EPA releases progress report on hydraulic fracturing study
NASA Astrophysics Data System (ADS)
Showstack, Randy
2013-01-01
The U.S. Environmental Protection Agency (EPA) provided a 21 December progress report on its ongoing national study about the potential impacts of hydraulic fracturing on drinking water resources. The agency said that a draft of the congressionally requested study will be released in 2014 for public and peer review and that its progress report does not draw conclusions about the potential impacts of hydraulic fracturing, often referred to as fracking.
The Lure of Casino Gambling and Its Potential Impact on College Students in Mississippi.
ERIC Educational Resources Information Center
Bailey, E. Ann; Burroughs, Susie W.; Dabit, Jean S.; Hambrick, Rosalind S.; Theriot, Patricia B.
1997-01-01
Investigates the lure and potential impact of casino gambling on college students in Mississippi. Findings suggest that casino gambling may significantly impact college students in regard to financial management, alcohol consumption, academic progress, and behavioral changes. (MKA)
Progress in modelling agricultural impacts of and adaptations to climate change.
Rötter, R P; Hoffmann, M P; Koch, M; Müller, C
2018-06-01
Modelling is a key tool to explore agricultural impacts of and adaptations to climate change. Here we report recent progress made especially referring to the large project initiatives MACSUR and AgMIP; in particular, in modelling potential crop impacts from field to global using multi-model ensembles. We identify two main fields where further progress is necessary: a more mechanistic understanding of climate impacts and management options for adaptation and mitigation; and focusing on cropping systems and integrative multi-scale assessments instead of single season and crops, especially in complex tropical and neglected but important cropping systems. Stronger linking of experimentation with statistical and eco-physiological crop modelling could facilitate the necessary methodological advances. Copyright © 2018 Elsevier Ltd. All rights reserved.
Talarowska, Monika; Florkowski, Antoni; Gałecki, Piotr; Szemraj, Janusz; Zboralski, Krzysztof; Pietras, Tadeusz; Górski, Paweł
2009-01-01
Chronic respiratory system diseases become serious public health problem all over the world. The most prevalent are obstructive diseases (asthma and COPD). The prevalence of asthma is still high and concern patients representing wide range of age and socio-economic status. Despite progress in diagnostic and therapeutic options several studies showed that asthma has an impact on health-related quality of life and patients' coping. Asthma as chronic condition results in limitations of patients activity and social relations. Thus psychosocial variables, which may have an impact on asthma symptoms presentation and disease progress, should be considered. There are only few reports concerning cognitive functions in asthma. The aim of the study was to assess the potential impact of psychosocial factors on asthma symptoms presentation, and cognitive function in asthma patients.
Austin, S Bryn
2016-01-01
The public health burden of eating disorders is well documented, and over the past several decades, researchers have made important advances in the prevention of eating disorders and related problems with body image. Despite these advances, however, several critical limitations to the approaches developed to date leave the field far from achieving the large-scale impact that is needed. This commentary provides a brief review of what achievements in prevention have been made and identifies the gaps that limit the potential for greater impact on population health. A plan is then offered with specific action steps to accelerate progress in high-impact prevention, most compellingly by promoting a shift in priorities to policy translation research and training for scholars through the adoption of a triggers-to-action framework. Finally, the commentary provides an example of the application of the triggers-to-action framework as practiced at the Strategic Training Initiative for the Prevention of Eating Disorders, a program based at the Harvard T. H. Chan School of Public Health and Boston Children's Hospital. Much has been achieved in the nearly 30 years of research carried out for the prevention of eating disorders and body image problems, but several critical limitations undermine the field's potential for meaningful impact. Through a shift in the field's priorities to policy translation research and training with an emphasis on macro-environmental influences, the pace of progress in prevention can be accelerated and the potential for large-scale impact substantially improved.
The future of planetary defense
NASA Astrophysics Data System (ADS)
Mainzer, A.
2017-04-01
Asteroids and comets have impacted Earth in the past and will do so in the future. While the frequency of impacts is reasonably well understood on geologic timescales, it is difficult to predict the next sizeable impact on human timescales by extrapolation from population statistics alone. Fortunately, by identifying and tracking individual objects, we can make precise predictions of any potential close encounters with Earth. As more advance notice is provided, the range of possible mitigation options expands. While the chance of an impact is very small, the potential consequences can be severe, meaning that sensible risk reduction measures should be undertaken. By implementing surveys, the risk of an unforeseen impact can be greatly reduced: the first step is finding the objects. Fortunately, the worldwide community of professional and amateur astronomers has made significant progress in discovering large near-Earth objects (NEOs). More than 95% of NEOs capable of causing global devastation (objects larger than 1 km in diameter) have been discovered, and none of these pose an impact hazard in the near future. Infrastructure is in place to link observations and compute close approaches in real time. Interagency and international collaborations have been undertaken to strengthen cooperative efforts to plan potential mitigation and civil defense campaigns. Yet much remains to be done. Approximately 70% of NEOs larger than 140 m (large enough to cause severe regional damage) remain undiscovered. With the existing surveys, it will take decades to identify the rest. Progress can be accelerated by undertaking new surveys with improved sensitivity.
DOT National Transportation Integrated Search
2010-10-05
The scope, severity, and pace of : future climate change impacts are : difficult to predict. However, : observations and long-term scientific : trends indicate that the potential : impacts of a changing climate on : society and the environment will b...
Cleary, Margot P.
2013-01-01
Overweight and/or obesity are known risk factors for postmenopausal breast cancer. More recently increased body weight has also been associated with poor prognosis for both pre- and postmenopausal breast cancer. This relationship has primarily been identified through epidemiological studies. Additional information from in vitro studies has also been produced in attempts to delineate mechanisms of action for the association of obesity and body weight and breast cancer. This approach has identified potential growth factors such as insulin, leptin, estrogen and IGF-I which are reported to be modulated by body weight changes. However, in vitro studies are limited in scope and frequently use non-physiological concentrations of growth factors, while long follow-up is needed for human studies. Preclinical animal models provide an intermediary approach to investigate the impact of body weight and potential growth factors on mammary/breast tumor development and progression. Here results of a number of studies addressing this issue are presented. In the majority of the studies either genetically-obese or diet-induced obese rodent models have been used to investigate spontaneous, transgenic and carcinogen-induced mammary tumor development. To study tumor progression the major focus has been allograft studies in mice with either genetic or dietary-induced obesity. In general, obesity has been demonstrated to shorten mammary tumor latency and to impact tumor pathology. However, in rodents with defects in leptin and other growth factors the impact of obesity is not as straightforward. Future studies using more physiologically relevant obesity models and clearly distinguishing diet composition from body weight effects will be important in continuing to understand the factors associated with body weight’s impact on the mammary/breast cancer development and progression. PMID:24122258
Prevalence of obesity in paediatric psoriasis and its impact on disease severity and progression.
Ergun, Tulin; Seckin Gencosmanoglu, Dilek; Karakoc-Aydiner, Elif; Salman, Andac; Tekin, Burak; Bulbul-Baskan, Emel; Alpsoy, Erkan; Cakıroglu, Aylin; Onsun, Nahide
2017-11-01
The current literature suggests there is a possible connection between paediatric psoriasis and obesity. However, there is a paucity of research on the influence of increased adiposity on the severity of paediatric psoriasis and disease progression. We aimed to compare the prevalence of being overweight or obese in paediatric psoriasis patients and controls and assess the potential impact of being overweight/obese on disease severity and progression of disease. This multicentre prospective case-control study included 289 psoriasis patients (aged < 18 years) treated and followed up by one of the four university hospitals in Turkey. The control group consisted of 151 consecutive age-matched and sex-matched children who lacked a personal or family history of psoriasis. The participants' characteristics, psoriasis-related parametres (e.g., initial subtype, psoriasis area and severity index, presence of psoriatic arthritis) and body mass index were determined. The difference between the prevalence of being overweight/obese among psoriatics (28%) and the control group (19%) was significant (P = 0.024). Being overweight/obese had no significant impact on disease severity and unresponsiveness to topical treatment. Within a median follow-up time of 12 months, 23% of our patients with localised disease at disease onset progressed to generalised disease. The impact of being overweight/obese on disease progression was found to be non-significant; however, disease duration was found to have a significant impact on disease progression (P = 0.026). Although it is not associated with disease severity and course, increased bodyweight may be a health problem for psoriatic children. © 2016 The Australasian College of Dermatologists.
Ficarra, Vincenzo; Rossanese, Marta; Zazzara, Michele; Giannarini, Gianluca; Abbinante, Maria; Bartoletti, Riccardo; Mirone, Vincenzo; Scaglione, Francesco
2014-12-01
A chronic prostatic inflammation seems to play a crucial role in benign prostatic hyperplasia (BPH) pathogenesis and progression. Therefore, inflammation could represent a new potential target for medical therapy of lower urinary tract symptoms (LUTS) due to BPH (LUTS/BPH). This review article analyzes the evidence supporting the role of inflammation in the onset and progression of BPH, and it assesses the potential impact of previous mechanisms on medical therapy of LUTS/BPH. Literature data support the role of inflammation as a relevant factor in the pathogenesis of BPH. Indeed, several data favour the role of infiltrating lymphocytes in the development and progression of prostate adenoma as an effect of a self-maintaining remodeling process. Although available drugs commonly used in the treatment of LUTS/BPH do not exhibit an anti-inflammatory activity, it seems to be obvious considering the inflammation as a new target in the treatment of LUTS/BPH. Drugs currently investigated for the treatment of prostatic inflammation include the hexanic lipidosterolic extract of Serenoa repens, nonsteroidal anti-inflammatory drugs, and vitamin D receptor agonists.
Beshr, Mohamed; Aute, Vikrant; Abdelaziz, Omar; ...
2016-08-24
Refrigeration and air conditioning systems have high, negative environmental impacts due to refrigerant charge leaks from the system and their corresponding high global warming potential. Thus, many efforts are in progress to obtain suitable low GWP alternative refrigerants and more environmentally friendly systems for the future. In addition, the system’s life cycle climate performance (LCCP) is a widespread metric proposed for the evaluation of the system’s environmental impact.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Beshr, Mohamed; Aute, Vikrant; Abdelaziz, Omar
Refrigeration and air conditioning systems have high, negative environmental impacts due to refrigerant charge leaks from the system and their corresponding high global warming potential. Thus, many efforts are in progress to obtain suitable low GWP alternative refrigerants and more environmentally friendly systems for the future. In addition, the system’s life cycle climate performance (LCCP) is a widespread metric proposed for the evaluation of the system’s environmental impact.
Wang, Shuhong; Song, Malin
2017-10-01
As a newly appeared trade mode in recent years, reverse outsourcing has made a great impact on traditional trade modes. This paper researched the influences of reverse outsourcing on green technological progress from the perspective of a global supply chain by using micro-data of enterprises. It worked out the rate of green technological progress from two innovative concepts: potential production technology and practical production technology. The empirical analysis results indicated that reverse outsourcing stimulates, and enterprise size and ownership type potentially affects, green technological progress. State-owned or foreign enterprises with high income levels would pay more attention to environmental protection, energy saving, and emission reduction, while small and micro enterprises with low incomes would choose to ignore environmental protection. Copyright © 2017 Elsevier B.V. All rights reserved.
Needs and challenges for assessing the environmental impacts of engineered nanomaterials (ENMs)
Romero-Franco, Michelle; Godwin, Hilary A; Bilal, Muhammad
2017-01-01
The potential environmental impact of nanomaterials is a critical concern and the ability to assess these potential impacts is top priority for the progress of sustainable nanotechnology. Risk assessment tools are needed to enable decision makers to rapidly assess the potential risks that may be imposed by engineered nanomaterials (ENMs), particularly when confronted by the reality of limited hazard or exposure data. In this review, we examine a range of available risk assessment frameworks considering the contexts in which different stakeholders may need to assess the potential environmental impacts of ENMs. Assessment frameworks and tools that are suitable for the different decision analysis scenarios are then identified. In addition, we identify the gaps that currently exist between the needs of decision makers, for a range of decision scenarios, and the abilities of present frameworks and tools to meet those needs. PMID:28546894
High doses of biotin in chronic progressive multiple sclerosis: a pilot study.
Sedel, Frédéric; Papeix, Caroline; Bellanger, Agnès; Touitou, Valérie; Lebrun-Frenay, Christine; Galanaud, Damien; Gout, Olivier; Lyon-Caen, Olivier; Tourbah, Ayman
2015-03-01
No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. Uncontrolled, non-blinded proof of concept study 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Bierhaus, E. B.
2017-11-01
Impacts on Europa mix surface and subsurface material, introduce fracturing, and at progressively larger sizes, result in deeper melting (and mixing) within the ice shell. The largest sizes punch through the ice, providing a direct, albeit temporary, conduit between the ocean and the surface.
Impact of proteolytic enzymes in colorectal cancer development and progression.
Herszényi, László; Barabás, Loránd; Hritz, István; István, Gábor; Tulassay, Zsolt
2014-10-07
Tumor invasion and metastasis is a highly complicated, multi-step phenomenon. In the complex event of tumor progression, tumor cells interact with basement membrane and extracellular matrix components. Proteolytic enzymes (proteinases) are involved in the degradation of extracellular matrix, but also in cancer invasion and metastasis. The four categories of proteinases (cysteine-, serine-, aspartic-, and metalloproteinases) are named and classified according to the essential catalytic component in their active site. We and others have shown that proteolytic enzymes play a major role not only in colorectal cancer (CRC) invasion and metastasis, but also in malignant transformation of precancerous lesions into cancer. Tissue and serum-plasma antigen concentrations of proteinases might be of great value in identifying patients with poor prognosis in CRC. Our results, in concordance with others indicate the potential tumor marker impact of proteinases for the early diagnosis of CRC. In addition, proteinases may also serve as potential target molecules for therapeutic agents.
CASTOR: Widely Distributed Scalable Infospaces
2008-11-01
1 i Progress against Planned Objectives Enable nimble apps that react fast as...generation of scalable, reliable, ultra- fast event notification in Linux data centers. • Maelstrom, a spin-off from Ricochet, offers a powerful new option...out potential enhancements to WS-EVENTING and WS-NOTIFICATION based on our work. Potential impact for the warflighter. QSM achieves extremely fast
Knura, Miłosz; Dragon, Jonasz; Łabuzek, Krzysztof; Okopień, Bogusław
2018-01-23
The exponetial growth in popularity of electronic cigarettes in the world markets intensifies the debate about their health effects. The smoking of traditional tabacoo products is a factor associated with the endothelium damage and progression of atherosclerosis. The elimination of the combustion process in electronic cigarettes allows to conclude that they are less harmful to a vascular endothelium than traditional tobacco products. E-cigarette aerosol contains many compounds that have an influence on initiation and progression of atherosclerosis. Nicotine protherogenic action is not fully explained. On one hand, nicotine modifies metabolic pathways leading to atherosclerosis, whereas epidemiological studies do not show an increased risk of cardiovascular disease in the population using nicotine replacement therapy or snuff. Acrolein, formaldehyde and the ultrafine particles generated during e-liquid heating have an impact on initiation and progression of atherosclerosis, but their level is lower than that of tobacco smoke. In order to assess accurately the longterm effects of e-cigarettes, it is necessary to conduct epidemiological studies measuring the effects of using e-cigarettes. It is claimed that the use of electronic cigarettes has a potential impact on the development of atherosclerosis, but is significantly lower than that of traditional cigarettes.
2013-12-01
carcinoma (CRC) in IBD patients and experimental models. Nonetheless, the pathogenic link, interrelationship, and practical clinical application of these...and are continuing final data analysis and latest imaging studies. This project has potentially high impact because of the substantial incidence of...pathogenic link, interrelationship, and practical clinical application of these various theories of progression have remained elusive. We proposed that
Liu, Ya-Ling; Nascimento, Marcelle; Burne, Robert A
2012-01-01
Alkali production by oral bacteria is believed to have a major impact on oral microbial ecology and to be inibitory to the initiation and progression of dental caries. A substantial body of evidence is beginning to accumulate that indicates the modulation of the alkalinogenic potential of dental biofilms may be a promising strategy for caries control. This brief review highlights recent progress toward understanding molecular genetic and physiologic aspects of important alkali-generating pathways in oral bacteria, and the role of alkali production in the ecology of dental biofilms in health and disease. PMID:22996271
NASA Research in aeropropulsion
NASA Technical Reports Server (NTRS)
Stewart, W. L.; Weber, R. J.
1981-01-01
Selected examples of recent accomplishments and current activities that are relevant to the principal classes of civil and military vehicles: subsonic transports, commuters, supersonic transports, general aviation, rotorcraft, V/STOL, and high performance. Some instances of emerging technologies with potential high impact on further progress are discussed.
McCormick, Barry; Lukito, Veny; Wilson, Kirsten L.
2017-01-01
C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1–10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. PMID:28576935
Cyanobacteria Toxin and Cell Propagation through Six Lake Erie Treatment Plants
Over the past five years, Lake Erie has been experiencing harmful algal blooms (HABs) of progressively increasing severity. Cognizant of the potential health and economic impacts, the United States Environmental Protection Agency’s (USEPA’s) Water Supply and Water Resources Divi...
Multifaceted Leptin network: the molecular connection between obesity and breast cancer
Saxena, Neeraj K.; Sharma, Dipali
2016-01-01
High plasma levels of leptin, a major adipocytokine produced by adipocytes, are correlated with increased fat mass in obese state. Leptin is emerging as a key candidate molecule linking obesity with breast cancer. Acting via endocrine, paracrine, and autocrine manner, leptin impacts various stages of breast tumorigenesis from initiation and primary tumor growth to metastatic progression. Leptin also modulates the tumor microenvironment mainly through supporting migration of endothelial cells, neo-angiogenesis and sustaining recruitment of macrophage and monocytes. Various studies have shown that hyperactive leptin-signaling network leads to concurrent activation of multiple oncogenic pathways resulting in enhanced proliferation, decreased apoptosis, acquisition of mesenchymal phenotype, potentiated migration and enhanced invasion potential of tumor cells. Furthermore, the capability of leptin to interact with other molecular effectors of obese state including, estrogen, IGF-1, insulin, VEGF and inflammatory cytokines further increases its impact on breast tumor progression in obese state. This article presents an overview of the studies investigating the involvement of leptin in breast cancer. PMID:24214584
Johnson, William P; Frederick, Logan E; Millington, Mallory R; Vala, David; Reese, Barbara K; Freedman, Dina R; Stenten, Christina J; Trauscht, Jacob S; Tingey, Christopher E; Kip Solomon, D; Fernandez, Diego P; Bowen, Gabriel J
2015-11-01
Similar to fracking, the development of tar sand mining in the U.S. has moved faster than understanding of potential water quality impacts. Potential water quality impacts of tar sand mining, processing, and disposal to springs in canyons incised approximately 200 m into the Tavaputs Plateau, at the Uinta Basin southern rim, Utah, USA, were evaluated by hydrogeochemical sampling to determine potential sources of recharge, and chemical thermodynamic estimations to determine potential changes in transfer of bitumen compounds to water. Because the ridgetops in an area of the Tavaputs Plateau named PR Spring are starting to be developed for their tar sand resource, there is concern for potential hydrologic connection between these ridgetops and perennial springs in adjacent canyons on which depend ranching families, livestock, wildlife and recreationalists. Samples were collected from perennial springs to examine possible progression with elevation of parameters such as temperature, specific conductance, pH, dissolved oxygen, isotopic tracers of phase change, water-rock interaction, and age since recharge. The groundwater age dates indicate that the springs are recharged locally. The progression of hydrogeochemical parameters with elevation, in combination with the relatively short groundwater residence times, indicate that the recharge zone for these springs includes the surrounding ridges, and thereby suggests a hydrologic connection between the mining, processing, disposal area and the springs. Estimations based on chemical thermodynamic approaches indicate that bitumen compounds will have greatly enhanced solubility in water that comes into contact with the residual bitumen-solvent mixture in disposed tailings relative to water that currently comes into contact with natural tar. Copyright © 2015 Elsevier B.V. All rights reserved.
Evaluating the effect of microalgal biomass on soil-plant-water systems
USDA-ARS?s Scientific Manuscript database
Exploring all possible applications of microalgal biomass is crucial to strengthen the current algal industry and reducing the environmental impacts of agriculture is a major global challenge. Microalgae can play a progressive role as they have the potential to improve soil structure, reduce erosion...
A ROBUST PROCESS FOR BIODIESEL PRODUCTION USING SUPERCRITICAL METHANOL
A literature review was conducted in order to insure the feedstock choice had the potential to bring about positive impacts in making progress toward sustainability. The use of algae for a biodiesel feedstock was chosen for the many benefits it provides. Algae produced via the...
Energy Innovations: Science & Technology at NREL, Winter 2010 (Brochure)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
2010-02-01
The Energy Innovations newsletter serves as a key outreach tool for NREL to tout the lab's accomplishments, progress, and activities to key stakeholders who can impact the lab's level of funding and potential resources. Audiences include VIP visitors to NREL, current and potential partners in our work, and key decision makers who want to know about NREL's R&D directions and the quality and significance of our results.
Energy Innovations: Science & Technology at NREL, Fall 2009
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
2009-09-01
The Energy Innovations newsletter serves as a key outreach tool for NREL to tout the lab's accomplishments, progress, and activities to key stakeholders who can impact the lab's level of funding and potential resources. Audiences include VIP visitors to NREL, current and potential partners in our work, and key decision makers who want to know about NREL's R&D directions and the quality and significance of our results.
Rethinking the bile acid/gut microbiome axis in cancer
Phelan, John P.; Reen, F. Jerry; Caparros-Martin, Jose A.; O'Connor, Rosemary; O'Gara, Fergal
2017-01-01
Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles. These in turn have been associated with cancer development and progression. Exposure to high levels of bile acids, combined with localised molecular/genome instability leads to the acquisition of bile mediated neoplastic alterations, generating apoptotic resistant proliferation phenotypes. However, in recent years, several studies have emerged advocating the therapeutic benefits of bile acid signalling in suppressing molecular and phenotypic hallmarks of cancer progression. These studies suggest that in some instances, bile acids may reduce cancer phenotypic effects, thereby limiting metastatic potential. In this review, we contextualise the current state of the art to propose that the bile acid/gut microbiome axis can influence cancer progression to the extent that classical in vitro cancer hallmarks of malignancy (cell invasion, cell migration, clonogenicity, and cell adhesion) are significantly reduced. We readily acknowledge the existence of a bile acid/gut microbiome axis in cancer initiation, however, in light of recent advances, we focus exclusively on the role of bile acids as potentially beneficial molecules in suppressing cancer progression. Finally, we theorise that suppressing aggressive malignant phenotypes through bile acid/gut microbiome axis modulation could uncover new and innovative disease management strategies for managing cancers in vulnerable cohorts. PMID:29383197
Amores, Gerardo Ruiz; Guazzaroni, María-Eugenia; Arruda, Letícia Magalhães; Silva-Rocha, Rafael
2016-04-01
Filamentous fungi are remarkable organisms naturally specialized in deconstructing plant biomass and this feature has a tremendous potential for biofuel production from renewable sources. The past decades have been marked by a remarkable progress in the genetic engineering of fungi to generate industry-compatible strains needed for some biotech applications. In this sense, progress in this field has been marked by the utilization of high-throughput techniques to gain deep understanding of the molecular machinery controlling the physiology of these organisms, starting thus the Systems Biology era of fungi. Additionally, genetic engineering has been extensively applied to modify wellcharacterized promoters in order to construct new expression systems with enhanced performance under the conditions of interest. In this review, we discuss some aspects related to significant progress in the understating and engineering of fungi for biotechnological applications, with special focus on the construction of synthetic promoters and circuits in organisms relevant for industry. Different engineering approaches are shown, and their potential and limitations for the construction of complex synthetic circuits in these organisms are examined. Finally, we discuss the impact of engineered promoter architecture in the single-cell behavior of the system, an often-neglected relationship with a tremendous impact in the final performance of the process of interest. We expect to provide here some new directions to drive future research directed to the construction of high-performance, engineered fungal strains working as microbial cell factories.
