomorphics and knowledge. Results 23 studies (15 RCTs) met criteria for analysis with 7 from Western countries (n=2532) and 16 from South Asia (n=1081). Interventions in Western countries included translated diabetes education, additional clinical care, written materials, visual aids, and bilingual community-based peers and/or health professionals. Interventions conducted in South Asia included yoga, meditation or exercise, community-based peers, health professionals and dietary education (cooking exercises). Among RCTs in India (5 trials; n=390), 4 demonstrated significant reductions in HbA1c in the intervention group compared with usual care (yoga and exercise interventions). Among the 4 RCTs conducted in Europe (n=2161), only 1 study, an education intervention of 113 patients, reported a significant reduction in HbA1c with the intervention. Lipids, blood pressure and knowledge improved in both groups with studies from India more often reporting reductions in body mass index and waist circumference. Conclusions Overall, there was little improvement in HbA1c level in diabetes management interventions targeted at South Asians living in Europe compared with usual care, although other outcomes did improve. The smaller studies in India demonstrated significant improvements in glycaemic and other end points. Novel strategies are needed to improve glycaemic control in South Asians living outside of India. PMID:27098819

Cinacalcet: a pharmacoeconomic review of its use in secondary hyperparathyroidism in end-stage renal disease.

PubMed

Plosker, Greg L

2011-09-01

This article provides an overview of the clinical profile of the calcimimetic agent cinacalcet (Mimpara®, Sensipar®) in the treatment of patients with secondary hyperparathyroidism (SHPT) undergoing dialysis for end-stage renal disease (ESRD), followed by a comprehensive review of pharmacoeconomic analyses with cinacalcet in this patient population. Most patients with ESRD undergoing dialysis develop SHPT, which is associated with disturbances in bone mineral metabolism and the development of fractures, cardiovascular disease and other clinical events. Standard treatment of SHPT includes phosphate binders and active vitamin D derivatives. However, standard treatment alone seldom achieves recommended target plasma or serum levels of parathyroid hormone (PTH), calcium and phosphorous. The addition of cinacalcet to standard therapy in patients with SHPT undergoing dialysis for ESRD improves the likelihood of achieving target biochemical levels compared with standard therapy alone. On the basis of association studies, improvements in these intermediate endpoints are likely to reduce the risk of clinical events, such as fractures and cardiovascular disease. Therefore, part of the acquisition cost of cinacalcet is likely to be offset by reductions in other healthcare resource use, such as reductions in costs associated with a lower likelihood of clinical events, as well as potential reductions in dosages of standard treatment. A number of pharmacoeconomic analyses across various country settings indicate that cinacalcet plus standard therapy is cost effective relative to standard therapy alone if dialysis costs are excluded, or that early initiation of cinacalcet is cost effective compared with delaying cinacalcet treatment until PTH levels become very uncontrolled. However, across analyses with cinacalcet, results were variable and not always favourable. This wide range of results stems from differences in selection of data sources used to populate the models, regional differences in healthcare resource use and costs, as well as other factors. Future cost-effectiveness analyses with cinacalcet should incorporate data on hard clinical outcomes from the EVOLVE study once this information becomes available.

A review of the efficacy of rosuvastatin in patients with type 2 diabetes.

PubMed

Tuomilehto, J; Leiter, L A; Kallend, D

2004-10-01

It has been estimated that 92% of individuals with type 2 diabetes, without cardiovascular disease (CVD), have a dyslipidaemic profile. Several guidelines on cardiovascular risk now recommend that patients with diabetes should be considered at high risk of CVD and should thus receive lipid-lowering therapy to reduce low-density lipoprotein cholesterol (LDL-C) to below 2.5 mmol/L. Since their introduction in 1987, statins have revolutionized the management of CVD. The most recent statin to be introduced, rosuvastatin, has been shown to be the most effective at lowering LDL-C, as well as consistently raising HDL-C across the 10-40 mg dose range. This has been confirmed by many studies, including the Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study in which rosuvastatin 10 mg was shown to be more effective than commonly used doses of other statins, both for LDL-C reduction and achieving treatment target goals. The effectiveness of rosuvastatin has also been studied in type 2 diabetes patients in three studies: the URANUS (Use of Rosuvastatin vs. Atorvastatin iN type 2 diabetes mellitUS), ANDROMEDA (A raNdomized, Double-blind study to compare Rosuvastatin [10 & 20 mg] and atOrvastatin [10 & 20 Mg] in patiEnts with type II DiAbetes) and CORALL (COmpare Rosuvastatin [10-40 mg] with Atorvastatin [20-80 mg] on apo B/apo A-1 ratio in patients with type 2 diabetes meLLitus and dyslipidaemia) studies. URANUS and ANDROMEDA showed rosuvastatin to be more effective than atorvastatin at reducing LDL-C and achieving treatment target goals. CORALL demonstrated rosuvastatin 10, 20 and 40 mg to be more effective at lowering LDL-C than 20, 40 and 80 mg of atorvastatin, respectively. Ongoing studies will evaluate whether these properties of rosuvastatin translate into beneficial effects on atherosclerosis and significant reductions in cardiovascular events.

Reductive nanocomplex encapsulation of cRGD-siRNA conjugates for enhanced targeting to cancer cells

PubMed Central

Zhang, Yanfen; Yang, Xiantao; Ma, Yuan; Guan, Zhu; Wu, Yun; Zhang, Lihe; Yang, Zhenjun

2017-01-01

In this study, through covalent conjugation and lipid material entrapment, a combined modification strategy was established for effective delivery of small interfering RNA (siRNA). Single strands of siRNA targeting to BRAFV600E gene (siMB3) conjugated with cRGD peptide at 3′-terminus or 5′-terminus via cleavable disulfide bond was synthesized and then annealed with corresponding strands to obtain single and bis-cRGD-siRNA conjugates. A cationic lipid material (CLD) developed by our laboratory was mixed with the conjugates to generate nanocomplexes; their uniformity and electrical property were revealed by particle size and zeta potential measurement. Compared with CLD/siBraf, CLD/cRGD-siBraf achieved higher cell uptake and more excellent tumor-targeting ability, especially 21 (sense-5′/antisense-3″-cRGD-congjugate) nanocomplex. Moreover, they can regulate multiple pathways to varying degree and reduce acidification of endosome. Compared with the gene silencing of different conjugates, single or bis-cRGD-conjugated siRNA showed little differences except 22 (5/5) which cRGD was conjugated at 5′-terminus of antisense strand and sense strand. However bis-cRGD conjugate 21 nanocomplex exhibited better specific target gene silencing at multiple time points. Furthermore, the serum stabilities of the bis-cRGD conjugates were higher than those of the single-cRGD conjugates. In conclusion, all these data suggested that CLD/bis-conjugates, especially CLD/21, can be an effective system for delivery of siRNA to target BRAFV600E gene for therapy of melanoma. PMID:29042774

Hyperspectral and Hypertemporal Longwave Infrared Data Characterization

NASA Astrophysics Data System (ADS)

Jeganathan, Nirmalan

The Army Research Lab conducted a persistent imaging experiment called the Spectral and Polarimetric Imagery Collection Experiment (SPICE) in 2012 and 2013 which focused on collecting and exploiting long wave infrared hyperspectral and polarimetric imagery. A part of this dataset was made for public release for research and development purposes. This thesis investigated the hyperspectral portion of this released dataset through data characterization and scene characterization of man-made and natural objects. First, the data were contrasted with MODerate resolution atmospheric TRANsmission (MODTRAN) results and found to be comparable. Instrument noise was characterized using an in-scene black panel, and was found to be comparable with the sensor manufacturer's specication. The temporal and spatial variation of certain objects in the scene were characterized. Temporal target detection was conducted on man-made objects in the scene using three target detection algorithms: spectral angle mapper (SAM), spectral matched lter (SMF) and adaptive coherence/cosine estimator (ACE). SMF produced the best results for detecting the targets when the training and testing data originated from different time periods, with a time index percentage result of 52.9%. Unsupervised and supervised classification were conducted using spectral and temporal target signatures. Temporal target signatures produced better visual classification than spectral target signature for unsupervised classification. Supervised classification yielded better results using the spectral target signatures, with a highest weighted accuracy of 99% for 7-class reference image. Four emissivity retrieval algorithms were applied on this dataset. However, the retrieved emissivities from all four methods did not represent true material emissivity and could not be used for analysis. This spectrally and temporally rich dataset enabled to conduct analysis that was not possible with other data collections. Regarding future work, applying noise-reduction techniques before applying temperature-emissivity retrieval algorithms may produce more realistic emissivity values, which could be used for target detection and material identification.

Potential impact of spatially targeted adult tuberculosis vaccine in Gujarat, India

PubMed Central

Chatterjee, Susmita; Rao, Krishna D.; Dowdy, David W.

2016-01-01

Some of the most promising vaccines in the pipeline for tuberculosis (TB) target adolescents and adults. Unlike for childhood vaccines, high-coverage population-wide vaccination is significantly more challenging for adult vaccines. Here, we aimed to estimate the impact of vaccine delivery strategies that were targeted to high-incidence geographical ‘hotspots’ compared with randomly allocated vaccination. We developed a spatially explicit mathematical model of TB transmission that distinguished these hotspots from the general population. We evaluated the impact of targeted and untargeted vaccine delivery strategies in India—a country that bears more than 25% of global TB burden, and may be a potential early adopter of the vaccine. We collected TB notification data and conducted a demonstration study in the state of Gujarat to validate our estimates of heterogeneity in TB incidence. We then projected the impact of randomly vaccinating 8% of adults in a single mass campaign to a spatially targeted vaccination preferentially delivered to 80% of adults in the hotspots, with both strategies augmented by continuous adolescent vaccination. In consultation with vaccine developers, we considered a vaccine efficacy of 60%, and evaluated the population-level impact after 10 years of vaccination. Spatial heterogeneity in TB notification (per 100 000/year) was modest in Gujarat: 190 in the hotspots versus 125 in the remaining population. At this level of heterogeneity, the spatially targeted vaccination was projected to reduce TB incidence by 28% after 10 years, compared with a 24% reduction projected to achieve via untargeted vaccination—a 1.17-fold augmentation in the impact of vaccination by spatially targeting. The degree of the augmentation was robust to reasonable variation in natural history assumptions, but depended strongly on the extent of spatial heterogeneity and mixing between the hotspot and general population. Identifying high-incidence hotspots and quantifying spatial mixing patterns are critical to accurate estimation of the value of targeted intervention strategies. PMID:27009179

Effect of molecule-particle binding on the reduction in the mixed-frequency alternating current magnetic susceptibility of magnetic bio-reagents

NASA Astrophysics Data System (ADS)

Yang, C. C.; Yang, S. Y.; Chen, H. H.; Weng, W. L.; Horng, H. E.; Chieh, J. J.; Hong, C. Y.; Yang, H. C.

2012-07-01

By specifically bio-functionalizing magnetic nanoparticles, magnetic nanoparticles are able to label target bio-molecules. This property can be applied to quantitatively detect molecules invitro by measuring the related magnetic signals of nanoparticles bound with target molecules. One of the magnetic signals is the reduction in the mixed-frequency ac magnetic susceptibility of suspended magnetic nanoparticles due to the molecule-particle association. Many experimental results show empirically that the molecular-concentration dependent reduction in ac magnetic susceptibility follows the logistic function. In this study, it has been demonstrated that the logistic behavior is originated from the growth of particle sizes due to the molecule-particle association. The analytic relationship between the growth of particle sizes and the reduction in ac magnetic susceptibility is developed.

Targeted Assessment for Prevention of Healthcare-Associated Infections: A New Prioritization Metric

PubMed Central

Soe, Minn M.; Gould, Carolyn V.; Pollock, Daniel; Edwards, Jonathan

2015-01-01

OBJECTIVE To develop a method for calculating the number of healthcare-associated infections (HAIs) that must be prevented to reach a HAI reduction goal and identifying and prioritizing healthcare facilities where the largest reductions can be achieved. SETTING Acute care hospitals that report HAI data to the Centers for Disease Control and Prevention’s National Healthcare Safety Network. METHODS The cumulative attributable difference (CAD) is calculated by subtracting a numerical prevention target from an observed number of HAIs. The prevention target is the product of the predicted number of HAIs and a standardized infection ratio goal, which represents a HAI reduction goal. The CAD is a numeric value that if positive is the number of infections to prevent to reach the HAI reduction goal. We calculated the CAD for catheter-associated urinary tract infections for each of the 3,639 hospitals that reported such data to National Healthcare Safety Network in 2013 and ranked the hospitals by their CAD values in descending order. RESULTS Of 1,578 hospitals with positive CAD values, preventing 10,040 catheter-associated urinary tract infections at 293 hospitals (19%) with the highest CAD would enable achievement of the national 25% catheter-associated urinary tract infection reduction goal. CONCLUSION The CAD is a new metric that facilitates ranking of facilities, and locations within facilities, to prioritize HAI prevention efforts where the greatest impact can be achieved toward a HAI reduction goal. PMID:26310913

Cardiotoxicity of novel HER2-targeted therapies.

PubMed

Sendur, Mehmet A N; Aksoy, Sercan; Altundag, Kadri

2013-08-01

Trastuzumab, an anti-HER2 humanized monoclonal antibody, is the standard treatment for both early and metastatic HER2-positive breast cancer. In addition to other chemotherapeutic agents, trastuzumab significantly improves response rate and survival in HER2-positive early and metastatic breast cancer. Although it is well known that trastuzumab therapy is closely associated with both symptomatic and asymptomatic cardiotoxicity, less is known about novel HER2-targeted therapies. The aim of this review is to discuss the cardiac safety data from recent studies of novel anti-HER2 drugs other than trastuzumab. Novel HER2-targeted therapies showed favorable results in HER2 positive metastatic breast cancer patients. Pubmed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched until January 2013 using the following search keywords; 'trastuzumab, trastuzumab cardiotoxicity, HER-2 targeted therapies, lapatinib, pertuzumab, trastuzumab emtansine, afatinib and neratinib'; papers which were considered relevant for the aim of this review were selected by the authors. Lapatinib, pertuzumab, T-DM1, neratinib and afatinib molecules are evaluated in the study. In a comprehensive analysis, 3689 lapatinib treated patients enrolled in 49 trials; asymptomatic cardiac events were reported in 53 patients (1.4%) and symptomatic grade III and IV systolic dysfunction was observed only in 7 patients (0.2%) treated with lapatinib. In phase I-III trials of pertuzumab, cardiac dysfunction was seen in 4.5-14.5% of patients with pertuzumab treatment and cardiac dysfunction was usually grade I and II. Cardiotoxicity of pertuzumab was usually reported with the trastuzumab combination and no additive cardiotoxicity was reported with addition of pertuzumab to trastuzumab. T-DM1 had a better safety profile compared to trastuzumab, no significant cardiotoxicity was observed with T-DM1 in heavily pre-treated patients. In the EMILIA study, only in 1.7% of patients in the T-DM1 group experienced reduction of left ventricular ejection fraction (LVEF) and grade III LVEF reduction developed only in one patient (0.2%) in the T-DM1 group compared to the lapatinib plus capacitabine group. In phase I-II trials with neratinib no cardiotoxicity was reported whereas cardiotoxicity was seen between 0-5.3% with afatinib treatment. Although cardiac toxicity has been reported as an adverse event for novel HER2-targeted therapies, cardiac dysfunction rate of the novel HER2-targeted therapies is significantly lower than the trastuzumab and combination of these agents with trastuzumab did not significantly increase the cardiac adverse events.

Assessing the response to targeted therapies in renal cell carcinoma: technical insights and practical considerations.

PubMed

Bex, Axel; Fournier, Laure; Lassau, Nathalie; Mulders, Peter; Nathan, Paul; Oyen, Wim J G; Powles, Thomas

2014-04-01

The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to significant necrosis without significant reduction in tumour size. In addition, the vascular effects of antiangiogenic therapy may occur long before there is any reduction in tumour size. To perform a systematic review of conventional and novel imaging methods for the assessment of response to targeted agents in RCC and to discuss their use from a clinical perspective. Relevant databases covering the period January 2006 to April 2013 were searched for studies reporting on the use of anatomic and functional imaging techniques to predict response to targeted therapy in RCC. Inclusion criteria were randomised trials, nonrandomised controlled studies, retrospective case series, and cohort studies. Reviews, animal and preclinical studies, case reports, and commentaries were excluded. A narrative synthesis of the evidence is presented. A total of 331 abstracts and 76 full-text articles were assessed; 34 studies met the inclusion criteria. Current methods of response assessment in RCC include anatomic methods--based on various criteria including Choi, size and attenuation CT, and morphology, attenuation, size, and structure--and functional techniques including dynamic contrast-enhanced (DCE) CT, DCE-magnetic resonance imaging, DCE-ultrasonography, positron emission tomography, and approaches utilising radiolabelled monoclonal antibodies. Functional imaging techniques are promising surrogate biomarkers of response in RCC and may be more appropriate than anatomic CT-based methods. By enabling quantification of tumour vascularisation, functional techniques can directly and rapidly detect the biologic effects of antiangiogenic therapies compared with the indirect detection of belated effects on tumour size by anatomic methods. However, larger prospective studies are needed to validate early results and standardise techniques. Copyright © 2013 European Association of Urology. All rights reserved.

First beryllium capsule implosions on the National Ignition Facility

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

Kline, J. L.; Yi, S. A.; Simakov, A. N.

2016-05-15

The first indirect drive implosion experiments using Beryllium (Be) capsules at the National Ignition Facility confirm the superior ablation properties and elucidate possible Be-ablator issues such as hohlraum filling by ablator material. Since the 1990s, Be has been the preferred Inertial Confinement Fusion (ICF) ablator because of its higher mass ablation rate compared to that of carbon-based ablators. This enables ICF target designs with higher implosion velocities at lower radiation temperatures and improved hydrodynamic stability through greater ablative stabilization. Recent experiments to demonstrate the viability of Be ablator target designs measured the backscattered laser energy, capsule implosion velocity, core implosionmore » shape from self-emission, and in-flight capsule shape from backlit imaging. The laser backscatter is similar to that from comparable plastic (CH) targets under the same hohlraum conditions. Implosion velocity measurements from backlit streaked radiography show that laser energy coupling to the hohlraum wall is comparable to plastic ablators. The measured implosion shape indicates no significant reduction of laser energy from the inner laser cone beams reaching the hohlraum wall as compared with plastic and high-density carbon ablators. These results indicate that the high mass ablation rate for beryllium capsules does not significantly alter hohlraum energetics. In addition, these data, together with data for low fill-density hohlraum performance, indicate that laser power multipliers, required to reconcile simulations with experimental observations, are likely due to our limited understanding of the hohlraum rather than the capsule physics since similar multipliers are needed for both Be and CH capsules as seen in experiments.« less

First beryllium capsule implosions on the National Ignition Facility

DOE PAGES

Kline, J. L.; Yi, S. A.; Simakov, A. N.; ...

2016-05-01

The first indirect drive implosion experiments using Beryllium (Be) capsules at the National Ignition Facility confirm the superior ablation properties and elucidate possible Be-ablator issues such as hohlraum filling by ablator material. Since the 1990s, Be has been the preferred Inertial Confinement Fusion (ICF) ablator because of its higher mass ablation rate compared to that of carbon-based ablators. This enables ICF target designs with higher implosion velocities at lower radiation temperatures and improved hydrodynamic stability through greater ablative stabilization. Recent experiments to demonstrate the viability of Be ablator target designs measured the backscattered laser energy, capsule implosion velocity, core implosionmore » shape from self-emission, and in-flight capsule shape from backlit imaging. The laser backscatter is similar to that from comparable plastic (CH) targets under the same hohlraum conditions. Implosion velocity measurements from backlit streaked radiography show that laser energy coupling to the hohlraum wall is comparable to plastic ablators. The measured implosion shape indicates no significant reduction of laser energy from the inner laser cone beams reaching the hohlraum wall as compared with plastic and high-density carbon ablators. These results indicate that the high mass ablation rate for beryllium capsules does not significantly alter hohlraum energetics. In addition, these data, together with data for low fill-density hohlraum performance, indicate that laser power multipliers, required to reconcile simulations with experimental observations, are likely due to our limited understanding of the hohlraum rather than the capsule physics since similar multipliers are needed for both Be and CH capsules as seen in experiments.« less

A Processing-Centered Look at the Contribution of Givenness to Durational Reduction

ERIC Educational Resources Information Center

Kahn, Jason M.; Arnold, Jennifer E.

2012-01-01

Givenness tends to lead to acoustic reduction in speech, but little is known about whether linguistic and non-linguistic givenness affect reduction similarly, and there is little consensus about the underlying psychological mechanisms. We examined speakers' pronunciations of target object nouns in an instruction-giving task, where speakers saw…

Economic choice for hardwood sawmill operations (ECHO)

Treesearch

P.H. Steele; Philip A. Araman; C. Boden

2002-01-01

Reductions in sawkerf on headrigs and resaws can dramatically increase lumber recovery. Research has also shown that lumber target size reductions are even more important than kerf reductions in providing increased lumber recovery. Decreases in either sawkerf or lumber size, however, always come at some cost in both capital and variable costs. Determining whether the...

Predicted Rate of Secondary Malignancies Following Adjuvant Proton Versus Photon Radiation Therapy for Thymoma.

PubMed

Vogel, J; Lin, L; Litzky, L A; Berman, A T; Simone, C B

2017-10-01

Thymic malignancies are the most common tumors of the anterior mediastinum. The benefit of adjuvant radiation therapy for stage II disease remains controversial, and patients treated with adjuvant radiation therapy are at risk of late complications, including radiation-induced secondary malignant neoplasms (SMNs), that may reduce the overall benefit of treatment. We assess the risk of predicted SMNs following adjuvant proton radiation therapy compared with photon radiation therapy after resection of stage II thymic malignancies to determine whether proton therapy improves the risk-benefit ratio. Ten consecutive patients treated with double-scattered proton beam radiation therapy (DS-PBT) were prospectively enrolled in an institutional review board-approved proton registry study. All patients were treated with DS-PBT. Intensity modulated radiation therapy (IMRT) plans for comparison were generated. SMN risk was calculated based on organ equivalent dose. Patients had a median age of 65 years (range, 25-77 years), and 60% were men. All patients had stage II disease, and many had close or positive margins (60%). The median dose was 50.4 Gy (range, 50.4-54.0 Gy) in 1.8-Gy relative biological effectiveness daily fractions. No differences in target coverage were seen with DS-PBT compared with IMRT plans. Significant reductions were seen in mean and volumetric lung, heart, and esophageal doses with DS-PBT compared with IMRT plans (all P≤.01). Significant reductions in SMNs in the lung, breast, esophagus, skin, and stomach were seen with DS-PBT compared with IMRT. For patients with thymoma diagnosed at the median national age, 5 excess secondary malignancies per 100 patients would be avoided by treating them with protons instead of photons. Treatment with proton therapy can achieve comparable target coverage but significantly reduced doses to critical normal structures, which can lead to fewer predicted SMNs compared with IMRT. By decreasing expected late complications, proton therapy may improve the therapeutic ratio of adjuvant radiation therapy for patients with stage II thymic malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

The Impact of Pollution Prevention on Toxic Environmental Releases from U.S. Manufacturing Facilities.