Collier, Marcus J; Mullins, Ewen
2010-01-01
While significant progress has been made on the modification of crops for the benefit of producers, the same cannot be said in regards to eliciting the potential impact that these crops may have on the wider landscape and the diversity of life therein. Management impacts can create difficulties when making policy, regulation and licensing decisions in those countries where agriculture has a significant social and ecological position in the landscape. To begin to gauge the potential impacts of the management of a selection of GM crops on an agricultural landscape, four key biodiversity stressors (Chemicals, Introgression, Nutrients and Management: CINMa) were identified and a grading system developed using published data. Upon application to five selected GM crops in a case study area, CINMa identifies areas in the wider landscape where biodiversity is likely to be negatively or positively impacted, as well as agricultural zones which may benefit from the land use change associated with the management of GM crops and their associated post market environmental monitoring. © ISBR, EDP Sciences, 2011.
NASA Astrophysics Data System (ADS)
McIver, R.; Milewski, I.; Loucks, R.; Smith, R.
2018-05-01
Far-field nutrient impacts associated with finfish aquaculture have been identified as a topic of concern for regulators, managers, scientists, and the public for over two decades but disentangling aquaculture impacts from those caused by other natural and anthropogenic sources has impeded the development of monitoring metrics and management plans. We apply a bulk, steady-state nitrogen loading model (NLM) framework to estimate the annual input of Total Dissolved Nitrogen (TDN) from point and non-point sources to the watershed surrounding Port Mouton Bay, Nova Scotia (Canada). We then use the results of the NLM together with estimates of dissolved inorganic nitrogen (DIN) loading from a sea-cage trout farm in the Bay and progressive vector diagrams to illustrate potential patterns of DIN dispersal from the trout farm. Our estimated anthropogenic nitrogen contribution to Port Mouton Bay from all terrestrial and atmospheric sources is ∼211,703 kg TDN/year with atmospheric deposition accounting for almost all (98.6%). At a stocking level of ∼400,000 rainbow trout, the Port Mouton Bay sea-cage farm increases the annual anthropogenic TDN loading to the bay by 14.4% or 30,400 kg. Depending on current flow rates, nitrogen flux from the trout farm can be more than double the background concentrations of TDN near the farm site. Although it is unlikely that nitrogen loading from this single fish farm is saturating the DIN requirements of the entire bay, progressive vector diagrams suggest that the dispersal potential may be insufficient to mitigate potential symptoms of eutrophication associated with nitrogen fluxes. We present an accessible and user-friendly tool for managers to estimate baseline nutrient loading in relation to aquaculture and our use of progressive vector diagrams illustrate a practical and simple method for characterizing potential nutrient dispersal based on local conditions and spatial scales. Our study joins numerous studies which have highlighted the need for more effective monitoring and assessment methods to improve the detection of aquaculture effects at far-field scales and to assess those effects in relation to other natural and anthropogenic factors impacting coastal habitats.
Professional Involvement: Requirements as Students and Trends after Certification
ERIC Educational Resources Information Center
Lancaster, Jennifer N.; Myers, Bettye; Nichols, David L.; Webb, Kerry S.
2014-01-01
Context: The field of athletic training needs young engaged professionals for continued progress in allied health care. Academic and clinical requirements during the entry-level education could potentially impact the decisions and directions these students choose to pursue as young professionals. Objective: To determine the difference in…
A Professor Realizes the Potential Poison of Ivy.
ERIC Educational Resources Information Center
Machell, David F.
1991-01-01
A form of melancholia characterized by the negating of a college faculty member's professional motivation, positive attitudinal focus, and personal self-esteem is described. This "professorial melancholia" has three stages: (1) causal factors are beginning to have an effect; (2) progressive influence and noticeable impact; and (3) serious impact…
Over the past five years, Lake Erie has been experiencing harmful algal blooms (HABs) of progressively increasing severity. Cognizant of the potential health and economic impacts, the United States Environmental Protection Agency’s (USEPA’s) Water Supply and Water Resources Divis...
Manufacturing process applications team (MATeam)
NASA Technical Reports Server (NTRS)
Bangs, E. R.
1980-01-01
Progress in the transfer of aerospace technology to solve key problems in the manufacturing sector of the economy is reported. Potential RTOP programs are summarized along with dissemination activities. The impact of transferred NASA manufacturing technology is discussed. Specific areas covered include aircraft production, robot technology, machining of alloys, and electrical switching systems.
A Review on the Perforated Impact Energy Absorption of Kenaf Fibres Reinforced Composites
NASA Astrophysics Data System (ADS)
Ismail, Al Emran; Khalid, S. N. A.; Nor, Nik Hisyamudin Muhd
2017-10-01
This paper reviews the potential of mechanical energy absorption of natural fiber reinforced composites subjected to perforated impact. According to literature survey, several research works discussing on the impact performances on natural fiber reinforced composites are available. However, most of these composite fibers are randomly arranged. Due to high demand for sustainable materials, many researches give high attention to enhance the mechanical capability of natural fiber composites especially focused on the fiber architecture. Therefore, it is important to review the progress of impact energy absorption on woven fiber composite in order to identify the research opportunities in the future.
Dickie, Allen C; McCormick, Barry; Lukito, Veny; Wilson, Kirsten L; Torsney, Carole
2017-07-05
C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1-10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. Copyright © 2017 Dickie et al.
Economic impact of disease progression in follicular non-Hodgkin lymphoma
Beveridge, Roy; Satram-Hoang, Sacha; Sail, Kavita; Darragh, Joseph; Chen, Clara; Forsyth, Michael; Reyes, Carolina
2011-01-01
Using a retrospective claims database, we estimated the economic costs of progression among patients with follicular non-Hodgkin lymphoma (f-NHL) treated in an outpatient community-based setting. Patients with f-NHL who received care between 1 July 2006 and 31 December 2009 were categorized into two cohorts based on whether they experienced progressive disease (PD) or not. Costs per patient per month (PPPM) were compared between patients with PD versus non-PD. Follow-up time was censored at the last entry for disease status or 6 months after the date of remission/stable disease or progression. Of the 1002 patients with f-NHL identified, 268 progressed and 734 did not. The mean overall costs PPPM over the 6-month follow-up period were significantly higher for patients with PD versus non-PD ($3527 vs. $860; difference = $2667; p < 0.001). This cost difference persisted within all resource categories evaluated. Results of this study indicate that therapies which delay progression for patients with f-NHL may result in potential cost savings. PMID:21745172
H2@Scale Resource and Market Analysis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ruth, Mark
This presentation overviews progress to date on the H2@Scale resource and market analysis work. The work finds, for example, that hydrogen demand of 60 MMT/yr is possible when transportation and industry are considered; resources are available to meet that demand; using renewable resources would reduce emissions and fossil use by over 15%; further impacts are possible when considering synergistic benefits; additional analysis is underway to improve understanding of potential markets and synergistic impacts; and further analysis will be necessary to estimate impacts due to spatial characteristics, feedback effects in the economy, and inertia characteristics.
N.P. Havill; Gina Davis; David Mausel; Joanne Klein; Richard McDonald; Cera Jones; Melissa Fischer; Scott Salom; Adelgisa Caccone
2012-01-01
Hybridization between introduced biological control agents and native species has the potential to impact native biodiversity and pest control efforts. This study reports progress towards predicting the outcome of hybridization between two beetle species, the introduced Laricobius nigrinus Fender and the native L. rubidus LeConte...
ERIC Educational Resources Information Center
DeVito, Pasquale J., Ed.; Koenig, Judith A., Ed.
A committee of the National Research Council studied the desirability, feasibility, and potential impact of two reporting practices for National Assessment of Educational Progress (NAEP) results: district-level reporting and market-basket reporting. NAEP's sponsors believe that reporting district-level NAEP results would support state and local…
ERIC Educational Resources Information Center
Balliet, Russell N.
2012-01-01
Understanding how geologists conduct fieldwork through analysis of problem solving has significant potential impact on field instruction methods. Recent progress has been made in this area but the problem solving behaviors displayed by geologists during fieldwork and the associated underlying cognition remains poorly understood. We present…
The Third Wave and Education's Futures. Fastback 155.
ERIC Educational Resources Information Center
Miller, William C.
This booklet describes Alvin Toffler's future society and culture and examines its potential impact on education. In his book, "The Third Wave," Toffler describes our civilization's progress through two major phases (waves). The First Wave began some 8,000 years ago when man became agricultural. The Industrial Revolution began the Second Wave. The…
Impacts devalue the potential of large-scale terrestrial CO2 removal through biomass plantations
NASA Astrophysics Data System (ADS)
Boysen, L. R.; Lucht, W.; Gerten, D.; Heck, V.
2016-09-01
Large-scale biomass plantations (BPs) are often considered a feasible and safe climate engineering proposal for extracting carbon from the atmosphere and, thereby, reducing global mean temperatures. However, the capacity of such terrestrial carbon dioxide removal (tCDR) strategies and their larger Earth system impacts remain to be comprehensively studied—even more so under higher carbon emissions and progressing climate change. Here, we use a spatially explicit process-based biosphere model to systematically quantify the potentials and trade-offs of a range of BP scenarios dedicated to tCDR, representing different assumptions about which areas are convertible. Based on a moderate CO2 concentration pathway resulting in a global mean warming of 2.5 °C above preindustrial level by the end of this century—similar to the Representative Concentration Pathway (RCP) 4.5—we assume tCDR to be implemented when a warming of 1.5 °C is reached in year 2038. Our results show that BPs can slow down the progression of increasing cumulative carbon in the atmosphere only sufficiently if emissions are reduced simultaneously like in the underlying RCP4.5 trajectory. The potential of tCDR to balance additional, unabated emissions leading towards a business-as-usual pathway alike RCP8.5 is therefore very limited. Furthermore, in the required large-scale applications, these plantations would induce significant trade-offs with food production and biodiversity and exert impacts on forest extent, biogeochemical cycles and biogeophysical properties.
The impact of oil revenues on Arab Gulf development
DOE Office of Scientific and Technical Information (OSTI.GOV)
El Azhary, M.S.
1984-01-01
This book presents papers on Middle East oil policy. Topics considered include oil production policies in the Gulf States, oil planning, the philosophy of state development planning, prospects for Gulf economic coordination, the philosophy of infrastructural development, industrialization in the Arab Gulf, the agricultural potential of the Arab Gulf states, the future of banking as a Gulf industry, manpower problems and projections in the Gulf, education as an instrument of progress in the Arab Gulf states, and the impact of development on Gulf society.
Impact of sarcopenia in the management of urological cancer patients.
Fukushima, Hiroshi; Koga, Fumitaka
2017-05-01
Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, develops as a consequence of the progression of cancer cachexia. Recent studies suggest that sarcopenia may be used as a biomarker in the management of patients with several cancers. Areas covered: In this article, the authors review 1) the methods to simply and optimally evaluate and define sarcopenia using computed tomography images in daily clinical practice and 2) the impact of sarcopenia in the management of urological cancers, specifically focusing on the usefulness in predicting treatment-related complications and prognosis. The authors also discuss the prognostic importance of changes in skeletal muscle mass in the course of treatment and the potential roles of nutritional support and exercise to prevent progression of sarcopenia. Expert commentary: Sarcopenia is associated with treatment-related complications and unfavorable prognosis in urological cancer patients. Nutritional support and exercise might be helpful in improving sarcopenia. The impact of these interventions on clinical outcomes would be elucidated by ongoing or future clinical studies.
Distress improves after mindfulness training for progressive MS: A pilot randomised trial.
Bogosian, A; Chadwick, P; Windgassen, S; Norton, S; McCrone, P; Mosweu, I; Silber, E; Moss-Morris, R
2015-08-01
Mindfulness-based interventions have been shown to effectively reduce anxiety, depression and pain in patients with chronic physical illnesses. We assessed the potential effectiveness and cost-effectiveness of a specially adapted Skype distant-delivered mindfulness intervention, designed to reduce distress for people affected by primary and secondary progressive MS. Forty participants were randomly assigned to the eight-week intervention (n = 19) or a waiting-list control group (n = 21). Participants completed standardised questionnaires to measure mood, impact of MS and symptom severity, quality of life and service costs at baseline, post-intervention and three-month follow-up. Distress scores were lower in the intervention group compared with the control group at post-intervention and follow-up (p < 0.05), effect size -0.67 post-intervention and -0.97 at follow-up. Mean scores for pain, fatigue, anxiety, depression and impact of MS were reduced for the mindfulness group compared with control group at post-therapy and follow-up; effect sizes ranged from -0.27 to -0.99 post-intervention and -0.29 to -1.12 at follow-up. There were no differences in quality-adjusted life years, but an 87.4% probability that the intervention saves on service costs and improves outcome. A mindfulness intervention delivered through Skype video conferences appears accessible, feasible and potentially effective and cost-effective for people with progressive MS. © The Author(s), 2015.
Progress In Fresnel-Köhler Concentrators
NASA Astrophysics Data System (ADS)
Mohedano, Rubén; Cvetković, Aleksandra; Benítez, Pablo; Chaves, Julio; Miñano, Juan C.; Zamora, Pablo; Hernandez, Maikel; Vilaplana, Juan
2011-12-01
The Fresnel Köhler (FK) concentrator was first presented in 2008. Since then, various CPV companies have adopted this technology as base for their future commercial product. The key for this rapid penetration is a mixture of simplicity (the FK is essentially a Fresnel lens concentrator, a technology that dominates the market) and excellent performance: high concentration without giving up large manufacturing/aiming tolerances, enabling high efficiency even at the array level. All these features together have a great potential to lower energy costs. This work shows recent results and progress regarding this device, covering new design features, measurements and tests along with first performance achievements at the array level (pilot 6.5 Kwp plant). The work also discusses the potential impact of the FK enhanced performance on the Levelized Cost Of Electricity (LCOE).
Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances
Dhanasekaran, Renumathy; Bandoh, Salome; Roberts, Lewis R.
2016-01-01
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and has an increasing incidence worldwide. HCC can be induced by multiple etiologies, is influenced by many risk factors, and has a complex pathogenesis. Furthermore, HCCs exhibit substantial heterogeneity, which compounds the difficulties in developing effective therapies against this highly lethal cancer. With advances in cancer biology and molecular and genetic profiling, a number of different mechanisms involved in the development and progression of HCC have been identified. Despite the advances in this area, the molecular pathogenesis of hepatocellular carcinoma is still not completely understood. This review aims to elaborate our current understanding of the most relevant genetic alterations and molecular pathways involved in the development and progression of HCC, and anticipate the potential impact of future advances on therapeutic drug development. PMID:27239288
Progress in understanding the immunopathogenesis of psoriasis
Mak, R.K.H.; Hundhausen, C.; Nestle, F.O.
2010-01-01
This review emphasizes how translation from bench research to clinical knowledge and vice versa has resulted in considerable progress in understanding the immunopathogenesis of psoriasis. First, the journey in understanding the pathogenic mechanisms behind psoriasis is described. The roles of different components of the adaptive and innate immune systems involved in driving the inflammatory response are explained. Discovery of new immune pathways i.e. the IL23/Th17 axis and its subsequent impact on the development of novel biological therapies is highlighted. Identification of potential targets warranting further research for future therapeutic development are also discussed. PMID:20096156
Gattenlöhner, Stefan; Stühmer, Thorsten; Leich, Ellen; Reinhard, Matthias; Etschmann, Benjamin; Völker, Hans-Ulrich; Rosenwald, Andreas; Serfling, Edgar; Christian Bargou, Ralf; Ertl, Georg; Einsele, Hermann; Müller-Hermelink, Hans-Konrad
2009-01-01
Alternative splicing of transcripts from many cancer-associated genes is believed to play a major role in carcinogenesis as well as in tumor progression. Alternative splicing of one such gene, the neural cell adhesion molecule CD56 (NCAM), impacts the progression, inadequate therapeutic response, and reduced total survival of patients who suffer from numerous malignant neoplasms. Although previous investigations have determined that CD56 exists in three major isoforms (CD56120kD, CD56140kD, and CD56180kD) with individual structural and functional properties, neither the expression profiles nor the functional relevance of these isoforms in malignant tumors have been consistently investigated. Using new quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) strategies and novel CD56 isoform-specific antibodies, CD56140kD was shown to be exclusively expressed in a number of highly malignant CD56+ neoplasms and was associated with the progression of CD56+ precursor lesions of unclear malignant potential. Moreover, only CD56140kD induced antiapoptotic/proliferative pathways and specifically phosphorylated calcium-dependent kinases that are relevant for tumorigenesis. We conclude, therefore, that the specific detection of CD56 isoforms will help to elucidate their individual functions in the pathogenesis and progression of malignant neoplasms and may have a positive impact on the development of CD56-based immunotherapeutic strategies. PMID:19246644
Stripping the Wizard's Curtain: Examining the Practice of Online Grade Booking in K-12 Schools
ERIC Educational Resources Information Center
Miller, Roxanne Greitz; Brady, John T.; Izumi, Jared T.
2016-01-01
Online grade booking, where parents and students have access to teachers' grade books through the Internet, has become the prevailing method for transmitting daily academic progress for students across the United States. However, this practice has proliferated without consideration of the potential relational impacts of the practice on parents,…
Relations between the CCSS and RTI in Literacy and Language
ERIC Educational Resources Information Center
Wixson, Karen K.; Lipson, Marjorie Y.
2012-01-01
Initiatives such as Response to Intervention (RTI) and the Common Core State Standards for English Language Arts (CCSS-ELA) have the potential to positively impact progress toward the goal of literacy for all. Because the CCSS-ELA will guide the content of the curriculum, instruction and assessment in the large number of adopting states, they will…
Operational Group Sandy technical progress report
,
2013-01-01
This report documents results from the March 2013 deployment of the OGS. It includes background information on Hurricane Sandy and the federal response; the OGS methodology; scenarios for Hurricane Sandy’s impact on coastal communities and urban ecosystems; potential interventions to improve regional resilience to future major storms; a discussion of scenario results; and lessons learned about the OGS process.
Climate change impacts on global food security.
Wheeler, Tim; von Braun, Joachim
2013-08-02
Climate change could potentially interrupt progress toward a world without hunger. A robust and coherent global pattern is discernible of the impacts of climate change on crop productivity that could have consequences for food availability. The stability of whole food systems may be at risk under climate change because of short-term variability in supply. However, the potential impact is less clear at regional scales, but it is likely that climate variability and change will exacerbate food insecurity in areas currently vulnerable to hunger and undernutrition. Likewise, it can be anticipated that food access and utilization will be affected indirectly via collateral effects on household and individual incomes, and food utilization could be impaired by loss of access to drinking water and damage to health. The evidence supports the need for considerable investment in adaptation and mitigation actions toward a "climate-smart food system" that is more resilient to climate change influences on food security.
Progress and perils in the juvenile justice and mental health movement.
Grisso, Thomas
2007-01-01
The juvenile justice system in the United States is experiencing a social movement aimed at responding to the mental and emotional problems of delinquent youths. Ironically, this movement arose in the wake of a decade of reform in juvenile justice that had set aside the system's 100-year tradition of rehabilitation for delinquents in the interests of their punishment and a primary emphasis on public safety. This article describes the recent juvenile justice and mental health movement, discusses the circumstances that motivated it, and provides examples of its progress. Now that the movement has taken hold, however, its future is threatened by several unintended consequences of the motives and strategies of those who succeeded in promoting the movement. Those potential perils are described with an eye to reducing their impact, thereby sustaining the movement and its potentially positive effects.
Douglas, P; Hayes, E T; Williams, W B; Tyrrel, S F; Kinnersley, R P; Walsh, K; O'Driscoll, M; Longhurst, P J; Pollard, S J T; Drew, G H
2017-12-01
With the increase in composting asa sustainable waste management option, biological air pollution (bioaerosols) from composting facilities have become a cause of increasing concern due to their potential health impacts. Estimating community exposure to bioaerosols is problematic due to limitations in current monitoring methods. Atmospheric dispersion modelling can be used to estimate exposure concentrations, however several issues arise from the lack of appropriate bioaerosol data to use as inputs into models, and the complexity of the emission sources at composting facilities. This paper analyses current progress in using dispersion models for bioaerosols, examines the remaining problems and provides recommendations for future prospects in this area. A key finding is the urgent need for guidance for model users to ensure consistent bioaerosol modelling practices. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
ERIC Educational Resources Information Center
Humbyrd, Michele
2010-01-01
A shift toward shared practice in schools has emerged and teachers are moving from isolation to collaboration (Hindin, Morocco, Mott, & Aguilar, 2007). One of the structures that supports collaboration is the collaborative team. Teams have great potential, however, their failure can impact the organization's progress and the team members'…
Microsurgery robots: addressing the needs of high-precision surgical interventions.
Mattos, Leonardo S; Caldwell, Darwin G; Peretti, Giorgio; Mora, Francesco; Guastini, Luca; Cingolani, Roberto
2016-01-01
Robotics has a significant potential to enhance the overall capacity and efficiency of healthcare systems. Robots can help surgeons perform better quality operations, leading to reductions in the hospitalisation time of patients and in the impact of surgery on their postoperative quality of life. In particular, robotics can have a significant impact on microsurgery, which presents stringent requirements for superhuman precision and control of the surgical tools. Microsurgery is, in fact, expected to gain importance in a growing range of surgical specialties as novel technologies progressively enable the detection, diagnosis and treatment of diseases at earlier stages. Within such scenarios, robotic microsurgery emerges as one of the key components of future surgical interventions, and will be a vital technology for addressing major surgical challenges. Nonetheless, several issues have yet to be overcome in terms of mechatronics, perception and surgeon-robot interfaces before microsurgical robots can achieve their full potential in operating rooms. Research in this direction is progressing quickly and microsurgery robot prototypes are gradually demonstrating significant clinical benefits in challenging applications such as reconstructive plastic surgery, ophthalmology, otology and laryngology. These are reassuring results offering confidence in a brighter future for high-precision surgical interventions.
Guieysse, Benoit; Norvill, Zane N
2014-02-28
When direct wastewater biological treatment is unfeasible, a cost- and resource-efficient alternative to direct chemical treatment consists of combining biological treatment with a chemical pre-treatment aiming to convert the hazardous pollutants into more biodegradable compounds. Whereas the principles and advantages of sequential treatment have been demonstrated for a broad range of pollutants and process configurations, recent progresses (2011-present) in the field provide the basis for refining assessment of feasibility, costs, and environmental impacts. This paper thus reviews recent real wastewater demonstrations at pilot and full scale as well as new process configurations. It also discusses new insights on the potential impacts of microbial community dynamics on process feasibility, design and operation. Finally, it sheds light on a critical issue that has not yet been properly addressed in the field: integration requires complex and tailored optimization and, of paramount importance to full-scale application, is sensitive to uncertainty and variability in the inputs used for process design and operation. Future research is therefore critically needed to improve process control and better assess the real potential of sequential chemical-biological processes for industrial wastewater treatment. Copyright © 2013 Elsevier B.V. All rights reserved.
Gard, Tracy L; Hoover, Donald R; Shi, Qiuhu; Cohen, Mardge H; Mutimura, Eugene; Adedimeji, Adebola A; Anastos, Kathryn
2013-10-01
We examined whether established associations between HIV disease and HIV disease progression on worse health-related quality of life (HQOL) were applicable to women with severe trauma histories, in this case Rwandan women genocide survivors, the majority of whom were HIV-infected. Additionally, this study attempted to clarify whether post-traumatic stress symptoms were uniquely associated with HQOL or confounded with depression. The Rwandan Women's Interassociation Study and Assessment was a longitudinal prospective study of HIV-infected and uninfected women. At study entry, 922 women (705 HIV+ and 217 HIV-) completed measures of symptoms of post-traumatic stress and HQOL as well as other demographic, clinical, and behavioral characteristics. Even after controlling for potential confounders and mediators, HIV+ women, in particular those with the lowest CD4 counts, scored significantly worse on HQOL and overall quality of life (QOL) than did HIV- women. Even after controlling for depression and HIV disease progression, women with more post-traumatic stress symptoms scored worse on HQOL and overall QOL than women with fewer post-traumatic stress symptoms. This study demonstrated that post-traumatic stress symptoms were independently associated with HQOL and overall QOL, independent of depression and other confounders or potential mediators. Future research should examine whether the long-term impact of treatment on physical and psychological symptoms of HIV and post-traumatic stress symptoms would generate improvement in HQOL.