PubMed

Ranson, Matthew; Cox, Brendan; Keenan, Cheryl; Teitelbaum, Daniel

2015-11-03

Between 1991 and 2012, the facilities that reported to the U.S. Environmental Protection Agency's Toxic Release Inventory (TRI) Program conducted 370,000 source reduction projects. We use this data set to conduct the first quasi-experimental retrospective evaluation of how implementing a source reduction (pollution prevention) project affects the quantity of toxic chemicals released to the environment by an average industrial facility. We use a differences-in-differences methodology, which measures how implementing a source reduction project affects a facility's releases of targeted chemicals, relative to releases of (a) other untargeted chemicals from the same facility, or (b) the same chemical from other facilities in the same industry. We find that the average source reduction project causes a 9-16% decrease in releases of targeted chemicals in the year of implementation. Source reduction techniques vary in effectiveness: for example, raw material modification causes a large decrease in releases, while inventory control has no detectable effect. Our analysis suggests that in aggregate, the source reduction projects carried out in the U.S. since 1991 have prevented between 5 and 14 billion pounds of toxic releases.

The impact of temporal contingencies between cue and target onset on spatial attentional capture by subliminal onset cues.

PubMed

Schoeberl, Tobias; Ansorge, Ulrich

2018-05-15

Prior research suggested that attentional capture by subliminal abrupt onset cues is stimulus driven. In these studies, reacting was faster when a searched-for target appeared at the location of a preceding abrupt onset cue compared to when the same target appeared at a location away from the cue (cueing effect), although the earlier onset of the cue was subliminal, because it appeared as one out of three horizontally aligned placeholders with a lead time that was too short to be noticed by the participants. Because the cueing effects seemed to be independent of top-down search settings for target features, the effect was attributed to stimulus-driven attentional capture. However, prior studies did not investigate if participants experienced the cues as useful temporal warning signals and, therefore, attended to the cues in a top-down way. Here, we tested to which extent search settings based on temporal contingencies between cue and target onset could be responsible for spatial cueing effects. Cueing effects were replicated, and we showed that removing temporal contingencies between cue and target onset did not diminish the cueing effects (Experiments 1 and 2). Neither presenting the cues in the majority of trials after target onset (Experiment 1) nor presenting cue and target unrelated to one another (Experiment 2) led to a significant reduction of the spatial cueing effects. Results thus support the hypothesis that the subliminal cues captured attention in a stimulus-driven way.

Identification of watershed priority management areas under water quality constraints: A simulation-optimization approach with ideal load reduction

NASA Astrophysics Data System (ADS)

Dong, Feifei; Liu, Yong; Wu, Zhen; Chen, Yihui; Guo, Huaicheng

2018-07-01

Targeting nonpoint source (NPS) pollution hot spots is of vital importance for placement of best management practices (BMPs). Although physically-based watershed models have been widely used to estimate nutrient emissions, connections between nutrient abatement and compliance of water quality standards have been rarely considered in NPS hotspot ranking, which may lead to ineffective decision-making. It's critical to develop a strategy to identify priority management areas (PMAs) based on water quality response to nutrient load mitigation. A water quality constrained PMA identification framework was thereby proposed in this study, based on the simulation-optimization approach with ideal load reduction (ILR-SO). It integrates the physically-based Soil and Water Assessment Tool (SWAT) model and an optimization model under constraints of site-specific water quality standards. To our knowledge, it was the first effort to identify PMAs with simulation-based optimization. The SWAT model was established to simulate temporal and spatial nutrient loading and evaluate effectiveness of pollution mitigation. A metamodel was trained to establish a quantitative relationship between sources and water quality. Ranking of priority areas is based on required nutrient load reduction in each sub-watershed targeting to satisfy water quality standards in waterbodies, which was calculated with genetic algorithm (GA). The proposed approach was used for identification of PMAs on the basis of diffuse total phosphorus (TP) in Lake Dianchi Watershed, one of the three most eutrophic large lakes in China. The modeling results demonstrated that 85% of diffuse TP came from 30% of the watershed area. Compared with the two conventional targeting strategies based on overland nutrient loss and instream nutrient loading, the ILR-SO model identified distinct PMAs and narrowed down the coverage of management areas. This study addressed the urgent need to incorporate water quality response into PMA identification and showed that the ILR-SO approach is effective to guide watershed management for aquatic ecosystem restoration.

Non-target time trend screening: a data reduction strategy for detecting emerging contaminants in biological samples.

PubMed

Plassmann, Merle M; Tengstrand, Erik; Åberg, K Magnus; Benskin, Jonathan P

2016-06-01

Non-targeted mass spectrometry-based approaches for detecting novel xenobiotics in biological samples are hampered by the occurrence of naturally fluctuating endogenous substances, which are difficult to distinguish from environmental contaminants. Here, we investigate a data reduction strategy for datasets derived from a biological time series. The objective is to flag reoccurring peaks in the time series based on increasing peak intensities, thereby reducing peak lists to only those which may be associated with emerging bioaccumulative contaminants. As a result, compounds with increasing concentrations are flagged while compounds displaying random, decreasing, or steady-state time trends are removed. As an initial proof of concept, we created artificial time trends by fortifying human whole blood samples with isotopically labelled standards. Different scenarios were investigated: eight model compounds had a continuously increasing trend in the last two to nine time points, and four model compounds had a trend that reached steady state after an initial increase. Each time series was investigated at three fortification levels and one unfortified series. Following extraction, analysis by ultra performance liquid chromatography high-resolution mass spectrometry, and data processing, a total of 21,700 aligned peaks were obtained. Peaks displaying an increasing trend were filtered from randomly fluctuating peaks using time trend ratios and Spearman's rank correlation coefficients. The first approach was successful in flagging model compounds spiked at only two to three time points, while the latter approach resulted in all model compounds ranking in the top 11 % of the peak lists. Compared to initial peak lists, a combination of both approaches reduced the size of datasets by 80-85 %. Overall, non-target time trend screening represents a promising data reduction strategy for identifying emerging bioaccumulative contaminants in biological samples. Graphical abstract Using time trends to filter out emerging contaminants from large peak lists.

GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy

PubMed Central

Hu, Danrong; Mezghrani, Omar; Zhang, Lei; Chen, Yi; Ke, Xue; Ci, Tianyuan

2016-01-01

Novel breast carcinoma dual-targeted redox-responsive nanoparticles (NPs) based on cholesteryl-hyaluronic acid conjugates were designed for intracellular delivery of the antitumor drug doxorubicin (DOX). A series of reduction-responsive hyaluronic acid derivatives grafted with hydrophobic cholesteryl moiety (HA-ss-Chol) and GE11 peptide conjugated HA-ss-Chol (GE11–HA-ss-Chol) were synthesized. The obtained conjugates showed attractive self-assembly characteristics and high drug loading capacity. GE11–HA-ss-Chol NPs were highly stable under conditions mimicking normal physiological conditions, while showing a fast degradation of the vehicle’s structure and accelerating the drug release dramatically in the presence of intracellular reductive environment. Furthermore, the cellular uptake assay confirmed GE11–HA-ss-Chol NPs were taken up by MDA-MB-231 cells through CD44- and epidermal growth factor receptor-mediated endocytosis. The internalization pathways of GE11–HA-ss-Chol NPs might involve clathrin-mediated endocytosis and macropinocytosis. The intracellular distribution of DOX in GE11–HA-ss-Chol NPs showed a faster release and more efficient nuclear delivery than the insensitive control. Enhanced in vitro cytotoxicity of GE11–HA-ss-Chol DOX-NPs further confirmed the superiority of their dual-targeting and redox-responsive capacity. Moreover, in vivo imaging investigation in MDA-MB-231 tumor-bearing mice confirmed that GE11–HA-ss-Chol NPs labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide, a near-infrared fluorescence dye, possessed a preferable tumor accumulation ability as compared to the single-targeting counterpart (HA-ss-Chol NPs). The antitumor efficacy showed an improved therapy efficacy and lower systemic side effect. These results suggest GE11–HA-ss-Chol NPs provide a good potential platform for antitumor drugs. PMID:27785019

Assessment of environmental co-benefits of energy system decarbonisation - the case of UK air quality using Remote Sensing and Model simulations

NASA Astrophysics Data System (ADS)

Sobral Mourao, Z.; Konadu, D. D.; Damoah, R.

2016-12-01

The UK has a binding obligation to reduce GHG emission by 80% (based on 1990 levels) by 2050. Meeting this target requires extensive decarbonisation of the UK energy system. Different pathways that achieve this target at the lowest system costs are being explored at different levels of policy and decisions on future energy infrastructure. Whilst benefits of decarbonisation are mainly focused on the impacts on climate change, there are other potential environmental and health impacts such as air-quality. In particular, a decrease in fossil fuel use by directly substituting current systems with low-carbon technologies could lead to significant reductions in the concentrations of SO2, NOX, CO and other atmospheric pollutants. So far, the proposed decarbonisation pathways tend to target the electricity sector first, followed by a transition in transport and heating technologies and use. However, the spatial dimension of where short term changes in the energy sector occur in relation to high density population areas is not taken into account when defining the energy transition strategies. This may lead to limited short-term improvements in air quality within urban areas, where use of fossil fuels for heating and transport is the main contribution to overall atmospheric pollutant levels. It is therefore imperative to explore decarbonisation strategies that prioritise transition in sectors of the energy system that produce immediate improvements in air quality in key regions of the UK. This study aims to use a combination of Remote Sensing observations and atmospheric chemistry/transport modelling approaches to estimate and map the atmospheric pollutants impact of the traditional approach of decarbonising electricity first compared to a slower transition in the electricity sector, but faster change in end use sectors (heating and transport). This would provide an additional standard to compare future energy system pathways beyond the traditional metrics of cost and GHG emissions reductions.

Cardiac dose reduction with deep inspiration breath hold for left-sided breast cancer radiotherapy patients with and without regional nodal irradiation.

PubMed

Yeung, Rosanna; Conroy, Leigh; Long, Karen; Walrath, Daphne; Li, Haocheng; Smith, Wendy; Hudson, Alana; Phan, Tien

2015-09-22

Deep inspiration breath hold (DIBH) reduces heart and left anterior descending artery (LAD) dose during left-sided breast radiation therapy (RT); however there is limited information about which patients derive the most benefit from DIBH. The primary objective of this study was to determine which patients benefit the most from DIBH by comparing percent reduction in mean cardiac dose conferred by DIBH for patients treated with whole breast RT ± boost (WBRT) versus those receiving breast/chest wall plus regional nodal irradiation, including internal mammary chain (IMC) nodes (B/CWRT + RNI) using a modified wide tangent technique. A secondary objective was to determine if DIBH was required to meet a proposed heart dose constraint of Dmean < 4 Gy in these two cohorts. Twenty consecutive patients underwent CT simulation both free breathing (FB) and DIBH. Patients were grouped into two cohorts: WBRT (n = 11) and B/CWRT + RNI (n = 9). 3D-conformal plans were developed and FB was compared to DIBH for each cohort using Wilcoxon signed-rank tests for continuous variables and McNemar's test for discrete variables. The percent relative reduction conferred by DIBH in mean heart and LAD dose, as well as lung V20 were compared between the two cohorts using Wilcox rank-sum testing. The significance level was set at 0.05 with Bonferroni correction for multiple testing. All patients had comparable target coverage on DIBH and FB. DIBH statistically significantly reduced mean heart and LAD dose for both cohorts. Percent reduction in mean heart and LAD dose with DIBH was significantly larger in the B/CWRT + RNI cohort compared to WBRT group (relative reduction in mean heart and LAD dose: 55.9 % and 72.1 % versus 29.2 % and 43.5 %, p < 0.02). All patients in the WBRT group and five patients (56 %) in the B/CWBRT + RNI group met heart Dmean <4 Gy with FB. All patients met this constraint with DIBH. All patients receiving WBRT met Dmean Heart < 4 Gy on FB, while only slightly over half of patients receiving B/CWRT + RNI were able to meet this constraint in FB. DIBH allowed a greater reduction in mean heart and LAD dose in patients receiving B/CWRT + RNI, including IMC nodes than patients receiving WBRT. These findings suggest greatest benefit from DIBH treatment for patients receiving regional nodal irradiation.

A modeling analysis of alternative primary and secondary US ozone standards in urban and rural areas

NASA Astrophysics Data System (ADS)

Nopmongcol, Uarporn; Emery, Chris; Sakulyanontvittaya, Tanarit; Jung, Jaegun; Knipping, Eladio; Yarwood, Greg

2014-12-01

This study employed the High-Order Decoupled Direct Method (HDDM) of sensitivity analysis in a photochemical grid model to determine US anthropogenic emissions reductions required from 2006 levels to meet alternative US primary (health-based) and secondary (welfare-based) ozone (O3) standards. Applying the modeling techniques developed by Yarwood et al. (2013), we specifically evaluated sector-wide emission reductions needed to meet primary standards in the range of 60-75 ppb, and secondary standards in the range of 7-15 ppm-h, in 22 cities and at 20 rural sites across the US for NOx-only, combined NOx and VOC, and VOC-only scenarios. Site-specific model biases were taken into account by applying adjustment factors separately for the primary and secondary standard metrics, analogous to the US Environmental Protection Agency's (EPA) relative response factor technique. Both bias-adjusted and unadjusted results are presented and analyzed. We found that the secondary metric does not necessarily respond to emission reductions the same way the primary metric does, indicating sensitivity to their different forms. Combined NOx and VOC reductions are most effective for cities, whereas NOx-only reductions are sufficient at rural sites. Most cities we examined require more than 50% US anthropogenic emission reductions from 2006 levels to meet the current primary 75 ppb US standard and secondary 15 ppm-h target. Most rural sites require less than 20% reductions to meet the primary 75 ppb standard and less than 40% reductions to meet the secondary 15 ppm-h target. Whether the primary standard is protective of the secondary standard depends on the combination of alternative standard levels. Our modeling suggests that the current 75 ppb standard achieves a 15 ppm-h secondary target in most (17 of 22) cities, but only half of the rural sites; the inability for several western cities and rural areas to achieve the seasonally-summed secondary 15 ppm-h target while meeting the 75 ppb primary target is likely driven by higher background O3 that is commonly reported in the western US. However, a 70 ppb primary standard is protective of a 15 ppm-h secondary standard in all cities and 18 of 20 rural sites we examined, and a 60 ppb primary standard is protective of a 7 ppm-h secondary standard in all cities and 19 of 20 rural sites. If EPA promulgates separate primary and secondary standards, exceedance areas will need to develop and demonstrate control strategies to achieve both. This HDDM analysis provides an illustrative screening assessment by which to estimate emissions reductions necessary to satisfy both standards.

Moab, Utah: Using Energy Data to Target Carbon Reductions from Building Energy Efficiency (City Energy: From Data to Decisions)

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

Strategic Priorities and Impact Analysis Team, Office of Strategic Programs

This fact sheet "Moab, Utah: Using Energy Data to Target Carbon Reductions from Building Energy Efficiency" explains how the City of Moab used data from the U.S. Department of Energy's Cities Leading through Energy Analysis and Planning (Cities-LEAP) and the State and Local Energy Data (SLED) programs to inform its city energy planning. It is one of ten fact sheets in the "City Energy: From Data to Decisions" series.

Cytoplasmic delivery of ribozymes leads to efficient reduction in alpha-lactalbumin mRNA levels in C127I mouse cells.

PubMed Central

L'Huillier, P J; Davis, S R; Bellamy, A R

1992-01-01

Ribozymes targeted to five sites along the alpha-lactalbumin (alpha-lac) mRNA were delivered to the cytoplasm of mouse C127I mammary cells using the T7-vaccinia virus delivery system and the amount of alpha-lac mRNA was monitored 24-48 h post-transfection. Three target sites were selected in the alpha-lac coding region (nucleotides 15, 145 and 361) and two were located in the 3' non-coding region (nucleotides 442 and 694). Acting in trans and at a target:ribozyme ratio of 1:1000, ribozymes targeting sites 361 and 694 reduced alpha-lac mRNA by > 80%; another two ribozymes (targeting nucleotides 442 and 145) reduced mRNA levels by 80 and 60% respectively; the fifth ribozyme (targeting nucleotide 15, near the AUG) was largely ineffective. The kinetic activity (kcat) of each ribozyme in vitro was somewhat predictive of the activity of the two ribozymes that targeted nucleotides 361 and 694, but was not predictive of the in vivo activity of the other three ribozymes. Down-regulation of the intracellular levels of alpha-lac paralleled the ribozyme-dependent reduction achieved for mRNA. For site 442, the reduction in both mRNA and protein was attributed to the catalytic activity of the ribozyme rather than to the antisense effects of the flanking arms, because delivery of an engineered (catalytically-inactive) variant had no effect on mRNA levels and a minimal effect on the level of alpha-lac present in the cell. Images PMID:1425576

Educational Targeting in the Fight against Poverty: Limits, Omissions and Opportunities

ERIC Educational Resources Information Center

Tarabini, Aina

2008-01-01

Educational targeting has become one of the hegemonic mechanisms in the fight against poverty. Both international organisms and developing countries support targeting as one of the best strategies in order to simultaneously guarantee poverty reduction and economic growth, and consequently to tackle the challenges generated by globalisation. 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

Multiple models guide strategies for agricultural nutrient reductions

USGS Publications Warehouse

Scavia, Donald; Kalcic, Margaret; Muenich, Rebecca Logsdon; Read, Jennifer; Aloysius, Noel; Bertani, Isabella; Boles, Chelsie; Confesor, Remegio; DePinto, Joseph; Gildow, Marie; Martin, Jay; Redder, Todd; Robertson, Dale M.; Sowa, Scott P.; Wang, Yu-Chen; Yen, Haw

2017-01-01

In response to degraded water quality, federal policy makers in the US and Canada called for a 40% reduction in phosphorus (P) loads to Lake Erie, and state and provincial policy makers in the Great Lakes region set a load-reduction target for the year 2025. Here, we configured five separate SWAT (US Department of Agriculture's Soil and Water Assessment Tool) models to assess load reduction strategies for the agriculturally dominated Maumee River watershed, the largest P source contributing to toxic algal blooms in Lake Erie. Although several potential pathways may achieve the target loads, our results show that any successful pathway will require large-scale implementation of multiple practices. For example, one successful pathway involved targeting 50% of row cropland that has the highest P loss in the watershed with a combination of three practices: subsurface application of P fertilizers, planting cereal rye as a winter cover crop, and installing buffer strips. Achieving these levels of implementation will require local, state/provincial, and federal agencies to collaborate with the private sector to set shared implementation goals and to demand innovation and honest assessments of water quality-related programs, policies, and partnerships.

Improved Efficiency and Robustness in qPCR and Multiplex End-Point PCR by Twisted Intercalating Nucleic Acid Modified Primers

PubMed Central

Schneider, Uffe Vest; Mikkelsen, Nikolaj Dam; Lindqvist, Anja; Okkels, Limei Meng; Jøhnk, Nina; Lisby, Gorm

2012-01-01

We introduce quantitative polymerase chain reaction (qPCR) primers and multiplex end-point PCR primers modified by the addition of a single ortho-Twisted Intercalating Nucleic Acid (o-TINA) molecule at the 5′-end. In qPCR, the 5′-o-TINA modified primers allow for a qPCR efficiency of 100% at significantly stressed reaction conditions, increasing the robustness of qPCR assays compared to unmodified primers. In samples spiked with genomic DNA, 5′-o-TINA modified primers improve the robustness by increased sensitivity and specificity compared to unmodified DNA primers. In unspiked samples, replacement of unmodified DNA primers with 5′-o-TINA modified primers permits an increased qPCR stringency. Compared to unmodified DNA primers, this allows for a qPCR efficiency of 100% at lowered primer concentrations and at increased annealing temperatures with unaltered cross-reactivity for primers with single nucleobase mismatches. In a previously published octaplex end-point PCR targeting diarrheagenic Escherichia coli, application of 5′-o-TINA modified primers allows for a further reduction (>45% or approximately one hour) in overall PCR program length, while sustaining the amplification and analytical sensitivity for all targets in crude bacterial lysates. For all crude bacterial lysates, 5′-o-TINA modified primers permit a substantial increase in PCR stringency in terms of lower primer concentrations and higher annealing temperatures for all eight targets. Additionally, crude bacterial lysates spiked with human genomic DNA show lesser formation of non-target amplicons implying increased robustness. Thus, 5′-o-TINA modified primers are advantageous in PCR assays, where one or more primer pairs are required to perform at stressed reaction conditions. PMID:22701644

Optimal Normal Tissue Sparing in Craniospinal Axis Irradiation Using IMRT With Daily Intrafractionally Modulated Junction(s)

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

Kusters, Johannes M.A.M.; Louwe, Rob J.W.; Kollenburg, Peter G.M. van

2011-12-01

Purpose: To develop a treatment technique for craniospinal irradiation using intensity-modulated radiotherapy (IMRT) with improved dose homogeneity at the field junction(s), increased target volume conformity, and minimized dose to the organs at risk (OARs). Methods and Materials: Five patients with high-risk medulloblastoma underwent CT simulation in supine position. For each patient, an IMRT plan with daily intrafractionally modulated junction(s) was generated, as well as a treatment plan based on conventional three-dimensional planning (3DCRT). A dose of 39.6 Gy in 22 daily fractions of 1.8 Gy was prescribed. Dose-volume parameters for target volumes and OARs were compared for the two techniques.more » Results: The maximum dose with IMRT was <107% in all patients. V{sub <95} and V{sub >107} were <1 cm{sup 3} for IMRT compared with 3-9 cm{sup 3} for the craniospinal and 26-43 cm{sup 3} for the spinal-spinal junction with 3DCRT. These observations corresponded with a lower homogeneity index and a higher conformity index for the spinal planning target volume with IMRT. IMRT provided considerable sparing of acute and late reacting tissues. V{sub 75} for the esophagus, gastroesophageal junction, and intestine was 81%, 81%, and 22% with 3DCRT versus 5%, 0%, and 1% with IMRT, respectively. V{sub 75} for the heart and thyroid was 42% and 32% vs. 0% with IMRT. Conclusion: IMRT with daily intrafractionally modulated junction results in a superior target coverage and junction homogeneity compared with 3DCRT. A significant dose reduction can be obtained for acute as well as late-reacting tissues.« less

Recommendations for Methicillin-Resistant Staphylococcus aureus Prevention in Adult ICUs: A Cost-Effectiveness Analysis.