Gard, Tracy L.; Hoover, Donald R.; Shi, Qiuhu; Cohen, Mardge H.; Mutimura, Eugene; Adedimeji, Adebola A.; Anastos, Kathryn
2014-01-01
Purpose We examined whether established associations between HIV disease and HIV disease progression on worse health-related quality of life (HQOL) were applicable to women with severe trauma histories, in this case Rwandan women genocide survivors, the majority of whom were HIV infected. Additionally, this study attempted to clarify whether post-traumatic stress symptoms were uniquely associated with HQOL or confounded with depression. Methods The Rwandan Women’s Interassociation Study and Assessment (RWISA) was a longitudinal prospective study of HIV-infected and uninfected women. At study entry 922 women (705 HIV+ and 217 HIV−) completed measures of symptoms of post-traumatic stress and HQOL as well as other demographic, clinical and behavioral characteristics. Results Even after controlling for potential confounders and mediators, HIV+ women, in particular those with the lowest CD4 counts, scored significantly worse on HQOL and overall QOL than did HIV− women. Even after controlling for depression and HIV disease progression, women with more post-traumatic stress symptoms scored worse on HQOL and overall QOL than women with fewer post-traumatic stress symptoms. Conclusions This study demonstrated that post-traumatic stress symptoms were independently associated with HQOL and overall QOL, independent of depression and other confounders or potential mediators. Future research should examine whether the long term impact of treatment on physical and psychological symptoms of HIV and post-traumatic stress symptoms would generate improvement in HQOL. PMID:23271207
Reform towards National Health Insurance in Malaysia: the equity implications.
Yu, Chai Ping; Whynes, David K; Sach, Tracey H
2011-05-01
This paper assesses the potential equity impact of Malaysia's projected reform of its current tax financed system towards National Health Insurance (NHI). The Kakwani's progressivity index was used to assess the equity consequences of the new NHI system (with flat rate NHI scheme) compared to the current tax financed system. It was also used to model a proposed system (with a progressive NHI scheme) that can generate the same amount of funding more equitably. The new NHI system would be less equitable than the current tax financed system, as evident from the reduction of Kakwani's index to 0.168 from 0.217. The new flat rate NHI scheme, if implemented, would reduce the progressivity of the health finance system because it is a less progressive finance source than that of general government revenue. We proposed a system with a progressive NHI scheme that generates the same amount of funding whilst preserving the equity at the Kakwani's progressivity index of 0.213. A NHI system with a progressive NHI scheme is proposed to be implemented to raise health funding whilst preserving the equity in health care financing. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
THE TUMOR MACROENVIRONMENT: CANCER-PROMOTING NETWORKS BEYOND TUMOR BEDS
Rutkowski, Melanie R.; Svoronos, Nikolaos; Puchalt, Alfredo Perales; Conejo-Garcia, Jose R.
2015-01-01
During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, and myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. PMID:26216635
The Potential Roles of Bisphenol A (BPA) Pathogenesis in Autoimmunity
2014-01-01
Bisphenol A (BPA) is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA's impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity. PMID:24804084
Rose, Darya B; Nellesen, Dave; Neary, Maureen P; Cai, Beilei
2017-04-01
Advanced neuroendocrine tumors (NETs) are a rare malignancy with considerable need for effective therapies. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2016 for treatment of adults with progressive, well-differentiated, non-functional NETs of gastrointestinal (GI) or lung origin that are unresectable, locally advanced, or metastatic. To assess the 3-year budget impact for a typical US health plan following availability of everolimus for treatment of GI and lung NETs. Methods An economic model was developed that considered two perspectives: an entire health plan and a pharmacy budget. The total budget impact included costs of drug therapies, administration, hospitalizations, physician visits, monitoring, and adverse events (AEs). The pharmacy model only considered drug costs. In a US health plan with 1 million members, the model estimated 66 patients with well-differentiated, non-functional, and advanced or metastatic GI NETs and 20 with lung NETs undergoing treatment each year. Total budget impact in the first through third year after FDA approval ranged from $0.0568-$0.1443 per member per month (PMPM) for GI NETs and from $0.0181-$0.0355 PMPM for lung NETs. The total budget impact was lower than the pharmacy budget impact because it included cost offsets from administration and AE management for everolimus compared with alternative therapies (e.g. chemotherapies). Because GI and lung NETs are rare diseases with limited published data, several assumptions were made that may influence interpretation of results. The budget impact for everolimus was minimal in this rare disease area with a high unmet need, largely due to low disease prevalence. These results should be considered in the context of significant clinical benefits potentially provided by everolimus, including significantly longer progression-free survival (PFS) for advanced GI and lung NET patients.
US-Europe Workshop on Impact of Multifunctionality on Damage Evolution in Composite Materials
2015-09-01
Inventions (DD882) Scientific Progress See Attachment Technology Transfer Not applicable UNIVERSITY OF ILLINOIS AEROSPACE ENGINEERING...Composite Materials PI: Ioannis Chasiotis Aerospace Engineering University of Illinois at Urbana-Champaign Talbot Lab, 104 S. Wright Street, Urbana, IL...focused on the current state of corporate research in the aerospace industry which is a major potential adopter of multifunctional composites. The two
Sant'Ana, Jader; Franchini, Emerson; da Silva, Vinicius; Diefenthaeler, Fernando
2017-06-01
Reaction time and response time are considered important abilities and can potentially affect combat performance. This study investigated the effect of a specific fatigue protocol on reaction time, response time, performance time, and kick impact. Seven male athletes reported to the laboratory on two different days. During day one, athletes performed a specific progressive taekwondo test, and on day two, a protocol for determining reaction time, response time, performance time, and kick impact before and after a time to exhaustion test at an intensity level corresponding to the maximal kick frequency obtained during the specific progressive taekwondo test. Muscle activation from rectus femoris and kick impact of the preferred limb were assessed. No differences were observed for response time and performance time. However, kick impact decreased (43 ± 27 to 13 ± 10 g, p < 0.01) while reaction time increased (145 ± 51 to 223 ± 133 ms, p < 0.05). Moderate correlation was observed between kick impact and response time (r = 0.565; p < 0.01), and kick impact and performance time (r = 0.494; p < 0.05). Results indicate that coaches and athletes may use taekwondo training programmes on coordination-based exercises leading to improve response time and to reduce fatigue effects in order to improve technique effectiveness and enhance the possibilities of scoring in a competitive situation.
Epidemiology of osteoarthritis: state of the evidence
Allen, Kelli D.; Golightly, Yvonne M.
2015-01-01
Purpose of review This review focuses on recent studies of osteoarthritis epidemiology, including research on prevalence, incidence, and a broad array of potential risk factors at the person level and joint level. Recent findings Studies continue to illustrate the high impact of osteoarthritis worldwide, with increasing incidence. Person-level risk factors with strong evidence regarding osteoarthritis incidence and/or progression include age, sex, socioeconomic status, family history, and obesity. Joint-level risk factors with strong evidence for incident osteoarthritis risk include injury and occupational joint loading; the associations of injury and joint alignment with osteoarthritis progression are compelling. Moderate levels of physical activity have not been linked to increased osteoarthritis risk. Some topics of high recent interest or emerging evidence for association with osteoarthritis include metabolic pathways, vitamins, joint shape, bone density, limb length inequality, muscle strength and mass, and early structural damage. Summary Osteoarthritis is a complex, multifactorial disease, and there is still much to learn regarding mechanisms underlying incidence and progression. However, there are several known modifiable and preventable risk factors, including obesity and joint injury; efforts to mitigate these risks can help to lessen the impact of osteoarthritis. PMID:25775186
Ruhago, George M; Ngalesoni, Frida N; Norheim, Ole F
2012-12-27
Inequity in access to and use of child and maternal health interventions is impeding progress towards the maternal and child health Millennium Development Goals. This study explores the potential health gains and equity impact if a set of priority interventions for mothers and under fives were scaled up to reach national universal coverage targets for MDGs in Tanzania. We used the Lives Saved Tool (LiST) to estimate potential reductions in maternal and child mortality and the number of lives saved across wealth quintiles and between rural and urban settings. High impact maternal and child health interventions were modelled for a five-year scale up, by linking intervention coverage, effectiveness and cause of mortality using data from Tanzania. Concentration curves were drawn and the concentration index estimated to measure the equity impact of the scale up. In the poorest population quintiles in Tanzania, the lives of more than twice as many mothers and under-fives were likely to be saved, compared to the richest quintile. Scaling up coverage to equal levels across quintiles would reduce inequality in maternal and child mortality from a pro rich concentration index of -0.11 (maternal) and -0.12 (children) to a more equitable concentration index of -0,03 and -0.03 respectively. In rural areas, there would likely be an eight times greater reduction in maternal deaths than in urban areas and a five times greater reduction in child deaths than in urban areas. Scaling up priority maternal and child health interventions to equal levels would potentially save far more lives in the poorest populations, and would accelerate equitable progress towards maternal and child health MDGs.
2012-01-01
Background Inequity in access to and use of child and maternal health interventions is impeding progress towards the maternal and child health Millennium Development Goals. This study explores the potential health gains and equity impact if a set of priority interventions for mothers and under fives were scaled up to reach national universal coverage targets for MDGs in Tanzania. Methods We used the Lives Saved Tool (LiST) to estimate potential reductions in maternal and child mortality and the number of lives saved across wealth quintiles and between rural and urban settings. High impact maternal and child health interventions were modelled for a five-year scale up, by linking intervention coverage, effectiveness and cause of mortality using data from Tanzania. Concentration curves were drawn and the concentration index estimated to measure the equity impact of the scale up. Results In the poorest population quintiles in Tanzania, the lives of more than twice as many mothers and under-fives were likely to be saved, compared to the richest quintile. Scaling up coverage to equal levels across quintiles would reduce inequality in maternal and child mortality from a pro rich concentration index of −0.11 (maternal) and −0.12 (children) to a more equitable concentration index of −0,03 and −0.03 respectively. In rural areas, there would likely be an eight times greater reduction in maternal deaths than in urban areas and a five times greater reduction in child deaths than in urban areas. Conclusions Scaling up priority maternal and child health interventions to equal levels would potentially save far more lives in the poorest populations, and would accelerate equitable progress towards maternal and child health MDGs. PMID:23270489
Offshore Breaking of Impact Tsunami: Van Dorn was Right
NASA Technical Reports Server (NTRS)
Korycansky, D. G.; Lynett, P. J.
2005-01-01
Tsunami generated by the impacts of asteroids and comets into the Earth s oceans are widely recognized as a potentially catastrophic hazard to the Earth s population (e.g. Chapman and Morrison 1994, Nature, 367, 33; Hills et al. 1994, in Hazards Due to Comets and Asteroids, (ed. T. Gehrels), 779; Atkinson et al. 2000, Report of the UK Task Force on Potentially Hazardous NEOs; Ward and Asphaug 2000, Icarus, 145, 64). A peculiarity of ocean impacts is the potential global effects of an impact that would otherwise be of only regional or local importance should it occur on land. This is, of course, due to the ability of waves to propagate globally, as seen by the terrible effects of the recent earthquake off the coast of Sumatra. The overall process of an impact tsunami is complex and falls into several distinct phases: 1) initial impact of the bolide into the ocean and formation of a transient cavity in the water, 2) collapse of the cavity and propagation of large waves from the impact center outward over deep water (typically several km in depth), 3) initial effects on wave amplitude as shallower water of the continental slope is reached ("wave shoaling"), possible breaking of waves in relatively shallow water (less than 100 m depth), on continental shelves, and 5) final contact of waves with the shore and their progression onto dry land ("run-up" and "run-in"). Here we report on numerical calculations (and semi-analytic theory) covering phases 3 and 4.
TUTORIAL: 'Mind the gap': science and ethics in nanotechnology
NASA Astrophysics Data System (ADS)
Mnyusiwalla, Anisa; Daar, Abdallah S.; Singer, Peter A.
2003-03-01
Nanotechnology (NT) is a rapidly progressing field. Advances will have a tremendous impact on fields such as materials, electronics, and medicine. A thorough review of the current literature, governmental funding, and policy documents was undertaken. Despite the potential impact of NT, and the abundance of funds, our research revealed that there is a paucity of serious, published research into the ethical, legal, and social implications of NT. As the science leaps ahead, the ethics lags behind. There is danger of derailing NT if the study of ethical, legal, and social implications does not catch up with the speed of scientific development.
Nutrient enrichment enhances black band disease progression in corals
NASA Astrophysics Data System (ADS)
Voss, Joshua D.; Richardson, Laurie L.
2006-11-01
Infectious diseases are recognized as significant contributors to the dramatic loss of corals observed worldwide. However, the causes of increased coral disease prevalence and severity are not well understood. One potential factor is elevated nutrient concentration related to localized anthropogenic activities such as inadequate waste water treatment or terrestrial runoff. In this study the effect of nutrient enrichment on the progression of black band disease (BBD) was investigated using both in situ and laboratory experiments. Experimental increases in localized nutrient availability using commercial time release fertilizer in situ resulted in doubling of BBD progression and coral tissue loss in the common reef framework coral Siderastrea siderea. Laboratory experiments in which artificially infected S. siderea colonies were exposed to increased nitrate concentrations (up to 3 μM) demonstrated similar increases in BBD progression. These findings provide evidence that the impacts of this disease on coral populations are exacerbated by nutrient enrichment and that management to curtail excess nutrient loading may be important for reducing coral cover loss due to BBD.
NASA Astrophysics Data System (ADS)
Hultine, K. R.; Bush, S.; Nagler, P. L.; Morino, K.; Burtch, K.; Dennison, P. E.; Glenn, E. P.; Ehleringer, J.
2010-12-01
Global change processes such as climate change and intensive land use pose significant threats to water resources, particularly in arid regions where potential evapotranspiration far exceeds annual rainfall. Potentially compounding these shortages is the progressive expansion of introduced plant species in riparian areas along streams, canals and rivers in geographically arid regions. The question of whether these invasive species have had or will have impacts on water resources is currently under intense debate. We identify a framework for assessing when and where introduced riparian plant species are likely to have the highest potential impact on hydrologic fluxes of arid and semi-arid river systems. We focus on three introduced plant systems that currently dominate southwestern U.S. riparian forests: tamarisk (Tamarix spp.), Russian olive (Eleagnus angustifolia), and Russian knapweed (Acroptilon repens). Our framework focuses on two main criteria: 1) the ecophysiological traits that promote establishment of invasive species across environmental gradients, and 2) an assessment of how hydrologic fluxes are altered by the establishment of introduced species at varying scales. The framework identifies when and where introduced species should have the highest potential impact on the water cycle. This framework will assist land managers and policy makers with restoration and conservation priorities to preserve water resources and valued riparian habitat given limited economic resources.
The Impacts of Climate-Induced Drought on Biogeochemical Cycles
NASA Astrophysics Data System (ADS)
Peng, C.
2014-12-01
Terrestrial ecosystems and, in particular, forests exert strong controls on the global biogeochemical cycles and influence regional hydrology and climatology directly through water and surface energy budgets. Recent studies indicated that forest mortality caused by rising temperature and drought from around the world have unexpectedly increased in the past decade and they collectively illustrate the vulnerability of many forested ecosystems to rapid increases in tree mortality due to warmer temperatures and more severe drought. Persistent changes in tree mortality rates can alter forest structure, composition, and ecosystem services (such as albedo and carbon sequestration). Quantifying potential impacts of tree mortality on ecosystem processes requires research into mortality effects on carbon, energy, and water budgets at both site and regional levels. Despite recent progress, the uncertainty around mortality responses still limits our ability to predict the likelihood and anticipate the impacts of tree die-off. Studies are needed that explore tree death physiology for a wide variety of functional types, connect patterns of mortality with climate events, and quantify the impacts on carbon, energy, and water flux. In this presentation, I will highlight recent research progress, and identify key research needs and future challenges to predict the consequence and impacts of drought-induced large-scale forest mortality on biogeochemical cycles. I will focus on three main forest ecosystems (tropic rainforest in Amazon, temperate forest in Western USA, and boreal forest in Canada) as detailed case studies.
The Tumor Macroenvironment: Cancer-Promoting Networks Beyond Tumor Beds.
Rutkowski, Melanie R; Svoronos, Nikolaos; Perales-Puchalt, Alfredo; Conejo-Garcia, Jose R
2015-01-01
During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. © 2015 Elsevier Inc. All rights reserved.
Obesity and cancer: inflammation bridges the two
Kolb, Ryan; Sutterwala, Fayyaz S.; Zhang, Weizhou
2016-01-01
Obesity is a growing public health problem and affects 35% US adults. Obesity increases the risk of many cancer types and is associated with poor outcomes. Clinical management of cancer patients has been essentially the same between normal weight and obese individuals. Understanding causal mechanisms by which obesity drives cancer initiation and progression is essential for the development of novel precision therapy for obese cancer patients. One caveat is that various mechanisms have been proposed for different cancer types for their progression under obesity. Since obesity is known to have global impact on inflammation, here we will summarize recent literature and discuss the potential of inflammation being the common causal mechanism to promote cancer promotion across cancer types. PMID:27429211
Bozkaya, Duygu; Livingston, Terrie; Migliaccio-Walle, Kristen; Odom, Tanner
2017-03-01
The safety and efficacy of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has been established; however, it is not clear which provides optimal value, given benefit-risk profiles and costs. To compare the cost-effectiveness of current DMTs for patients with RRMS in the US. A Markov model predicting RRMS course following initiation of a DMT was created comparing outcomes (e.g. relapses, disease progression) and costs of natalizumab (NTZ), dimethyl fumarate (DMF), and peginterferon beta-1a (PEG) with fingolimod (FIN), glatiramer acetate (GA, 20 mg daily), and subcutaneous interferon beta-1a (IFN, 44 mcg), respectively, over 10 years. RRMS and secondary-progressive MS (SPMS) EDSS state transitions were predicted in 3-month cycles in which patients were at risk of death, relapse, or discontinuation. Upon DMT discontinuation, natural history progression and relapse rates were applied. Incremental cost-effectiveness ratios (ICERs) were estimated for the cost per relapse avoided, relapse-free years gained, progression avoided, and progression-free years gained. The impact of model parameters on outcomes was evaluated via one-way sensitivity analyses. Costs ranged from $561,177 (NTZ) to $616,251 (GA). NTZ, DMF, and PEG were dominant (less costly and more effective) compared to FIN, GA, and IFN, respectively, for all ICERs. Variability in drug costs and parameters that affected drug cost accrual (e.g. discontinuation rates and the decision to drop out after SPMS conversion) had a considerable impact on ICERs. Several simplifying assumptions were made that may represent potential limitations of this analysis (e.g. a constant treatment effect over time was assumed). The results from this analysis suggest that the NTZ, DMF, and PEG are cost-effective DMT choices compared to FIN, GA, and IFN, respectively. The actual impact on a particular plan will vary based on drug pricing and other factors affecting drug cost accrual.
ERIC Educational Resources Information Center
Jacobs, Patricia
2012-01-01
The ability to write well is more important today than ever to prepare students for success in school and later in the 21st century global workplace. When children are able to express their knowledge and their beliefs in writing they experience the joy and power of making an impact on the world and reaching to their full potential. Children with…
The Impact of Human Factors on Decision Making in Combat
1990-06-01
positive attitude and intellectual reach speak volumes for the aggressive approach necessary for progress in human factors research. * Professor Glenn...stimuli, while the third focuses on the change in combat potential/combat power resulting from stimuli on factors related to either the individual...predict the behavior of a member of this society, all possible combina- tions of variables must be tested. At the point where every variable combination
Astrobiology and society: building an interdisciplinary research community.
Race, Margaret; Denning, Kathryn; Bertka, Constance M; Dick, Steven J; Harrison, Albert A; Impey, Christopher; Mancinelli, Rocco
2012-10-01
This paper reports recent efforts to gather experts from the humanities and social sciences along with astrobiologists to consider the cultural, societal, and psychological implications of astrobiology research and exploration. We began by convening a workshop to draft a research roadmap on astrobiology's societal implications and later formed a Focus Group on Astrobiology and Society under the auspices of the NASA Astrobiology Institute (NAI). Just as the Astrobiology Science Roadmap and various astrobiology science focus groups have helped researchers orient and understand their work across disciplinary contexts, our intent was to apply the same approach to examine areas beyond the physical and life sciences and expand interdisciplinary interaction and scholarly understanding. These efforts continue as an experiment in progress, with an open invitation to interested researchers-astrobiologists as well as scholars in the humanities and social sciences-to become involved in research, analysis, and proactive discussions concerning the potential impacts of astrobiology on society as well as the possible impacts of society on progress in astrobiology.
Garnier, Jean-Pierre; Klont, Ronald; Plastow, Graham
2003-01-01
Progress in animal nutrition, reproduction, quantitative genetics, and the development of molecular genetics, proteomics, and functional genomics open new perspectives for the meat sector. The most promising developments include a wider utilisation of molecular markers, the possibilities of semen sexing and the targeted use of nutrition to modify the composition of meat. The increased use of biotechnology will have a considerable impact on the economics of production of meat and further processed products. New technologies will increase the possibilities for product differentiation and improve homogeneity of live animals. The consumer and society in general will influence the direction of these developments. This review will focus on the long-term impact of new technologies for the meat production chain.
NASA Technical Reports Server (NTRS)
Blanchard, M. B.; Oberbeck, V. R.; Bunch, T. E.; Reynolds, R. T.; Canning, T. N.; Jackson, R. W.
1976-01-01
The feasibility of employing penetrators for exploring Mars was examined. Eight areas of interest for key scientific experiments were identified. These include: seismic activity, imaging, geochemistry, water measurement, heatflow, meteorology, magnetometry, and biochemistry. In seven of the eight potential experiment categories this year's progress included: conceptual design, instrument fabrication, instrument performance evaluation, and shock loading of important components. Most of the components survived deceleration testing with negligible performance changes. Components intended to be placed inside the penetrator forebody were tested up to 3,500 g and components intended to be placed on the afterbody were tested up to 21,000 g. A field test program was conducted using tentative Mars penetrator mission constraints. Drop tests were performed at two selected terrestrial analog sites to determine the range of penetration depths for anticipated common Martian materials. Minimum penetration occurred in basalt at Amboy, California. Three full-scale penetrators penetrated 0.4 to 0.9 m into the basalt after passing through 0.3 to 0.5 m of alluvial overburden. Maximum penetration occurred in unconsolidated sediments at McCook, Nebraska. Two full-scale penetrators penetrated 2.5 to 8.5 m of sediment. Impact occurred in two kinds of sediment: loess and layered clay. Deceleration g loads of nominally 2,000 for the forebody and 20,000 for the afterbody did not present serious design problems for potential experiments. Penetrators have successfully impacted into terrestrial analogs of the probable extremes of potential Martian sites.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Austin Brown, Brittany Repac, Jeff Gonder
Self-driving or “autonomous” vehicles (AVs) have leapt from science fiction into the forefront of transportation technology news. The technology is likely still years away from widespread commercial adoption, but the recent progress makes it worth considering the potential national impacts of widespread implementation. This poster makes an initial assessment of the energy impacts of AV adoptionon a per-vehicle basis and on total personal vehicle fuel use. While AVs offer numerous potential advantages in energy use, there are significant factors that could decrease or even eliminate the energy benefits under some circumstances. This analysis attempts to describe, quantify, and combine manymore » of the possible effects. The nature and magnitude of these effects remain highly uncertain. This set of effects is very unlikely to be exhaustive, but this analysis approach can serve as a base for future estimates.« less
Ghrelin and cancer progression.