PubMed

Whittington, Melanie D; Atherly, Adam J; Curtis, Donna J; Lindrooth, Richard C; Bradley, Cathy J; Campbell, Jonathan D

2017-08-01

Patients in the ICU are at the greatest risk of contracting healthcare-associated infections like methicillin-resistant Staphylococcus aureus. This study calculates the cost-effectiveness of methicillin-resistant S aureus prevention strategies and recommends specific strategies based on screening test implementation. A cost-effectiveness analysis using a Markov model from the hospital perspective was conducted to determine if the implementation costs of methicillin-resistant S aureus prevention strategies are justified by associated reductions in methicillin-resistant S aureus infections and improvements in quality-adjusted life years. Univariate and probabilistic sensitivity analyses determined the influence of input variation on the cost-effectiveness. ICU. Hypothetical cohort of adults admitted to the ICU. Three prevention strategies were evaluated, including universal decolonization, targeted decolonization, and screening and isolation. Because prevention strategies have a screening component, the screening test in the model was varied to reflect commonly used screening test categories, including conventional culture, chromogenic agar, and polymerase chain reaction. Universal and targeted decolonization are less costly and more effective than screening and isolation. This is consistent for all screening tests. When compared with targeted decolonization, universal decolonization is cost-saving to cost-effective, with maximum cost savings occurring when a hospital uses more expensive screening tests like polymerase chain reaction. Results were robust to sensitivity analyses. As compared with screening and isolation, the current standard practice in ICUs, targeted decolonization, and universal decolonization are less costly and more effective. This supports updating the standard practice to a decolonization approach.

Aptamer-conjugated Magnetic Nanoparticles as Targeted Magnetic Resonance Imaging Contrast Agent for Breast Cancer.

PubMed

Keshtkar, Mohammad; Shahbazi-Gahrouei, Daryoush; Khoshfetrat, Seyyed Mehdi; Mehrgardi, Masoud A; Aghaei, Mahmoud

2016-01-01

Early detection of breast cancer is the most effective way to improve the survival rate in women. Magnetic resonance imaging (MRI) offers high spatial resolution and good anatomic details, and its lower sensitivity can be improved by using targeted molecular imaging. In this study, AS1411 aptamer was conjugated to Fe 3 O 4 @Au nanoparticles for specific targeting of mouse mammary carcinoma (4T1) cells that overexpress nucleolin. In vitro cytotoxicity of aptamer-conjugated nanoparticles was assessed on 4T1 and HFFF-PI6 (control) cells. The ability of the synthesized nanoprobe to target specifically the nucleolin overexpressed cells was assessed with the MRI technique. Results show that the synthesized nanoprobe produced strongly darkened T 2 -weighted magnetic resonance (MR) images with 4T1 cells, whereas the MR images of HFFF-PI6 cells incubated with the nanoprobe are brighter, showing small changes compared to water. The results demonstrate that in a Fe concentration of 45 μg/mL, the nanoprobe reduced by 90% MR image intensity in 4T1 cells compared with the 27% reduction in HFFF-PI6 cells. Analysis of MR signal intensity showed statistically significant signal intensity difference between 4T1 and HFFF-PI6 cells treated with the nanoprobe. MRI experiments demonstrate the high potential of the synthesized nanoprobe as a specific MRI contrast agent for detection of nucleolin-expressing breast cancer cells.

Sacroiliac joint pain: Prospective, randomised, experimental and comparative study of thermal radiofrequency with sacroiliac joint block.

PubMed

Cánovas Martínez, L; Orduña Valls, J; Paramés Mosquera, E; Lamelas Rodríguez, L; Rojas Gil, S; Domínguez García, M

2016-05-01

To compare the analgesic effects between the blockade and bipolar thermal radiofrequency in the treatment of sacroiliac joint pain. Prospective, randomised and experimental study conducted on 60 patients selected in the two hospitals over a period of nine months, who had intense sacroiliac joint pain (Visual Analogue Scale [VAS]>6) that lasted more than 3 months. Patients were randomised into three groups (n=20): Group A (two intra-articular sacroiliac injections of local anaesthetic/corticosteroid guided by ultrasound in 7 days). Group B: conventional bipolar radiofrequency "palisade". Target points were the lateral branch nerves of S1, S2, and S3, distance needles 1cm. Group C: modified bipolar radiofrequency "palisade" (needle distance >1cm). Patients were evaluated at one month, three months, and one year. Demographic data, VAS reduction, and side effects of the techniques were assessed. One month after the treatment, pain reduction was >50% in the three groups P<.001. Three and 12 months after the technique, the patients of the group A did not have a significant reduction in pain. At 3 months, almost 50% patients of the group B referred to improvement of the pain (P=.03), and <25% at 12 months, and those results were statistically significant (P=.01) compared to the baseline. Group C showed an improvement of 50% at 3 and 12 months (P<.001). All patients completed the study. Bipolar radiofrequency "palisade", especially when the distance between the needles was increased, was more effective and lasted longer, compared to join block and steroids, in relieving pain sacroiliac joint. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

A cooperative reduction model for regional air pollution control in China that considers adverse health effects and pollutant reduction costs.

PubMed

Xie, Yujing; Zhao, Laijun; Xue, Jian; Hu, Qingmi; Xu, Xiang; Wang, Hongbo

2016-12-15

How to effectively control severe regional air pollution has become a focus of global concern recently. The non-cooperative reduction model (NCRM) is still the main air pollution control pattern in China, but it is both ineffective and costly, because each province must independently fight air pollution. Thus, we proposed a cooperative reduction model (CRM), with the goal of maximizing the reduction in adverse health effects (AHEs) at the lowest cost by encouraging neighboring areas to jointly control air pollution. CRM has two parts: a model of optimal pollutant removal rates using two optimization objectives (maximizing the reduction in AHEs and minimizing pollutant reduction cost) while meeting the regional pollution control targets set by the central government, and a model that allocates the cooperation benefits (i.e., health improvement and cost reduction) among the participants according to their contributions using the Shapley value method. We applied CRM to the case of sulfur dioxide (SO 2 ) reduction in Yangtze River Delta region. Based on data from 2003 to 2013, and using mortality due to respiratory and cardiovascular diseases as the health endpoints, CRM saves 437 more lives than NCRM, amounting to 12.1% of the reduction under NCRM. CRM also reduced costs by US $65.8×10 6 compared with NCRM, which is 5.2% of the total cost of NCRM. Thus, CRM performs significantly better than NCRM. Each province obtains significant benefits from cooperation, which can motivate them to actively cooperate in the long term. A sensitivity analysis was performed to quantify the effects of parameter values on the cooperation benefits. Results shown that the CRM is not sensitive to the changes in each province's pollutant carrying capacity and the minimum pollutant removal capacity, but sensitive to the maximum pollutant reduction capacity. Moreover, higher cooperation benefits will be generated when a province's maximum pollutant reduction capacity increases. Copyright © 2016 Elsevier B.V. All rights reserved.

Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

PubMed Central

Crowe, Scott B; Kairn, Tanya; Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T; Kenny, John; Langton, Christian M; Trapp, Jamie V

2013-01-01

Introduction This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Methods Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. Results The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. Conclusions This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT. PMID:26229621

Dosimetric comparison of helical tomotherapy, intensity-modulated radiation therapy, volumetric-modulated arc therapy, and 3-dimensional conformal therapy for the treatment of T1N0 glottic cancer

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

Ekici, Kemal, E-mail: drkemal06@hotmail.com; Pepele, Eda K.; Yaprak, Bahaddin

2016-01-01

Various radiotherapy planning methods for T1N0 laryngeal cancer have been proposed to decrease normal tissue toxicity. We compare helical tomotherapy (HT), linac-based intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and 3-D conformal radiotherapy (3D-CRT) techniques for T1N0 laryngeal cancer. Overall, 10 patients with T1N0 laryngeal cancer were selected and evaluated. Furthermore, 10 radiotherapy treatment plans have been created for all 10 patients, including HT, IMRT, VMAT, and 3D-CRT. IMRT, VMAT, and HT plans vs 3D-CRT plans consistently provided superior planning target volume (PTV) coverage. Similar target coverage was observed between the 3 IMRT modalities. Compared with 3D-CRT, IMRT, HT,more » and VMAT significantly reduced the mean dose to the carotid arteries. VMAT resulted in the lowest mean dose to the submandibular and thyroid glands. Compared with 3D-CRT, IMRT, HT, and VMAT significantly increased the maximum dose to the spinal cord It was observed that the 3 IMRT modalities studied showed superior target coverage with less variation between each plan in comparison with 3D-CRT. The 3D-CRT plans performed better at the D{sub max} of the spinal cord. Clinical investigation is warranted to determine if these treatment approaches would translate into a reduction in radiation therapy–induced toxicities.« less

Value of Public Health Funding in Preventing Hospital Bloodstream Infections in the United States.

PubMed

Whittington, Melanie D; Bradley, Cathy J; Atherly, Adam J; Campbell, Jonathan D; Lindrooth, Richard C

2017-11-01

To estimate the association of 1 activity of the Prevention and Public Health Fund with hospital bloodstream infections and calculate the return on investment (ROI). The activity was funded for 1 year (2013). A difference-in-differences specification evaluated hospital standardized infection ratios (SIRs) before funding allocation (years 2011 and 2012) and after funding allocation (years 2013 and 2014) in the 15 US states that received the funding compared with hospital SIRs in states that did not receive the funding. We estimated the association of the funded public health activity with SIRs for bloodstream infections. We calculated the ROI by dividing cost offsets from infections averted by the amount invested. The funding was associated with a 33% (P < .05) reduction in SIRs and an ROI of $1.10 to $11.20 per $1 invested in the year of funding allocation (2013). In 2014, after the funding stopped, significant reductions were no longer evident. This activity was associated with a reduction in bloodstream infections large enough to recoup the investment. Public health funding of carefully targeted areas may improve health and reduce health care costs.

Different systolic blood pressure targets for people with history of stroke or transient ischaemic attack: PAST-BP (Prevention After Stroke—Blood Pressure) randomised controlled trial

PubMed Central

McManus, Richard J; Roalfe, Andrea; Fletcher, Kate; Taylor, Clare J; Martin, Una; Virdee, Satnam; Greenfield, Sheila; Hobbs, F D Richard

2016-01-01

Objective To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease. Design Open label randomised controlled trial. Setting 99 general practices in England, with participants recruited in 2009-11. Participants People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above. Interventions Intensive systolic blood pressure target (<130 mm Hg or 10 mm Hg reduction from baseline if this was <140 mm Hg) or standard target (<140 mm Hg). Apart from the different target, patients in both arms were actively managed in the same way with regular reviews by the primary care team. Main outcome measure Change in systolic blood pressure between baseline and 12 months. Results 529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period (52 intensive arm; 32 standard arm). Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm (difference between groups 2.9 (95% confidence interval 0.2 to 5.7) mm Hg; P=0.03). Conclusions Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a <140 mm Hg target led to a clinically important reduction in blood pressure. Trial registration Current Controlled Trials ISRCTN29062286. PMID:26919870

Metaproteomics Identifies the Protein Machinery Involved in Metal and Radionuclide Reduction in Subsurface Microbiomes and Elucidates Mechanisms and U(VI) Reduction Immobilization

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

Pfiffner, Susan M.; Löffler, Frank; Ritalahti, Kirsti

The overall goal for this funded project was to develop and exploit environmental metaproteomics tools to identify biomarkers for monitoring microbial activity affecting U speciation at U-contaminated sites, correlate metaproteomics profiles with geochemical parameters and U(VI) reduction activity (or lack thereof), elucidate mechanisms contributing to U(VI) reduction, and provide remediation project managers with additional information to make science-based site management decisions for achieving cleanup goals more efficiently. Although significant progress has been made in elucidating the microbiology contribution to metal and radionuclide reduction, the cellular components, pathway(s), and mechanisms involved in U trans-formation remain poorly understood. Recent advances in (meta)proteomicsmore » technology enable detailed studies of complex samples, including environmental samples, which differ between sites and even show considerable variability within the same site (e.g., the Oak Ridge IFRC site). Additionally, site-specific geochemical conditions affect microbial activity and function, suggesting generalized assessment and interpretations may not suffice. This research effort integrated current understanding of the microbiology and biochemistry of U(VI) reduction and capitalize on advances in proteomics technology made over the past few years. Field-related analyses used Oak Ridge IFRC field ground water samples from locations where slow-release substrate biostimulation has been implemented to accelerate in situ U(VI) reduction rates. Our overarching hypothesis was that the metabolic signature in environmental samples, as deciphered by the metaproteome measurements, would show a relationship with U(VI) reduction activity. Since metaproteomic and metagenomic characterizations were computationally challenging and time-consuming, we used a tiered approach that combines database mining, controlled laboratory studies, U(VI) reduction activity measurements, phylogenetic analyses, and gene expression studies to support the metaproteomics characterizations. Growth experiments of target microorganisms (Anaeromyxobacter, Shewanella, Geobacter) revealed tremendous respiratory versatility, as evidenced by the ability to utilize a range of electron donors (e.g. acetate, hydrogen, pyruvate, lactate, succinate, formate) and electron acceptors (e.g. nitrate, fumarate, halogenated phenols, ferric iron, nitrous oxide, etc.). In particular, the dissimilatory metabolic reduction of metals, including radionuclides, by target microorganisms spurred interest for in situ bioremediation of contaminated soils and sediments. Distinct c-type cytochrome expression patterns were observed in target microorganisms grown with the different electron acceptors. For each target microorganism, the core proteome covered almost all metabolic pathways represented by their corresponding pan-proteomes. Unique proteins were detected for each target microorganism, and their expression and possible functionalities were linked to specific growth conditions through proteomics measurements. Optimization of the proteomic tools included in-depth comprehensive metagenomic and metaproteomic analyses on a limited number of samples. The optimized metaproteomic analyses were then applied to Oak Ridge IFRC field samples from the slow-release substrate biostimulation. Metaproteomic analysis and pathway mapping results demonstrated the distinct effects of metal and non-metal growth conditions on the proteome expression. With these metaproteomic tools, we identified which previously hypothetical metabolic pathways were active during the analyzed time points of the slow release substrate biostimulation. Thus, we demonstrated the utility of these tools for site assessment, efficient implementation of bioremediation and long-term monitoring. This research of detailed protein analysis linked with metal reduction activity did (1) show that c-type cytochrome isoforms, previously associated with radionuclide reduction activity, are suitable biomarkers, (2) identify new biomarker targets for site assessment and bioremediation monitoring, and (3) provide new information about specific proteins and mechanisms involved in U(VI) reduction and immobilization. This expanded metagenomic and metaproteomic toolbox contributed to implementing science-driven site management with broad benefits to the DOE mission.« less

Missing texture reconstruction method based on error reduction algorithm using Fourier transform magnitude estimation scheme.

PubMed

Ogawa, Takahiro; Haseyama, Miki

2013-03-01

A missing texture reconstruction method based on an error reduction (ER) algorithm, including a novel estimation scheme of Fourier transform magnitudes is presented in this brief. In our method, Fourier transform magnitude is estimated for a target patch including missing areas, and the missing intensities are estimated by retrieving its phase based on the ER algorithm. Specifically, by monitoring errors converged in the ER algorithm, known patches whose Fourier transform magnitudes are similar to that of the target patch are selected from the target image. In the second approach, the Fourier transform magnitude of the target patch is estimated from those of the selected known patches and their corresponding errors. Consequently, by using the ER algorithm, we can estimate both the Fourier transform magnitudes and phases to reconstruct the missing areas.

Feasibility of reaching world health organization targets for hepatitis C and the cost-effectiveness of alternative strategies.

PubMed

Wisløff, T; White, R; Dalgard, O; Amundsen, E J; Meijerink, H; Kløvstad, H

2018-04-06

New drugs for treating hepatitis C have considerably increased the probability of being cured. Treatment uptake, however, is still low. The objectives of this study were to analyse the impact of initiatives that may increase the proportion of infected people on treatment and interventions aimed at reducing the incidence of new infection among people who inject drugs. A compartmental model for Norway was used to simulate hepatitis C and related complications. We analysed 2 different screening initiatives aimed to increase the proportion of infected people on treatment. Interventions aiming at reducing the hepatitis C incidence analysed were opioid substitution therapy (OST), a clean needle and syringe programme and a combination of both. The most cost-effective strategy for increasing hepatitis C treatment uptake was screening by general practitioners while simultaneously allowing for all infected people to be treated. We estimated that this intervention reduces the incidence of hepatitis C by 2030 by 63% compared with the current incidence. The 2 harm reduction strategies both reduced the incidence of hepatitis C by about 70%. Combining an increase in the current clean needles and syringe programme with OST was clearly the most cost-effective option. This strategy would reduce the incidence of hepatitis C by 80% compared with the current incidence by 2030. Thus, interventions to reduce the burden and spread of hepatitis C are cost-effective. Reaching the WHO target of a 90% reduction in hepatitis C incidence by 2030 may be difficult without combining different initiatives. © 2018 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

Esophageal cancer dose escalation using a simultaneous integrated boost technique.

PubMed

Welsh, James; Palmer, Matthew B; Ajani, Jaffer A; Liao, Zhongxing; Swisher, Steven G; Hofstetter, Wayne L; Allen, Pamela K; Settle, Steven H; Gomez, Daniel; Likhacheva, Anna; Cox, James D; Komaki, Ritsuko

2012-01-01

We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. Treatment plans were generated using four different approaches (two-dimensional conformal radiotherapy [2D-CRT] to 50.4 Gy, 2D-CRT to 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. The 50.4 Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4 Gy 2D-CRT plan. The 64.8 Gy SIB-IMRT plan produced a 28% increase in GTV dose and comparable normal tissue doses as the 50.4 Gy IMRT plan; compared with the 50.4 Gy 2D-CRT plan, the 64.8 Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

Interventions to Reduce Harm from Smoking with Families in Infancy and Early Childhood: A Systematic Review

PubMed Central

Brown, Nicola; Luckett, Tim; Davidson, Patricia M.; Di Giacomo, Michelle

2015-01-01

Exposure to adult smoking can have deleterious effects on children. Interventions that assist families with smoking cessation/reduction and environmental tobacco smoke (ETS) avoidance can improve child health outcomes and reduce the risk of smoking initiation. The purpose of this review was to describe the state of the science of interventions with families to promote smoke-free home environments for infants and young children, including parent smoking reduction and cessation interventions, ETS reduction, and anti-smoking socialisation interventions, using the socio-ecological framework as a guide. A systematic review of peer-reviewed articles identified from journal databases from 2000 to 2014 was undertaken. Of 921 articles identified, 28 were included in the review. Considerable heterogeneity characterised target populations, intervention types, complexity and intensity, precluding meta-analysis. Few studies used socio-ecological approaches, such as family theories or concepts. Studies in early parenthood (child age newborn to one year) tended to focus on parent smoking cessation, where studies of families with children aged 1–5 years were more likely to target household SHSe reduction. Results suggest that interventions for reduction in ETS may be more successful than for smoking cessation and relapse prevention in families of children aged less than 5 years. There is a need for a range of interventions to support families in creating a smoke free home environment that are both tailored and targeted to specific populations. Interventions that target the social and psychodynamics of the family should be considered further, particularly in reaching vulnerable populations. Consideration is also required for approaches to interventions that may further stigmatise families containing smokers. Further research is required to identify successful elements of interventions and the contexts in which they are most effective. PMID:25785496

Targeted Delivery of Toxoplasma gondii Antigens to Dendritic Cells Promote Immunogenicity and Protective Efficiency against Toxoplasmosis

PubMed Central

Lakhrif, Zineb; Moreau, Alexis; Hérault, Bruno; Di-Tommaso, Anne; Juste, Matthieu; Moiré, Nathalie; Dimier-Poisson, Isabelle; Mévélec, Marie-Noëlle; Aubrey, Nicolas

2018-01-01

Toxoplasmosis is a major public health problem and the development of a human vaccine is of high priority. Efficient vaccination against Toxoplasma gondii requires both a mucosal and systemic Th1 immune response. Moreover, dendritic cells play a critical role in orchestrating the innate immune functions and driving specific adaptive immunity to T. gondii. In this study, we explore an original vaccination strategy that combines administration via mucosal and systemic routes of fusion proteins able to target the major T. gondii surface antigen SAG1 to DCs using an antibody fragment single-chain fragment variable (scFv) directed against DEC205 endocytic receptor. Our results show that SAG1 targeting to DCs by scFv via intranasal and subcutaneous administration improved protection against chronic T. gondii infection. A marked reduction in brain parasite burden is observed when compared with the intranasal or the subcutaneous route alone. DC targeting improved both local and systemic humoral and cellular immune responses and potentiated more specifically the Th1 response profile by more efficient production of IFN-γ, interleukin-2, IgG2a, and nasal IgA. This study provides evidence of the potential of DC targeting for the development of new vaccines against a range of Apicomplexa parasites. PMID:29515595

An efficient system for selectively altering genetic information within mRNAs

PubMed Central

Montiel-González, Maria Fernanda; Vallecillo-Viejo, Isabel C.; Rosenthal, Joshua J. C.

2016-01-01

Site-directed RNA editing (SDRE) is a strategy to precisely alter genetic information within mRNAs. By linking the catalytic domain of the RNA editing enzyme ADAR to an antisense guide RNA, specific adenosines can be converted to inosines, biological mimics for guanosine. Previously, we showed that a genetically encoded iteration of SDRE could target adenosines expressed in human cells, but not efficiently. Here we developed a reporter assay to quantify editing, and used it to improve our strategy. By enhancing the linkage between ADAR's catalytic domain and the guide RNA, and by introducing a mutation in the catalytic domain, the efficiency of converting a UAG premature termination codon (PTC) to tryptophan (UGG) was improved from ∼11 % to ∼70 %. Other PTCs were edited, but less efficiently. Numerous off-target edits were identified in the targeted mRNA, but not in randomly selected endogenous messages. Off-target edits could be eliminated by reducing the amount of guide RNA with a reduction in on-target editing. The catalytic rate of SDRE was compared with those for human ADARs on various substrates and found to be within an order of magnitude of most. These data underscore the promise of site-directed RNA editing as a therapeutic or experimental tool. PMID:27557710

Targeting TORC1/2 enhances sensitivity to EGFR inhibitors in head and neck cancer preclinical models.