Lin, Tsung-Chieh; Hsiao, Michael
2017-08-01
Ghrelin is a small peptide with 28 amino acids, and has been characterized as the ligand of the growth hormone secretagogue receptor (GHSR). In addition to its original function in stimulating pituitary growth hormone release, ghrelin is multifunctional and plays a role in the regulation of energy balance, gastric acid release, appetite, insulin secretion, gastric motility and the turnover of gastric and intestinal mucosa. The discovery of ghrelin and GHSR expression beyond normal tissues suggests its role other than physiological function. Emerging evidences have revealed ghrelin's function in regulating several processes related to cancer progression, especially in metastasis and proliferation. We further show the relative GHRL and GHSR expression in pan-cancers from The Cancer Genome Atlas (TCGA), suggesting the potential pathological role of the axis in cancers. This review focuses on ghrelin's biological function in cancer progression, and reveals its clinical significance especially the impact on cancer patient outcome. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Mast Cells: Pivotal Players in Cardiovascular Diseases
Bot, Ilze; van Berkel, Theo J.C; Biessen, Erik A.L
2008-01-01
The clinical outcome of cardiovascular diseases as myocardial infarction and stroke are generally caused by rupture of an atherosclerotic plaque. However, the actual cause of a plaque to rupture is not yet established. Interestingly, pathology studies have shown an increased presence of the mast cell, an important inflammatory effector cell in allergy and host defense, in (peri)vascular tissue during plaque progression, which may point towards a causal role for mast cells. Very recent data in mouse models show that mast cells and derived mediators indeed can profoundly impact plaque progression, plaque stability and acute cardiovascular syndromes such as vascular aneurysm or myocardial infarction. In this review, we discuss recent evidence on the role of mast cells in the progression of cardiovascular disorders and give insight in the therapeutic potential of modulation of mast cell function in these processes to improve the resilience of a plaque to rupture. PMID:19936193
Bording-Jorgensen, Michael; Dijk, Stephanie
2018-01-01
Cancer is a multifaceted condition, in which a senescent cell begins dividing in an irregular manner due to various factors such as DNA damage, growth factors and inflammation. Inflammation is not typically discussed as carcinogenic; however, a significant percentage of cancers arise from chronic microbial infections and damage brought on by chronic inflammation. A hallmark cancer-inducing microbe is Helicobacter pylori and its causation of peptic ulcers and potentially gastric cancer. This review discusses the recent developments in understanding microbes in health and disease and their potential role in the progression of cancer. To date, microbes can be linked to almost every cancer, including colon, pancreatic, gastric, and even prostate. We discuss the known mechanisms by which these microbes can induce cancer growth and development and how inflammatory cells may contribute to cancer progression. We also discuss new treatments that target the chronic inflammatory conditions and their associated cancers, and the impact microbes have on treatment success. Finally, we examine common dietary misconceptions in relation to microbes and cancer and how to avoid getting caught up in the misinterpretation and over inflation of the results. PMID:29558443
Franco, Nuno Henrique; Correia-Neves, Margarida; Olsson, I. Anna S.
2012-01-01
There is growing concern over the welfare of animals used in research, in particular when these animals develop pathology. The present study aims to identify the main sources of animal distress and to assess the possible implementation of refinement measures in experimental infection research, using mouse models of tuberculosis (TB) as a case study. This choice is based on the historical relevance of mouse studies in understanding the disease and the present and long-standing impact of TB on a global scale. Literature published between 1997 and 2009 was analysed, focusing on the welfare impact on the animals used and the implementation of refinement measures to reduce this impact. In this 12-year period, we observed a rise in reports of ethical approval of experiments. The proportion of studies classified into the most severe category did however not change significantly over the studied period. Information on important research parameters, such as method for euthanasia or sex of the animals, were absent in a substantial number of papers. Overall, this study shows that progress has been made in the application of humane endpoints in TB research, but that a considerable potential for improvement remains. PMID:23110093
Use of Windbreaks for Hurricane Protection of Critical Facilities
NASA Technical Reports Server (NTRS)
Hyater-Adams, Sinone; DeYoung, Russell J.
2012-01-01
The protection of NASA Langley Research Center from future hurricanes is important in order to allow the center to fulfill its mission. The impact of the center is not only great within NASA but the economy as well. The infrastructure of the Center is under potential risk in the future because of more intense hurricanes with higher speed winds and flooding. A potential method of protecting the Center s facilities is the placement of a windbreak barrier composed of indigenous trees. The New Town program that is now in progress creates a more condensed area of focus for protection. A potential design for an efficient tree windbreak barrier for Langley Research center is proposed.
The Functional Impact of Alternative Splicing in Cancer.
Climente-González, Héctor; Porta-Pardo, Eduard; Godzik, Adam; Eyras, Eduardo
2017-08-29
Alternative splicing changes are frequently observed in cancer and are starting to be recognized as important signatures for tumor progression and therapy. However, their functional impact and relevance to tumorigenesis remain mostly unknown. We carried out a systematic analysis to characterize the potential functional consequences of alternative splicing changes in thousands of tumor samples. This analysis revealed that a subset of alternative splicing changes affect protein domain families that are frequently mutated in tumors and potentially disrupt protein-protein interactions in cancer-related pathways. Moreover, there was a negative correlation between the number of these alternative splicing changes in a sample and the number of somatic mutations in drivers. We propose that a subset of the alternative splicing changes observed in tumors may represent independent oncogenic processes that could be relevant to explain the functional transformations in cancer, and some of them could potentially be considered alternative splicing drivers (AS drivers). Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Roos-Weil, Damien; Moreau, Philippe; Avet-Loiseau, Hervé; Golmard, Jean-Louis; Kuentz, Mathieu; Vigouroux, Stéphane; Socié, Gérard; Furst, Sabine; Soulier, Jean; Le Gouill, Steven; François, Sylvie; Thiebaut, Anne; Buzyn, Agnès; Maillard, Natacha; Yakoub-Agha, Ibrahim; Raus, Nicole; Fermand, Jean-Paul; Michallet, Mauricette; Blaise, Didier; Dhédin, Nathalie
2011-10-01
The impact of cytogenetic abnormalities in multiple myeloma after allogeneic stem cell transplantation has not been clearly defined. This study examines whether allogeneic stem cell transplantation could be of benefit for myeloma patients with high-risk cytogenetic abnormalities. This is a retrospective multicenter analysis of the registry of the Société Française de Greffe de Moelle et de Thérapie Cellulaire, including 143 myeloma patients transplanted between 1999 and 2008. The incidences of cytogenetic abnormalities were 59% for del(13q), 25% for t(4;14), 25% for del(17p) and 4% for t(14;16). When comparing the population carrying an abnormality to that without the same abnormality, no significant difference was found in progression-free survival, overall survival or progression rate. Patients were grouped according to the presence of any of the poor prognosis cytogenetic abnormalities t(4;14), del(17p) or t(14;16) (n=53) or their absence (n=32). No difference in outcomes was observed between these two groups: the 3-year progression-free survival, overall survival and progression rates were 30% versus 17% (P=0.9), 45% versus 39% (P=0.8) and 53% versus 75% (P=0.9), respectively. These data indicate that allogeneic stem cell transplantation could potentially be of benefit to high-risk myeloma patients.
Wind Power Electricity: The Bigger the Turbine, The Greener the Electricity?
2012-01-01
Wind energy is a fast-growing and promising renewable energy source. The investment costs of wind turbines have decreased over the years, making wind energy economically competitive to conventionally produced electricity. Size scaling in the form of a power law, experience curves and progress rates are used to estimate the cost development of ever-larger turbines. In life cycle assessment, scaling and progress rates are seldom applied to estimate the environmental impacts of wind energy. This study quantifies whether the trend toward larger turbines affects the environmental profile of the generated electricity. Previously published life cycle inventories were combined with an engineering-based scaling approach as well as European wind power statistics. The results showed that the larger the turbine is, the greener the electricity becomes. This effect was caused by pure size effects of the turbine (micro level) as well as learning and experience with the technology over time (macro level). The environmental progress rate was 86%, indicating that for every cumulative production doubling, the global warming potential per kWh was reduced by 14%. The parameters, hub height and rotor diameter were identified as Environmental Key Performance Indicators that can be used to estimate the environmental impacts for a generic turbine. PMID:22475003
Wind power electricity: the bigger the turbine, the greener the electricity?
Caduff, Marloes; Huijbregts, Mark A J; Althaus, Hans-Joerg; Koehler, Annette; Hellweg, Stefanie
2012-05-01
Wind energy is a fast-growing and promising renewable energy source. The investment costs of wind turbines have decreased over the years, making wind energy economically competitive to conventionally produced electricity. Size scaling in the form of a power law, experience curves and progress rates are used to estimate the cost development of ever-larger turbines. In life cycle assessment, scaling and progress rates are seldom applied to estimate the environmental impacts of wind energy. This study quantifies whether the trend toward larger turbines affects the environmental profile of the generated electricity. Previously published life cycle inventories were combined with an engineering-based scaling approach as well as European wind power statistics. The results showed that the larger the turbine is, the greener the electricity becomes. This effect was caused by pure size effects of the turbine (micro level) as well as learning and experience with the technology over time (macro level). The environmental progress rate was 86%, indicating that for every cumulative production doubling, the global warming potential per kWh was reduced by 14%. The parameters, hub height and rotor diameter were identified as Environmental Key Performance Indicators that can be used to estimate the environmental impacts for a generic turbine. © 2012 American Chemical Society
Genetic determinants of hepatic steatosis in man
Hooper, Amanda J.; Adams, Leon A.; Burnett, John R.
2011-01-01
Hepatic steatosis is one of the most common liver disorders in the general population. The main cause of hepatic steatosis is nonalcoholic fatty liver disease (NAFLD), representing the hepatic component of the metabolic syndrome, which is characterized by type 2 diabetes, obesity, and dyslipidemia. Insulin resistance and excess adiposity are considered to play key roles in the pathogenesis of NAFLD. Although the risk factors for NAFLD are well established, the genetic basis of hepatic steatosis is largely unknown. Here we review recent progress on genomic variants and their association with hepatic steatosis and discuss the potential impact of these genetic studies on clinical practice. Identifying the genetic determinants of hepatic steatosis will lead to a better understanding of the pathogenesis and progression of NAFLD. PMID:21245030
Gross national happiness as a framework for health impact assessment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pennock, Michael, E-mail: michael.pennock@viha.c; Ura, Karma
The incorporation of population health concepts and health determinants into Health Impact Assessments has created a number of challenges. The need for intersectoral collaboration has increased; the meaning of 'health' has become less clear; and the distinctions between health impacts, environmental impacts, social impacts and economic impacts have become increasingly blurred. The Bhutanese concept of Gross National Happiness may address these issues by providing an over-arching evidence-based framework which incorporates health, social, environmental and economic contributors as well as a number of other key contributors to wellbeing such as culture and governance. It has the potential to foster intersectoral collaborationmore » by incorporating a more limited definition of health which places the health sector as one of a number of contributors to wellbeing. It also allows for the examination of the opportunity costs of health investments on wellbeing, is consistent with whole-of-government approaches to public policy and emerging models of social progress.« less
Lamy, Philippe; Nordentoft, Iver; Birkenkamp-Demtröder, Karin; Thomsen, Mathilde Borg Houlberg; Villesen, Palle; Vang, Søren; Hedegaard, Jakob; Borre, Michael; Jensen, Jørgen Bjerggaard; Høyer, Søren; Pedersen, Jakob Skou; Ørntoft, Torben F; Dyrskjøt, Lars
2016-10-01
Greater knowledge concerning tumor heterogeneity and clonality is needed to determine the impact of targeted treatment in the setting of bladder cancer. In this study, we performed whole-exome, transcriptome, and deep-focused sequencing of metachronous tumors from 29 patients initially diagnosed with early-stage bladder tumors (14 with nonprogressive disease and 15 with progressive disease). Tumors from patients with progressive disease showed a higher variance of the intrapatient mutational spectrum and a higher frequency of APOBEC-related mutations. Allele-specific expression was also higher in these patients, particularly in tumor suppressor genes. Phylogenetic analysis revealed a common origin of the metachronous tumors, with a higher proportion of clonal mutations in the ancestral branch; however, 19 potential therapeutic targets were identified as both ancestral and tumor-specific alterations. Few subclones were present based on PyClone analysis. Our results illuminate tumor evolution and identify candidate therapeutic targets in bladder cancer. Cancer Res; 76(19); 5894-906. ©2016 AACR. ©2016 American Association for Cancer Research.
The HALT Polycystic Kidney Disease Trials: Design and Implementation
Torres, Vicente E.; Perrone, Ronald D.; Steinman, Theodore I.; Bae, Kyongtae T.; Miller, J. Philip; Miskulin, Dana C.; Oskoui, Frederic Rahbari; Masoumi, Amirali; Hogan, Marie C.; Winklhofer, Franz T.; Braun, William; Thompson, Paul A.; Meyers, Catherine M.; Kelleher, Cass; Schrier, Robert W.
2010-01-01
Background and objectives: Two HALT PKD trials will investigate interventions that potentially slow kidney disease progression in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. Studies were designed in early and later stages of ADPKD to assess the impact of intensive blockade of the renin-angiotensin-aldosterone system and level of BP control on progressive renal disease. Design, settings, participants, and measurements: PKD-HALT trials are multicenter, randomized, double-blind, placebo-controlled trials studying 1018 hypertensive ADPKD patients enrolled over 3 yr with 4 to 8 yr of follow-up. In study A, 548 participants, estimated GFR (eGFR) of >60 ml/min per 1.73 m2 were randomized to one of four arms in a 2-by-2 design: combination angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) therapy versus ACEi monotherapy at two levels of BP control. In study B, 470 participants, eGFR of 25 to 60 ml/min per 1.73 m2 compared ACEi/ARB therapy versus ACEi monotherapy, with BP control of 120 to 130/70 to 80 mmHg. Primary outcomes of studies A and B are MR-based percent change kidney volume and a composite endpoint of time to 50% reduction of baseline estimated eGFR, ESRD, or death, respectively. Results: This report describes design issues related to (1) novel endpoints such as kidney volume, (2) home versus office BP measures, and (3) the impact of RAAS inhibition on kidney and patient outcomes, safety, and quality of life. Conclusions: HALT PKD will evaluate potential benefits of rigorous BP control and inhibition of the renin-angiotensin-aldosterone system on kidney disease progression in ADPKD. PMID:20089507
Partners in Progress or Economic Enemies China’s Impact on U.S. National Interests in West Africa
2017-06-09
PARTNERS IN PROGRESS OR ECONOMIC ENEMIES? CHINA’S IMPACT ON U.S. NATIONAL INTERESTS IN WEST AFRICA A thesis presented to the Faculty...COVERED (From - To) AUG 2016 – JUNE 2017 4. TITLE AND SUBTITLE Partners in Progress or Economic Enemies? China’s Impact on U.S. National Interests...has led to its ability to project power, both economic and military, beyond its borders in ways not seen in centuries. One region where the Chinese
Renovascular disease, microcirculation, and the progression of renal injury: role of angiogenesis
2011-01-01
Emerging evidence supports the pivotal role of renal microvascular disease as a determinant of tubulo-interstitial and glomerular fibrosis in chronic kidney disease. An intact microcirculation is vital to restore blood flow to the injured tissues, which is a crucial step to achieve a successful repair response. The purpose of this review is to discuss the impact and mechanisms of the functional and structural changes of the renal microvascular network, as well as the role of these changes in the progression and irreversibility of renal injury. Damage of the renal microcirculation and deterioration of the angiogenic response may constitute early steps in the complex pathways involved in progressive renal injury. There is limited but provocative evidence that stimulation of vascular proliferation and repair may stabilize renal function and slow the progression of renal disease. The feasibility of novel potential therapeutic interventions for stabilizing the renal microvasculature is also discussed. Targeted interventions to enhance endogenous renoprotective mechanisms focused on the microcirculation, such as cell-based therapy or the use of angiogenic cytokines have shown promising results in some experimental and clinical settings. PMID:21307362
NASA Technical Reports Server (NTRS)
1971-01-01
The economic impact of technological progress in communications satellites is considered, as well as how these impacts affect the firms involved. Influences, if any, on the three major inputs of a nation's economic output (capital, labor, and technology) is discussed.
Bonitsky, Craig M; McGann, Megan E; Selep, Michael J; Ovaert, Timothy C; Trippel, Stephen B; Wagner, Diane R
2017-03-01
High energy trauma to cartilage causes surface fissures and microstructural damage, but the degree to which this damage renders the tissue more susceptible to wear and contributes to the progression of post-traumatic osteoarthritis (PTOA) is unknown. Additionally, no treatments are currently available to strengthen cartilage after joint trauma and to protect the tissue from subsequent degradation and wear. The purposes of this study were to investigate the role of mechanical damage in the degradation and wear of cartilage, to evaluate the effects of impact and subsequent genipin crosslinking on the changes in the viscoelastic parameters of articular cartilage, and to test the hypothesis that genipin crosslinking is an effective treatment to enhance the resistance to biochemical degradation and mechanical wear. Results demonstrate that cartilage stiffness decreases after impact loading, likely due to the formation of fissures and microarchitectural damage, and is partially or fully restored by crosslinking. The wear resistance of impacted articular cartilage was diminished compared to undamaged cartilage, suggesting that mechanical damage that is directly induced by the impact may contribute to the progression of PTOA. However, the decrease in wear resistance was completely reversed by the crosslinking treatments. Additionally, the crosslinking treatments improved the resistance to collagenase digestion at the impact-damaged articular surface. These results highlight the potential therapeutic value of collagen crosslinking via genipin in the prevention of cartilage degeneration after traumatic injury. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:558-565, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Impact of the Level of State Tax Code Progressivity on Children's Health Outcomes
ERIC Educational Resources Information Center
Granruth, Laura Brierton; Shields, Joseph J.
2011-01-01
This research study examines the impact of the level of state tax code progressivity on selected children's health outcomes. Specifically, it examines the degree to which a state's tax code ranking along the progressive-regressive continuum relates to percentage of low birthweight babies, infant and child mortality rates, and percentage of…
NASA Technical Reports Server (NTRS)
1971-01-01
Investigations were performed at the national economic level to explore the aggregate effects of technological progress on economic growth. Inadequacies in existing marco-economic yardsticks forced the study to focus on the cost savings effects achieved through technological progress. The central questions discussed in this report cover: (1) role of technological progress in economic growth, (2) factors determining the rate of economic growth due to technological progress; (3) quantitative measurements of relationships between technological progress, its determinants, and subsequent economic growth; and (4) effects of research and development activities of the space program. For Part 2, see N72-32174.
NASA Technical Reports Server (NTRS)
Park, Michael A.; Krakos, Joshua A.; Michal, Todd; Loseille, Adrien; Alonso, Juan J.
2016-01-01
Unstructured grid adaptation is a powerful tool to control discretization error for Computational Fluid Dynamics (CFD). It has enabled key increases in the accuracy, automation, and capacity of some fluid simulation applications. Slotnick et al. provides a number of case studies in the CFD Vision 2030 Study: A Path to Revolutionary Computational Aerosciences to illustrate the current state of CFD capability and capacity. The authors forecast the potential impact of emerging High Performance Computing (HPC) environments forecast in the year 2030 and identify that mesh generation and adaptivity continue to be significant bottlenecks in the CFD work flow. These bottlenecks may persist because very little government investment has been targeted in these areas. To motivate investment, the impacts of improved grid adaptation technologies are identified. The CFD Vision 2030 Study roadmap and anticipated capabilities in complementary disciplines are quoted to provide context for the progress made in grid adaptation in the past fifteen years, current status, and a forecast for the next fifteen years with recommended investments. These investments are specific to mesh adaptation and impact other aspects of the CFD process. Finally, a strategy is identified to diffuse grid adaptation technology into production CFD work flows.
Finite element modelling of aluminum alloy 2024-T3 under transverse impact loading
NASA Astrophysics Data System (ADS)
Abdullah, Ahmad Sufian; Kuntjoro, Wahyu; Yamin, A. F. M.
2017-12-01
Fiber metal laminate named GLARE is a new aerospace material which has great potential to be widely used in future lightweight aircraft. It consists of aluminum alloy 2024-T3 and glass-fiber reinforced laminate. In order to produce reliable finite element model of impact response or crashworthiness of structure made of GLARE, one can initially model and validate the finite element model of the impact response of its constituents separately. The objective of this study was to develop a reliable finite element model of aluminum alloy 2024-T3 under low velocity transverse impact loading using commercial software ABAQUS. Johnson-Cook plasticity and damage models were used to predict the alloy's material properties and impact behavior. The results of the finite element analysis were compared to the experiment that has similar material and impact conditions. Results showed good correlations in terms of impact forces, deformation and failure progressions which concluded that the finite element model of 2024-T3 aluminum alloy under low velocity transverse impact condition using Johnson-Cook plastic and damage models was reliable.
Measuring hope among families impacted by cognitive impairment
Hunsaker, Amanda E.; Terhorst, Lauren; Gentry, Amanda; Lingler, Jennifer H.
2014-01-01
The current exploratory investigation aims to establish the reliability and validity of a hope measure, the Herth Hope Index (HHI), among families impacted by early cognitive impairment (N=96). Exploratory factor analysis was used to examine the dimensionality of the measure. Bivariate analyses were used to examine construct validity. The sample had moderately high hope scores. A two-factor structure emerged from the factor analysis, explaining 51.44% of the variance. Both factors exhibited strong internal consistency (Cronbach’s alphas ranged from .83 to .86). Satisfaction with social support was positively associated with hope, supporting convergent validity. Neurocognitive status, illness insight and depression were not associated with hope, indicating discriminant validity. Families impacted by cognitive impairment may maintain hope in the face of a potentially progressive illness, regardless of cognitive status. The HHI can be utilized as a reliable and valid measure of hope by practitioners providing support to families impacted by cognitive impairment. PMID:24784938
2018-05-01
the descriptors were correlated to experimental rate constants. The five descriptors fell into one of two categories: whole molecule descriptors or...model based on these correlations . Although that goal was not achieved in full, considerable progress has been made, and there is potential for a...readme.txt) and compiled. We then searched for correlations between the calculated properties from theory and the experimental measurements of reaction rate
Glutaminolysis and autophagy in cancer
Villar, Victor H; Merhi, Faten; Djavaheri-Mergny, Mojgan; Durán, Raúl V
2015-01-01
The remarkable metabolic differences between cancer cells and normal cells result in the potential for targeted cancer therapy. The upregulation of glutaminolysis provides energetic advantages to cancer cells. The recently described link between glutaminolysis and autophagy, mediated by MTORC1, may constitute an attractive target for therapeutic strategies. A combination of therapies targeting simultane-ously cell signaling, cancer metabolism, and autophagy can solve therapy resistance and tumor relapse problems, commonly observed in patients treated with most of the current targeted therapies. In this review we summarize the mechanistic link between glutaminolysis and autophagy, and discuss the impacts of these processes on cancer progression and the potential for therapeutic intervention. PMID:26054373
Technical Feasibility Aspects of the Geothermal Resource Reporting Methodology (GRRM)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Badgett, Alex; Young, Katherine R; Dobson, Patrick F.
This paper reviews the technical assessment of the Geothermal Research Reporting Methodology (GRRM, http://en.openei.org/wiki/GRRM) being developed for reporting geothermal resources and project progress. The goal of the methodology is to provide the U.S. Department of Energy's Geothermal Technologies Office (GTO) with a consistent and comprehensible means of evaluating the impacts of its funding programs. The GRRM is designed to provide uniform assessment criteria for geothermal resource grades and developmental phases of geothermal resource exploration and development. This resource grade system provides information on twelve attributes of geothermal resource locations (e.g., temperature, permeability, land access) to indicate potential for geothermal development.more » The GTO plans to use these Protocols to help quantitatively identify the greatest barriers to geothermal development, develop measureable program goals that will have the greatest impact to geothermal deployment, objectively evaluate proposals based (in part) on a project's ability to contribute to program goals, monitor project progress, and report on GTO portfolio performance. The GRRM assesses three areas of geothermal potential: geological, socio-economic, and technical. Previous work and publications have discussed the work done on the geological aspects of this methodology (Young et al. 2015c); this paper details the development of the technical assessment of the GRRM. Technical development attributes considered include: reservoir management, drilling, logistics, and power conversion.« less
Kim, Esther S; Figeys, Mathieu; Hubbard, H Isabel; Wilson, Carlee
2018-07-01
Individuals with primary progressive aphasia (PPA) and their caregivers are at risk for decreased quality of life (QoL) due to their progressive condition. Aphasia camps are an intervention that can improve QoL, yet individuals with PPA are underrepresented at aphasia camps relative to those with poststroke aphasia. The purpose of this exploratory case study was to examine the effect of participation in aphasia camp on the QoL of a couple impacted by PPA. The Living with Aphasia: Framework for Outcome Measurement (A-FROM) was used to guide a semistructured interview with an individual with PPA and her spouse, both of whom had attended the Alberta Aphasia Camp for 4 years. Conventional content analysis with an inductive approach was used to analyze results. Concepts that emerged from the interview were organized into pre-camp, during, and post-camp categories. Aspects of camp that had an effect on post-camp QoL for this couple with PPA included expanding social connections and introduction to new activities. Personal characteristics exhibited by the couple had an impact on their experience of aphasia camp and how they incorporated their experiences into their everyday lives post-camp. Aphasia camps are a participation-based service approach that can benefit people with aphasia regardless of etiology. A consideration of personal factors of potential campers with PPA, and the provision of PPA-specific resources, is recommended for programs such as aphasia camps that incorporate participants with mixed etiologies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
ERIC Educational Resources Information Center
Nelson, Peter M.; Van Norman, Ethan R.; Klingbeil, Dave A.; Parker, David C.
2017-01-01
Although extensive research exists on the use of curriculum-based measures for progress monitoring, little is known about using computer adaptive tests (CATs) for progress-monitoring purposes. The purpose of this study was to evaluate the impact of the frequency of data collection on individual and group growth estimates using a CAT. Data were…
A Journal-Level Analysis of Progress in Transplantation.
Feeley, Thomas; Lee, Seyoung; Moon, Shin-Il
2018-03-01
Citations to articles published in academic journals represent a proxy for influence in bibliometrics. To measure the journal impact factor for Progress in Transplantation over time and to also identify related journals indexed in transplantation and surgery. Data from Journal Citation Reports (ISI web of science) were used to rank Progress in Transplantation compared to peer journals using journal impact and journal relatedness measures. Social network analysis was used to measure relationships between pairs of journals in Progress in Transplantation's relatedness network. Journal impact factor and journal relatedness. Data from 2010 through 2015 indicate the average journal article in PIT was cited 0.87 times (standard deviation [SD] = 0.12) and this estimate was stable over time. Progress in Transplantation most often cited American Journal of Transplantation, Transplantation, American Journal of Kidney Diseases, and Liver Transplantation. In terms of cited data, the journal was most often referenced by Clinical Transplantation, Transplant International, and Current Opinion in Organ Transplantation. The journal is listed both in surgery and transplantation categories of Journal Citation Reports and its impact factors over time fare better with surgery journals than with transplant journals. Network data using betweenness centrality indicate Progress in Transplantation links transplantation-focused journals and journals indexed in health sciences categories.
Augmented reality for personalized nanomedicines.
Lee, Yugyung; Lee, Chi H
As our understanding of onset and progress of diseases at the genetic and molecular level rapidly progresses, the potential of advanced technologies, such as 3D-printing, Socially-Assistive Robots (SARs) or augmented reality (AR), that are applied to personalized nanomedicines (PNMs) to alleviate pathological conditions, has become more prominent. Among advanced technologies, AR in particular has the greatest potential to address those challenges and facilitate the translation of PNMs into formidable clinical application of personalized therapy. As AR is about to adapt additional new methods, such as speech, voice recognition, eye tracing and motion tracking, to enable interaction with host response or biological systems in 3-D space, a combination of multiple approaches to accommodate varying environmental conditions, such as public noise and atmosphere brightness, will be explored to improve its therapeutic outcomes in clinical applications. For instance, AR glasses still being developed by Facebook or Microsoft will serve as new platform that can provide people with the health information they are interested in or various measures through which they can interact with medical services. This review has addressed the current progress and impact of AR on PNMs and its application to the biomedical field. Special emphasis is placed on the application of AR based PNMs to the treatment strategies against senior care, drug addiction and medication adherence. Published by Elsevier Inc.
De Schutter, Alban; Lavie, Carl J; Milani, Richard V
2014-01-01
Obesity is associated with a host of cardiovascular risk factors and its prevalence is rising rapidly. Despite strong evidence that obesity predisposes to the development and progression of coronary heart disease (CHD), numerous studies have shown an inverse relationship between various measures of obesity (most commonly body mass index) and outcomes in established CHD. In this article we review the evidence surrounding the ≪obesity paradox≫ in the secondary care of CHD patients and the CHD presentations where a paradox has been found. Finally we discuss the impact of cardiorespiratory fitness and a number of mechanisms which may offer potential explanations for this puzzling phenomenon. © 2014.
Palma-Cruz, Felipe de J; Pérez-Vargas, Josefina; Rivera Casado, Noemí Araceli; Gómez Guzmán, Octavio; Calva-Calva, Graciano
2016-08-01
Pioneer native plant species from weathered oil spill-affected sites were selected to study their potential for phytoremediation on the basis of their ecological and phenological changes during the phytoremediation process. Experiments were conducted in field and in greenhouse. In field, native plants from aged oil spill-impacted sites with up 400 g of weathered petroleum hydrocarbons per kilogram soil were selected. In the impacted sites, the principal dominant plant species with potential for hydrocarbons removal were Cyperus laxus, Cyperus esculentus, and Ludwigia peploides. In greenhouse, the phenology of the selected plant species was drastically affected by the hydrocarbons level above 325 g total petroleum hydrocarbons (TPH) per kilogram soil after 2 years of phytoremediation of soils from the aged oil spill-impacted sites. From the phytoremediation treatments, a mix-culture of C. laxus, C. esculentus, and L. peploides in soil containing 325 g TPH/kg soil, from which 20.3 % were polyaromatic hydrocarbons (PAH) and 34.2 % were asphaltenes (ASF), was able to remove up 93 % of the TPH, while in unvegetated soil the TPH removal was 12.6 %. Furthermore, evaluation of the biodiversity and life forms of plant species in the impacted sites showed that phytoremediation with C. esculentus, alone or in a mix-culture with C. laxus and L. peploides, reduces the TPH to such extent that the native plant community was progressively reestablished by replacing the cultivated species resulting in the ecological recovery of the affected soil. These results demonstrate that native Cyperus species from weathered oil spill-affected sites, specifically C. esculentus and C. laxus, alone or in a mix-culture, have particular potential for phytoremediation of soils from tropical wetlands contaminated with weathered oil hydrocarbons.
Impact of climate change on crop yield and role of model for achieving food security.
Kumar, Manoj
2016-08-01
In recent times, several studies around the globe indicate that climatic changes are likely to impact the food production and poses serious challenge to food security. In the face of climate change, agricultural systems need to adapt measures for not only increasing food supply catering to the growing population worldwide with changing dietary patterns but also to negate the negative environmental impacts on the earth. Crop simulation models are the primary tools available to assess the potential consequences of climate change on crop production and informative adaptive strategies in agriculture risk management. In consideration with the important issue, this is an attempt to provide a review on the relationship between climate change impacts and crop production. It also emphasizes the role of crop simulation models in achieving food security. Significant progress has been made in understanding the potential consequences of environment-related temperature and precipitation effect on agricultural production during the last half century. Increased CO2 fertilization has enhanced the potential impacts of climate change, but its feasibility is still in doubt and debates among researchers. To assess the potential consequences of climate change on agriculture, different crop simulation models have been developed, to provide informative strategies to avoid risks and understand the physical and biological processes. Furthermore, they can help in crop improvement programmes by identifying appropriate future crop management practises and recognizing the traits having the greatest impact on yield. Nonetheless, climate change assessment through model is subjected to a range of uncertainties. The prediction uncertainty can be reduced by using multimodel, incorporating crop modelling with plant physiology, biochemistry and gene-based modelling. For devloping new model, there is a need to generate and compile high-quality field data for model testing. Therefore, assessment of agricultural productivity to sustain food security for generations is essential to maintain a collective knowledge and resources for preventing negative impact as well as managing crop practises.
Astrobiology and Society: Building an Interdisciplinary Research Community
Denning, Kathryn; Bertka, Constance M.; Dick, Steven J.; Harrison, Albert A.; Impey, Christopher; Mancinelli, Rocco
2012-01-01
Abstract This paper reports recent efforts to gather experts from the humanities and social sciences along with astrobiologists to consider the cultural, societal, and psychological implications of astrobiology research and exploration. We began by convening a workshop to draft a research roadmap on astrobiology's societal implications and later formed a Focus Group on Astrobiology and Society under the auspices of the NASA Astrobiology Institute (NAI). Just as the Astrobiology Science Roadmap and various astrobiology science focus groups have helped researchers orient and understand their work across disciplinary contexts, our intent was to apply the same approach to examine areas beyond the physical and life sciences and expand interdisciplinary interaction and scholarly understanding. These efforts continue as an experiment in progress, with an open invitation to interested researchers—astrobiologists as well as scholars in the humanities and social sciences—to become involved in research, analysis, and proactive discussions concerning the potential impacts of astrobiology on society as well as the possible impacts of society on progress in astrobiology. Key Words: Astrobiology—Extraterrestrial life—Life detection. Astrobiology 12, 958–965. PMID:23046203
Kravchenko, Julia; Corsini, Emanuela; Williams, Marc A.; Decker, William; Manjili, Masoud H.; Otsuki, Takemi; Singh, Neetu; Al-Mulla, Faha; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A. Ivana; Raju, Jayadev; Hamid, Roslida A.; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K.; Ryan, Elizabeth P.; Brown, Dustin G.; Lowe, Leroy; Lyerly, H.Kim
2015-01-01
An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-β, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. PMID:26002081
Chen, Yu; Chen, Mengjun; Li, Yungui; Wang, Bin; Chen, Shu; Xu, Zhonghui
2018-05-08
Technology innovation has accelerated progress in Information and Communications Technology (ICT), especially in the mobile phones sector. Concurrently, local, national, and international governments are enforcing stricter regulations to protect natural resources and human health. The paper attempts to address the question: Have technological innovations and regulation development had a positive impact on ecosystems and public health? We identified 36 waste mobile phones (WMPs) manufactured between 2002 and 2013, assessed their metals concentration, leachability, and potential impact on environment and human health using digestion, Toxicity Characteristic Leaching Procedure (TCLP), and USEtox model, respectively. The results highlight that regulations did not have significant impact on total metal content, except some heavy metals, while technology innovation recorded stronger impact. WMPs should be classified as hazardous due to excessive lead content. Copper posed the most significant ecotoxicity risk, and chromium showed the most significant risk for both cancerous and non-cancerous diseases. Additionally, we demonstrated that WMPs toxicity increased with technology innovation.
Economic impact of stimulated technological activity: Bibliography
NASA Technical Reports Server (NTRS)
1971-01-01
This bibliography is divided into three parts and covers: (1) overall economic impact of technological progress and its measurement; (2) technological progress and commercialization of communications satellites; and (3) knowledge additions and earth links from space crew systems.
TGFβ lengthens the G1 phase of stem cells in aged mouse brain.
Daynac, Mathieu; Pineda, Jose R; Chicheportiche, Alexandra; Gauthier, Laurent R; Morizur, Lise; Boussin, François D; Mouthon, Marc-André
2014-12-01
Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells. © 2014 AlphaMed Press.
DEK oncogene is overexpressed during melanoma progression.
Riveiro-Falkenbach, Erica; Ruano, Yolanda; García-Martín, Rosa M; Lora, David; Cifdaloz, Metehan; Acquadro, Francesco; Ballestín, Claudio; Ortiz-Romero, Pablo L; Soengas, María S; Rodríguez-Peralto, José L
2017-03-01
DEK is an oncoprotein involved in a variety of cellular functions, such as DNA repair, replication, and transcriptional control. DEK is preferentially expressed in actively proliferating and malignant cells, including melanoma cell lines in which DEK was previously demonstrated to play a critical role in proliferation and chemoresistance. Still, the impact of this protein in melanoma progression remains unclear. Thus, we performed a comprehensive analysis of DEK expression in different melanocytic tumors. The immunostaining results of 303 tumors demonstrated negligible DEK expression in benign lesions. Conversely, malignant lesions, particularly in metastatic cases, were largely positive for DEK expression, which was partially associated with genomic amplification. Importantly, DEK overexpression was correlated with histological features of aggressiveness in primary tumors and poor prognosis in melanoma patients. In conclusion, our study provides new insight into the involvement of DEK in melanoma progression, as well as proof of concept for its potential application as a marker and therapeutic target of melanoma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Insights into interventions in managing COPD patients: lessons from the TORCH and UPLIFT® studies
Miravitlles, Marc; Anzueto, Antonio
2009-01-01
Influencing the progression of COPD has long been an elusive goal of drug therapy. Directly or indirectly, this has again been investigated in two of the largest, long-term drug trials in COPD: Towards a Revolution in COPD Health (TORCH) and Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT®). Neither trial achieved statistical significance in their respective primary outcomes; however, both make considerable contributions to understanding of how the progression of COPD may be influenced. The objective of this article is to review the data from these different trials with a view to what can be learnt about the management of COPD. The long-term improvements in lung function, health-related quality of life, and possibly survival from the use of long-acting bronchodilators in these trials suggest an influence on progression of the disease. With the more optimistic view of benefits from drug treatment of COPD that these trials provide, a review of prescribing practices is warranted. PMID:19516917
Shifts of tundra bacterial and archaeal communities along a permafrost thaw gradient in Alaska.
Deng, Jie; Gu, Yunfu; Zhang, Jin; Xue, Kai; Qin, Yujia; Yuan, Mengting; Yin, Huaqun; He, Zhili; Wu, Liyou; Schuur, Edward A G; Tiedje, James M; Zhou, Jizhong
2015-01-01
Understanding the response of permafrost microbial communities to climate warming is crucial for evaluating ecosystem feedbacks to global change. This study investigated soil bacterial and archaeal communities by Illumina MiSeq sequencing of 16S rRNA gene amplicons across a permafrost thaw gradient at different depths in Alaska with thaw progression for over three decades. Over 4.6 million passing 16S rRNA gene sequences were obtained from a total of 97 samples, corresponding to 61 known classes and 470 genera. Soil depth and the associated soil physical-chemical properties had predominant impacts on the diversity and composition of the microbial communities. Both richness and evenness of the microbial communities decreased with soil depth. Acidobacteria, Verrucomicrobia, Alpha- and Gamma-Proteobacteria dominated the microbial communities in the upper horizon, whereas abundances of Bacteroidetes, Delta-Proteobacteria and Firmicutes increased towards deeper soils. Effects of thaw progression were absent in microbial communities in the near-surface organic soil, probably due to greater temperature variation. Thaw progression decreased the abundances of the majority of the associated taxa in the lower organic soil, but increased the abundances of those in the mineral soil, including groups potentially involved in recalcitrant C degradation (Actinomycetales, Chitinophaga, etc.). The changes in microbial communities may be related to altered soil C sources by thaw progression. Collectively, this study revealed different impacts of thaw in the organic and mineral horizons and suggests the importance of studying both the upper and deeper soils while evaluating microbial responses to permafrost thaw. © 2014 John Wiley & Sons Ltd.
ERIC Educational Resources Information Center
Gallacher, Jim
2014-01-01
This paper addresses the issue of the impact of expansion and differentiation on widening access to higher education. In particular, it considers the impact of the growing importance of full-time short-cycle higher education in Scotland's colleges of further and higher education, the progression pathways which have now been established from these…
Impact of Self-Correction on Extrovert and Introvert Students in EFL Writing Progress
ERIC Educational Resources Information Center
Hajimohammadi, Reza; Makundan, Jayakaran
2011-01-01
To investigate the impact of self-correction method as an alternative to the traditional teacher-correction method, on the one side, and to evaluate the impact of personality traits of Extroversion/Introversion, on the other side, on the writing progress of the pre-intermediate learners three null-hypotheses were proposed. In spite of students…
Caffrey, Louise; Mattingley, Helena; Williamson, Catherine; McKevitt, Christopher
2016-01-01
Objectives Gender inequity has persisted in academic medicine. Yet equity is vital for countries to achieve their full potential in terms of translational research and patient benefit. This study sought to understand how the gender equity programme, Athena SWAN, can be enabled and constrained by interactions between the programme and the context it is implemented into, and whether these interactions might produce unintended consequences. Design Multimethod qualitative case studies using a realist evaluation approach. Setting 5 departments from a university medical school hosting a Translational Research Organisation. Participants 25 hours of observations of gender equality committee meetings, 16 in-depth interviews with Heads of Departments, Committee Leads and key personnel involved in the initiative. 4 focus groups with 15 postdoctoral researchers, lecturers and senior lecturers. Results The implementation of Athena SWAN principles was reported to have created social space to address gender inequity and to have highlighted problematic practices to staff. However, a number of factors reduced the programme's potential to impact gender inequity. Gender inequity was reproduced in the programme's enactment as female staff was undertaking a disproportionate amount of Athena SWAN work, with potential negative impacts on individual women's career progression. Early career researchers experienced problems accessing Athena SWAN initiatives. Furthermore, the impact of the programme was perceived to be undermined by wider institutional practices, national policies and societal norms, which are beyond the programme's remit. Conclusions Gender equity programmes have the potential to address inequity. However, paradoxically, they can also unintentionally reproduce and reinforce gender inequity through their enactment. Potential programme impacts may be undermined by barriers to staff availing of career development and training initiatives, and by wider institutional practices, national policies and societal norms. PMID:27609850
NASA Astrophysics Data System (ADS)
Aryanto, Daniel Eko; Hardiman, Gagoek
2018-02-01
Floods and droughts in Purworejo regency are an indication of problems in groundwater management. The current development progress has led to land conversion which has an impact on the problem of water infiltration in Purworejo regency. This study aims to determine the distribution of groundwater recharge potential zones by using geographic information system as the basis for ground water management. The groundwater recharge potential zone is obtained by overlaying all the thematic maps that affect the groundwater infiltration. Each thematic map is weighted according to its effect on groundwater infiltration such as land-use - 25%, rainfall - 20%, litology - 20%, soil - 15%, slope - 10%, lineament - 5%, and river density - 5% to find groundwater recharge potential zones. The groundwater recharge potential zones thus obtained were divided into five categories, viz., very high, high, medium, low and very low zones. The results of this study may be useful for better groundwater planning and management.
Could Sirtuin Activities Modify ALS Onset and Progression?
Tang, Bor Luen
2017-10-01
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a complex etiology. Sirtuins have been implicated as disease-modifying factors in several neurological disorders, and in the past decade, attempts have been made to check if manipulating Sirtuin activities and levels could confer benefit in terms of neuroprotection and survival in ALS models. The efforts have largely focused on mutant SOD1, and while limited in scope, the results were largely positive. Here, the body of work linking Sirtuins with ALS is reviewed, with discussions on how Sirtuins and their activities may impact on the major etiological mechanisms of ALS. Moving forward, it is important that the potentially beneficial effect of Sirtuins in ALS disease onset and progression are assessed in ALS models with TDP-43, FUS, and C9orf72 mutations.
Research Priorities from Animal Behaviour for Maximising Conservation Progress.
Greggor, Alison L; Berger-Tal, Oded; Blumstein, Daniel T; Angeloni, Lisa; Bessa-Gomes, Carmen; Blackwell, Bradley F; St Clair, Colleen Cassady; Crooks, Kevin; de Silva, Shermin; Fernández-Juricic, Esteban; Goldenberg, Shifra Z; Mesnick, Sarah L; Owen, Megan; Price, Catherine J; Saltz, David; Schell, Christopher J; Suarez, Andrew V; Swaisgood, Ronald R; Winchell, Clark S; Sutherland, William J
2016-12-01
Poor communication between academic researchers and wildlife managers limits conservation progress and innovation. As a result, input from overlapping fields, such as animal behaviour, is underused in conservation management despite its demonstrated utility as a conservation tool and countless papers advocating its use. Communication and collaboration across these two disciplines are unlikely to improve without clearly identified management needs and demonstrable impacts of behavioural-based conservation management. To facilitate this process, a team of wildlife managers and animal behaviour researchers conducted a research prioritisation exercise, identifying 50 key questions that have great potential to resolve critical conservation and management problems. The resulting agenda highlights the diversity and extent of advances that both fields could achieve through collaboration. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Trait Mindfulness and Progression to Injection Use in Youth With Opioid Addiction.
Wilson, J Deanna; Vo, Hoa; Matson, Pamela; Adger, Hoover; Barnett, Gabriela; Fishman, Marc
2017-09-19
Many youth initiate opioid misuse with prescription opioids and transition over time to more severe substance-using behaviors, including injection. Trait mindfulness is a potentially protective factor. This is a cross-sectional study characterizing a sample of opioid-using youth by level of mindfulness and examines the potential effect modification of emotion regulation on the relationship between mindfulness and progression to injection opioid use. A convenience sample of 112 youth (ages 14-24) was recruited during an episode of inpatient detoxification and residential treatment for opioid use disorders. We examined emotion regulation (Difficulties in Emotion Regulation Scale), mindfulness (Child Acceptance and Mindfulness Measure), and opioid use. We completed multivariable regressions stratified by degree of emotion regulation looking at relationship of mindfulness on time to injection use from age of first prescription opioid. Youth had difficulties in emotion regulation (m = 104.2; SD = 2.41) and low mindfulness (m = 19.1;SD = 0.59). While we found overall that mindfulness was associated with time to progression to injection opioid use, there was significant effect modification. Among youth with high levels of difficulty in emotion regulation, those with high mindfulness trait had quicker progressions to injection (-1.31 years; p =.003). In contrast, youth with normal emotion regulation and high mindfulness trait had a slower progression to injection (1.67 years; p =.041). Conclusion/Importance: Our study showed a majority of youth presenting with opioid use disorders have impairments in emotion regulation and deficits in trait mindfulness. The relationship between mindfulness and opioid use is impacted by emotion regulation capacity. More research is needed to understand the various facets of mindfulness and how they interact with emotion regulation in youth.
Garcia-Montero, Andres C; Jara-Acevedo, Maria; Alvarez-Twose, Ivan; Teodosio, Cristina; Sanchez-Muñoz, Laura; Muñiz, Carmen; Muñoz-Gonzalez, Javier I; Mayado, Andrea; Matito, Almudena; Caldas, Carolina; Morgado, Jose M; Escribano, Luis; Orfao, Alberto
2016-02-11
Multilineage involvement of bone marrow (BM) hematopoiesis by the somatic KIT D816V mutation is present in a subset of adult indolent systemic mastocytosis (ISM) patients in association with a poorer prognosis. Here, we investigated the potential involvement of BM mesenchymal stem cells (MSCs) from ISM patients by the KIT D816V mutation and its potential impact on disease progression and outcome. This mutation was investigated in highly purified BM MSCs and other BM cell populations from 83 ISM patients followed for a median of 116 months. KIT D816V-mutated MSCs were detected in 22 of 83 cases. All MSC-mutated patients had multilineage KIT mutation (100% vs 30%, P = .0001) and they more frequently showed involvement of lymphoid plus myeloid BM cells (59% vs 22%; P = .03) and a polyclonal pattern of inactivation of the X-chromosome of KIT-mutated BM mast cells (64% vs 0%; P = .01) vs other multilineage ISM cases. Moreover, presence of KIT-mutated MSCs was associated with more advanced disease features, a greater rate of disease progression (50% vs 17%; P = .04), and a shorter progression-free survival (P ≤ .003). Overall, these results support the notion that ISM patients with mutated MSCs may have acquired the KIT mutation in a common pluripotent progenitor cell, prior to differentiation into MSCs and hematopoietic precursor cells, before the X-chromosome inactivation process occurs. From a clinical point of view, acquisition of the KIT mutation in an earlier BM precursor cell confers a significantly greater risk for disease progression and a poorer outcome. © 2016 by The American Society of Hematology.