PubMed

Cassell, Andre; Freilino, Maria L; Lee, Jessica; Barr, Sharon; Wang, Lin; Panahandeh, Mary C; Thomas, Sufi M; Grandis, Jennifer R

2012-11-01

Head and neck squamous cell carcinoma (HNSCC) is characterized by overexpression of the epidermal growth factor receptor (EGFR) where treatments targeting EGFR have met with limited clinical success. Elucidation of the key downstream-pathways that remain activated in the setting of EGFR blockade may reveal new therapeutic targets. The present study was undertaken to test the hypothesis that inhibition of the mammalian target of rapamycin (mTOR) complex would enhance the effects of EGFR blockade in HNSCC preclinical models. Treatment of HNSCC cell lines with the newly developed TORC1/TORC2 inhibitor OSI-027/ASP4876 resulted in dose-dependent inhibition of proliferation with abrogation of phosphorylation of known downstream targets including phospho-AKT (Ser473), phospho-4E-BP1, phospho-p70s6K, and phospho-PRAS40. Furthermore, combined treatment with OSI-027 and erlotinib resulted in enhanced biochemical effects and synergistic growth inhibition in vitro. Treatment of mice bearing HNSCC xenografts with a combination of the Food and Drug Administration (FDA)-approved EGFR inhibitor cetuximab and OSI-027 demonstrated a significant reduction of tumor volumes compared with either treatment alone. These findings suggest that TORC1/TORC2 inhibition in conjunction with EGFR blockade represents a plausible therapeutic strategy for HNSCC.

Targeting TORC1/2 Enhances Sensitivity to EGFR Inhibitors in Head and Neck Cancer Preclinical Models1

PubMed Central

Cassell, Andre; Freilino, Maria L; Lee, Jessica; Barr, Sharon; Wang, Lin; Panahandeh, Mary C; Thomas, Sufi M; Grandis, Jennifer R

2012-01-01

Head and neck squamous cell carcinoma (HNSCC) is characterized by overexpression of the epidermal growth factor receptor (EGFR) where treatments targeting EGFR have met with limited clinical success. Elucidation of the key downstream-pathways that remain activated in the setting of EGFR blockade may reveal new therapeutic targets. The present study was undertaken to test the hypothesis that inhibition of the mammalian target of rapamycin (mTOR) complex would enhance the effects of EGFR blockade in HNSCC preclinical models. Treatment of HNSCC cell lines with the newly developed TORC1/TORC2 inhibitor OSI-027/ASP4876 resulted in dose-dependent inhibition of proliferation with abrogation of phosphorylation of known downstream targets including phospho-AKT (Ser473), phospho-4E-BP1, phospho-p70s6K, and phospho-PRAS40. Furthermore, combined treatment with OSI-027 and erlotinib resulted in enhanced biochemical effects and synergistic growth inhibition in vitro. Treatment of mice bearing HNSCC xenografts with a combination of the Food and Drug Administration (FDA)-approved EGFR inhibitor cetuximab and OSI-027 demonstrated a significant reduction of tumor volumes compared with either treatment alone. These findings suggest that TORC1/TORC2 inhibition in conjunction with EGFR blockade represents a plausible therapeutic strategy for HNSCC. PMID:23226094

Needle Steering in 3-D Via Rapid Replanning

PubMed Central

Patil, Sachin; Burgner, Jessica; Webster, Robert J.; Alterovitz, Ron

2014-01-01

Steerable needles have the potential to improve the effectiveness of needle-based clinical procedures such as biopsy and drug delivery by improving targeting accuracy and reaching previously inaccessible targets that are behind sensitive or impenetrable anatomical regions. We present a new needle steering system capable of automatically reaching targets in 3-D environments while avoiding obstacles and compensating for real-world uncertainties. Given a specification of anatomical obstacles and a clinical target (e.g., from preoperative medical images), our system plans and controls needle motion in a closed-loop fashion under sensory feedback to optimize a clinical metric. We unify planning and control using a new fast algorithm that continuously replans the needle motion. Our rapid replanning approach is enabled by an efficient sampling-based rapidly exploring random tree (RRT) planner that achieves orders-of-magnitude reduction in computation time compared with prior 3-D approaches by incorporating variable curvature kinematics and a novel distance metric for planning. Our system uses an electromagnetic tracking system to sense the state of the needle tip during the procedure. We experimentally evaluate our needle steering system using tissue phantoms and animal tissue ex vivo. We demonstrate that our rapid replanning strategy successfully guides the needle around obstacles to desired 3-D targets with an average error of less than 3 mm. PMID:25435829

The effect of functional groups on reduction and activation of quinone bioreductive agents by DT-diaphorase.

PubMed

Fourie, Jeanne; Oleschuk, Curtis J; Guziec, Frank; Guziec, Lynn; Fiterman, Derek J; Monterrosa, Cielo; Begleiter, Asher

2002-02-01

Bioreductive antitumor agents are an important class of anticancer drugs that include the clinically used drug, mitomycin C, and new agents such as EO9 and tirapazamine that have recently been tested in clinical trials. These agents require activation by reductive enzymes such as DT-diaphorase or NADPH:cytochrome P450 reductase. A major focus for improving cancer chemotherapy has been to increase the selectivity and targeting of antitumor drugs to tumor cells. Bioreductive antitumor agents are ideally suited to improving tumor selectivity by an enzyme-directed approach to tumor targeting. However, none of the bioreductive agents developed to date has been specific for activation by a single reductive enzyme. This is in part due to a lack of knowledge about structural factors that confer selectivity for activation by reductive enzymes. The purpose of this study was to investigate the ability of specific functional groups to modify reduction and activation of quinone bioreductive agents by DT-diaphorase. We used a series of model benzoquinone mustard (BM) bioreductive agents and compared the parent compound BM to MBM, which has a strong electron-donating methoxy group, MeBM, which has a weaker electron-donating methyl group, CBM, which has an electron-withdrawing chloro group, and PBM and its structural isomer, meta-PBM (m-PBM), which both have sterically bulky benzene rings attached to the quinone moiety. We determined the rate of reduction of these agents by purified human DT-diaphorase under hypoxic and aerobic conditions. We also measured the cytotoxic activity of these agents in human tumor cell lines with and without the DT-diaphorase inhibitor, dicoumarol. Under hypoxic conditions in vitro, the t(1/2) values for reduction of the analogs by purified DT-diaphorase were 4, 6, 8, 9, 10 and 21 min for BM, MeBM, CBM, MBM, PBM and m-PBM, respectively. Under aerobic conditions the rank order of redox cycling after two-electron reduction by DT-diaphorase was MBM > MeBM > BM approximately CBM approximately PBM approximately m-PBM. The rate of reduction by DT-diaphorase of HBM, a non-alkylating analog of BM, was similar to that of BM under hypoxic conditions, and the rate of redox cycling under aerobic conditions was comparable to that of BM, suggesting that structural changes to the cytotoxic group of these BMs do not affect DT-diaphorase-mediated reduction and redox cycling potential. MBM, MeBM and PBM were more toxic than BM in the NCI-H661 human non-small-cell lung cancer cells and SK-MEL-28 human melanoma cells, while CBM displayed significantly increased cytotoxic activity compared to BM only in the NCI H661 cells. m-PBM had similar cytotoxic activity compared with BM in both cell lines. These cell lines have moderate to high levels of DT-diaphorase activity. When cells were pretreated with the DT-diaphorase inhibitor, dicoumarol, the cytotoxic activity of BM increased while that of MBM decreased in both cell lines, suggesting that BM was inactivated by DT-diaphorase while MBM was activated by this enzyme. Pretreatment of the SK-MEL-28 melanoma cells with dicoumarol resulted in an increased cytotoxic activity of MeBM, but pretreatment of the NCI-H661 cells did not affect the cytotoxicity of MeBM. This suggests, that similar to the results with BM, DT-diaphorase is an inactivating enzyme for MeBM in the SK-MEL-28 cell line. Dicoumarol had no significant effect on the cytotoxicity of CBM, PBM or m-PBM in both cell lines. These studies demonstrated that functional groups can significantly affect the reduction and activation of bioreductive agents by DT-diaphorase. All the functional groups decreased the rate of reduction of the quinone group by DT-diaphorase. Since MeBM and MBM, with electron-donating functional groups, and CBM with an electron-withdrawing functional group had similar half-lives of reduction by DT-diaphorase, steric rather than electronic effects of the functional groups appear to be more important for modifying the rate of reduction by DT-diaphorase. Steric effects on reduction by DT-diaphorase were also influenced by the position of the functional group on the quinone ring moiety, as the reduction of m-PBM was much slower than the reduction of PBM. The electron-donating methoxy and methyl functional groups increased the ability of the reduced products of MBM and MeBM to undergo redox cycling. DT-diaphorase appeared to be an activating enzyme for MBM. This may have resulted in part from increased formation of reactive oxygen species resulting from the increased redox cycling by MBM. In contrast, DT-diaphorase was an inactivating enzyme for BM, and for MeBM in the SK-MEL-28 melanoma cells, possibly because the hydroquinone product of BM and MeBM may be less cytotoxic than the semiquinone produced by one-electron reduction by NADPH:cytochrome P450 reductase.

Drinking water to reduce alcohol craving? A randomized controlled study on the impact of ghrelin in mediating the effects of forced water intake in alcohol addiction.

PubMed

Koopmann, Anne; Lippmann, Katharina; Schuster, Rilana; Reinhard, Iris; Bach, Patrick; Weil, Georg; Rietschel, Marcella; Witt, Stephanie H; Wiedemann, Klaus; Kiefer, Falk

2017-11-01

Recent data suggest that ghrelin is involved in the pathophysiology of alcohol use disorders, affecting alcohol self-administration and craving. Gastric ghrelin secretion is reduced by stomach distension. We now tested the hypothesis whether the clinically well-known effects of high-volume water intake on craving reduction in alcoholism is mediated by acute changes in ghrelin secretion. In this randomized human laboratory study, we included 23 alcohol-dependent male inpatient subjects who underwent alcohol cue exposure. Participants of the intervention group drank 1000ml of mineral water within 10min directly thereafter, compared to the participants of the control group who did not. Craving and plasma concentrations of acetylated ghrelin were measured ten times during the 120min following the alcohol cue exposure session. In the intervention group, a significant decrease in acetylated ghrelin in plasma compared to the control group was observed. This decrease was correlated to a reduction in patients' subjective level of craving. In the control group, no decrease of acetylated ghrelin in plasma and no association between alcohol craving and changes in plasma concentrations of acetylated ghrelin were observed. Our results present new evidence that the modulation in the ghrelin system by oral water intake mediates the effects of volume intake with craving reduction in alcohol use disorders. Hence, in addition to pharmacological interventions with ghrelin antagonists, the reduction of physiological ghrelin secretion might be a target for future interventions in the treatment of alcohol craving. Copyright © 2017 Elsevier Ltd. All rights reserved.

Full dose reduction potential of statistical iterative reconstruction for head CT protocols in a predominantly pediatric population

PubMed Central

Mirro, Amy E.; Brady, Samuel L.; Kaufman, Robert. A.

2016-01-01

Purpose To implement the maximum level of statistical iterative reconstruction that can be used to establish dose-reduced head CT protocols in a primarily pediatric population. Methods Select head examinations (brain, orbits, sinus, maxilla and temporal bones) were investigated. Dose-reduced head protocols using an adaptive statistical iterative reconstruction (ASiR) were compared for image quality with the original filtered back projection (FBP) reconstructed protocols in phantom using the following metrics: image noise frequency (change in perceived appearance of noise texture), image noise magnitude, contrast-to-noise ratio (CNR), and spatial resolution. Dose reduction estimates were based on computed tomography dose index (CTDIvol) values. Patient CTDIvol and image noise magnitude were assessed in 737 pre and post dose reduced examinations. Results Image noise texture was acceptable up to 60% ASiR for Soft reconstruction kernel (at both 100 and 120 kVp), and up to 40% ASiR for Standard reconstruction kernel. Implementation of 40% and 60% ASiR led to an average reduction in CTDIvol of 43% for brain, 41% for orbits, 30% maxilla, 43% for sinus, and 42% for temporal bone protocols for patients between 1 month and 26 years, while maintaining an average noise magnitude difference of 0.1% (range: −3% to 5%), improving CNR of low contrast soft tissue targets, and improving spatial resolution of high contrast bony anatomy, as compared to FBP. Conclusion The methodology in this study demonstrates a methodology for maximizing patient dose reduction and maintaining image quality using statistical iterative reconstruction for a primarily pediatric population undergoing head CT examination. PMID:27056425

Energy, chemical disequilibrium, and geological constraints on Europa.

PubMed

Hand, Kevin P; Carlson, Robert W; Chyba, Christopher F

2007-12-01

Europa is a prime target for astrobiology. The presence of a global subsurface liquid water ocean and a composition likely to contain a suite of biogenic elements make it a compelling world in the search for a second origin of life. Critical to these factors, however, may be the availability of energy for biological processes on Europa. We have examined the production and availability of oxidants and carbon-containing reductants on Europa to better understand the habitability of the subsurface ocean. Data from the Galileo Near-Infrared Mapping Spectrometer were used to constrain the surface abundance of CO(2) to 0.036% by number relative to water. Laboratory results indicate that radiolytically processed CO(2)-rich ices yield CO and H(2)CO(3); the reductants H(2)CO, CH(3)OH, and CH(4) are at most minor species. We analyzed chemical sources and sinks and concluded that the radiolytically processed surface of Europa could serve to maintain an oxidized ocean even if the surface oxidants (O(2), H(2)O(2), CO(2), SO(2), and SO(4) (2)) are delivered only once every approximately 0.5 Gyr. If delivery periods are comparable to the observed surface age (30-70 Myr), then Europa's ocean could reach O(2) concentrations comparable to those found in terrestrial surface waters, even if approximately 10(9) moles yr(1) of hydrothermally delivered reductants consume most of the oxidant flux. Such an ocean would be energetically hospitable for terrestrial marine macrofauna. The availability of reductants could be the limiting factor for biologically useful chemical energy on Europa.

Target Salt 2025: A Global Overview of National Programs to Encourage the Food Industry to Reduce Salt in Foods

PubMed Central

Webster, Jacqui; Trieu, Kathy; Dunford, Elizabeth; Hawkes, Corinna

2014-01-01

Reducing population salt intake has been identified as a priority intervention to reduce non-communicable diseases. Member States of the World Health Organization have agreed to a global target of a 30% reduction in salt intake by 2025. In countries where most salt consumed is from processed foods, programs to engage the food industry to reduce salt in products are being developed. This paper provides a comprehensive overview of national initiatives to encourage the food industry to reduce salt. A systematic review of the literature was supplemented by key informant questionnaires to inform categorization of the initiatives. Fifty nine food industry salt reduction programs were identified. Thirty eight countries had targets for salt levels in foods and nine countries had introduced legislation for some products. South Africa and Argentina have both introduced legislation limiting salt levels across a broad range of foods. Seventeen countries reported reductions in salt levels in foods—the majority in bread. While these trends represent progress, many countries have yet to initiate work in this area, others are at early stages of implementation and further monitoring is required to assess progress towards achieving the global target. PMID:25195640

Target salt 2025: a global overview of national programs to encourage the food industry to reduce salt in foods.

PubMed

Webster, Jacqui; Trieu, Kathy; Dunford, Elizabeth; Hawkes, Corinna

2014-08-21

Reducing population salt intake has been identified as a priority intervention to reduce non-communicable diseases. Member States of the World Health Organization have agreed to a global target of a 30% reduction in salt intake by 2025. In countries where most salt consumed is from processed foods, programs to engage the food industry to reduce salt in products are being developed. This paper provides a comprehensive overview of national initiatives to encourage the food industry to reduce salt. A systematic review of the literature was supplemented by key informant questionnaires to inform categorization of the initiatives. Fifty nine food industry salt reduction programs were identified. Thirty eight countries had targets for salt levels in foods and nine countries had introduced legislation for some products. South Africa and Argentina have both introduced legislation limiting salt levels across a broad range of foods. Seventeen countries reported reductions in salt levels in foods-the majority in bread. While these trends represent progress, many countries have yet to initiate work in this area, others are at early stages of implementation and further monitoring is required to assess progress towards achieving the global target.

Nanoengineered capsules for selective SERS analysis of biological samples

NASA Astrophysics Data System (ADS)

You, Yil-Hwan; Schechinger, Monika; Locke, Andrea; Coté, Gerard; McShane, Mike

2018-02-01

Metal nanoparticles conjugated with DNA oligomers have been intensively studied for a variety of applications, including optical diagnostics. Assays based on aggregation of DNA-coated particles in proportion to the concentration of target analyte have not been widely adopted for clinical analysis, however, largely due to the nonspecific responses observed in complex biofluids. While sample pre-preparation such as dialysis is helpful to enable selective sensing, here we sought to prove that assay encapsulation in hollow microcapsules could remove this requirement and thereby facilitate more rapid analysis on complex samples. Gold nanoparticle-based assays were incorporated into capsules comprising polyelectrolyte multilayer (PEMs), and the response to small molecule targets and larger proteins were compared. Gold nanoparticles were able to selectively sense small Raman dyes (Rhodamine 6G) in the presence of large protein molecules (BSA) when encapsulated. A ratiometric based microRNA-17 sensing assay exhibited drastic reduction in response after encapsulation, with statistically-significant relative Raman intensity changes only at a microRNA-17 concentration of 10 nM compared to a range of 0-500 nM for the corresponding solution-phase response.

Suggestion-Induced Modulation of Semantic Priming during Functional Magnetic Resonance Imaging

PubMed Central

Ulrich, Martin; Kiefer, Markus; Bongartz, Walter; Grön, Georg; Hoenig, Klaus

2015-01-01

Using functional magnetic resonance imaging during a primed visual lexical decision task, we investigated the neural and functional mechanisms underlying modulations of semantic word processing through hypnotic suggestions aimed at altering lexical processing of primes. The priming task was to discriminate between target words and pseudowords presented 200 ms after the prime word which was semantically related or unrelated to the target. In a counterbalanced study design, each participant performed the task once at normal wakefulness and once after the administration of hypnotic suggestions to perceive the prime as a meaningless symbol of a foreign language. Neural correlates of priming were defined as significantly lower activations upon semantically related compared to unrelated trials. We found significant suggestive treatment-induced reductions in neural priming, albeit irrespective of the degree of suggestibility. Neural priming was attenuated upon suggestive treatment compared with normal wakefulness in brain regions supporting automatic (fusiform gyrus) and controlled semantic processing (superior and middle temporal gyri, pre- and postcentral gyri, and supplementary motor area). Hence, suggestions reduced semantic word processing by conjointly dampening both automatic and strategic semantic processes. PMID:25923740

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

Nguyen, Kham, E-mail: khamdiep@gmail.com; UT MD Anderson Cancer Center, School of Health Professions—Unit 2, Houston, TX; Cummings, David

The purpose of this study was to evaluate the differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) in the treatment of nasal cavity carcinomas. The treatment of 10 patients, who had completed IMRT treatment for resected tumors of the nasal cavity, was replanned with the Philips Pinnacle{sup 3} Version 9 treatment-planning system. The IMRT plans used a 9-beam technique whereas the VMAT (known as SmartArc) plans used a 3-arc technique. Both types of plans were optimized using Philips Pinnacle{sup 3} Direct Machine Parameter Optimization algorithm. IMRT and VMAT plans' quality was compared by evaluating the maximum,more » minimum, and mean doses to the target volumes and organs at risk, monitor units (MUs), and the treatment delivery time. Our results indicate that VMAT is capable of greatly reducing treatment delivery time and MUs compared with IMRT. The reduction of treatment delivery time and MUs can decrease the effects of intrafractional uncertainties that can occur because of patient movement during treatment delivery. VMAT's plans further reduce doses to critical structures that are in close proximity to the target volume.« less

HS-SPME-GC-MS analysis of body odor to test the efficacy of foot deodorant formulations.

PubMed

Caroprese, Alessandro; Gabbanini, Simone; Beltramini, Claudia; Lucchi, Elena; Valgimigli, Luca

2009-11-01

Foot malodor is mostly due to short-chain fatty acids produced by bacterial metabolism of eccrine sweating. We aimed to develop a protocol for an objective (instrumental) efficacy evaluation of foot deodorant formulations. Head-space solid-phase microextractions of target fatty acids from the feet of six healthy volunteers were analyzed by GC-MS. A comparative analysis of the treated vs. the untreated foot was performed in each subject after washing the feet with a physiologic solution and incubating at 36 degrees C for 24-72 h in tryptic soy agar growth medium. Acetic, butyric, isobutyric and isovaleric acids were identified as the main contributors to foot malodor in the majority of volunteers. Propionic, valeric and isocaproic acids were also detected in some subjects. Comparative analysis according to the protocol developed showed a statistically significant (P<0.01) reduction of target fatty acids ranging from -26.6% to -77.0%. The protocol developed is a convenient, sensitive and non-invasive method to test the efficacy of foot deodorant formulations in human volunteers.

Reduced generation of lung tissue–resident memory T cells during infancy

PubMed Central

Zens, Kyra D.; Chen, Jun Kui; Wu, Felix L.; Cvetkovski, Filip

2017-01-01

Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRMs, and heterosubtypic protection was reduced compared with adults. Impaired TRM establishment was infant–T cell intrinsic, and infant effectors displayed distinct transcriptional profiles enriched for T-bet–regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression after activation, and reduction of T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses, and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage. PMID:28855242

GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis.

PubMed

Beam, Craig A; MacCallum, Colleen; Herold, Kevan C; Wherrett, Diane K; Palmer, Jerry; Ludvigsson, Johnny

2017-01-01

GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). We estimate that there is a 98% probability that 20 μg GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.

TEM Cell Testing of Cable Noise Reduction Techniques from 2 MHz to 200 MHz -- Part 2

NASA Technical Reports Server (NTRS)

Bradley, Arthur T.; Evans, William C.; Reed, Joshua L.; Shimp, Samuel K., III; Fitzpatrick, Fred D.

2008-01-01

This paper presents empirical results of cable noise reduction techniques as demonstrated in a TEM cell operating with radiated fields from 2 - 200 MHz. It is the second part of a two-paper series. The first paper discussed cable types and shield connections. In this second paper, the effects of load and source resistances and chassis connections are examined. For each topic, well established theories are compared to data from a real-world physical system. Finally, recommendations for minimizing cable susceptibility (and thus cable emissions) are presented. There are numerous papers and textbooks that present theoretical analyses of cable noise reduction techniques. However, empirical data is often targeted to low frequencies (e.g. <50 KHz) or high frequencies (>100 MHz). Additionally, a comprehensive study showing the relative effects of various noise reduction techniques is needed. These include the use of dedicated return wires, twisted wiring, cable shielding, shield connections, changing load or source impedances, and implementing load- or source-to-chassis isolation. We have created an experimental setup that emulates a real-world electrical system, while still allowing us to independently vary a host of parameters. The goal of the experiment was to determine the relative effectiveness of various noise reduction techniques when the cable is in the presence of radiated emissions from 2 MHz to 200 MHz.

Effect of a gravity-compensating orthosis on reaching after stroke: evaluation of the Therapy Assistant WREX.

PubMed

Iwamuro, Bridget T; Cruz, Erik G; Connelly, Lauri L; Fischer, Heidi C; Kamper, Derek G

2008-11-01

Within-subjects repeated-measures design evaluating reaching with and without the Therapy Assistant Wilmington Robotic Exoskeleton (WREX). Laboratory. Stroke survivors (N=10) with chronic upper-extremity hemiparesis. Not applicable. Arm movement kinematics (Optotrak Certus motion detection system), muscle activity for biceps, triceps, anterior deltoid, and brachioradialis muscles (bipolar surface electromyography). Significant improvements of reaching distance occurred for all subjects across all targets (P<.001) when using the Therapy Assistant WREX. While the self-selected peak speed of hand movement during the reach decreased significantly with the Therapy Assistant WREX (P<.001), use of the Therapy Assistant WREX led to improved quality of movement as signified by a decrease in jerk (P<.001) and a shift in the timing of the peak speed to an earlier point in the movement (P<.001). Electromyographic muscle activity analysis showed that use of the Therapy Assistant WREX led to a reduction in biceps activity across all targets during the reach (P<.05), in conjunction with a marginally significant reduction in activity of the anterior deltoid (P<.055). No changes were observed in triceps (P=.47) or brachioradialis activity (P=.28). By reducing requirements for shoulder activation, the Therapy Assistant WREX improved reaching performance among stroke survivors compared with free reaching, thereby potentially facilitating practice of functional tasks.

Reduction of photographic observations of asteroids to the reference frame of a single catalog

NASA Astrophysics Data System (ADS)

Chernetenko, Yu. A.

2008-04-01

In 2000, the last international program of photographic observations of selected asteroids aimed at the determination of the mutual orientation of the dynamic and stellar coordinate systems came to an end. The Institute of Applied Astronomy of the Russian Academy of Sciences collected more than 25 000 observations for 15 asteroids spanning from 1949 through 1995. These observations were reduced to the reference frame of the Hipparcos catalog using dependencies published along with observations. The accuracy of observations of selected asteroids was 0.30 arcsec, which is comparable to that of modern CCD observations of minor planets. The observations are available at ftp://quasar.ipa.nw.ru/pub/SMP . An important advantage of these observations is that they are already reduced to the reference frame of a single catalog. Our criteria for the quality of the reduction methods and the accuracy of the observations are based on estimating the parameters of the orientation of the reference frames of the PPM and Hipparcos catalogs with respect to DE200/LE200. The most reliable results are those obtained when reducing old optical observations along with modern ground-based and space-borne observations.

Reactive oxygen species and associated reactivity of peroxymonosulfate activated by soluble iron species

NASA Astrophysics Data System (ADS)

Watts, Richard J.; Yu, Miao; Teel, Amy L.

2017-10-01

The activation of peroxymonosulfate by iron (II), iron (III), and iron (III)-EDTA for in situ chemical oxidation (ISCO) was compared using nitrobenzene as a hydroxyl radical probe, anisole as a hydroxyl radical + sulfate radical probe, and hexachloroethane as a reductant + nucleophile probe. In addition, activated peroxymonosulfate was investigated for the treatment of the model groundwater contaminants perchloroethylene (PCE) and trichloroethylene (TCE). The relative activities of hydroxyl radical and sulfate radical in the degradation of the probe compounds and PCE and TCE were isolated using the radical scavengers tert-butanol and isopropanol. Iron (II), iron (III), and iron (III)-EDTA effectively activated peroxymonosulfate to generate hydroxyl radical and sulfate radical, but only a minimal flux of reductants or nucleophiles. Iron (III)-EDTA was a more effective activator than iron (II) and iron (III), and also provided a non-hydroxyl radical, non-sulfate radical degradation pathway. The contribution of sulfate radical relative to hydroxyl radical followed the order of anisole > > TCE > PCE > > nitrobenzene; i.e., sulfate radical was less dominant in the oxidation of more oxidized target compounds. Sulfate radical is often assumed to be the primary oxidant in activated peroxymonosulfate and persulfate systems, but the results of this research demonstrate that the reactivity of sulfate radical with the target compound must be considered before drawing such a conclusion.

Radio-Frequency-Controlled Urea Dosing for NH3-SCR Catalysts: NH3 Storage Influence to Catalyst Performance under Transient Conditions

PubMed Central

Dietrich, Markus; Hagen, Gunter; Reitmeier, Willibald; Burger, Katharina; Hien, Markus; Grass, Philippe; Kubinski, David; Visser, Jaco; Moos, Ralf

2017-01-01

Current developments in exhaust gas aftertreatment led to a huge mistrust in diesel driven passenger cars due to their NOx emissions being too high. The selective catalytic reduction (SCR) with ammonia (NH3) as reducing agent is the only approach today with the capability to meet upcoming emission limits. Therefore, the radio-frequency-based (RF) catalyst state determination to monitor the NH3 loading on SCR catalysts has a huge potential in emission reduction. Recent work on this topic proved the basic capability of this technique under realistic conditions on an engine test bench. In these studies, an RF system calibration for the serial type SCR catalyst Cu-SSZ-13 was developed and different approaches for a temperature dependent NH3 storage were determined. This paper continues this work and uses a fully calibrated RF-SCR system under transient conditions to compare different directly measured and controlled NH3 storage levels, and NH3 target curves. It could be clearly demonstrated that the right NH3 target curve, together with a direct control on the desired level by the RF system, is able to operate the SCR system with the maximum possible NOx conversion efficiency and without NH3 slip. PMID:29182589

Development and evaluation of a mobile intervention for heavy drinking and smoking among college students.

PubMed

Witkiewitz, Katie; Desai, Sruti A; Bowen, Sarah; Leigh, Barbara C; Kirouac, Megan; Larimer, Mary E

2014-09-01

Nearly all college student smokers also drink alcohol, and smoking and heavy episodic drinking (HED) commonly co-occur. However, few studies have examined the factors that concurrently influence smoking and HED among college students and, to date, no interventions have been developed that target both HED and smoking in this population. The objective of the current study was to develop and evaluate a mobile feedback intervention that targets HED and smoking. Participants (N = 94) were non-treatment-seeking college students (M(age) = 20.5 years, SD = 1.7) who engaged in at least a single HED episode in the past 2 weeks and reported concurrent smoking and drinking at least once a week. Participants were randomized to receive either the mobile intervention for 14 days, complete mobile assessments (without intervention) for 14 days, or complete minimal assessments (without intervention or mobile assessments). At a 1-month follow-up, compared with the minimal assessment condition, we observed significant reductions in the number of cigarettes per smoking day in both the mobile intervention (d = 0.55) and mobile assessment (d = 0.45) conditions. Among those randomized to the mobile intervention, receiving more modules of the intervention was significantly associated with a lower likelihood of any drinking during the 14-day assessment period and significant reductions in smoking at 1-month follow-up. The mobile intervention did not result in significant reductions in HED or concurrent smoking and drinking. Future research should continue to examine ways of using technology and the real-time environment to improve interventions for HED and smoking.

Dynamic Geospatial Modeling of the Building Stock to Project Urban Energy Demand.

PubMed

Breunig, Hanna Marie; Huntington, Tyler; Jin, Ling; Robinson, Alastair; Scown, Corinne Donahue

2018-06-26

In the United States, buildings account for more than 40 percent of total energy consumption, and the evolution of the urban form will impact the effectiveness of strategies to reduce energy use and mitigate emissions. This paper presents a broadly applicable approach for modeling future commercial, residential, and industrial floorspace, thermal consumption (heating and cooling), and associated GHG emissions at the tax assessor land parcel level. The approach accounts for changing building standards and retrofitting, climate change, and trends in housing and industry. We demonstrate the automated workflow for California, and project building stock, thermal energy consumption, and associated GHG emissions out to 2050. Our results suggest that if buildings in California have long lifespans, and minimal energy efficiency improvements compared to building codes reflective of 2008, then the state will face a 20% or higher increase in thermal energy consumption by 2050. Baseline annual GHG emissions associated with thermal energy consumption in the modeled building stock in 2016 is 34% below 1990 levels (110 Mt CO2eq/y).While the 2020 targets for the reduction of GHG emissions set by the California Senate Bill 350 have already been met, none of our scenarios achieve >80% reduction from 1990 levels by 2050, despite assuming an 86% reduction in electricity carbon intensity in our "Low Carbon" scenario. The results highlight the challenge California faces in meeting its new energy efficiency targets unless the State's building stock undergoes timely and strategic turnover, paired with deep retrofitting of existing buildings and natural gas equipment.

Research and Development Project Summaries, October 1991

DTIC Science & Technology

1991-10-01

delivery methods, training cost reduction, demonstration of technology’ effectiveness, and the reduction of acquisition risk . The majority of the work...demonstrations, risk reduction developments, and cost-effectiveness investigations in simulator and training technologzv. This advanced development program is a...systems. The program is organized around specific demonstration tasks that target critical technical risks that confront future weapons system

ECHO: Machine feasibility program

Treesearch

Philip H. Steele; Craig Boden; Philip A. Araman

2000-01-01

Reductions in saw kerf (the term saw kerf refers to both the sawtooth width as well as the actual sawline made in sawing) on headrigs and resaws can dramatically increase lumber recovery. Research has also shown that lumber target size reductions are even more important than kerf reductions in providing increased lumber recovery. Decreases in either kerf or lumber size...

What would it take to achieve the Paris temperature targets?

NASA Astrophysics Data System (ADS)

Sanderson, Benjamin M.; O'Neill, Brian C.; Tebaldi, Claudia

2016-07-01

The 2015 Paris Agreement aims to limit warming to 2 or 1.5°C above preindustrial level, although combined Intended Nationally Determined Contributions (INDCs) are likely insufficient to achieve these targets. We propose a set of idealized emission pathways consistent with the targets. If countries reduce emissions in line with their INDCs, the 2°C threshold could be avoided only if net zero greenhouse gas emissions (GHGEs) are achieved by 2085 and late century negative emissions are considerably in excess of those assumed in Representative Concentration Pathway (RCP) 2.6 (net -5 Gt CO2/yr, compared with -1.5 Gt CO2/yr in RCP2.6). More aggressive near-term reductions would allow 2°C to be avoided with less end-of-century carbon removal capacity. A 10% cut in GHGEs by 2030 (relative to 2015) could likely achieve 2°C with RCP2.6 level negative emissions. The 1.5°C target requires GHGEs to be reduced by almost a third by 2030 and net zero by 2050, while a 50 year overshoot of 1.5°C allows net zero GHGEs by 2060.

A comparison of error bounds for a nonlinear tracking system with detection probability Pd < 1.

PubMed

Tong, Huisi; Zhang, Hao; Meng, Huadong; Wang, Xiqin

2012-12-14

Error bounds for nonlinear filtering are very important for performance evaluation and sensor management. This paper presents a comparative study of three error bounds for tracking filtering, when the detection probability is less than unity. One of these bounds is the random finite set (RFS) bound, which is deduced within the framework of finite set statistics. The others, which are the information reduction factor (IRF) posterior Cramer-Rao lower bound (PCRLB) and enumeration method (ENUM) PCRLB are introduced within the framework of finite vector statistics. In this paper, we deduce two propositions and prove that the RFS bound is equal to the ENUM PCRLB, while it is tighter than the IRF PCRLB, when the target exists from the beginning to the end. Considering the disappearance of existing targets and the appearance of new targets, the RFS bound is tighter than both IRF PCRLB and ENUM PCRLB with time, by introducing the uncertainty of target existence. The theory is illustrated by two nonlinear tracking applications: ballistic object tracking and bearings-only tracking. The simulation studies confirm the theory and reveal the relationship among the three bounds.

A Comparison of Error Bounds for a Nonlinear Tracking System with Detection Probability Pd < 1

PubMed Central

Tong, Huisi; Zhang, Hao; Meng, Huadong; Wang, Xiqin

2012-01-01

Error bounds for nonlinear filtering are very important for performance evaluation and sensor management. This paper presents a comparative study of three error bounds for tracking filtering, when the detection probability is less than unity. One of these bounds is the random finite set (RFS) bound, which is deduced within the framework of finite set statistics. The others, which are the information reduction factor (IRF) posterior Cramer-Rao lower bound (PCRLB) and enumeration method (ENUM) PCRLB are introduced within the framework of finite vector statistics. In this paper, we deduce two propositions and prove that the RFS bound is equal to the ENUM PCRLB, while it is tighter than the IRF PCRLB, when the target exists from the beginning to the end. Considering the disappearance of existing targets and the appearance of new targets, the RFS bound is tighter than both IRF PCRLB and ENUM PCRLB with time, by introducing the uncertainty of target existence. The theory is illustrated by two nonlinear tracking applications: ballistic object tracking and bearings-only tracking. The simulation studies confirm the theory and reveal the relationship among the three bounds. PMID:23242274

Stereotypical rapid source level regulation in the harbour porpoise biosonar.

PubMed

Linnenschmidt, Meike; Kloepper, Laura N; Wahlberg, Magnus; Nachtigall, Paul E

2012-09-01

Some odontocetes and bats vary both click intensity and receiver sensitivity during echolocation, depending on target range. It is not known how this so-called automatic gain control is regulated by the animal. The source level of consecutive echolocation clicks from a harbour porpoise was measured with a hydrophone array while the animal detected an aluminium cylinder at 2, 4 or 8 m distance in a go/no-go paradigm. On-axis clicks had source levels of 145-174 dB re 1 μPa peak-to-peak. During target-present trials the click trains reached comparable source levels independent of the range to the target after three clicks. After an additional click, the source level was reduced for the 2 and 4 m trials until it equalled the one-way transmission loss. During target-absent trials, the source level remained high throughout the entire click train. Given typical values of harbour porpoise inter-click intervals, the source level reduction commenced within a few 100 ms from the first click in the click train. This may indicate a sub-cortically regulated source level regulation in the harbour porpoise.

What would it take to achieve the Paris temperature targets?

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

Sanderson, Benjamin M.; O'Neill, Brian C.; Tebaldi, Claudia

Here, the 2015 Paris Agreement aims to limit warming to 2 or 1.5°C above preindustrial level, although combined Intended Nationally Determined Contributions (INDCs) are likely insufficient to achieve these targets. We propose a set of idealized emission pathways consistent with the targets. If countries reduce emissions in line with their INDCs, the 2°C threshold could be avoided only if net zero greenhouse gas emissions (GHGEs) are achieved by 2085 and late century negative emissions are considerably in excess of those assumed in Representative Concentration Pathway (RCP) 2.6 (net –5 Gt CO 2/yr, compared with –1.5 Gt CO 2/yr in RCP2.6).more » More aggressive near-term reductions would allow 2°C to be avoided with less end-of-century carbon removal capacity. A 10% cut in GHGEs by 2030 (relative to 2015) could likely achieve 2°C with RCP2.6 level negative emissions. The 1.5°C target requires GHGEs to be reduced by almost a third by 2030 and net zero by 2050, while a 50 year overshoot of 1.5°C allows net zero GHGEs by 2060.« less

What would it take to achieve the Paris temperature targets?

DOE PAGES

Sanderson, Benjamin M.; O'Neill, Brian C.; Tebaldi, Claudia

2016-06-27

Here, the 2015 Paris Agreement aims to limit warming to 2 or 1.5°C above preindustrial level, although combined Intended Nationally Determined Contributions (INDCs) are likely insufficient to achieve these targets. We propose a set of idealized emission pathways consistent with the targets. If countries reduce emissions in line with their INDCs, the 2°C threshold could be avoided only if net zero greenhouse gas emissions (GHGEs) are achieved by 2085 and late century negative emissions are considerably in excess of those assumed in Representative Concentration Pathway (RCP) 2.6 (net –5 Gt CO 2/yr, compared with –1.5 Gt CO 2/yr in RCP2.6).more » More aggressive near-term reductions would allow 2°C to be avoided with less end-of-century carbon removal capacity. A 10% cut in GHGEs by 2030 (relative to 2015) could likely achieve 2°C with RCP2.6 level negative emissions. The 1.5°C target requires GHGEs to be reduced by almost a third by 2030 and net zero by 2050, while a 50 year overshoot of 1.5°C allows net zero GHGEs by 2060.« less

Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids.

PubMed

Karandish, Fataneh; Haldar, Manas K; You, Seungyong; Brooks, Amanda E; Brooks, Benjamin D; Guo, Bin; Choi, Yongki; Mallik, Sanku

2016-11-30

Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly ( p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems.

Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids

PubMed Central

2016-01-01

Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly (p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems. PMID:27917408

Acoustic Performance of Novel Fan Noise Reduction Technologies for a High Bypass Model Turbofan at Simulated Flights Conditions

NASA Technical Reports Server (NTRS)

Elliott, David M.; Woodward, Richard P.; Podboy, Gary G.

2010-01-01

Two novel fan noise reduction technologies, over the rotor acoustic treatment and soft stator vane technologies, were tested in an ultra-high bypass ratio turbofan model in the NASA Glenn Research Center s 9- by 15-Foot Low-Speed Wind Tunnel. The performance of these technologies was compared to that of the baseline fan configuration, which did not have these technologies. Sideline acoustic data and hot film flow data were acquired and are used to determine the effectiveness of the various treatments. The material used for the over the rotor treatment was foam metal and two different types were used. The soft stator vanes had several internal cavities tuned to target certain frequencies. In order to accommodate the cavities it was necessary to use a cut-on stator to demonstrate the soft vane concept.

Adapted RF pulse design for SAR reduction in parallel excitation with experimental verification at 9.4 T.

PubMed

Wu, Xiaoping; Akgün, Can; Vaughan, J Thomas; Andersen, Peter; Strupp, John; Uğurbil, Kâmil; Van de Moortele, Pierre-François

2010-07-01

Parallel excitation holds strong promises to mitigate the impact of large transmit B1 (B+1) distortion at very high magnetic field. Accelerated RF pulses, however, inherently tend to require larger values in RF peak power which may result in substantial increase in Specific Absorption Rate (SAR) in tissues, which is a constant concern for patient safety at very high field. In this study, we demonstrate adapted rate RF pulse design allowing for SAR reduction while preserving excitation target accuracy. Compared with other proposed implementations of adapted rate RF pulses, our approach is compatible with any k-space trajectories, does not require an analytical expression of the gradient waveform and can be used for large flip angle excitation. We demonstrate our method with numerical simulations based on electromagnetic modeling and we include an experimental verification of transmit pattern accuracy on an 8 transmit channel 9.4 T system.

Shock-induced damage in rocks: Application to impact cratering

NASA Astrophysics Data System (ADS)

Ai, Huirong

Shock-induced damage beneath impact craters is studied in this work. Two representative terrestrial rocks, San Marcos granite and Bedford limestone, are chosen as test target. Impacts into the rock targets with different combinations of projectile material, size, impact angle, and impact velocity are carried out at cm scale in the laboratory. Shock-induced damage and fracturing would cause large-scale compressional wave velocity reduction in the recovered target beneath the impact crater. The shock-induced damage is measured by mapping the compressional wave velocity reduction in the recovered target. A cm scale nondestructive tomography technique is developed for this purpose. This technique is proved to be effective in mapping the damage in San Marcos granite, and the inverted velocity profile is in very good agreement with the result from dicing method and cut open directly. Both compressional velocity and attenuation are measured in three orthogonal directions on cubes prepared from one granite target impacted by a lead bullet at 1200 m/s. Anisotropy is observed from both results, but the attenuation seems to be a more useful parameter than acoustic velocity in studying orientation of cracks. Our experiments indicate that the shock-induced damage is a function of impact conditions including projectile type and size, impact velocity, and target properties. Combined with other crater phenomena such as crater diameter, depth, ejecta, etc., shock-induced damage would be used as an important yet not well recognized constraint for impact history. The shock-induced damage is also calculated numerically to be compared with the experiments for a few representative shots. The Johnson-Holmquist strength and failure model, initially developed for ceramics, is applied to geological materials. Strength is a complicated function of pressure, strain, strain rate, and damage. The JH model, coupled with a crack softening model, is used to describe both the inelastic response of rocks in the compressive field near the impact source and the tensile failure in the far field. The model parameters are determined either from direct static measurements, or from indirect numerical adjustment. The agreement between the simulation and experiment is very encouraging.

Method comparison of ultrasound and kilovoltage x-ray fiducial marker imaging for prostate radiotherapy targeting

NASA Astrophysics Data System (ADS)

Fuller, Clifton David; Thomas, Charles R., Jr.; Schwartz, Scott; Golden, Nanalei; Ting, Joe; Wong, Adrian; Erdogmus, Deniz; Scarbrough, Todd J.

2006-10-01

Several measurement techniques have been developed to address the capability for target volume reduction via target localization in image-guided radiotherapy; among these have been ultrasound (US) and fiducial marker (FM) software-assisted localization. In order to assess interchangeability between methods, US and FM localization were compared using established techniques for determination of agreement between measurement methods when a 'gold-standard' comparator does not exist, after performing both techniques daily on a sequential series of patients. At least 3 days prior to CT simulation, four gold seeds were placed within the prostate. FM software-assisted localization utilized the ExacTrac X-Ray 6D (BrainLab AG, Germany) kVp x-ray image acquisition system to determine prostate position; US prostate targeting was performed on each patient using the SonArray (Varian, Palo Alto, CA). Patients were aligned daily using laser alignment of skin marks. Directional shifts were then calculated by each respective system in the X, Y and Z dimensions before each daily treatment fraction, previous to any treatment or couch adjustment, as well as a composite vector of displacement. Directional shift agreement in each axis was compared using Altman-Bland limits of agreement, Lin's concordance coefficient with Partik's grading schema, and Deming orthogonal bias-weighted correlation methodology. 1019 software-assisted shifts were suggested by US and FM in 39 patients. The 95% limits of agreement in X, Y and Z axes were ±9.4 mm, ±11.3 mm and ±13.4, respectively. Three-dimensionally, measurements agreed within 13.4 mm in 95% of all paired measures. In all axes, concordance was graded as 'poor' or 'unacceptable'. Deming regression detected proportional bias in both directional axes and three-dimensional vectors. Our data suggest substantial differences between US and FM image-guided measures and subsequent suggested directional shifts. Analysis reveals that the vast majority of all individual US and FM directional measures may be expected to agree with each other within a range of 1-1.5 cm. Since neither system represents a gold standard, clinical judgment must dictate whether such a difference is of import. As IMRT protocols seek dose escalation and PTV reduction predicated on US- and FM-guided imaging, future studies are needed to address these potential clinically relevant issues regarding the interchangeability and accuracy of novel positional verification techniques. Comparison series with multiple image-guidance systems are needed to refine comparisons between targeting methods. However, we do not advocate interchangeability of US and FM localization methods. Portions of this data were presented at the American Society of Clinical Oncology/American Society for Therapeutic Radiology and Oncology/Society of Surgical Oncology 2006 Prostate Cancer Symposium, San Francisco, CA, USA.

Collaborative Care for Adolescents With Persistent Postconcussive Symptoms: A Randomized Trial

PubMed Central

Zatzick, Douglas; Stein, Elizabeth; Wang, Jin; Hilt, Robert; Rivara, Frederick P.