NASA Astrophysics Data System (ADS)
Usikov, Denis A.
2013-09-01
The 2007 Planetary Defense Conference recommends "to provide or enhance Internet sites to show how threats evolve and to illustrate possible action scenarios". Thereby, establishment of informational and communicational AsteroidAware web-site with the exact, authentic data about the past and the present of Earth's impact events will assist in achievement of positive results and progress in different directions on political, international, social and scientific levels. Expanded ICT's capabilities for popularization of planetary defense can help in resolving the problem of low public interest. The project's primary intent lies in popularizing the concept of planetary defenses and attracting attention to the potential dangers that threaten the Earth from outer space. The result of the efforts falling into the boundaries of this project would be an increased amount of social participation in the process of developing solutions for and increasing awareness of potential collisions between various astral bodies and the Earth. The project is also aimed at creating a foundation for the interaction between scientists and executives from around the world to facilitate international efforts of searching for fitting measures towards lowering threat levels and developing strategies revolving around united actions against potential threats.
Diagnostic Changes to DSM-5: The Potential Impact on Juvenile Justice.
Haney-Caron, Emily; Brogan, Leah; NeMoyer, Amanda; Kelley, Sharon; Heilbrun, Kirk
2016-12-01
Legal decision-makers have discretion at every stage of processing in the juvenile justice system, and individual youth characteristics (e.g., a particular psychiatric diagnosis) influence how a youth progresses through the system. As a result, changes in diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) may affect the rates of diagnoses among justice-involved youths and subsequently influence youths' experiences within the justice system. In this article, we identify the diagnoses most likely to exert such influences and review the prevalence of diagnosis and psychiatric disorder symptomatology in justice-involved youths. We highlight the DSM-5 changes in diagnostic criteria for internalizing and externalizing disorders that commonly occur among justice-involved youths and the potential impact of these changes on the rates of diagnoses within this population. Finally, we address the limitations of using psychiatric diagnoses in juvenile justice decision making, including the potential for biasing legal decision-makers and the importance of considering context as part of diagnosis. © 2016 American Academy of Psychiatry and the Law.
Ashton, Ruth A.; Bennett, Adam; Yukich, Joshua; Bhattarai, Achuyt; Keating, Joseph; Eisele, Thomas P.
2017-01-01
Abstract. Coverage of malaria control interventions is increasing dramatically across endemic countries. Evaluating the impact of malaria control programs and specific interventions on health indicators is essential to enable countries to select the most effective and appropriate combination of tools to accelerate progress or proceed toward malaria elimination. When key malaria interventions have been proven effective under controlled settings, further evaluations of the impact of the intervention using randomized approaches may not be appropriate or ethical. Alternatives to randomized controlled trials are therefore required for rigorous evaluation under conditions of routine program delivery. Routine health management information system (HMIS) data are a potentially rich source of data for impact evaluation, but have been underused in impact evaluation due to concerns over internal validity, completeness, and potential bias in estimates of program or intervention impact. A range of methodologies were identified that have been used for impact evaluations with malaria outcome indicators generated from HMIS data. Methods used to maximize internal validity of HMIS data are presented, together with recommendations on reducing bias in impact estimates. Interrupted time series and dose-response analyses are proposed as the strongest quasi-experimental impact evaluation designs for analysis of malaria outcome indicators from routine HMIS data. Interrupted time series analysis compares the outcome trend and level before and after the introduction of an intervention, set of interventions or program. The dose-response national platform approach explores associations between intervention coverage or program intensity and the outcome at a subnational (district or health facility catchment) level. PMID:28990915
DOE Office of Scientific and Technical Information (OSTI.GOV)
Young, Katherine R.; Wall, Anna M.; Dobson, Patrick F.
This paper reviews a methodology being developed for reporting geothermal resources and project progress. The goal is to provide the U.S. Department of Energy's (DOE) Geothermal Technologies Office (GTO) with a consistent and comprehensible means of evaluating the impacts of its funding programs. This framework will allow the GTO to assess the effectiveness of research, development, and deployment (RD&D) funding, prioritize funding requests, and demonstrate the value of RD&D programs to the U.S. Congress and the public. Standards and reporting codes used in other countries and energy sectors provide guidance to develop the relevant geothermal methodology, but industry feedback andmore » our analysis suggest that the existing models have drawbacks that should be addressed. In order to formulate a comprehensive metric for use by the GTO, we analyzed existing resource assessments and reporting methodologies for the geothermal, mining, and oil and gas industries, and sought input from industry, investors, academia, national labs, and other government agencies. Using this background research as a guide, we describe a methodology for evaluating and reporting on GTO funding according to resource grade (geological, technical and socio-economic) and project progress. This methodology would allow GTO to target funding, measure impact by monitoring the progression of projects, or assess geological potential of targeted areas for development.« less
NASA Astrophysics Data System (ADS)
Bouma, Brett E.
1998-09-01
The pace of technological advancement of Optical Coherence Tomography (OCT) over the last several years has been extremely rapid. The field has progressed from one-dimensional low-coherence ranging to full three-dimensional imaging with individual two-dimensional images aquired at near video rate in a span of less than eight years. Imaging applications have included polymers and advanced composites, Ophthalmology, Developmental Biology, Gastroenterology, Urology, Cardiology, Neurology, and Gynecology. These preliminary studies indicate the great potential for OCT to make a significant impact, especially in clinical medicine.
Application of remote sensing to state and regional problems. [Mississippi
NASA Technical Reports Server (NTRS)
Miller, W. F.; Carter, B. D.; Solomon, J. L.; Williams, S. G.; Powers, J. S.; Clark, J. R. (Principal Investigator)
1980-01-01
Progress is reported in the following areas: remote sensing applications to land use planning Lowndes County, applications of LANDSAT data to strip mine inventory and reclamation, white tailed deer habitat evaluation using LANDSAT data, remote sensing data analysis support system, and discrimination of unique forest habitats in potential lignite areas of Mississippi. Other projects discussed include LANDSAT change discrimination in gravel operations, environmental impact modeling for highway corridors, and discrimination of fresh water wetlands for inventory and monitoring.
Enzymatic approaches in paper industry for pulp refining and biofilm control.
Torres, C E; Negro, C; Fuente, E; Blanco, A
2012-10-01
The use of enzymes has a high potential in the pulp and paper industry to improve the economics of the paper production process and to achieve, at the same time, a reduced environmental impact. Specific enzymes contribute to reduce the amount of chemicals and energy required for the modification of fibers and helps to prevent the formation or development of biofilms. This review is aimed at presenting the latest progresses made in the application of enzymes as refining aids and biofilm control agents.
Storming the Citadel: The Fundamental Revolution Against Progressive Education.
ERIC Educational Resources Information Center
Vetterli, Richard
The first four chapters ("Progressive Education,""The Impact of Progressive Education,""The Remedies: Focusing on the Wrong Problems," and "Progressive Education Challenged") examine the deleterious effect that progressive education has had on student achievement and on society as a whole. The last five…
Lehne, Gesa; Bolte, Gabriele
2017-02-10
Physical activity is one of the most important contributors to healthy aging. Public health strategies aiming to promote physical activity among older adults are increasingly being implemented. However, little is known about their impact on social inequalities. Purpose of the study was to analyze whether and how studies of interventions consider effects on social inequalities in physical activity among older adults. Nine electronic databases were searched to identify quantitative studies evaluating the effects of interventions on self-reported or objectively measured physical activity among the general population of older adults (≥50 years). English and German language peer-reviewed journal articles published between 2005 and 2015 were included. Using the PROGRESS-Plus framework, data on whether and how social factors were considered both for describing participants' baseline characteristics and for measuring intervention effects were systematically extracted. Studies examining differential intervention effects by at least one PROGRESS-Plus factor were quality assessed. Results were presented in narrative synthesis. Fifty-nine studies were included. Beside age and sex, 44 studies used at least 1 further PROGRESS-Plus factor for the description of participants' baseline characteristics. When measuring intervention effects, 22 studies considered PROGRESS-Plus factors as control variables. Eleven studies reported having analyzed potential effects on inequalities by testing interaction effects, stratifying effect analyses, or exploring associations between PROGRESS-Plus factors and increases in physical activity following an intervention. Effects were most often analyzed by gender/sex (n = 9) and age (n = 9), followed by education (n = 3), marital status (n = 2), and race/ethnicity (n = 2). Five studies pointed to gender/sex- or age-specific intervention effects, indicating that some interventions affect males and females, and younger and older individuals differently. Many studies evaluating the effects of interventions on physical activity among older adults have not exploited the potential for assessing effects on social inequalities so far. There is an urgent need for systematic application of appropriate methodological approaches and transparent reporting of social inequalities-related findings which can provide important indications for the design of those interventions most likely to be effective across all social groups of older adults. PROSPERO registration number: CRD42015025066.
Ushigome, Emi; Oyabu, Chikako; Tanaka, Toru; Hasegawa, Goji; Ohnishi, Masayoshi; Tsunoda, Sei; Ushigome, Hidetaka; Yokota, Isao; Nakamura, Naoto; Oda, Yohei; Asano, Mai; Tanaka, Muhei; Yamazaki, Masahiro; Fukui, Michiaki
2018-05-01
The prognostic significance of masked hypertension (MH) on the progression of diabetic nephropathy among patients with type II diabetes is not well documented. We examined the relationship between clinic systolic blood pressure (SBP) and morning home SBP measurements and progression to macroalbuminuria in patients with type II diabetes. We analyzed prospective cohort study data from 712 patients with type II diabetes. We classified the patients into the following four groups according to their clinic (130 mm Hg) and home (125 mm Hg) SBP measurements: controlled blood pressure group, white-coat hypertension group, MH group, and sustained hypertension (SH) group. The patients were instructed to perform triplicate morning and evening blood pressure measurements for 14 consecutive days. During the 2-year follow-up period, 23 patients progressed to macroalbuminuria. The unadjusted odds ratio (95% confidence interval) for progression to macroalbuminuria among the patients with MH was significantly higher than that among the patients with controlled blood pressure (8.89 [1.06-74.88]). No significant relationship was observed between white-coat hypertension or SH and progression to macroalbuminuria. In analyses adjusted for various potential confounders, the adjusted odds ratio for progression to macroalbuminuria in the MH group was more than 8-fold higher than that in the controlled blood pressure group. MH might be a predictor of progression to macroalbuminuria among patients with type II diabetes. This rate of progression is comparable with or greater than the results reported for patients with SH. Copyright © 2018 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.
Impact force as a scaling parameter
NASA Technical Reports Server (NTRS)
Poe, Clarence C., Jr.; Jackson, Wade C.
1994-01-01
The Federal Aviation Administration (FAR PART 25) requires that a structure carry ultimate load with nonvisible impact damage and carry 70 percent of limit flight loads with discrete damage. The Air Force has similar criteria (MIL-STD-1530A). Both civilian and military structures are designed by a building block approach. First, critical areas of the structure are determined, and potential failure modes are identified. Then, a series of representative specimens are tested that will fail in those modes. The series begins with tests of simple coupons, progresses through larger and more complex subcomponents, and ends with a test on a full-scale component, hence the term 'building block.' In order to minimize testing, analytical models are needed to scale impact damage and residual strength from the simple coupons to the full-scale component. Using experiments and analysis, the present paper illustrates that impact damage can be better understood and scaled using impact force than just kinetic energy. The plate parameters considered are size and thickness, boundary conditions, and material, and the impact parameters are mass, shape, and velocity.
Drivers of inequality in Millennium Development Goal progress: a statistical analysis.
Stuckler, David; Basu, Sanjay; McKee, Martin
2010-03-02
Many low- and middle-income countries are not on track to reach the public health targets set out in the Millennium Development Goals (MDGs). We evaluated whether differential progress towards health MDGs was associated with economic development, public health funding (both overall and as percentage of available domestic funds), or health system infrastructure. We also examined the impact of joint epidemics of HIV/AIDS and noncommunicable diseases (NCDs), which may limit the ability of households to address child mortality and increase risks of infectious diseases. We calculated each country's distance from its MDG goals for HIV/AIDS, tuberculosis, and infant and child mortality targets for the year 2005 using the United Nations MDG database for 227 countries from 1990 to the present. We studied the association of economic development (gross domestic product [GDP] per capita in purchasing-power-parity), the relative priority placed on health (health spending as a percentage of GDP), real health spending (health system expenditures in purchasing-power-parity), HIV/AIDS burden (prevalence rates among ages 15-49 y), and NCD burden (age-standardised chronic disease mortality rates), with measures of distance from attainment of health MDGs. To avoid spurious correlations that may exist simply because countries with high disease burdens would be expected to have low MDG progress, and to adjust for potential confounding arising from differences in countries' initial disease burdens, we analysed the variations in rates of change in MDG progress versus expected rates for each country. While economic development, health priority, health spending, and health infrastructure did not explain more than one-fifth of the differences in progress to health MDGs among countries, burdens of HIV and NCDs explained more than half of between-country inequalities in child mortality progress (R(2)-infant mortality = 0.57, R(2)-under 5 mortality = 0.54). HIV/AIDS and NCD burdens were also the strongest correlates of unequal progress towards tuberculosis goals (R(2) = 0.57), with NCDs having an effect independent of HIV/AIDS, consistent with micro-level studies of the influence of tobacco and diabetes on tuberculosis risks. Even after correcting for health system variables, initial child mortality, and tuberculosis diseases, we found that lower burdens of HIV/AIDS and NCDs were associated with much greater progress towards attainment of child mortality and tuberculosis MDGs than were gains in GDP. An estimated 1% lower HIV prevalence or 10% lower mortality rate from NCDs would have a similar impact on progress towards the tuberculosis MDG as an 80% or greater rise in GDP, corresponding to at least a decade of economic growth in low-income countries. Unequal progress in health MDGs in low-income countries appears significantly related to burdens of HIV and NCDs in a population, after correcting for potentially confounding socioeconomic, disease burden, political, and health system variables. The common separation between NCDs, child mortality, and infectious syndromes among development programs may obscure interrelationships of illness affecting those living in poor households--whether economic (e.g., as money spent on tobacco is lost from child health expenditures) or biological (e.g., as diabetes or HIV enhance the risk of tuberculosis).
Cornelis, Marilyn C
2012-01-01
Coffee is one of the most widely consumed beverages in the world. Its widespread popularity and availability has fostered public health concerns of the potential health consequences of regular coffee consumption. Epidemiological studies of coffee intake and certain health outcomes have been inconsistent. The precise component of coffee potentially contributing to development of these conditions also remains unclear. One step toward addressing the challenges in studying the impact coffee has on health is a better understanding of the factors contributing to its consumption and physiological effects. This chapter focuses on those factors that are genetically determined and briefly summarizes progress in applying this knowledge to epidemiological studies of coffee and disease. Copyright © 2012 Elsevier Inc. All rights reserved.
Fuel Cell Seminar, 1992: Program and abstracts
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1992-12-31
This year`s theme, ``Fuel Cells: Realizing the Potential,`` focuses on progress being made toward commercial manufacture and use of fuel cell products. Fuel cell power plants are competing for market share in some applications and demonstrations of market entry power plants are proceeding for additional applications. Development activity on fuel cells for transportation is also increasing; fuel cell products have potential in energy and transportation industries, with very favorable environmental impacts. This Seminar has the purpose of fostering communication by providing a forum for the international community interested in development, application, and business opportunities related fuel cells. Over 190 technicalmore » papers are included, the majority being processed for the data base.« less
Responsible decision-making for plant research and breeding innovations in the European Union.
Eriksson, Dennis; Chatzopoulou, Sevasti
2018-01-02
Plant research and breeding has made substantial technical progress over the past few decades, indicating a potential for tremendous societal impact. Due to this potential, the development of policies and legislation on plant breeding and the technical progress should preferably involve all relevant stakeholders. However, we argue here that there is a substantial imbalance in the European Union (EU) regarding the influence of the various stakeholder groups on policy makers. We use evidence from three examples in order to show that the role of science is overlooked: 1) important delays in the decision process concerning the authorization of genetically modified (GM) maize events, 2) the significance attributed to non-scientific reasons in new legislation concerning the prohibition of GM events in EU member states, and 3) failure of the European Commission to deliver legal guidance to new plant breeding techniques despite sufficient scientific evidence and advisory reports. We attribute this imbalance to misinformation and misinterpretation of public perceptions and a disproportionate attention to single outlier reports, and we present ideas on how to establish a better stakeholder balance within this field.
Mowery, Paul D.; Babb, Steve; Hobart, Robin; Tworek, Cindy; MacNeil, Allison
2012-01-01
Introduction. Preemption is a legislative or judicial arrangement in which a higher level of government precludes lower levels of government from exercising authority over a topic. In the area of smoke-free policy, preemption typically takes the form of a state law that prevents communities from adopting local smoking restrictions. Background. A broad consensus exists among tobacco control practitioners that preemption adversely impacts tobacco control efforts. This paper examines the effect of state provisions preempting local smoking restrictions in enclosed public places and workplaces. Methods. Multiple data sources were used to assess the impact of state preemptive laws on the proportion of indoor workers covered by smoke-free workplace policies and public support for smoke-free policies. We controlled for potential confounding variables. Results. State preemptive laws were associated with fewer local ordinances restricting smoking, a reduced level of worker protection from secondhand smoke, and reduced support for smoke-free policies among current smokers. Discussion. State preemptive laws have several effects that could impede progress in secondhand smoke protections and broader tobacco control efforts. Conclusion. Practitioners and advocates working on other public health issues should familiarize themselves with the benefits of local policy making and the potential impact of preemption. PMID:22654921
Low-Impact Exploration for Gold in the Scottish Caledonides.
NASA Astrophysics Data System (ADS)
Rice, Samuel; Cuthbert, Simon; Hursthouse, Andrew; Broetto, Gabriele
2017-04-01
The Caledonian orogenic belt of the northern British Isles hosts some significant gold deposits. However, gold mineralization in the region is underexplored. Some of the most prospective areas identified by rich alluvial gold anomalies are environmentally and culturally sensitive. Traditional mineral exploration methods can have a range of negative environmental, social and economic impacts. The regional tourism economy is dependent on outdoor activities, landscape quality, wildlife and industrial heritage and has the potential to be disrupted by mineral resource developments. Low-cost, low-impact exploration strategies are therefore, key to sustainably developing the mineral resource potential. Research currently in progress in part of the Scottish Caledonides aims to develop protocols for more sustainable exploration. We are using a range of geoscience techniques to characterize the mineral system, improve exploration targeting and reduce negative impacts. To do this we targeted an area with a large preexisting dataset (e.g. stream sediment geochemistry, geomorphology, structural geology, petrology, geophysics, mine data) that can be synthesized and analyzed in a GIS. Part of the work aims to develop and test a model for gold dispersion in the surface environment that accounts for climatic and anthropogenic influences in order to locate bedrock sources. This multidisciplinary approach aims to reduce the target areas for subsequent exploration activities such as soil sampling, excavation and drilling.
Treatment of helminth co-infection in HIV-1 infected individuals in resource-limited settings
Walson, Judd L; John-Stewart, Grace
2012-01-01
Background The HIV-1 pandemic has disproportionately affected individuals in resource-constrained settings. These areas often also have high prevalence of other infectious diseases, such as helminth infections. It is important to determine if helminth infection affects the progression of HIV-1 in these co-infected individuals. There are biologically plausible reasons for possible effects of helminth infection in HIV-1 infected individuals and findings from some observational studies suggest that helminth infection may adversely affect HIV-1 progression. We sought to evaluate the available evidence from published and unpublished studies to determine if treatment of helminth infection in HIV-1 co-infected individuals impacts HIV-1 progression. Objectives Our objective was to determine if treating helminth infection in individuals with HIV-1 can reduce the progression of HIV-1 as determined by changes in CD4 count, viral load, or clinical disease progression (including mortality). Search strategy We searched online for published and unpublished studies in The Cochrane Library (Issue 3, 2006), MEDLINE (November 2006), EMBASE (November 2006), CENTRAL (July 2006), AIDSEARCH (August 2006). We also searched databases listing conference abstracts, scanned reference lists of articles, and contacted authors of included studies. Selection criteria We searched for randomized and quasi-randomized controlled trials that compared HIV-1 progression as measured by changes in CD4 count, viral load, or clinical disease progression in HIV-1 infected individuals receiving anti-helminth therapy. Observational studies with relevant data were also included. Data collection and analysis Data regarding changes in CD4 count, HIV-1 RNA levels, clinical staging and/or mortality after treatment of helminth co-infection were extracted from the reports of the studies. Main results Of 6,384 abstracts identified, 15 met criteria for potential inclusion, of which five were eligible for inclusion. In the single randomized controlled trial (RCT) identified, HIV-1 and schistosomiasis co-infected individuals receiving treatment for schistosomiasis had a significantly lower change in plasma HIV-1 RNA over three months (−0.001 log10 copies/mL) compared to those receiving no treatment (+0.21 log10 copies/mL), (p=0.03). Four observational studies met inclusion criteria and all of these suggested a possible beneficial effect of helminth eradication on plasma HIV-1 RNA levels when compared to plasma HIV-1 RNA changes prior to helminth treatment or to helminth-uninfected or persistently helminth-infected individuals. Follow-up duration in these studies ranged from three to six months. The reported magnitude of effect on HIV-1 RNA was variable, ranging from 0.07–1.05 log10 copies/mL. None of the included studies showed a significant benefit of helminth treatment on CD4 decline, clinical staging, or mortality. Authors' conclusions There are insufficient data available to determine the potential benefit of helminth eradication in HIV-1 and helminth co-infected adults. Data from a single RCT and multiple observational studies suggest possible benefit in reducing plasma viral load. The impact of de-worming on markers of HIV-1 progression should be addressed in larger randomized studies evaluating species-specific effects and with a sufficient duration of follow-up to document potential differences on clinical outcomes and CD4 decline. PMID:18254104
Low-gravity impact experiments: Progress toward a facility definition
NASA Technical Reports Server (NTRS)
Cintala, M. J.
1986-01-01
Innumerable efforts were made to understand the cratering process and its ramifications in terms of planetary observations, during which the role of gravity has often come into question. Well known facilities and experiments both were devoted in many cases to unraveling the contribution of gravitational acceleration to cratering mechanisms. Included among these are the explosion experiments in low gravity aircraft, the drop platform experiments, and the high gravity centrifuge experiments. Considerable insight into the effects of gravity was gained. Most investigations were confined to terrestrial laboratories. It is in this light that the Space Station is being examined as a vehicle with the potential to support otherwise impractical impact experiments. The results of studies performed by members of the planetary cratering community are summarized.
Solar thermal plant impact analysis and requirements definition
NASA Technical Reports Server (NTRS)
Gupta, Y. P.
1980-01-01
Progress on a continuing study comprising of ten tasks directed at defining impact and requirements for solar thermal power systems (SPS), 1 to 10 MWe each in capacity, installed during 1985 through year 2000 in a utility or a nonutility load in the United States is summarized. The point focus distributed receiver (PFDR) solar power systems are emphasized. Tasks 1 through 4, completed to date, include the development of a comprehensive data base on SPS configurations, their performance, cost, availability, and potential applications; user loads, regional characteristics, and an analytic methodology that incorporates the generally accepted utility financial planning methods and several unique modifications to treat the significant and specific characteristics of solar power systems deployed in either central or distributed power generation modes, are discussed.