2016-01-01

BACKGROUND AND OBJECTIVES: Postconcussive and co-occurring psychological symptoms are not uncommon after sports-related concussion and are associated with functional impairment and societal costs. There is no evidence-based treatment targeting postconcussive symptoms in children and adolescents. The goal of this study was to test a collaborative care intervention model with embedded cognitive–behavioral therapy, care management, and psychopharmacological consultation. We hypothesized that patients in collaborative care would demonstrate greater reductions in postconcussive, depressive, and anxiety symptoms and improvement in functioning over the course of 6 months, compared with usual care control. METHODS: Patients aged 11 to 17 years with persistent symptoms ≥1 month after sports-related concussion were randomly assigned to receive collaborative care (n = 25) or care as usual (n = 24). Patients were assessed before randomization and after 1, 3, and 6 months. Groups were compared over time via linear mixed effects regression models. RESULTS: Adolescents assigned to collaborative care experienced clinically and statistically significant improvements in postconcussive symptoms in addition to functional gains at 6 months compared with controls. Six months after the baseline assessment, 13.0% of intervention patients and 41.7% of control patients reported high levels of postconcussive symptoms (P = .03), and 78% of intervention patients and 45.8% of control patients reported ≥50% reduction in depression symptoms (P = .02). No changes between groups were demonstrated in anxiety symptoms. CONCLUSIONS: Orchestrated efforts to systematically implement collaborative care treatment approaches for slow-to-recover adolescents may be useful given the reductions in postconcussive and co-occurring psychological symptoms in addition to improved quality of life. PMID:27624513

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.

Reduction of Human Norovirus GI, GII, and Surrogates by Peracetic Acid and Monochloramine in Municipal Secondary Wastewater Effluent.

PubMed

Dunkin, Nathan; Weng, ShihChi; Coulter, Caroline G; Jacangelo, Joseph G; Schwab, Kellogg J

2017-10-17

The objective of this study was to characterize human norovirus (hNoV) GI and GII reductions during disinfection by peracetic acid (PAA) and monochloramine in secondary wastewater (WW) and phosphate buffer (PB) as assessed by reverse transcription-qPCR (RT-qPCR). Infectivity and RT-qPCR reductions are also presented for surrogate viruses murine norovirus (MNV) and bacteriophage MS2 under identical experimental conditions to aid in interpretation of hNoV molecular data. In WW, RT-qPCR reductions were less than 0.5 log 10 for all viruses at concentration-time (CT) values up to 450 mg-min/L except for hNoV GI, where 1 log 10 reduction was observed at CT values of less than 50 mg-min/L for monochloramine and 200 mg-min/L for PAA. In PB, hNoV GI and MNV exhibited comparable resistance to PAA and monochloramine with CT values for 2 log 10 RT-qPCR reduction between 300 and 360 mg-min/L. Less than 1 log 10 reduction was observed for MS2 and hNoV GII in PB at CT values for both disinfectants up to 450 mg-min/L. Our results indicate that hNoVs exhibit genogroup dependent resistance and that disinfection practices targeting hNoV GII will result in equivalent or greater reductions for hNoV GI. These data provide valuable comparisons between hNoV and surrogate molecular signals that can begin the process of informing regulators and engineers on WW treatment plant design and operational practices necessary to inactivate hNoVs.

Voluntary Deep Inspiration Breath-hold Reduces the Heart Dose Without Compromising the Target Volume Coverage During Radiotherapy for Left-sided Breast Cancer.

PubMed

Al-Hammadi, Noora; Caparrotti, Palmira; Naim, Carole; Hayes, Jillian; Rebecca Benson, Katherine; Vasic, Ana; Al-Abdulla, Hissa; Hammoud, Rabih; Divakar, Saju; Petric, Primoz

2018-03-01

During radiotherapy of left-sided breast cancer, parts of the heart are irradiated, which may lead to late toxicity. We report on the experience of single institution with cardiac-sparing radiotherapy using voluntary deep inspiration breath hold (V-DIBH) and compare its dosimetric outcome with free breathing (FB) technique. Left-sided breast cancer patients, treated at our department with postoperative radiotherapy of breast/chest wall +/- regional lymph nodes between May 2015 and January 2017, were considered for inclusion. FB-computed tomography (CT) was obtained and dose-planning performed. Cases with cardiac V25Gy ≥ 5% or risk factors for heart disease were coached for V-DIBH. Compliant patients were included. They underwent additional CT in V-DIBH for planning, followed by V-DIBH radiotherapy. Dose volume histogram parameters for heart, lung and optimized planning target volume (OPTV) were compared between FB and BH. Treatment setup shifts and systematic and random errors for V-DIBH technique were compared with FB historic control. Sixty-three patients were considered for V-DIBH. Nine (14.3%) were non-compliant at coaching, leaving 54 cases for analysis. When compared with FB, V-DIBH resulted in a significant reduction of mean cardiac dose from 6.1 +/- 2.5 to 3.2 +/- 1.4 Gy (p < 0.001), maximum cardiac dose from 51.1 +/- 1.4 to 48.5 +/- 6.8 Gy (p = 0.005) and cardiac V25Gy from 8.5 +/- 4.2 to 3.2 +/- 2.5% (p < 0.001). Heart volumes receiving low (10-20 Gy) and high (30-50 Gy) doses were also significantly reduced. Mean dose to the left anterior coronary artery was 23.0 (+/- 6.7) Gy and 14.8 (+/- 7.6) Gy on FB and V-DIBH, respectively (p < 0.001). Differences between FB- and V-DIBH-derived mean lung dose (11.3 +/- 3.2 vs. 10.6 +/- 2.6 Gy), lung V20Gy (20.5 +/- 7 vs. 19.5 +/- 5.1 Gy) and V95% for the OPTV (95.6 +/- 4.1 vs. 95.2 +/- 6.3%) were non-significant. V-DIBH-derived mean shifts for initial patient setup were ≤ 2.7 mm. Random and systematic errors were ≤ 2.1 mm. These results did not differ significantly from historic FB controls. When compared with FB, V-DIBH demonstrated high setup accuracy and enabled significant reduction of cardiac doses without compromising the target volume coverage. Differences in lung doses were non-significant.

Assessing Community Coalition Capacity and its Association with Underage Drinking Prevention Effectiveness in the Context of the SPF SIG.

PubMed

Flewelling, Robert L; Hanley, Sean M

2016-10-01

Community coalitions are a prominent organizational structure through which community-based substance abuse prevention efforts are implemented. There is little empirical evidence, however, regarding the association between coalition attributes and success in achieving community-level reductions in substance abuse behaviors. In this study, we assessed the relationship between coalition capacity, based on coalition coordinator responses to 16 survey items, and reductions in underage drinking prevalence rates. The coalitions were funded through the federally sponsored Strategic Prevention Framework State Incentive Grant (SPF SIG). We first examined whether coalition capacity increased over the life of the projects. Mean capacity scores increased for all 16 capacity items examined (N = 318 coalitions), the majority of which were statistically significant. Analysis of the associations between capacity and reductions in underage drinking was limited to coalitions that targeted underage drinking and provided usable outcome measures based on student survey data for either past 30-day alcohol use (N = 129) or binge drinking (N = 100). Bivariate associations between the capacity items and prevalence reductions for each outcome were consistently positive, although many were not statistically significant. Composite measures of correlated items were then created to represent six different capacity constructs, and included in multivariate models to predict reductions in the targeted outcomes. Constructs that significantly predicted reductions in one or both outcome measures included internal organization and structure, community connections and outreach, and funding from multiple sources. The findings provide support for the expectation that high functioning community coalitions can be effective agents for producing desirable community-level changes in targeted substance abuse behaviors.

Dose reduction and cost-benefit analysis at Japan`s Tokai No. 2 Plant

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

Humamoto, Hisao; Suzuki, Seishiro; Taniguchi, Kazufumi

1995-03-01

In the Tokai No. 2 power plant of the Japan Atomic Power Company, about 80% of the annual dose equivalent is received during periodic maintenance outages. A project group for dose reduction was organized at the company`s headquarters in 1986; in 1988, they proposed a five-year program to reduce by half the collective dose of 4 person-Sv per normal outage work. To achieve the target dose value, some dose-reduction measures were undertaken, namely, permanent radiation shielding, decontamination, automatic, operating machines, and ALARA organization. As the result, the collective dose from normal outage work was 1.6 person-Sv in 1992, which wasmore » less than the initial target value.« less

Using awareness training to decrease nervous habits during public speaking.

PubMed

Spieler, Claire; Miltenberger, Raymond

2017-01-01

This study evaluated the effectiveness of awareness training for the reduction of three nervous habits that manifest during public speaking: filled pauses, tongue clicks, and inappropriate use of the word "like." Four university students delivered short speeches during baseline and assessment sessions. Awareness training resulted in meaningful reductions in target behaviors for all participants. Booster awareness training sessions were necessary for all participants to achieve further reductions in target behaviors. Generality probes conducted in front of a small audience indicated that treatment effects generally maintained. Social validity scores indicated that the treatment was acceptable, and participants indicated not only decreased use of verbal fillers, but also improved overall public speaking ability posttreatment. © 2016 Society for the Experimental Analysis of Behavior.

Estimating the Public Health Impact of Setting Targets at the European Level for the Reduction of Zoonotic Salmonella in Certain Poultry Populations

PubMed Central

Messens, Winy; Vivas-Alegre, Luis; Bashir, Saghir; Amore, Giusi; Romero-Barrios, Pablo; Hugas, Marta

2013-01-01

In the European Union (EU), targets are being set for the reduction of certain zoonotic Salmonella serovars in different animal populations, including poultry populations, within the framework of Regulation (EC) No. 2160/2003 on the control of zoonoses. For a three-year transitional period, the EU targets were to cover only Salmonella Enteritidis and S. Typhimurium (and in addition S. Hadar, S. Infantis and S. Virchow for breeding flocks of Gallus gallus). Before the end of that transitional period, the revision of the EU targets was to be considered, including the potentially addition of other serovars with public health significance to the permanent EU targets. This review article aims at providing an overview of the assessments carried out by the Scientific Panel on Biological Hazards of the European Food Safety Authority in the field of setting targets for Salmonella in poultry populations (breeding flocks of Gallus gallus, laying flocks of Gallus gallus, broiler flocks of Gallus gallus and flocks of breeding and fattening turkeys) and their impact in subsequent changes in EU legislation. PMID:24157508

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.

Lucid Provides Energy Reduction Software to DC Government

EPA Pesticide Factsheets

Earlier this year, Lucid, a 2014 U.S. EPA SBIR award recipient, announced that the D.C. government was using Lucid's BuildingOS® software in order to reach an an energy reduction target of 20 percent in 20 months

Efficacy and Safety of Insulin Glargine 300 U/mL Versus Insulin Glargine 100 U/mL in High-Risk and Low-Risk Patients with Type 2 Diabetes Stratified Using Common Clinical Performance Measures.

PubMed

Lingvay, Ildiko; Chao, Jason; Dalal, Mehul R; Meneghini, Luigi F

2017-05-01

To determine whether previously reported reductions in hypoglycemia associated with insulin glargine 300 U/mL (Gla-300) compared with insulin glargine 100 U/mL (Gla-100) are impacted by patient risk category in type 2 diabetes (T2D), clinical performance measures based on the Healthcare Effectiveness Data and Information Set (HEDIS) were applied to patient-level data from the EDITION 2 and EDITION 3 clinical trials that compared Gla-300 and Gla-100. In this post hoc analysis, patients were stratified as low risk (LR) if patients were <65 years old with no comorbidities derived from HEDIS (HbA1c target <7.0% [53 mmol/mol]), or as high risk (HR) if patients were either ≥65 years old or had one or more HEDIS-defined comorbidities (HbA1c target <8.0% [64 mmol/mol]). Primary endpoint was a composite of patients achieving HbA1c target without confirmed or severe hypoglycemia over 6 months in the different treatment groups in each of the EDITION trials. There was a statistically nonsignificant trend of more patients treated with Gla-300 achieving the composite endpoint compared with Gla-100 in both the LR and HR patient cohorts, regardless of prior insulin experience. A similar trend was observed for the composite endpoint of HbA1c target without nocturnal hypoglycemia. There is a consistent, nonsignificant trend suggesting that Gla-300 might reduce the burden of hypoglycemia compared with Gla-100 in patients with T2D irrespective of whether they are classed as LR or HR based on age- and National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set-derived comorbidities.

Uptake and impact of a new live attenuated influenza vaccine programme in England: early results of a pilot in primary school-age children, 2013/14 influenza season.

PubMed

Pebody, R G; Green, H K; Andrews, N; Zhao, H; Boddington, N; Bawa, Z; Durnall, H; Singh, N; Sunderland, A; Letley, L; Ellis, J; Elliot, A J; Donati, M; Smith, G E; de Lusignan, S; Zambon, M

2014-06-05

As part of the introduction and roll-out of a universal childhood live-attenuated influenza vaccination programme, 4–11 year-olds were vaccinated in seven pilot areas in England in the 2013/14 influenza season. This paper presents the uptake and impact of the programme for a range of disease indicators. End-of-season uptake was defined as the number of children in the target population who received at least one dose of influenza vaccine. Between week 40 2013 and week 15 2014, cumulative disease incidence per 100,000 population (general practitioner consultations for influenza-like illness and laboratory-confirmed influenza hospitalisations), cumulative influenza swab positivity in primary and secondary care and cumulative proportion of emergency department respiratory attendances were calculated. Indicators were compared overall and by age group between pilot and non-pilot areas. Direct impact was defined as reduction in cumulative incidence based on residence in pilot relative to non-pilot areas in 4–11 year-olds. Indirect impact was reduction between pilot and non-pilot areas in <4 year-olds and >11 year-olds. Overall vaccine uptake of 52.5% (104,792/199,475) was achieved. Although influenza activity was low, a consistent, though not statistically significant, decrease in cumulative disease incidence and influenza positivity across different indicators was seen in pilot relative to non-pilot areas in both targeted and non-targeted age groups, except in older age groups, where no difference was observed for secondary care indicators.

Improved systemic metabolism and adipocyte biology in miR-150 knockout mice.

PubMed

Kang, Minsung; Liu, Xiaobing; Fu, Yuchang; Timothy Garvey, W

2018-06-01

Short non-coding micro-RNAs (miRNAs) are post-transcriptional factors that directly regulate protein expression by degrading or inhibiting target mRNAs; however, the role of miRNAs in obesity and cardiometabolic disease remains unclarified. Based on our earlier study demonstrating that miR-150 influences lipid metabolism, we have studied effects of miR-150 on systemic metabolism and adipocyte biology. Metabolic phenotypes including body weight, food intake, body composition, glucose tolerance and insulin sensitivity were assessed in WT and global miR-150 KO male mice fed a high-fat diet. Molecular changes in epididymal adipose tissue were evaluated through qRT-PCR and Western blotting. miR-150 KO mice displayed lower body weight characterized by a reduction in % fat mass while % lean mass was increased. Lower body weight was associated with reduced food consumption and an increase in circulating leptin concentrations, as well as enhanced insulin sensitivity and glucose tolerance compared with WT mice. Absence of miR-150 resulted in increased mTOR expression known to participate in increased leptin production leading to reduction of food intake. Expression of PGC-1α, another target gene of miR-150, was also increased together with upregulation of PPARα and glycerol kinase in adipose tissue as well as other genes participating in triglyceride degradation and lipid oxidation. miR-150 KO mice showed metabolic benefits accompanied by reduced body weight, decreased energy intake, and enhanced lipid metabolism. miR-150 may represent both a biomarker and novel therapeutic target regarding obesity and insulin resistance. Copyright © 2018. Published by Elsevier Inc.

Changing the renewable fuel standard to a renewable material standard: bioethylene case study.

PubMed

Posen, I Daniel; Griffin, W Michael; Matthews, H Scott; Azevedo, Inês L

2015-01-06

The narrow scope of the U.S. renewable fuel standard (RFS2) is a missed opportunity to spur a wider range of biomass use. This is especially relevant as RFS2 targets are being missed due to demand-side limitations for ethanol consumption. This paper examines the greenhouse gas (GHG) implications of a more flexible policy based on RFS2, which includes credits for chemical use of bioethanol (to produce bioethylene). A Monte Carlo simulation is employed to estimate the life-cycle GHG emissions of conventional low-density polyethylene (LDPE), made from natural gas derived ethane (mean: 1.8 kg CO2e/kg LDPE). The life-cycle GHG emissions from bioethanol and bio-LDPE are examined for three biomass feedstocks: U.S. corn (mean: 97g CO2e/MJ and 2.6 kg CO2e/kg LDPE), U.S. switchgrass (mean: -18g CO2e/MJ and -2.9 kg CO2e/kg LDPE), and Brazilian sugar cane (mean: 33g CO2e/MJ and -1.3 kg CO2e/kg LDPE); bioproduct and fossil-product emissions are compared. Results suggest that neither corn product (bioethanol or bio-LDPE) can meet regulatory GHG targets, while switchgrass and sugar cane ethanol and bio-LDPE likely do. For U.S. production, bioethanol achieves slightly greater GHG reductions than bio-LDPE. For imported Brazilian products, bio-LDPE achieves greater GHG reductions than bioethanol. An expanded policy that includes bio-LDPE provides added flexibility without compromising GHG targets.

Sodium levels in Canadian fast-food and sit-down restaurants.

PubMed

Scourboutakos, Mary J; L'Abbé, Mary R

2013-01-31

To evaluate the sodium levels in Canadian restaurant and fast-food chain menu items. Nutrition information was collected from the websites of major sit-down (n=20) and fast-food (n=65) restaurants across Canada in 2010 and a database was constructed. Four thousand and forty-four meal items, baked goods, side dishes and children's items were analyzed. Sodium levels were compared to the recommended adequate intake level (AI), tolerable upper intake level (UL) and the US National Sodium Reduction Initiative (NSRI) targets. On average, individual sit-down restaurant menu items contained 1455 mg sodium/serving (or 97% of the AI level of 1500 mg/day). Forty percent of all sit-down restaurant items exceeded the AI for sodium and more than 22% of sit-down restaurant stir fry entrées, sandwiches/wraps, ribs, and pasta entrées with meat/seafood exceeded the daily UL for sodium (2300 mg). Fast-food restaurant meal items contained, on average, 1011 mg sodium (68% of the daily AI), while side dishes (from sit-down and fast-food restaurants) contained 736 mg (49%). Children's meal items contained, on average, 790 mg/serving (66% of the sodium AI for children of 1200 mg/day); a small number of children's items exceeded the children's daily UL. On average, 52% of establishments exceeded the 2012 NSRI density targets and 69% exceeded the 2014 targets. The sodium content in Canadian restaurant foods is alarmingly high. A population-wide sodium reduction strategy needs to address the high levels of sodium in restaurant foods.

Are brief alcohol interventions targeting alcohol use efficacious in military and veteran populations? A meta-analysis.

PubMed

Doherty, A M; Mason, C; Fear, N T; Rona, R; Greenberg, N; Goodwin, L

2017-09-01

Rates of hazardous and harm-related drinking are higher in the military and veteran populations compared to the general population. Brief alcohol interventions (BAIs) targeting alcohol use appear to reduce harmful drinking in the general population. However, less is known about the efficacy of BAIs targeting alcohol in military and veteran populations. A systematic review and meta-analysis was conducted to assess the type and efficacy of BAIs used to reduce alcohol use in military and veteran populations conducted from 2000 onwards. The meta-analysis was conducted using a standardised outcome measure of change in average weekly drinks (AWDs) from baseline to follow-up. The search revealed 10 papers that met the search criteria, and that reported data on 11 interventions included in the systematic review. 8 papers (reporting on 9 different interventions) were included in the meta-analysis after 2 papers were excluded for which the relevant outcome data were not available. There was no overall effect of BAIs; a non-significant weekly drink reduction of 0.95 drinks was found (95% CI, -0.17 to 2.07). This lack of efficacy persisted regardless of military group (conscripts, serving or veterans) and method of delivery (i.e., face-to-face, web-based or written information). Furthermore, sensitivity analyses revealed this small drink reduction was driven mainly by a single study. Based on these findings, existing BAIs do not seem to be efficacious in reducing alcohol use in military populations, despite some encouraging results from one electronic intervention which was of extensive duration. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Yeh, Sonia; Yang, Christopher; Gibbs, Michael

California aims to reduce greenhouse gas (GHG) emissions to 40% below 1990 levels by 2030. We compare six energy models that have played various roles in informing the state policymakers in setting climate policy goals and targets. These models adopt a range of modeling structures, including stock-turnover back-casting models, a least-cost optimization model, macroeconomic/macro-econometric models, and an electricity dispatch model. Results from these models provide useful insights in terms of the transformations in the energy system required, including efficiency improvements in cars, trucks, and buildings, electrification of end-uses, low- or zero-carbon electricity and fuels, aggressive adoptions of zero-emission vehicles (ZEVs),more » demand reduction, and large reductions of non-energy GHG emissions. Some of these studies also suggest that the direct economic costs can be fairly modest or even generate net savings, while the indirect macroeconomic benefits are large, as shifts in employment and capital investments could have higher economic returns than conventional energy expenditures. These models, however, often assume perfect markets, perfect competition, and zero transaction costs. They also do not provide specific policy guidance on how these transformative changes can be achieved. Greater emphasis on modeling uncertainty, consumer behaviors, heterogeneity of impacts, and spatial modeling would further enhance policymakers' ability to design more effective and targeted policies. Here, this paper presents an example of how policymakers, energy system modelers and stakeholders interact and work together to develop and evaluate long-term state climate policy targets. Lastly, even though this paper focuses on California, the process of dialogue and interactions, modeling results, and lessons learned can be generally adopted across different regions and scales.« less

Anxiety sensitivity risk reduction in smokers: A randomized control trial examining effects on panic

PubMed Central

Schmidt, Norman B.; Raines, Amanda M.; Allan, Nicholas P.; Zvolensky, Michael J.

2016-01-01

Empirical evidence has identified several risk factors for panic psychopathology, including smoking and anxiety sensitivity (AS; the fear of anxiety-related sensations). Smokers with elevated AS are therefore a particularly vulnerable population for panic. Yet, there is little knowledge about how to reduce risk of panic among high AS smokers. The present study prospectively evaluated panic outcomes within the context of a controlled randomized risk reduction program for smokers. Participants (N = 526) included current smokers who all received a state-of-the-art smoking cessation intervention with approximately half randomized to the AS reduction intervention termed Panic-smoking Program (PSP). The primary hypotheses focus on examining the effects of a PSP on panic symptoms in the context of this vulnerable population. Consistent with prediction, there was a significant effect of treatment condition on AS, such that individuals in the PSP condition, compared to those in the control condition, demonstrated greater decreases in AS throughout treatment and the follow-up period. In addition, PSP treatment resulted in lower rates of panic-related symptomatology. Moreover, mediation analyses indicated that reductions in AS resulted in lower panic symptoms. The present study provides the first empirical evidence that brief, targeted psychoeducational interventions can mitigate panic risk among smokers. PMID:26752327

Anxiety sensitivity risk reduction in smokers: A randomized control trial examining effects on panic.