Goodwin, Justin; Choi, Hyunsung; Hsieh, Meng-Hsiung; Neugent, Michael L; Ahn, Jung-Mo; Hayenga, Heather N; Singh, Pankaj K; Shackelford, David B; Lee, In-Kyu; Shulaev, Vladimir; Dhar, Shanta; Takeda, Norihiko; Kim, Jung-Whan
2018-02-01
Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are the primary pathological driver of fibrotic progression, yet how various microenvironmental influences, such as hypoxia, contribute to their sustained activation and differentiation is poorly understood. As a defining feature of hypoxia is its impact on cellular metabolism, we sought to investigate how hypoxia-induced metabolic reprogramming affects myofibroblast differentiation and fibrotic progression, and to test the preclinical efficacy of targeting glycolytic metabolism for the treatment of pulmonary fibrosis. Bleomycin-induced pulmonary fibrotic progression was evaluated in two independent, fibroblast-specific, promoter-driven, hypoxia-inducible factor (Hif) 1A knockout mouse models and in glycolytic inhibitor, dichloroacetate-treated mice. Genetic and pharmacological approaches were used to explicate the role of metabolic reprogramming in myofibroblast differentiation. Hypoxia significantly enhanced transforming growth factor-β-induced myofibroblast differentiation through HIF-1α, whereas overexpression of the critical HIF-1α-mediated glycolytic switch, pyruvate dehydrogenase kinase 1 (PDK1) was sufficient to activate glycolysis and potentiate myofibroblast differentiation, even in the absence of HIF-1α. Inhibition of the HIF-1α/PDK1 axis by genomic deletion of Hif1A or pharmacological inhibition of PDK1 significantly attenuated bleomycin-induced pulmonary fibrosis. Our findings suggest that HIF-1α/PDK1-mediated glycolytic reprogramming is a critical metabolic alteration that acts to promote myofibroblast differentiation and fibrotic progression, and demonstrate that targeting glycolytic metabolism may prove to be a potential therapeutic strategy for the treatment of pulmonary fibrosis.
Soofi, Ammarah Y; Bello-Haas, Vanina Dal; Kho, Michelle E; Letts, Lori
2018-04-01
The nature of amyotrophic lateral sclerosis (ALS) is progressive and degenerative, thus influencing individuals physically, emotionally, and socially. A broad review of qualitative studies that describe the personal experiences of people with ALS with physiotherapy, occupational therapy and speech and language pathology interventions, and how those affect QoL is warranted. This study synthesizes qualitative research regarding the potential that rehabilitation interventions have to maintain and/or improve QoL from the perspective of people with ALS. The SPIDER search strategy was applied and five articles met inclusion criteria addressing the perceived impact of rehabilitation on QoL for individuals with ALS. Four themes emerged: the concept of control; adapting interventions to disease stage; struggles with interventions; and barriers between healthcare providers and patients. Rehabilitation interventions were perceived to have potential to support QoL by people with ALS. Advantages and limitations of rehabilitation services within this population were identified.
Ebi, Kristie L.; Mills, David M.; Smith, Joel B.; Grambsch, Anne
2006-01-01
The health sector component of the first U.S. National Assessment, published in 2000, synthesized the anticipated health impacts of climate variability and change for five categories of health outcomes: impacts attributable to temperature, extreme weather events (e.g., storms and floods), air pollution, water- and food-borne diseases, and vector- and rodent-borne diseases. The Health Sector Assessment (HSA) concluded that climate variability and change are likely to increase morbidity and mortality risks for several climate-sensitive health outcomes, with the net impact uncertain. The objective of this study was to update the first HSA based on recent publications that address the potential impacts of climate variability and change in the United States for the five health outcome categories. The literature published since the first HSA supports the initial conclusions, with new data refining quantitative exposure–response relationships for several health end points, particularly for extreme heat events and air pollution. The United States continues to have a very high capacity to plan for and respond to climate change, although relatively little progress has been noted in the literature on implementing adaptive strategies and measures. Large knowledge gaps remain, resulting in a substantial need for additional research to improve our understanding of how weather and climate, both directly and indirectly, can influence human health. Filling these knowledge gaps will help better define the potential health impacts of climate change and identify specific public health adaptations to increase resilience. PMID:16966082
Taylor-Robinson, Andrew W; Walton, Simon; Swain, David L; Walsh, Kerry B; Vajta, Gábor
2014-08-01
Recent advances in embryology and related research offer considerable possibilities to accelerate genetic improvement in cattle breeding. Such progress includes optimization and standardization of laboratory embryo production (in vitro fertilization - IVF), introduction of a highly efficient method for cryopreservation (vitrification), and dramatic improvement in the efficiency of somatic cell nuclear transfer (cloning) in terms of required effort, cost, and overall outcome. Handmade cloning (HMC), a simplified version of somatic cell nuclear transfer, offers the potential for relatively easy and low-cost production of clones. A potentially modified method of vitrification used at a centrally located laboratory facility could result in cloned offspring that are economically competitive with elite animals produced by more traditional means. Apart from routine legal and intellectual property issues, the main obstacle that hampers rapid uptake of these technologies by the beef cattle industry is a lack of confidence from scientific and commercial sources. Once stakeholder support is increased, the combined application of these methods makes a rapid advance toward desirable traits (rapid growth, high-quality beef, optimized reproductive performance) a realistic goal. The potential impact of these technologies on genetic advancement in beef cattle herds in which improvement of stock is sought, such as in northern Australia, is hard to overestimate. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Reinert, T.R.; Peterson, J.T.
2008-01-01
Increased salinity in spawning and nursery grounds in the Savannah River estuary was cited as the primary cause of a 97% decrease in adult striped bass (Morone saxatilis) and a concomitant 96% decrease in striped bass egg production. Restoration efforts focused on environmental remediation and stock enhancement have resulted in restored salinity patterns and increased egg and adult abundances. However, future water needs or harbor development may preclude further recovery by reducing freshwater inflow or increasing salinity intrusion. To assess the effect of potential changes in the salinity regime, we developed models relating discharge, tidal phase, and salinity to striped bass egg and early larval survival and re-cast these in a quantitative Bayesian belief network. The model indicated that a small upstream shift (???1.67 km) in the salinity regime would have the least impact on striped bass early life history survival, whereas shifts >1.67 km would have progressively larger impacts, with a 8.33-km shift potentially reducing our estimated survival probability by >28%. Such an impact could have cumulative and long-term detrimental effects on the recovery of the Savannah River striped bass population. The available salinity data were collected during average and low flows, so our model represents some typical and some extreme conditions during a striped bass spawning season. Our model is a relatively simplistic, "first-order" attempt at evaluating potential effects of changes in the Savannah River estuarine salinity regime and points to areas of concern and potential future research. ?? 2008 Springer Science+Business Media, LLC.
Waste Isolation Safety Assessment Program. Technical progress report for FY-1978
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brandstetter, A.; Harwell, M.A.; Howes, B.W.
1979-07-01
Associated with commercial nuclear power production in the United States is the generation of potentially hazardous radioactive wastes. The Department of Energy (DOE) is seeking to develop nuclear waste isolation systems in geologic formations that will preclude contact with the biosphere of waste radionuclides in concentrations which are sufficient to cause deleterious impact on humans or their environments. Comprehensive analyses of specific isolation systems are needed to assess the expectations of meeting that objective. The Waste Isolation Safety Assessment Program (WISAP) has been established at the Pacific Northwest Laboratory (operated by Battelle Memorial Institute) for developing the capability of makingmore » those analyses. Progress on the following tasks is reported: release scenario analysis, waste form release rate analysis, release consequence analysis, sorption-desorption analysis, and societal acceptance analysis. (DC)« less
Eng, Jason W-L; Kokolus, Kathleen M; Reed, Chelsey B; Hylander, Bonnie L; Ma, Wen W; Repasky, Elizabeth A
2014-11-01
Long conserved mechanisms maintain homeostasis in living creatures in response to a variety of stresses. However, continuous exposure to stress can result in unabated production of stress hormones, especially catecholamines, which can have detrimental health effects. While the long-term effects of chronic stress have well-known physiological consequences, recent discoveries have revealed that stress may affect therapeutic efficacy in cancer. Growing epidemiological evidence reveals strong correlations between progression-free and long-term survival and β-blocker usage in cancer patients. In this review, we summarize the current understanding of how the catecholamines, epinephrine and norepinephrine, affect cancer cell survival and tumor progression. We also highlight new data exploring the potential contributions of stress to immunosuppression in the tumor microenvironment and the implications of these findings for the efficacy of immunotherapies.
Erickson, Larry E; Jennings, Merrisa
2017-01-01
The Paris Agreement on Climate Change has the potential to improve air quality and human health by encouraging the electrification of transportation and a transition from coal to sustainable energy. There will be human health benefits from reducing combustion emissions in all parts of the world. Solar powered charging infrastructure for electric vehicles adds renewable energy to generate electricity, shaded parking, and a needed charging infrastructure for electric vehicles that will reduce range anxiety. The costs of wind power, solar panels, and batteries are falling because of technological progress, magnitude of commercial activity, production experience, and competition associated with new trillion dollar markets. These energy and transportation transitions can have a very positive impact on health. The energy, transportation, air quality, climate change, health nexus may benefit from additional progress in developing solar powered charging infrastructure.
Emerging concepts on the role of innate immunity in the prevention and control of HIV infection.
Ackerman, Margaret E; Dugast, Anne-Sophie; Alter, Galit
2012-01-01
While neutralizing antibodies can provide sterilizing protection from HIV infection via their variable domains, the antibody constant domain provides a functional link between innate and adaptive immunity and offers a means to harness the potent antiviral properties of a wide spectrum of innate immune effector cells. There has been a growing appreciation of the role of these effector mechanisms across fields from cancer immunotherapy to autoimmunity and infectious disease, as well as speculation that this mechanism may be responsible for the protection observed in the RV144 HIV vaccine trial. This review summarizes these extraneutralizing humoral immune activities, progress in defining the importance of these effector mechanisms during progression in HIV infection, and the potential impact that such vaccine-induced immune responses may have on protection from infection.
Prevention of Age-Related Macular Degeneration.
Singh, Niharika; Srinivasan, Sangeetha; Muralidharan, Vinata; Roy, Rupak; V, Jayprakash; Raman, Rajiv
2017-01-01
Age-related macular degeneration (AMD) compromises quality of life. However, the available therapeutic options are limited. This has led to the identification of modifiable risk factors to prevent the development or alter the natural course and prognosis of AMD. The identification and modification of risk factors has the potential for greater public health impact on reducing morbidity from AMD. Likewise, identifying the imaging clues and genetic clues could serve as a guide to recognizing the propensity for progression to severe and end stages of the disease. Several attempts, both successful and unsuccessful, have been made for interventions that could delay the progression of AMD. Of these, pharmacological interventions have shown promising results. The Age-Related Eye Disease Study 1 and 2 have shown the beneficial role of antioxidants in a selected group of patients. Copyright 2017 Asia-Pacific Academy of Ophthalmology.
Assessment of the Effects of High-Speed Aircraft in the Stratosphere: 1998
NASA Technical Reports Server (NTRS)
Kawa, S. Randolph; Anderson, James G.; Baughcum, Steven L.; Brock, Charles A.; Brune, William H.; Cohen, Ronald C.; Kinnison, Douglas E.; Newman, Paul A.; Rodriquez, Jose M.; Stolarski, Richard S.;
1999-01-01
This report assesses the potential atmospheric impacts of a proposed fleet of high-speed civil transport (HSCT) aircraft. The purpose of the report is to assess the effects of HSCT's on atmospheric composition and climate in order to provide a scientific basis for making technical, commercial, and environmental policy decisions regarding the HSCT fleet. The work summarized here was carried out as part of NASA's Atmospheric Effects of Aviation Project (a component of the High-Speed Research Program) as well as other NASA, U.S., and international research programs. The principal focus is on change in stratospheric ozone concentrations. The impact on climate change is also a concern. The report describes progress in understanding atmospheric processes, the current state of understanding of HSCT emissions, numerical model predictions of HSCT impacts, the principal uncertainties in atmospheric predictions, and the associated sensitivities in predicted effects of HSCT's.
Assessment of the Effects of High-Speed Aircraft in the Stratosphere: 1998
NASA Technical Reports Server (NTRS)
Kawa, S. Randolph; Anderson, James G.; Baughcum, Steven L.; Brock, Charles A.; Brune, William H.; Cohen, Ronald C.; Kinnison, Douglas E.; Newman, Paul A.; Rodriguez, Jose M.; Stolarski, Richard S.;
1999-01-01
This report assesses the potential atmospheric impacts of a proposed fleet of high-speed civil transport (HSCT) aircraft. The purpose of the report is to assess the effects of HSCT's on atmospheric composition and climate in order to provide a scientific basis for making technical, commercial, and environmental policy decisions regarding the HSCT fleet. The work summarized here was carried out as part of NASA's Atmospheric Effects of Aviation Project (a component of the High-Speed Research Program) as well as other NASA, U.S., and international research programs. The principal focus is on change in stratospheric ozone concentrations. The impact on climate change is also a concern. The report describes progress in understanding atmospheric processes, the current state of understanding of HSCT emissions, numerical model predictions of HSCT impacts, the principal uncertainties in atmospheric predictions, and the associated sensitivities in predicted effects of HSCT'S.
Measuring hope among families impacted by cognitive impairment.
Hunsaker, Amanda E; Terhorst, Lauren; Gentry, Amanda; Lingler, Jennifer H
2016-07-01
The current exploratory investigation aims to establish the reliability and validity of a hope measure, the Herth Hope Index, among families impacted by early cognitive impairment (N = 96). Exploratory factor analysis was used to examine the dimensionality of the measure. Bivariate analyses were used to examine construct validity. The sample had moderately high hope scores. A two-factor structure emerged from the factor analysis, explaining 51.44% of the variance. Both factors exhibited strong internal consistency (Cronbach's alphas ranged from .83 to .86). Satisfaction with social support was positively associated with hope, supporting convergent validity. Neurocognitive status, illness insight, and depression were not associated with hope, indicating discriminant validity. Families impacted by cognitive impairment may maintain hope in the face of a potentially progressive illness, regardless of cognitive status. The Herth Hope Index can be utilized as a reliable and valid measure of hope by practitioners providing support to families impacted by cognitive impairment. © The Author(s) 2014.
NASA Astrophysics Data System (ADS)
Arsal, Zeki
2017-07-01
In the study, the impact of inquiry-based learning on pre-service teachers' critical thinking dispositions was investigated. The sample of the study comprised of 56 pre-service teachers in the science education teacher education programme at the public university in the north of Turkey. In the study, quasi-experimental design with an experimental and a control group were applied to find out the impact of inquiry-based learning on the critical thinking dispositions of the pre-service teachers in the teacher education programme. The results showed that the pre-service teachers in the experimental group did not show statistically significant greater progress in terms of critical thinking dispositions than those in the control group. Teacher educators who are responsible for pedagogical courses in the teacher education programme should consider that the inquiry-based learning could not be effective method to improve pre-service teachers' critical thinking dispositions. The results are discussed in relation to potential impact on science teacher education and implications for future research.
Calderon, Moises A; Demoly, Pascal; Gerth van Wijk, Roy; Bousquet, Jean; Sheikh, Aziz; Frew, Anthony; Scadding, Glenis; Bachert, Claus; Malling, Hans J; Valenta, Rudolph; Bilo, Beatrice; Nieto, Antonio; Akdis, Cezmi; Just, Jocelyne; Vidal, Carmen; Varga, Eva M; Alvarez-Cuesta, Emilio; Bohle, Barbara; Bufe, Albrecht; Canonica, Walter G; Cardona, Victoria; Dahl, Ronald; Didier, Alain; Durham, Stephen R; Eng, Peter; Fernandez-Rivas, Montserrat; Jacobsen, Lars; Jutel, Marek; Kleine-Tebbe, Jörg; Klimek, Ludger; Lötvall, Jan; Moreno, Carmen; Mosges, Ralph; Muraro, Antonella; Niggemann, Bodo; Pajno, Giovanni; Passalacqua, Giovanni; Pfaar, Oliver; Rak, Sabina; Senna, Gianenrico; Senti, Gabriela; Valovirta, Erkka; van Hage, Marianne; Virchow, Johannes C; Wahn, Ulrich; Papadopoulos, Nikolaos
2012-10-30
Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy.Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies.Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals' quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases.Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits.We call upon Europe's policy-makers to coordinate actions and improve individual and public health in allergy by:Promoting awareness of the effectiveness of allergen specific immunotherapyUpdating national healthcare policies to support allergen specific immunotherapyPrioritising funding for allergen specific immunotherapy researchMonitoring the macroeconomic and health economic parameters of allergyReinforcing allergy teaching in medical disciplines and specialtiesThe effective implementation of the above policies has the potential for a major positive impact on European health and well-being in the next decade.
Bourke, Liam; Bauld, Linda; Bullen, Christopher; Cumberbatch, Marcus; Giovannucci, Edward; Islami, Farhad; McRobbie, Hayden; Silverman, Debra T; Catto, James W F
2017-06-01
Use of electronic cigarettes (ECs) is on the rise in most high-income countries. Smoking conventional cigarettes is a known risk factor for urologic malignancy incidence, progression, and mortality, as well as for other urologic health indicators. The potential impact of EC use on urologic health is therefore of clinical interest to the urology community. To review the available data on current EC use, including potential benefits in urologic patients, potential issues linked to toxicology of EC constituents, and how this might translate into urologic health risks. A Medline search was carried out in August 2016 for studies reporting urologic health outcomes and EC use. Snowballing techniques were also used to identify relevant studies from recent systematic reviews. A narrative synthesis of data around EC health outcomes, toxicology, and potential use in smoking cessation and health policy was carried out. We found no studies to date that have been specifically designed to prospectively assess urologic health risks, even in an observational setting. Generating such data would be an important contribution to the debate on the role of ECs in public health and clinical practice. There is evidence from a recent Cochrane review of RCTs that ECs can support smoking cessation. There are emerging data indicating that potentially harmful components of ECs such as tobacco-specific nitrosamines, polyaromatic hydrocarbons, and heavy metals could be linked to possible urologic health risks. ECs might be a useful tool to encourage cessation of conventional cigarette smoking. However, data collection around the specific impact of ECs on urologic health is needed to clarify the possible patient benefits, outcomes, and adverse events. While electronic cigarettes might help some people to stop smoking, their overall impact on urologic health is not clear. Copyright © 2017 European Association of Urology. All rights reserved.
Adland, Emily; Paioni, Paolo; Thobakgale, Christina; Laker, Leana; Mori, Luisa; Muenchhoff, Maximilian; Csala, Anna; Clapson, Margaret; Flynn, Jacquie; Novelli, Vas; Hurst, Jacob; Naidoo, Vanessa; Shapiro, Roger; Huang, Kuan-Hsiang Gary; Frater, John; Prendergast, Andrew; Prado, Julia G.; Ndung’u, Thumbi; Walker, Bruce D.; Carrington, Mary; Jooste, Pieter; Goulder, Philip J. R.
2015-01-01
HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-naïve, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0.004). The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0.0001), but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0.007). Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0.0002). In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression. PMID:26076345
Kc, Ranjan; Li, Xin; Forsyth, Christopher B; Voigt, Robin M; Summa, Keith C; Vitaterna, Martha Hotz; Tryniszewska, Beata; Keshavarzian, Ali; Turek, Fred W; Meng, Qing-Jun; Im, Hee-Jeong
2015-11-20
A variety of environmental factors contribute to progressive development of osteoarthritis (OA). Environmental factors that upset circadian rhythms have been linked to various diseases. Our recent work establishes chronic environmental circadian disruption - analogous to rotating shiftwork-associated disruption of circadian rhythms in humans - as a novel risk factor for the development of OA. Evidence suggests shift workers are prone to obesity and also show altered eating habits (i.e., increased preference for high-fat containing food). In the present study, we investigated the impact of chronic circadian rhythm disruption in combination with a high-fat diet (HFD) on progression of OA in a mouse model. Our study demonstrates that when mice with chronically circadian rhythms were fed a HFD, there was a significant proteoglycan (PG) loss and fibrillation in knee joint as well as increased activation of the expression of the catabolic mediators involved in cartilage homeostasis. Our results, for the first time, provide the evidence that environmental disruption of circadian rhythms plus HFD potentiate OA-like pathological changes in the mouse joints. Thus, our findings may open new perspectives on the interactions of chronic circadian rhythms disruption with diet in the development of OA and may have potential clinical implications.
Pharmacological intervention for dengue virus infection.
Lai, Jenn-Haung; Lin, Yi-Ling; Hsieh, Shie-Liang
2017-04-01
Dengue virus (DENV) infection has a considerable health impact in tropical and subtropical countries worldwide. Escalation of infection rates greatly increases morbidity and mortality, most commonly from deaths due to dengue hemorrhagic fever and dengue shock syndrome. Although the development of an effective, long-lasting vaccine has been a major aim for control and prevention of DENV infection, the currently licensed vaccine has limitations and is less than satisfactory. Thus, there remains an important need to identify effective and tolerable medications for treatment of DENV-infected patients both in the early phase, to prevent progression to fatal outcomes, and to minimize deaths after patients develop severe complications. This review will address several specific points, including (1) approaches to identify anti-DENV medications, (2) recent advances in the development of potential compounds targeting DENV infection, (3) experience with clinical trials of regimens for DENV infection, (4) some available medications of potential for clinical trials against DENV infection, (5) reasons for unsuccessful outcomes and challenges of anti-DENV treatments, and (6) directions for developing or selecting better anti-DENV strategies. This review provides useful guidance for clinicians selecting drugs for DENV-infected patients with severe manifestations or potential fatal disease progression, and for basic researchers seeking to develop effective anti-DENV regimens. Copyright © 2017 Elsevier Inc. All rights reserved.
Yielder, Jill; Wearn, Andy; Chen, Yan; Henning, Marcus A; Weller, Jennifer; Lillis, Steven; Mogol, Vernon; Bagg, Warwick
2017-08-29
Progress testing was introduced to the MBChB programme at the University of Auckland in 2013. As there has been a focus in published literature on aspects relating to the format or function of progress tests, the purpose of this study was to explore a qualitative student perspective on the introduction of progress testing and its impact on approaches to learning and perceived stress. This article presents the qualitative aspects of a longitudinal evaluation study. The qualitative data were derived from eight focus groups of Year 2-5 medical students in the University of Auckland medical programme. Two themes, 'Impact on Learning' and 'Emotional Wellbeing' and their subthemes offered insight into student perceptions and behaviour. Students described a variety of learning responses to progress testing that clustered around the employment of a range of learning strategies based on their experience of sitting progress tests and their individualised feedback. A range of emotional responses were also expressed, with some finding progress tests stressful, while others enjoyed not needing to intensively cram before the tests. Progress tests appear to influence the approach of students to their learning. They employ a mix of learning strategies, shaped by their performance, individualised feedback and the learning environment. While students expressed some stress and anxiety with respect to sitting progress tests, this form of testing was viewed by these students as no worse, and sometimes better than traditional assessments.
Trentham-Dietz, Amy; Ergun, Mehmet Ali; Alagoz, Oguzhan; Stout, Natasha K; Gangnon, Ronald E; Hampton, John M; Dittus, Kim; James, Ted A; Vacek, Pamela M; Herschorn, Sally D; Burnside, Elizabeth S; Tosteson, Anna N A; Weaver, Donald L; Sprague, Brian L
2018-02-01
Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.
Price, Melanie A; Butow, Phyllis N; Bell, Melanie L; deFazio, Anna; Friedlander, Michael; Fardell, Joanna E; Protani, Melinda M; Webb, Penelope M
2016-06-01
Women with advanced ovarian cancer generally have a poor prognosis but there is significant variability in survival despite similar disease characteristics and treatment regimens. The aim of this study was to determine whether psychosocial factors predict survival in women with ovarian cancer, controlling for potential confounders. The sample comprised 798 women with invasive ovarian cancer recruited into the Australian Ovarian Cancer Study and a subsequent quality of life study. Validated measures of depression, optimism, minimization, helplessness/hopelessness, and social support were completed 3-6 monthly for up to 2 years. Four hundred nineteen women (52.5 %) died over the follow-up period. Associations between time-varying psychosocial variables and survival were tested using adjusted Cox proportional hazard models. There was a significant interaction of psychosocial variables measured prior to first progression and overall survival, with higher optimism (adjusted hazard ratio per 1 standard deviation (HR) = 0.80, 95 % confidence interval (CI) 0.65-0.97), higher minimization (HR = 0.79, CI 0.66-0.94), and lower helplessness/hopelessness (HR = 1.40, CI 1.15-1.71) associated with longer survival. After disease progression, these variables were not associated with survival (optimism HR = 1.10, CI 0.95-1.27; minimization HR = 1.12, CI 0.95-1.31; and helplessness/hopelessness HR = 0.86, CI 0.74-1.00). Depression and social support were not associated with survival. In women with invasive ovarian cancer, psychosocial variables prior to disease progression appear to impact on overall survival, suggesting a preventive rather than modifying role. Addressing psychosocial responses to cancer and their potential impact on treatment decision-making early in the disease trajectory may benefit survival and quality of life.