PubMed

Schmidt, Norman B; Raines, Amanda M; Allan, Nicholas P; Zvolensky, Michael J

2016-02-01

Empirical evidence has identified several risk factors for panic psychopathology, including smoking and anxiety sensitivity (AS; the fear of anxiety-related sensations). Smokers with elevated AS are therefore a particularly vulnerable population for panic. Yet, there is little knowledge about how to reduce risk of panic among high AS smokers. The present study prospectively evaluated panic outcomes within the context of a controlled randomized risk reduction program for smokers. Participants (N = 526) included current smokers who all received a state-of-the-art smoking cessation intervention with approximately half randomized to the AS reduction intervention termed Panic-smoking Program (PSP). The primary hypotheses focus on examining the effects of a PSP on panic symptoms in the context of this vulnerable population. Consistent with prediction, there was a significant effect of treatment condition on AS, such that individuals in the PSP condition, compared to those in the control condition, demonstrated greater decreases in AS throughout treatment and the follow-up period. In addition, PSP treatment resulted in lower rates of panic-related symptomatology. Moreover, mediation analyses indicated that reductions in AS resulted in lower panic symptoms. The present study provides the first empirical evidence that brief, targeted psychoeducational interventions can mitigate panic risk among smokers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dose-response effects of a Web-based physical activity program on body composition and metabolic health in inactive older adults: additional analyses of a randomized controlled trial.

PubMed

Vroege, David P; Wijsman, Carolien A; Broekhuizen, Karen; de Craen, Anton J M; van Heemst, Diana; van der Ouderaa, Frans J G; van Mechelen, Willem; Slagboom, P Eline; Catt, Michael; Westendorp, Rudi G J; Verhagen, Evert A L M; Mooijaart, Simon P

2014-12-04

Low physical activity is a major risk factor for several age-related diseases. Recently, we showed in a randomized controlled trial that a 12-week Web-based intervention (Philips DirectLife) to increase physical activity was effective in increasing physical activity levels and metabolic health in an inactive population aged 60-70 years. The goal of this paper was to assess how many participants successfully reached the physical activity level as targeted by the intervention and what the effects of the intervention on body composition and metabolic health in these successful individuals were to provide insight in the maximum attainable effect of the intervention. Among the 235 participants in a randomized controlled trial of the Actief en Gezond Oud (AGO) study, we assessed the effects of the intervention on metabolic parameters in those who had successfully reached their personalized physical activity target compared with the entire intervention group. Furthermore, we studied the dose-response effect of increase in physical activity on metabolic outcome within the intervention group. Of the intervention group, 50 of 119 (42.0%) participants successfully reached the physical activity target (corresponding to a 10% increased daily physical activity on average). This group showed markedly higher effects of the intervention compared to the entire intervention group, with greater decreases in body weight (2.74 vs 1.49 kg), waist circumference (3.74 vs 2.33 cm), insulin resistance (HOMA index: 0.23 vs 0.20), and in cholesterol/HDL ratio (0.39 vs 0.20) and Framingham risk score (0.90% vs 0.54%). We found that men compared to women were more likely to be successful. The dose-response analysis showed that there was a significant association between increase in minutes spent in moderate-to-vigorous activity and body weight loss, BMI reduction, waist circumference reduction, HDL cholesterol increasing, and cholesterol/HDL ratio lowering. Of the intervention group, 42.0% (50/119) reached their daily physical activity end goal, which was associated with a markedly better effect on body composition and metabolic health compared to the effect in the entire intervention group. In this population, men are more likely to be successful in increasing physical activity. Findings demonstrate that improving the effect of such physical activity interventions requires finding new ways to increase the proportion of the population reaching the targeted goal. Dutch Trial Registry: NTR 3045; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3045 (Archived by WebCite at http://www.webcitation.org/6KPw52dCc).

Using the Lives Saved Tool to aid country planning in meeting mortality targets: a case study from Mali.

PubMed

Keita, Youssouf; Sangho, Hamadoun; Roberton, Timothy; Vignola, Emilia; Traoré, Mariam; Munos, Melinda

2017-11-07

Mali is one of four countries implementing a National Evaluation Platform (NEP) to build local capacity to answer evaluation questions for maternal, newborn, child health and nutrition (MNCH&N). In 2014-15, NEP-Mali addressed questions about the potential impact of Mali's MNCH&N plans and strategies, and identified priority interventions to achieve targeted mortality reductions. The NEP-Mali team modeled the potential impact of three intervention packages in the Lives Saved Tool (LiST) from 2014 to 2023. One projection included the interventions and targets from Mali's ten-year health strategy (PDDSS) for 2014-2023, and two others modeled intervention packages that included scale up of antenatal, intrapartum, and curative interventions, as well as reductions in stunting and wasting. We modeled the change in maternal, newborn and under-five mortality rates under these three projections, as well as the number of lives saved, overall and by intervention. If Mali were to achieve the MNCH&N coverage targets from its health strategy, under-5 mortality would be reduced from 121 per 1000 live births to 93 per 1000, far from the target of 69 deaths per 1000. Projections 1 and 2 produced estimated mortality reductions from 121 deaths per 1000 to 70 and 68 deaths per 1000, respectively. With respect to neonatal mortality, the mortality rate would be reduced from 39 to 32 deaths per 1000 live births under the current health strategy, and to 25 per 1000 under projections 1 and 2. This study revealed that achieving the coverage targets for the MNCH&N interventions in the 2014-23 PDDSS would likely not allow Mali to achieve its mortality targets. The NEP-Mali team was able to identify two packages of MNCH&N interventions (and targets) that achieved under-5 and neonatal mortality rates at, or very near, the PDDSS targets. The Malian Ministry of Health and Public Hygiene is using these results to revise its plans and strategies.

Field Test Evaluation of Conservation Retrofits of Low-Income, Single-Family Buildings in Wisconsin: Blower-Door-Directed Infiltration Reduction Procedure, Field Test Implementation and Results

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

Gettings, M.B.

A blower-door-directed infiltration retrofit procedure was field tested on 18 homes in south central Wisconsin. The procedure, developed by the Wisconsin Energy Conservation Corporation, includes recommended retrofit techniques as well as criteria for estimating the amount of cost-effective work to be performed on a house. A recommended expenditure level and target air leakage reduction, in air changes per hour at 50 Pascal (ACH50), are determined from the initial leakage rate measured. The procedure produced an average 16% reduction in air leakage rate. For the 7 houses recommended for retrofit, 89% of the targeted reductions were accomplished with 76% of themore » recommended expenditures. The average cost of retrofits per house was reduced by a factor of four compared with previous programs. The average payback period for recommended retrofits was 4.4 years, based on predicted energy savings computed from achieved air leakage reductions. Although exceptions occurred, the procedure's 8 ACH50 minimum initial leakage rate for advising retrofits to be performed appeared a good choice, based on cost-effective air leakage reduction. Houses with initial rates of 7 ACH50 or below consistently required substantially higher costs to achieve significant air leakage reductions. No statistically significant average annual energy savings was detected as a result of the infiltration retrofits. Average measured savings were -27 therm per year, indicating an increase in energy use, with a 90% confidence interval of 36 therm. Measured savings for individual houses varied widely in both positive and negative directions, indicating that factors not considered affected the results. Large individual confidence intervals indicate a need to increase the accuracy of such measurements as well as understand the factors which may cause such disparity. Recommendations for the procedure include more extensive training of retrofit crews, checks for minimum air exchange rates to insure air quality, and addition of the basic cost of determining the initial leakage rate to the recommended expenditure level. Recommendations for the field test of the procedure include increasing the number of houses in the sample, more timely examination of metered data to detect anomalies, and the monitoring of indoor air temperature. Though not appropriate in a field test of a procedure, further investigation into the effects of air leakage rate reductions on heating loads needs to be performed.« less

A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation.

PubMed

Kleikers, Pamela W M; Hooijmans, Carlijn; Göb, Eva; Langhauser, Friederike; Rewell, Sarah S J; Radermacher, Kim; Ritskes-Hoitinga, Merel; Howells, David W; Kleinschnitz, Christoph; Schmidt, Harald H H W

2015-08-27

Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX2 to be a major therapeutic target in stroke. Systematic review and MA of all available NOX2(-/y) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX2 as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.

Targets set to reduce Lake Erie algae

USGS Publications Warehouse

Evans, Mary

2016-01-01

In February 2016, the Great Lakes Executive Committee, which oversees the implementation of the Great Lakes Water Quality Agreement (GLWQA) between the U.S. and Canada, approved phosphorus loading targets for Lake Erie to reduce the size of harmful algal blooms (HABs), reduce the presence of the low oxygen zone in the central basin, and protect nearshore water quality. The targets are set with respect to the nutrient loads calculated for 2008. To reduce the impacts of HABs on Lake Erie a target was set of a 40 percent reduction in total and soluble reactive phosphorus loads in the spring from two Canadian rivers and several Michigan and Ohio rivers, especially the Maumee River (https://binational.net/2016/02/22/ finalptargets-ciblesfinalesdep/). States and the province of Ontario are already developing Domestic Action Plans to accomplish the reductions and scientists are developing research and monitoring plans to assess progress.

Health co-benefits from air pollution and mitigation costs of the Paris Agreement: a modelling study

DOE PAGES

Markandya, Anil; Sampedro, Jon; Smith, Steven J.; ...

2018-03-02

While the co-benefits from addressing both climate change and air pollution related problems have been clearly recognized, there is not much evidence comparing the mitigation costs and economic benefits of air pollution reduction for alternative scenarios to reduce greenhouse gases. This study analyses the extent to which the health co-benefits would compensate the mitigation cost of achieving the targets of Paris Agreement (2ºC and 1·5ºC) under different scenarios where the emissions abatement effort is shared between countries according to three established equity criteria.

Health co-benefits from air pollution and mitigation costs of the Paris Agreement: a modelling study

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

Markandya, Anil; Sampedro, Jon; Smith, Steven J.

While the co-benefits from addressing both climate change and air pollution related problems have been clearly recognized, there is not much evidence comparing the mitigation costs and economic benefits of air pollution reduction for alternative scenarios to reduce greenhouse gases. This study analyses the extent to which the health co-benefits would compensate the mitigation cost of achieving the targets of Paris Agreement (2ºC and 1·5ºC) under different scenarios where the emissions abatement effort is shared between countries according to three established equity criteria.

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.

Evidence for Deficits in the Temporal Attention Span of Poor Readers

PubMed Central

Visser, Troy A. W.

2014-01-01

Background While poor reading is often associated with phonological deficits, many studies suggest that visual processing might also be impaired. In particular, recent research has indicated that poor readers show impaired spatial visual attention spans in partial and whole report tasks. Given the similarities between competition-based accounts for reduced visual attention span and similar explanations for impairments in sequential object processing, the present work examined whether poor readers show deficits in their “temporal attention span” – that is, their ability to rapidly and accurately process sequences of consecutive target items. Methodology/Principal Findings Poor and normal readers monitored a sequential stream of visual items for two (TT condition) or three (TTT condition) consecutive target digits. Target identification was examined using both unconditional and conditional measures of accuracy in order to gauge the overall likelihood of identifying a target and the likelihood of identifying a target given successful identification of previous items. Compared to normal readers, poor readers showed small but consistent deficits in identification across targets whether unconditional or conditional accuracy was used. Additionally, in the TTT condition, final-target conditional accuracy was poorer than unconditional accuracy, particularly for poor readers, suggesting a substantial cost arising from processing the previous two targets that was not present in normal readers. Conclusions/Significance Mirroring the differences found between poor and normal readers in spatial visual attention span, the present findings suggest two principal differences between the temporal attention spans of poor and normal readers. First, the consistent pattern of reduced performance across targets suggests increased competition amongst items within the same span for poor readers. Second, the steeper decline in final target performance amongst poor readers in the TTT condition suggests a reduction in the extent of their temporal attention span. PMID:24651313

Evidence for deficits in the temporal attention span of poor readers.

PubMed

Visser, Troy A W

2014-01-01

While poor reading is often associated with phonological deficits, many studies suggest that visual processing might also be impaired. In particular, recent research has indicated that poor readers show impaired spatial visual attention spans in partial and whole report tasks. Given the similarities between competition-based accounts for reduced visual attention span and similar explanations for impairments in sequential object processing, the present work examined whether poor readers show deficits in their "temporal attention span"--that is, their ability to rapidly and accurately process sequences of consecutive target items. Poor and normal readers monitored a sequential stream of visual items for two (TT condition) or three (TTT condition) consecutive target digits. Target identification was examined using both unconditional and conditional measures of accuracy in order to gauge the overall likelihood of identifying a target and the likelihood of identifying a target given successful identification of previous items. Compared to normal readers, poor readers showed small but consistent deficits in identification across targets whether unconditional or conditional accuracy was used. Additionally, in the TTT condition, final-target conditional accuracy was poorer than unconditional accuracy, particularly for poor readers, suggesting a substantial cost arising from processing the previous two targets that was not present in normal readers. Mirroring the differences found between poor and normal readers in spatial visual attention span, the present findings suggest two principal differences between the temporal attention spans of poor and normal readers. First, the consistent pattern of reduced performance across targets suggests increased competition amongst items within the same span for poor readers. Second, the steeper decline in final target performance amongst poor readers in the TTT condition suggests a reduction in the extent of their temporal attention span.

Crumb rubber filtration: a potential technology for ballast water treatment.

PubMed

Tang, Zhijian; Butkus, Michael A; Xie, Yuefeng F

2006-05-01

The removal of turbidity, particles, phytoplankton and zooplankton in water by crumb rubber filtration was investigated. A substantial reduction was achieved. Of the three variables, filter depth, media size and filtration rate, media size had the most significant influence. Smaller media size favored higher removal efficiency of all targeted matter. There was no apparent relationship between removal efficiency and filter depth. Higher filtration rate resulted in lower removal efficiency and higher head loss. Compared with conventional granular media filters, crumb rubber filters required less backwash, and developed lower head loss. Consequently crumb rubber filters could be run for a longer time or allow a higher filtration rate. The results also indicate that the crumb rubber filtration alone did not achieve the target removal of invasive species. However, crumb rubber filtration could potentially be used as a primary treatment technology to enhance the efficiency of a secondary treatment process (e.g., disinfection).

Squamous cell carcinoma – similarities and differences among anatomical sites

PubMed Central

Yan, Wusheng; Wistuba, Ignacio I; Emmert-Buck, Michael R; Erickson, Heidi S

2011-01-01

Squamous cell carcinoma (SCC) is an epithelial malignancy involving many anatomical sites and is the most common cancer capable of metastatic spread. Development of early diagnosis methods and novel therapeutics are important for prevention and mortality reduction. In this effort, numerous molecular alterations have been described in SCCs. SCCs share many phenotypic and molecular characteristics, but they have not been extensively compared. This article reviews SCC as a disease, including: epidemiology, pathology, risk factors, molecular characteristics, prognostic markers, targeted therapy, and a new approach to studying SCCs. Through this comparison, several themes are apparent. For example, HPV infection is a common risk factor among the four major SCCs (NMSC, HNSC, ESCC, and NSCLC) and molecular abnormalities in cell-cycle regulation and signal transduction predominate. These data reveal that the molecular insights, new markers, and drug targets discovered in individual SCCs may shed light on this type of cancer as a whole. PMID:21938273

Targeting Tumor Associated Phosphatidylserine with New Zinc Dipicolylamine-Based Drug Conjugates.

PubMed

Liu, Yu-Wei; Shia, Kak-Shan; Wu, Chien-Huang; Liu, Kuan-Liang; Yeh, Yu-Cheng; Lo, Chen-Fu; Chen, Chiung-Tong; Chen, Yun-Yu; Yeh, Teng-Kuang; Chen, Wei-Han; Jan, Jiing-Jyh; Huang, Yu-Chen; Huang, Chen-Lung; Fang, Ming-Yu; Gray, Brian D; Pak, Koon Y; Hsu, Tsu-An; Huang, Kuan-Hsun; Tsou, Lun K

2017-07-19

A series of zinc(II) dipicolylamine (ZnDPA)-based drug conjugates have been synthesized to probe the potential of phosphatidylserine (PS) as a new antigen for small molecule drug conjugate (SMDC) development. Using in vitro cytotoxicity and plasma stability studies, PS-binding assay, in vivo pharmacokinetic studies, and maximum tolerated dose profiles, we provided a roadmap and the key parameters required for the development of the ZnDPA based drug conjugate. In particular, conjugate 24 induced tumor regression in the COLO 205 xenograft model and exhibited a more potent antitumor effect with a 70% reduction of cytotoxic payload compared to that of the marketed irinotecan when dosed at the same regimen. In addition to the validation of PS as an effective pharmacodelivery target for SMDC, our work also provided the foundation that, if applicable, a variety of therapeutic agents could be conjugated in the same manner to treat other PS-associated diseases.

Strategically placing green infrastructure: cost-effective land conservation in the floodplain.

PubMed

Kousky, Carolyn; Olmstead, Sheila M; Walls, Margaret A; Macauley, Molly

2013-04-16

Green infrastructure approaches have attracted increased attention from local governments as a way to lower flood risk and provide an array of other environmental services. The peer-reviewed literature, however, offers few estimates of the economic impacts of such approaches at the watershed scale. We estimate the avoided flood damages and the costs of preventing development of floodplain parcels in the East River Watershed of Wisconsin's Lower Fox River Basin. Results suggest that the costs of preventing conversion of all projected floodplain development would exceed the flood damage mitigation benefits by a substantial margin. However, targeting of investments to high-benefit, low-cost parcels can reverse this equation, generating net benefits. The analysis demonstrates how any flood-prone community can use a geographic-information-based model to estimate the flood damage reduction benefits of green infrastructure, compare them to the costs, and target investments to design cost-effective nonstructural flood damage mitigation policies.

Dual-targeting Wnt and uPA receptors using peptide conjugated ultra-small nanoparticle drug carriers inhibited cancer stem-cell phenotype in chemo-resistant breast cancer.

PubMed

Miller-Kleinhenz, Jasmine; Guo, Xiangxue; Qian, Weiping; Zhou, Hongyu; Bozeman, Erica N; Zhu, Lei; Ji, Xin; Wang, Y Andrew; Styblo, Toncred; O'Regan, Ruth; Mao, Hui; Yang, Lily

2018-01-01

Heterogeneous tumor cells, high incidence of tumor recurrence, and decrease in overall survival are the major challenges for the treatment of chemo-resistant breast cancer. Results of our study showed differential chemotherapeutic responses among breast cancer patient derived xenograft (PDX) tumors established from the same patients. All doxorubicin (Dox)-resistant tumors expressed higher levels of cancer stem-like cell biomarkers, including CD44, Wnt and its receptor LRP5/6, relative to Dox-sensitive tumors. To effectively treat resistant tumors, we developed an ultra-small magnetic iron oxide nanoparticle (IONP) drug carrier conjugated with peptides that are dually targeted to Wnt/LRP5/6 and urokinase plasminogen activator receptor (uPAR). Our results showed that simultaneous binding to LRP5/6 and uPAR by the dual receptor targeted IONPs was required to inhibit breast cancer cell invasion. Molecular analysis revealed that the dual receptor targeted IONPs significantly inhibited Wnt/β-catenin signaling and cancer stem-like phenotype of tumor cells, with marked reduction of Wnt ligand, CD44 and uPAR. Systemic administration of the dual targeted IONPs led to nanoparticle-drug delivery into PDX tumors, resulting in stronger tumor growth inhibition compared to non-targeted or single-targeted IONP-Dox in a human breast cancer PDX model. Therefore, co-targeting Wnt/LRP and uPAR using IONP drug carriers is a promising therapeutic approach for effective drug delivery to chemo-resistant breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

A cooperative-binding split aptamer assay for rapid, specific and ultra-sensitive fluorescence detection of cocaine in saliva.

PubMed

Yu, Haixiang; Canoura, Juan; Guntupalli, Bhargav; Lou, Xinhui; Xiao, Yi

2017-01-01

Sensors employing split aptamers that reassemble in the presence of a target can achieve excellent specificity, but the accompanying reduction of target affinity mitigates any overall gains in sensitivity. We for the first time have developed a split aptamer that achieves enhanced target-binding affinity through cooperative binding. We have generated a split cocaine-binding aptamer that incorporates two binding domains, such that target binding at one domain greatly increases the affinity of the second domain. We experimentally demonstrate that the resulting cooperative-binding split aptamer (CBSA) exhibits higher target binding affinity and is far more responsive in terms of target-induced aptamer assembly compared to the single-domain parent split aptamer (PSA) from which it was derived. We further confirm that the target-binding affinity of our CBSA can be affected by the cooperativity of its binding domains and the intrinsic affinity of its PSA. To the best of our knowledge, CBSA-5335 has the highest cocaine affinity of any split aptamer described to date. The CBSA-based assay also demonstrates excellent performance in target detection in complex samples. Using this CBSA, we achieved specific, ultra-sensitive, one-step fluorescence detection of cocaine within fifteen minutes at concentrations as low as 50 nM in 10% saliva without signal amplification. This limit of detection meets the standards recommended by the European Union's Driving under the Influence of Drugs, Alcohol and Medicines program. Our assay also demonstrates excellent reproducibility of results, confirming that this CBSA-platform represents a robust and sensitive means for cocaine detection in actual clinical samples.

Effect of ezetimibe add-on therapy over 52 weeks extension analysis of prospective randomized trial (RESEARCH study) in type 2 diabetes subjects.

PubMed

Sakamoto, Kentaro; Kawamura, Mitsunobu; Watanabe, Takayuki; Ashidate, Keiko; Kohro, Takahide; Tanaka, Akira; Mori, Yasumichi; Tagami, Motoki; Hirano, Tsutomu; Yamazaki, Tsutomu; Shiba, Teruo

2017-06-24

Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles. We evaluated long-term ezetimibe add-on therapy in T2DM patients with hypercholesterolemia. In a randomized, multicenter, open-label, prospective study, a total of 109 T2DM patients not attaining LDL-C target value despite first-line dose statin (10 mg of atorvastatin or 1 mg of pitavastatin) therapy in Japan were recruited. We investigated the difference in cholesterol lowering effect between ezetimibe (10 mg) add-on statin (EAT) group and double-dose statin (DST) group. Changes of parameters related to atherosclerotic event risks were assessed. The reduction of LDL-C was larger in the EAT group (28.3%) than in the DST group (9.2%) at 52 weeks as well as the primary endpoint of 12 weeks. EAT achieved significant lower levels of TC and apo B, respectively. Both treatments attained significant reduction in sd-LDL-C or hsCRP on this long-term basis. Notably, sd-LDL-C in EAT reduced as low as 36.1 ± 14.9 mg/dl to reach near the threshold (35.0 mg/dl) for atherosclerosis with significantly higher achievement rate (55.6%) than DST treatment. Simultaneously, hsCRP reduction by EAT attained as low value as 0.52 ± 0.43 mg/l. In the present 52-week long-term period, ezetimibe add-on therapy showed a robust advantage in lowering LDL-C and in attaining target LDL-C values compared with the doubling of statin dose. Moreover, it's meaningful that sd-LDL, powerfully atherogenic lipoprotein, exhibited prominent decrease consistently prominently by ezetimibe add-on therapy. DM patients with hypercholesterolemia are at high risk for CAD, and adding ezetimibe onto usual-dose statin treatment in Japan has been suggested as the first-line therapy for those DM patients who failed to attain the target LDL-C value (UMIN000002593).

Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial.

PubMed

Slagman, Maartje C J; Waanders, Femke; Hemmelder, Marc H; Woittiez, Arend-Jan; Janssen, Wilbert M T; Lambers Heerspink, Hiddo J; Navis, Gerjan; Laverman, Gozewijn D

2011-07-26

To compare the effects on proteinuria and blood pressure of addition of dietary sodium restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose. Multicentre crossover randomised controlled trial. Outpatient clinics in the Netherlands. 52 patients with non-diabetic nephropathy. All patients were treated during four 6 week periods, in random order, with angiotensin receptor blockade (valsartan 320 mg/day) or placebo, each combined with, consecutively, a low sodium diet (target 50 mmol Na(+)/day) and a regular sodium diet (target 200 mmol Na(+)/day), with a background of ACE inhibition (lisinopril 40 mg/day) during the entire study. The drug interventions were double blind; the dietary interventions were open label. The primary outcome measure was proteinuria; the secondary outcome measure was blood pressure. Mean urinary sodium excretion, a measure of dietary sodium intake, was 106 (SE 5) mmol Na(+)/day during a low sodium diet and 184 (6) mmol Na(+)/day during a regular sodium diet (P<0.001). Geometric mean residual proteinuria was 1.68 (95% confidence interval 1.31 to 2.14) g/day during ACE inhibition plus a regular sodium diet. Addition of angiotensin receptor blockade to ACE inhibition reduced proteinuria to 1.44 (1.07 to 1.93) g/day (P=0.003), addition of a low sodium diet reduced it to 0.85 (0.66 to 1.10) g/day (P<0.001), and addition of angiotensin receptor blockade plus a low sodium diet reduced it to 0.67 (0.50 to 0.91) g/day (P<0.001). The reduction of proteinuria by the addition of a low sodium diet to ACE inhibition (51%, 95% confidence interval 43% to 58%) was significantly larger (P<0.001) than the reduction of proteinuria by the addition of angiotensin receptor blockade to ACE inhibition (21%, (8% to 32%) and was comparable (P=0.009, not significant after Bonferroni correction) to the reduction of proteinuria by the addition of both angiotensin receptor blockade and a low sodium diet to ACE inhibition (62%, 53% to 70%). Mean systolic blood pressure was 134 (3) mm Hg during ACE inhibition plus a regular sodium diet. Mean systolic blood pressure was not significantly altered by the addition of angiotensin receptor blockade (131 (3) mm Hg; P=0.12) but was reduced by the addition of a low sodium diet (123 (2) mm Hg; P<0.001) and angiotensin receptor blockade plus a low sodium diet (121 (3) mm Hg; P<0.001) to ACE inhibition. The reduction of systolic blood pressure by the addition of a low sodium diet (7% (SE 1%)) was significantly larger (P=0.003) than the reduction of systolic blood pressure by the addition of angiotensin receptor blockade (2% (1)) and was similar (P=0.14) to the reduction of systolic blood pressure by the addition of both angiotensin receptor blockade and low sodium diet (9% (1)), to ACE inhibition. Dietary sodium restriction to a level recommended in guidelines was more effective than dual blockade for reduction of proteinuria and blood pressure in non-diabetic nephropathy. The findings support the combined endeavours of patients and health professionals to reduce sodium intake. Trial registration Netherlands Trial Register NTR675.

Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial

PubMed Central

Slagman, Maartje C J; Waanders, Femke; Hemmelder, Marc H; Woittiez, Arend-Jan; Janssen, Wilbert M T; Lambers Heerspink, Hiddo J; Navis, Gerjan

2011-01-01

Objective To compare the effects on proteinuria and blood pressure of addition of dietary sodium restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose. Design Multicentre crossover randomised controlled trial. Setting Outpatient clinics in the Netherlands. Participants 52 patients with non-diabetic nephropathy. Interventions All patients were treated during four 6 week periods, in random order, with angiotensin receptor blockade (valsartan 320 mg/day) or placebo, each combined with, consecutively, a low sodium diet (target 50 mmol Na+/day) and a regular sodium diet (target 200 mmol Na+/day), with a background of ACE inhibition (lisinopril 40 mg/day) during the entire study. The drug interventions were double blind; the dietary interventions were open label. Main outcome measures The primary outcome measure was proteinuria; the secondary outcome measure was blood pressure. Results Mean urinary sodium excretion, a measure of dietary sodium intake, was 106 (SE 5) mmol Na+/day during a low sodium diet and 184 (6) mmol Na+/day during a regular sodium diet (P<0.001). Geometric mean residual proteinuria was 1.68 (95% confidence interval 1.31 to 2.14) g/day during ACE inhibition plus a regular sodium diet. Addition of angiotensin receptor blockade to ACE inhibition reduced proteinuria to 1.44 (1.07 to 1.93) g/day (P=0.003), addition of a low sodium diet reduced it to 0.85 (0.66 to 1.10) g/day (P<0.001), and addition of angiotensin receptor blockade plus a low sodium diet reduced it to 0.67 (0.50 to 0.91) g/day (P<0.001). The reduction of proteinuria by the addition of a low sodium diet to ACE inhibition (51%, 95% confidence interval 43% to 58%) was significantly larger (P<0.001) than the reduction of proteinuria by the addition of angiotensin receptor blockade to ACE inhibition (21%, (8% to 32%) and was comparable (P=0.009, not significant after Bonferroni correction) to the reduction of proteinuria by the addition of both angiotensin receptor blockade and a low sodium diet to ACE inhibition (62%, 53% to 70%). Mean systolic blood pressure was 134 (3) mm Hg during ACE inhibition plus a regular sodium diet. Mean systolic blood pressure was not significantly altered by the addition of angiotensin receptor blockade (131 (3) mm Hg; P=0.12) but was reduced by the addition of a low sodium diet (123 (2) mm Hg; P<0.001) and angiotensin receptor blockade plus a low sodium diet (121 (3) mm Hg; P<0.001) to ACE inhibition. The reduction of systolic blood pressure by the addition of a low sodium diet (7% (SE 1%)) was significantly larger (P=0.003) than the reduction of systolic blood pressure by the addition of angiotensin receptor blockade (2% (1)) and was similar (P=0.14) to the reduction of systolic blood pressure by the addition of both angiotensin receptor blockade and low sodium diet (9% (1)), to ACE inhibition. Conclusions Dietary sodium restriction to a level recommended in guidelines was more effective than dual blockade for reduction of proteinuria and blood pressure in non-diabetic nephropathy. The findings support the combined endeavours of patients and health professionals to reduce sodium intake. Trial registration Netherlands Trial Register NTR675. PMID:21791491

Electrochemical oxygen reduction catalysed by Ni3(hexaiminotriphenylene)2.

PubMed

Miner, Elise M; Fukushima, Tomohiro; Sheberla, Dennis; Sun, Lei; Surendranath, Yogesh; Dincă, Mircea

2016-03-08

Control over the architectural and electronic properties of heterogeneous catalysts poses a major obstacle in the targeted design of active and stable non-platinum group metal electrocatalysts for the oxygen reduction reaction. Here we introduce Ni3(HITP)2 (HITP=2, 3, 6, 7, 10, 11-hexaiminotriphenylene) as an intrinsically conductive metal-organic framework which functions as a well-defined, tunable oxygen reduction electrocatalyst in alkaline solution. Ni3(HITP)2 exhibits oxygen reduction activity competitive with the most active non-platinum group metal electrocatalysts and stability during extended polarization. The square planar Ni-N4 sites are structurally reminiscent of the highly active and widely studied non-platinum group metal electrocatalysts containing M-N4 units. Ni3(HITP)2 and analogues thereof combine the high crystallinity of metal-organic frameworks, the physical durability and electrical conductivity of graphitic materials, and the diverse yet well-controlled synthetic accessibility of molecular species. Such properties may enable the targeted synthesis and systematic optimization of oxygen reduction electrocatalysts as components of fuel cells and electrolysers for renewable energy applications.

Electrochemical oxygen reduction catalysed by Ni3(hexaiminotriphenylene)2

PubMed Central

Miner, Elise M.; Fukushima, Tomohiro; Sheberla, Dennis; Sun, Lei; Surendranath, Yogesh; Dincă, Mircea

2016-01-01

Control over the architectural and electronic properties of heterogeneous catalysts poses a major obstacle in the targeted design of active and stable non-platinum group metal electrocatalysts for the oxygen reduction reaction. Here we introduce Ni3(HITP)2 (HITP=2, 3, 6, 7, 10, 11-hexaiminotriphenylene) as an intrinsically conductive metal-organic framework which functions as a well-defined, tunable oxygen reduction electrocatalyst in alkaline solution. Ni3(HITP)2 exhibits oxygen reduction activity competitive with the most active non-platinum group metal electrocatalysts and stability during extended polarization. The square planar Ni-N4 sites are structurally reminiscent of the highly active and widely studied non-platinum group metal electrocatalysts containing M-N4 units. Ni3(HITP)2 and analogues thereof combine the high crystallinity of metal-organic frameworks, the physical durability and electrical conductivity of graphitic materials, and the diverse yet well-controlled synthetic accessibility of molecular species. Such properties may enable the targeted synthesis and systematic optimization of oxygen reduction electrocatalysts as components of fuel cells and electrolysers for renewable energy applications. PMID:26952523

Mediation Analysis of the Efficacy of the Eban HIV/STD Risk-Reduction Intervention for African American HIV Serodiscordant Couples.

PubMed

El-Bassel, Nabila; Jemmott, John B; Bellamy, Scarlett L; Pequegnat, Willo; Wingood, Gina M; Wyatt, Gail E; Landis, J Richard; Remien, Robert H

2016-06-01

Targeting couples is a promising behavioral HIV risk-reduction strategy, but the mechanisms underlying the effects of such interventions are unknown. We report secondary analyses testing whether Social-Cognitive-Theory variables mediated the Eban HIV-risk-reduction intervention's effects on condom-use outcomes. In a multisite randomized controlled trial conducted in four US cities, 535 African American HIV-serodiscordant couples were randomized to the Eban HIV risk-reduction intervention or attention-matched control intervention. Outcomes were proportion condom-protected sex, consistent condom use, and frequency of unprotected sex measured pre-, immediately post-, and 6 and 12 months post-intervention. Potential mediators included Social-Cognitive-Theory variables: outcome expectancies and self-efficacy. Mediation analyses using the product-of-coefficients approach in a generalized-estimating-equations framework revealed that condom-use outcome expectancy, partner-reaction outcome expectancy, intention, self-efficacy, and safer-sex communication improved post-intervention and mediated intervention-induced improvements in condom-use outcomes. These findings underscore the importance of targeting outcome expectancies, self-efficacy, and safer-sex communication in couples-level HIV risk-reduction interventions.

Electrochemical oxygen reduction catalysed by Ni 3(hexaiminotriphenylene) 2

DOE PAGES

Miner, Elise M.; Fukushima, Tomohiro; Sheberla, Dennis; ...

2016-03-08

Control over the architectural and electronic properties of heterogeneous catalysts poses a major obstacle in the targeted design of active and stable non-platinum group metal electrocatalysts for the oxygen reduction reaction. Here we introduce Ni 3(HITP) 2 (HITP=2, 3, 6, 7, 10, 11-hexaiminotriphenylene) as an intrinsically conductive metal-organic framework which functions as a well-defined, tunable oxygen reduction electrocatalyst in alkaline solution. Ni 3(HITP) 2 exhibits oxygen reduction activity competitive with the most active non-platinum group metal electrocatalysts and stability during extended polarization. The square planar Ni-N 4 sites are structurally reminiscent of the highly active and widely studied non-platinum groupmore » metal electrocatalysts containing M-N 4 units. Ni 3(HITP) 2 and analogues thereof combine the high crystallinity of metal-organic frameworks, the physical durability and electrical conductivity of graphitic materials, and the diverse yet well-controlled synthetic accessibility of molecular species. As a result, such properties may enable the targeted synthesis and systematic optimization of oxygen reduction electrocatalysts as components of fuel cells and electrolysers for renewable energy applications.« less

Peptidic β-sheet binding with Congo Red allows both reduction of error variance and signal amplification for immunoassays.

PubMed

Wang, Yunyun; Liu, Ye; Deng, Xinli; Cong, Yulong; Jiang, Xingyu

2016-12-15

Although conventional enzyme-linked immunosorbent assays (ELISA) and related assays have been widely applied for the diagnosis of diseases, many of them suffer from large error variance for monitoring the concentration of targets over time, and insufficient limit of detection (LOD) for assaying dilute targets. We herein report a readout mode of ELISA based on the binding between peptidic β-sheet structure and Congo Red. The formation of peptidic β-sheet structure is triggered by alkaline phosphatase (ALP). For the detection of P-Selectin which is a crucial indicator for evaluating thrombus diseases in clinic, the 'β-sheet and Congo Red' mode significantly decreases both the error variance and the LOD (from 9.7ng/ml to 1.1 ng/ml) of detection, compared with commercial ELISA (an existing gold-standard method for detecting P-Selectin in clinic). Considering the wide range of ALP-based antibodies for immunoassays, such novel method could be applicable to the analysis of many types of targets. Copyright © 2016 Elsevier B.V. All rights reserved.

Phosphorodiamidate morpholino targeting the 5' untranslated region of the ZIKV RNA inhibits virus replication.

PubMed

Popik, Waldemar; Khatua, Atanu; Hildreth, James E K; Lee, Benjamin; Alcendor, Donald J

2018-06-01

Zika virus (ZIKV) infection has been associated with microcephaly in infants. Currently there is no treatment or vaccine. Here we explore the use of a morpholino oligonucleotide targeted to the 5' untranslated region (5'-UTR) of the ZIKV RNA to prevent ZIKV replication. Morpholino DWK-1 inhibition of ZIKV replication in human glomerular podocytes was examined by qRT-PCR, reduction in ZIKV genome copy number, western blot analysis, immunofluorescence and proinflammatory cytokine gene expression. Podocytes pretreated with DWK-1 showed reduced levels of both viral mRNA and ZIKV E protein expression compared to controls. We observed suppression in proinflammatory gene expression for IFN-β (interferon β) RANTES (regulated on activation, normal T cell expressed and secreted), MIP-1α (macrophage inflammatory protein-1α), TNF-α (tumor necrosis factor-α) and IL1-α (interleukin 1-α) in ZIKV-infected podocytes pretreated with DWK-1. Morpholino DWK-1 targeting the ZIKV 5'-UTR effectively inhibits ZIKV replication and suppresses ZIKV-induced proinflammatory gene expression. Copyright © 2018 Elsevier Inc. All rights reserved.

An integrated approach to panic prevention targeting the empirically supported risk factors of smoking and anxiety sensitivity: theoretical basis and evidence from a pilot project evaluating feasibility and short-term efficacy.

PubMed

Feldner, Matthew T; Zvolensky, Michael J; Babson, Kimberly; Leen-Feldner, Ellen W; Schmidt, Norman B

2008-10-01

Consistent with a risk reduction model of targeted prevention, the present investigation piloted and empirically evaluated the feasibility and short-term efficacy of a first-generation panic prevention program that targeted two malleable risk factors for panic development-anxiety sensitivity and daily cigarette smoking. Members of a high risk cohort, defined by high levels of anxiety sensitivity and current daily smoking (n=96), were randomly assigned to either (1) a one session intervention focused on proximally increasing motivation to quit smoking and reducing anxiety sensitivity to distally prevent the development of panic or (2) a health information control condition of comparable length. Participants were followed for 6 months. Consistent with hypotheses, those in the treatment condition showed reduced anxiety sensitivity and this effect was maintained across the follow-up period. Limited evidence also suggested the intervention increased motivation to quit smoking. We discuss how this prevention protocol can be modified in the future to enhance its effects as part of second-generation larger-scale outcome evaluations.

Bovine milk-derived exosomes for drug delivery

PubMed Central

Gupta, Ramesh C.

2015-01-01

Exosomes are biological nanovesicles that are involved in cell-cell communication via the functionally-active cargo (such as miRNA, mRNA, DNA and proteins). Because of their nanosize, exosomes are explored as nanodevices for the development of new therapeutic applications. However, bulk, safe and cost-effective production of exosomes is not available. Here, we show that bovine milk can serve as a scalable source of exosomes that can act as a carrier for chemotherapeutic/chemopreventive agents. Drug-loaded exosomes showed significantly higher efficacy compared to free drug in cell culture studies and against lung tumor xenografts in vivo. Moreover, tumor targeting ligands such as folate increased cancer-cell targeting of the exosomes resulting in enhanced tumor reduction. Milk exosomes exhibited cross-species tolerance with no adverse immune and inflammatory response. Thus, we show the versatility of milk exosomes with respect to the cargo it can carry and ability to achieve tumor targetability. This is the first report to identify a biocompatible and cost-effective means of exosomes to enhance oral bioavailability, improve efficacy and safety of drugs. PMID:26604130

What is the added value of ultrasound joint examination for monitoring synovitis in rheumatoid arthritis and can it be used to guide treatment decisions? A systematic review and cost-effectiveness analysis.

PubMed

Simpson, Emma; Hock, Emma; Stevenson, Matt; Wong, Ruth; Dracup, Naila; Wailoo, Allan; Conaghan, Philip; Estrach, Cristina; Edwards, Christopher; Wakefield, Richard

2018-04-01

Synovitis (inflamed joint synovial lining) in rheumatoid arthritis (RA) can be assessed by clinical examination (CE) or ultrasound (US). To investigate the added value of US, compared with CE alone, in RA synovitis in terms of clinical effectiveness and cost-effectiveness. Electronic databases including MEDLINE, EMBASE and the Cochrane databases were searched from inception to October 2015. A systematic review sought RA studies that compared additional US with CE. Heterogeneity of the studies with regard to interventions, comparators and outcomes precluded meta-analyses. Systematic searches for studies of cost-effectiveness and US and treatment-tapering studies (not necessarily including US) were undertaken. A model was constructed that estimated, for patients in whom drug tapering was considered, the reduction in costs of disease-modifying anti-rheumatic drugs (DMARDs) and serious infections at which the addition of US had a cost per quality-adjusted life-year (QALY) gained of £20,000 and £30,000. Furthermore, the reduction in the costs of DMARDs at which US becomes cost neutral was also estimated. For patients in whom dose escalation was being considered, the reduction in number of patients escalating treatment and in serious infections at which the addition of US had a cost per QALY gained of £20,000 and £30,000 was estimated. The reduction in number of patients escalating treatment for US to become cost neutral was also estimated. Fifty-eight studies were included. Two randomised controlled trials compared adding US to a Disease Activity Score (DAS)-based treat-to-target strategy for early RA patients. The addition of power Doppler ultrasound (PDUS) to a Disease Activity Score 28 joints-based treat-to-target strategy in the Targeting Synovitis in Early Rheumatoid Arthritis (TaSER) trial resulted in no significant between-group difference for change in Disease Activity Score 44 joints (DAS44). This study found that significantly more patients in the PDUS group attained DAS44 remission ( p  = 0.03). The Aiming for Remission in Rheumatoid Arthritis (ARCTIC) trial found that the addition of PDUS and grey-scale ultrasound (GSUS) to a DAS-based strategy did not produce a significant between-group difference in the primary end point: composite DAS of < 1.6, no swollen joints and no progression in van der Heijde-modified total Sharp score (vdHSS). The ARCTIC trial did find that the erosion score of the vdHS had a significant advantage for the US group ( p  = 0.04). In the TaSER trial there was no significant group difference for erosion. Other studies suggested that PDUS was significantly associated with radiographic progression and that US had added value for wrist and hand joints rather than foot and ankle joints. Heterogeneity between trials made conclusions uncertain. No studies were identified that reported the cost-effectiveness of US in monitoring synovitis. The model estimated that an average reduction of 2.5% in the costs of biological DMARDs would be sufficient to offset the costs of 3-monthly US. The money could not be recouped if oral methotrexate was the only drug used. Heterogeneity of the trials precluded meta-analysis. Therefore, no summary estimates of effect were available. Additional costs and health-related quality of life decrements, relating to a flare following tapering or disease progression, have not been included. The feasibility of increased US monitoring has not been assessed. Limited evidence suggests that US monitoring of synovitis could provide a cost-effective approach to selecting RA patients for treatment tapering or escalation avoidance. Considerable uncertainty exists for all conclusions. Future research priorities include evaluating US monitoring of RA synovitis in longitudinal clinical studies. This study is registered as PROSPERO CRD42015017216. The National Institute for Health Research Health Technology Assessment programme.

Design and Implementation of Data Reduction Pipelines for the Keck Observatory Archive

NASA Astrophysics Data System (ADS)

Gelino, C. R.; Berriman, G. B.; Kong, M.; Laity, A. C.; Swain, M. A.; Campbell, R.; Goodrich, R. W.; Holt, J.; Lyke, J.; Mader, J. A.; Tran, H. D.; Barlow, T.

2015-09-01

The Keck Observatory Archive (KOA), a collaboration between the NASA Exoplanet Science Institute and the W. M. Keck Observatory, serves science and calibration data for all active and inactive instruments from the twin Keck Telescopes located near the summit of Mauna Kea, Hawaii. In addition to the raw data, we produce and provide quick look reduced data for four instruments (HIRES, LWS, NIRC2, and OSIRIS) so that KOA users can more easily assess the scientific content and the quality of the data, which can often be difficult with raw data. The reduced products derive from both publicly available data reduction packages (when available) and KOA-created reduction scripts. The automation of publicly available data reduction packages has the benefit of providing a good quality product without the additional time and expense of creating a new reduction package, and is easily applied to bulk processing needs. The downside is that the pipeline is not always able to create an ideal product, particularly for spectra, because the processing options for one type of target (eg., point sources) may not be appropriate for other types of targets (eg., extended galaxies and nebulae). In this poster we present the design and implementation for the current pipelines used at KOA and discuss our strategies for handling data for which the nature of the targets and the observers' scientific goals and data taking procedures are unknown. We also discuss our plans for implementing automated pipelines for the remaining six instruments.