Clifford, Katie L; Zaman, Muhammad H
2016-01-01
The recent drafting of the Sustainable Development Goals challenges the research community to rethink the traditional approach to global health and provides the opportunity for science, technology, engineering, and mathematical (STEM) disciplines, particularly engineering, to demonstrate their benefit to the field. Higher education offers a platform for engineering to intersect with global health research through interdisciplinary partnerships among international universities that provide excellence in education, attract nontraditional STEM students, and foster a sense of innovation. However, a traditional lack of engineering-global health collaborations, as well as limited faculty and inadequate STEM research funding in low-income countries, has stifled progress. Still, the impact of higher education on development efforts holds great potential. This value will be realized in low-income countries through strengthening local capacity, supporting innovation through educational initiatives, and encouraging the inclusion of women and minorities in STEM programs. Current international university-level partnerships are working towards integrating engineering into global health research and strengthening STEM innovation among universities in low-income countries, but more can be done. Global health research informs sustainable development, and through integrating engineering into research efforts through university partnerships, we can accelerate progress and work towards a healthier future for all.
Vidal-Lletjós, Sandra; Beaumont, Martin; Tomé, Daniel; Benamouzig, Robert; Blachier, François; Lan, Annaïg
2017-01-01
Inflammatory bowel diseases (IBD), after disease onset, typically progress in two cyclically repeated phases, namely inflammatory flare and remission, with possible nutritional status impairment. Some evidence, either from epidemiological, clinical, and experimental studies indicate that the quantity and the quality of dietary protein consumption and amino acid supplementation may differently influence the IBD course according to the disease phases. For instance, although the dietary protein needs for mucosal healing after an inflammatory episode remain undetermined, there is evidence that amino acids derived from dietary proteins display beneficial effects on this process, serving as building blocks for macromolecule synthesis in the wounded mucosal area, energy substrates, and/or precursors of bioactive metabolites. However, an excessive amount of dietary proteins may result in an increased intestinal production of potentially deleterious bacterial metabolites. This could possibly affect epithelial repair as several of these bacterial metabolites are known to inhibit colonic epithelial cell respiration, cell proliferation, and/or to affect barrier function. In this review, we present the available evidence about the impact of the amount of dietary proteins and supplementary amino acids on IBD onset and progression, with a focus on the effects reported in the colon. PMID:28335546
Night myopia is reduced in binocular vision.
Chirre, Emmanuel; Prieto, Pedro M; Schwarz, Christina; Artal, Pablo
2016-06-01
Night myopia, which is a shift in refraction with light level, has been widely studied but still lacks a complete understanding. We used a new infrared open-view binocular Hartmann-Shack wave front sensor to quantify night myopia under monocular and natural binocular viewing conditions. Both eyes' accommodative response, aberrations, pupil diameter, and convergence were simultaneously measured at light levels ranging from photopic to scotopic conditions to total darkness. For monocular vision, reducing the stimulus luminance resulted in a progression of the accommodative state that tends toward the subject's dark focus or tonic accommodation and a change in convergence following the induced accommodative error. Most subjects presented a myopic shift of accommodation that was mitigated in binocular vision. The impact of spherical aberration on the focus shift was relatively small. Our results in monocular conditions support the hypothesis that night myopia has an accommodative origin as the eye progressively changes its accommodation state with decreasing luminance toward its resting state in total darkness. On the other hand, binocularity restrains night myopia, possibly by using fusional convergence as an additional accommodative cue, thus reducing the potential impact of night myopia on vision at low light levels.
Giandolini, Marlène; Horvais, Nicolas; Farges, Yohann; Samozino, Pierre; Morin, Jean-Benoît
2013-08-01
Impact reduction has become a factor of interest in the prevention of running-related injuries such as stress fractures. Currently, the midfoot strike pattern (MFS) is thought as a potential way to decrease impact. The purpose was to test the effects of two long-term interventions aiming to reduce impact during running via a transition to an MFS: a foot strike retraining versus a low-drop/low-heel height footwear. Thirty rearfoot strikers were randomly assigned to two experimental groups (SHOES and TRAIN). SHOES progressively wore low-drop/low-heel height shoes and TRAIN progressively adopted an MFS, over a 3-month period with three 30-min running sessions per week. Measurement sessions (pre-training, 1, 2 and 3 months) were performed during which subjects were equipped with three accelerometers on the shin, heel and metatarsals, and ran for 15 min on an instrumented treadmill. Synchronized acceleration and vertical ground reaction force signals were recorded. Peak heel acceleration was significantly lower as compared to pre-training for SHOES (-33.5 ± 12.8 % at 2 months and -25.3 ± 18.8 % at 3 months, p < 0.001), and so was shock propagation velocity (-12.1 ± 9.3 %, p < 0.001 at 2 months and -11.3 ± 4.6 %, p < 0.05 at 3 months). No change was observed for TRAIN. Important inter-individual variations were noted in both groups and reported pains were mainly located at the shin and calf. Although it induced reversible pains, low-drop/low-heel height footwear seemed to be more effective than foot strike retraining to attenuate heel impact in the long term.
Impact Damage and Strain Rate Effects for Toughened Epoxy Composite Structures
NASA Technical Reports Server (NTRS)
Chamis, Christos C.; Minnetyan, Levon
2006-01-01
Structural integrity of composite systems under dynamic impact loading is investigated herein. The GENOA virtual testing software environment is used to implement the effects of dynamic loading on fracture progression and damage tolerance. Combinations of graphite and glass fibers with a toughened epoxy matrix are investigated. The effect of a ceramic coating for the absorption of impact energy is also included. Impact and post impact simulations include verification and prediction of (1) Load and Impact Energy, (2) Impact Damage Size, (3) Maximum Impact Peak Load, (4) Residual Strength, (5) Maximum Displacement, (6) Contribution of Failure Modes to Failure Mechanisms, (7) Prediction of Impact Load Versus Time, and (8) Damage, and Fracture Pattern. A computer model is utilized for the assessment of structural response, progressive fracture, and defect/damage tolerance characteristics. Results show the damage progression sequence and the changes in the structural response characteristics due to dynamic impact. The fundamental premise of computational simulation is that the complete evaluation of composite fracture requires an assessment of ply and subply level damage/fracture processes as the structure is subjected to loads. Simulation results for the graphite/epoxy composite were compared with the impact and tension failure test data, correlation and verification was obtained that included: (1) impact energy, (2) damage size, (3) maximum impact peak load, (4) residual strength, (5) maximum displacement, and (6) failure mechanisms of the composite structure.
Ductal carcinoma in situ of the breast: can biomarkers improve current management?
Bartlett, John M S; Nofech-Moses, Sharon; Rakovitch, Eileen
2014-01-01
Screening for invasive cancer has led to a marked increase in the detection of ductal carcinoma in situ (DCIS). DCIS is, if appropriately managed, a low-risk disease which has a small chance of impacting on patient life expectancy. However, despite significant advances in prognostic marker development in invasive breast cancer, there are no validated diagnostic assays to inform treatment choice for women with DCIS. Therefore we are unable to target effective treatment strategies to women at high risk and avoid over-treatment of women at low risk of progression to invasive breast cancer. Paradoxically, one effect of this uncertainty is undertreatment of some women. We review current practice and research in the field to identify key challenges in the management of DCIS. The impact of clinical research, particularly on the over and undertreatment of women with DCIS is assessed. We note slow progress toward development of diagnostic biomarkers and highlight key opportunities to accelerate advances in this area. DCIS is a low-risk disease, its incidence is increasing, and current treatment is effective. However, many women are either over- or undertreated. Despite repeated calls for development of diagnostic biomarkers, progress in this area has been slow, reflecting a relative lack of investment of research effort and funding. Given the low event rate in treated patients and the lateness of recurrences, many previous studies have only limited power to identify independent prognostic and predictive biomarkers. However, the potential for such biomarkers to personalize treatment for DCIS is extremely high.
Shuttle Risk Progression by Flight
NASA Technical Reports Server (NTRS)
Hamlin, Teri; Kahn, Joe; Thigpen, Eric; Zhu, Tony; Lo, Yohon
2011-01-01
Understanding the early mission risk and progression of risk as a vehicle gains insights through flight is important: . a) To the Shuttle Program to understand the impact of re-designs and operational changes on risk. . b) To new programs to understand reliability growth and first flight risk. . Estimation of Shuttle Risk Progression by flight: . a) Uses Shuttle Probabilistic Risk Assessment (SPRA) and current knowledge to calculate early vehicle risk. . b) Shows impact of major Shuttle upgrades. . c) Can be used to understand first flight risk for new programs.
Halpern, Michael T; Covert, David W; Robin, Alan L
2002-01-01
PURPOSE: We compared differences associated with use of travoprost and latanoprost on both progression of perimetric loss over time and associated costs among black patients. METHODS: Patients with primary open-angle glaucome or ocular hypertension were randomly assigned to one of four arms in a 12-month, double-masked study: travoprost (0.004% or 0.0015%), latanoprost (0.005%), or timolol (0.5%). Forty-nine patients received 0.004% travoprost, 43 received latanoprost, and 40 received timolol. We applied algorithms found in published studies that link intraocular pressure (IOP) control to visual field progression and calculated the likelihood of visual field deterioration based on IOP data. This was used to estimate differences in medical care costs. RESULTS: The average IOP was lower for patients receiving travoprost than for patients receiving latanoprost or timolol (17.3 versus 18.7 versus 20.5 mm Hg respectively, P < .05). Travoprost-treated patients had a smaller predicted change in visual field defect score (VFDS) than latanoprost-treated patients and timolol-treated patients, and significantly fewer were expected to demonstrate visual field progression. Medical care costs would be higher for latanoprost-treated and timolol-treated patients. CONCLUSIONS: Recent studies have provided algorithms linking IOP control to changes in visual fields. We found that treatment with travoprost was associated with less visual field progression and potential cost savings. PMID:12545683
Kozminski, Michael A; Wei, John T; Nelson, Jason; Kent, David M
2015-02-01
To better risk stratify patients, using baseline characteristics, to help optimise decision-making for men with moderate-to-severe lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) through a secondary analysis of the Medical Therapy of Prostatic Symptoms (MTOPS) trial. After review of the literature, we identified potential baseline risk factors for BPH progression. Using bivariate tests in a secondary analysis of MTOPS data, we determined which variables retained prognostic significance. We then used these factors in Cox proportional hazard modelling to: i) more comprehensively risk stratify the study population based on pre-treatment parameters and ii) to determine which risk strata stood to benefit most from medical intervention. In all, 3047 men were followed in MTOPS for a mean of 4.5 years. We found varying risks of progression across quartiles. Baseline BPH Impact Index score, post-void residual urine volume, serum prostate-specific antigen (PSA) level, age, American Urological Association Symptom Index score, and maximum urinary flow rate were found to significantly correlate with overall BPH progression in multivariable analysis. Using baseline factors permits estimation of individual patient risk for clinical progression and the benefits of medical therapy. A novel clinical decision tool based on these analyses will allow clinicians to weigh patient-specific benefits against possible risks of adverse effects for a given patient. © 2014 The Authors. BJU International © 2014 BJU International.
Molnar, Christoph; Scherer, Almut; de Hooge, Manouk; Micheroli, Raphael; Exer, Pascale; Kissling, Rudolf O; Tamborrini, Giorgio; Wildi, Lukas M; Nissen, Michael J; Zufferey, Pascal; Bernhard, Jürg; Weber, Ulrich; Landewé, Robert B M; Ciurea, Adrian
2018-01-01
Objectives To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). Methods Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. Results A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). Conclusion TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity. PMID:28939631
Reilly, P R; Page, D C
1998-09-01
We discuss some societal and legal ramifications of the human genetics revolution. Our reflections were stimulated by discussions among scientists, citizens and legal experts at a large public symposium. We outline key issues regarding oversight of genetic research on human subjects, banking of DNA data by governments and corporations, the potential impact of behavioural genetics and effects upon racial and racist thinking. We contend that, in some cases, well-intentioned but naive efforts to protect the rights of individuals and groups may hurt everyone by blocking the progress of useful research.
Application of Advanced Nondestructive Evaluation Techniques for Cylindrical Composite Test Samples
NASA Technical Reports Server (NTRS)
Martin, Richard E.; Roth, Donald J.; Salem, Jonathan A.
2013-01-01
Two nondestructive methods were applied to composite cylinder samples pressurized to failure in order to determine manufacturing quality and monitor damage progression under load. A unique computed tomography (CT) image processing methodology developed at NASA Glenn Research was used to assess the condition of the as-received samples while acoustic emission (AE) monitoring was used to identify both the extent and location of damage within the samples up to failure. Results show the effectiveness of both of these methods in identifying potentially critical fabrication issues and their resulting impact on performance.
Modeling bladder cancer in mice: opportunities and challenges
Kobayashi, Takashi; Owczarek, Tomasz B.; McKiernan, James M.; Abate-Shen, Cory
2015-01-01
The prognosis and treatment of bladder cancer have hardly improved in the last 20 years. Bladder cancer remains a debilitating and often fatal disease, and among the most costly cancers to treat. The generation of informative mouse models has the potential to improve our understanding of bladder cancer progression, as well as impact its diagnosis and treatment. However, relatively few mouse models of bladder cancer have been described and particularly few that develop invasive cancer phenotypes. This review focuses on opportunities for improving the landscape of mouse models of bladder cancer. PMID:25533675
Talbot, Nick P; Flight, William G
2016-08-01
Achromobacter spp. are emerging pathogens in the lungs of patients with cystic fibrosis. We report the case of an adult patient with cystic fibrosis and chronic A. xylosoxidans infection who experienced rapid, progressive clinical deterioration. Metagenomic analysis of the sputum revealed that the airway microbiota was almost entirely dominated by A. xylosoxidans. We review the impact of this organism on lung function and the airway microbiome in cystic fibrosis, and discuss the potential for cross-infection between patients. Copyright © 2016 Elsevier Ltd. All rights reserved.
The impact of heterogeneity in individual frailty on the dynamics of mortality.
Vaupel, J W; Manton, K G; Stallard, E
1979-08-01
Life table methods are developed for populations whose members differ in their endowment for longevity. Unlike standard methods, which ignore such heterogeneity, these methods use different calculations to construct cohort, period, and individual life tables. The results imply that standard methods overestimate current life expectancy and potential gains in life expectancy from health and safety interventions, while underestimating rates of individual aging, past progress in reducing mortality, and mortality differentials between pairs of populations. Calculations based on Swedish mortality data suggest that these errors may be important, especially in old age.
Aircraft Emissions: Potential Effects on Ozone and Climate - A Review and Progress Report
1977-03-01
which itself absorbs and reemits energy over a wide spectral range. In addition to such direct effects, various possible feedback effects can be...4.3.3 COMESA Climatic Effect Studies 4-17 4.4 Computed Mean Temperature Effects--Fleet Effects 4-24 4.4.1 Introduction 4-24 4.4.2 Mean Temperature Impact ...M B-13 B-2 The Chemical Kinetic Mechanism Used In . Model A B-19 B-3 Rate Coefficients for Model B (with Activation Energy in cal/mole) B-20 B-4
Nutritionally enhanced crops and food security: scientific achievements versus political expediency.
Farre, Gemma; Twyman, Richard M; Zhu, Changfu; Capell, Teresa; Christou, Paul
2011-04-01
Genetic engineering (GE) is one of a raft of strategies that can be used to tackle malnutrition. Recent scientific advances have shown that multiple deficiencies can be tackled simultaneously using engineered plant varieties containing high levels of different minerals and organic nutrients. However, the impact of this progress is being diluted by the unwillingness of politicians to see beyond immediate popular support, favoring political expediency over controversial but potentially life-saving decisions based on rational scientific evidence. Copyright © 2010 Elsevier Ltd. All rights reserved.
Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy.
Ravidà, Alessandra; Musante, Luca; Kreivi, Marjut; Miinalainen, Ilkka; Byrne, Barry; Saraswat, Mayank; Henry, Michael; Meleady, Paula; Clynes, Martin; Holthofer, Harry
2015-05-01
Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. A panel of 12 plant lectins was used in the screening of lectin blots. The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. Our data confirm a substantial link between glycosylation signature and diabetes progression. Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease.
A survey-based exploration of the impact of dyslexia on career progression of UK registered nurses.
Morris, David; Turnbull, Patricia
2007-01-01
To explore the effects of dyslexia on the practice and career progression of UK registered nurses (RN). Literature suggests dyslexia can have a negative impact in the workplace and may pose particular difficulties for nurses, where accuracy in information processing activities is essential for practice. A questionnaire was used to survey RNs with dyslexia (n = 116) and results analysed using content analysis. Dyslexia provided a challenge to the everyday work of RNs, which was often met successfully using a range of individualized strategies. Career progression was achievable but compared with peers, was perceived to take longer. Disclosure of dyslexia to work-colleagues was selective and dependent on the perceived benefits. Informal support mechanisms were commonly utilized with formal management support less well defined. Dyslexia appears to have a negative impact on working practices and career progression, but remains a poorly understood and often hidden disability.
Cha, Seungman
2017-01-01
As the Millennium Development Goals campaign (MDGs) came to a close, clear evidence was needed on the contribution of the worldwide MDG campaign. We seek to determine the degree of difference in the reduction rate between the pre-MDG and MDG campaign periods and its statistical significance by region. Unlike the prevailing studies that measured progress in 1990-2010, this study explores by percentage how much MDG progress has been achieved during the MDG campaign period and quantifies the impact of the MDG campaign on the maternal and under-five child mortality reduction during the MDG era by comparing observed values with counterfactual values estimated on the basis of the historical trend. The low accomplishment of sub-Saharan Africa toward the MDG target mainly resulted from the debilitated progress of mortality reduction during 1990-2000, which was not related to the worldwide MDG campaign. In contrast, the other regions had already achieved substantial progress before the Millennium Declaration was proclaimed. Sub-Saharan African countries have seen the most remarkable impact of the worldwide MDG campaign on maternal and child mortality reduction across all different measurements. In sub-Saharan Africa, the MDG campaign has advanced the progress of the declining maternal mortality ratio and under-five mortality rate, respectively, by 4.29 and 4.37 years. Sub-Saharan African countries were frequently labeled as 'off-track', 'insufficient progress', or 'no progress' even though the greatest progress was achieved here during the worldwide MDG campaign period and the impact of the worldwide MDG campaign was most pronounced in this region in all respects. It is time to learn from the success stories of the sub-Saharan African countries. Erroneous and biased measurement should be avoided for the sustainable development goals to progress.
ERIC Educational Resources Information Center
Booth, Char; Lowe, M. Sara; Tagge, Natalie; Stone, Sean M.
2015-01-01
The Claremont Colleges Library conducted direct rubric assessment of Pitzer College First-Year Seminar research papers to analyze the impact of diverse levels of librarian course collaborations on information literacy (IL) performance in student writing. Findings indicate that progressive degrees of librarian engagement in IL-related course…
The Impact of Task Difficulty and Performance Scores on Student Engagement and Progression
ERIC Educational Resources Information Center
Lynch, Raymond; Patten, James Vincent; Hennessy, Jennifer
2013-01-01
Background: This article considers the impact of differential task difficulty on student engagement and progression within an Irish primary school context. Gaining and maintaining student engagement during learning tasks such as homework is a significant and understandable on-going challenge for teachers. The findings of this study hold the…
NASA Astrophysics Data System (ADS)
Irby, Isaac D.; Friedrichs, Marjorie A. M.; Da, Fei; Hinson, Kyle E.
2018-05-01
The Chesapeake Bay region is projected to experience changes in temperature, sea level, and precipitation as a result of climate change. This research uses an estuarine-watershed hydrodynamic-biogeochemical modeling system along with projected mid-21st-century changes in temperature, freshwater flow, and sea level rise to explore the impact climate change may have on future Chesapeake Bay dissolved-oxygen (DO) concentrations and the potential success of nutrient reductions in attaining mandated estuarine water quality improvements. Results indicate that warming bay waters will decrease oxygen solubility year-round, while also increasing oxygen utilization via respiration and remineralization, primarily impacting bottom oxygen in the spring. Rising sea level will increase estuarine circulation, reducing residence time in bottom waters and increasing stratification. As a result, oxygen concentrations in bottom waters are projected to increase, while oxygen concentrations at mid-depths (3 < DO < 5 mg L-1) will typically decrease. Changes in precipitation are projected to deliver higher winter and spring freshwater flow and nutrient loads, fueling increased primary production. Together, these multiple climate impacts will lower DO throughout the Chesapeake Bay and negatively impact progress towards meeting water quality standards associated with the Chesapeake Bay Total Maximum Daily Load. However, this research also shows that the potential impacts of climate change will be significantly smaller than improvements in DO expected in response to the required nutrient reductions, especially at the anoxic and hypoxic levels. Overall, increased temperature exhibits the strongest control on the change in future DO concentrations, primarily due to decreased solubility, while sea level rise is expected to exert a small positive impact and increased winter river flow is anticipated to exert a small negative impact.
Whole Grains in Amelioration of Metabolic Derangements
Develaraja, Samir; Reddy, Anup; Yadav, Mukesh; Jain, Shalini; Yadav, Hariom
2017-01-01
Daily diet influences whole body metabolism, and intricately linked to the prevention or progression of metabolic diseases including obesity, diabetes and cardiovascular diseases. Several epidemiological and large scale studies have shown that diets enriched with whole grains improves metabolic function and protect from the development of metabolic diseases. Direct impact of whole grain diet can be mediated on several levels of metabolic functions i.e. reduced glycemic index, improved fat oxidation potential, increased cholesterol clearance or decreased cholesterol biosynthesis and modulation of gut microbiome. In this article we reviewed several studies indicating the beneficial effects of whole grain diets on metabolic functions, as well as discussed the potential active phytochemicals present in these whole grain foods to contribute in modulation of metabolic function in our body. PMID:28944285
Drivers of Inequality in Millennium Development Goal Progress: A Statistical Analysis
Stuckler, David; Basu, Sanjay; McKee, Martin
2010-01-01
Background Many low- and middle-income countries are not on track to reach the public health targets set out in the Millennium Development Goals (MDGs). We evaluated whether differential progress towards health MDGs was associated with economic development, public health funding (both overall and as percentage of available domestic funds), or health system infrastructure. We also examined the impact of joint epidemics of HIV/AIDS and noncommunicable diseases (NCDs), which may limit the ability of households to address child mortality and increase risks of infectious diseases. Methods and Findings We calculated each country's distance from its MDG goals for HIV/AIDS, tuberculosis, and infant and child mortality targets for the year 2005 using the United Nations MDG database for 227 countries from 1990 to the present. We studied the association of economic development (gross domestic product [GDP] per capita in purchasing-power-parity), the relative priority placed on health (health spending as a percentage of GDP), real health spending (health system expenditures in purchasing-power-parity), HIV/AIDS burden (prevalence rates among ages 15–49 y), and NCD burden (age-standardised chronic disease mortality rates), with measures of distance from attainment of health MDGs. To avoid spurious correlations that may exist simply because countries with high disease burdens would be expected to have low MDG progress, and to adjust for potential confounding arising from differences in countries' initial disease burdens, we analysed the variations in rates of change in MDG progress versus expected rates for each country. While economic development, health priority, health spending, and health infrastructure did not explain more than one-fifth of the differences in progress to health MDGs among countries, burdens of HIV and NCDs explained more than half of between-country inequalities in child mortality progress (R 2-infant mortality = 0.57, R 2-under 5 mortality = 0.54). HIV/AIDS and NCD burdens were also the strongest correlates of unequal progress towards tuberculosis goals (R 2 = 0.57), with NCDs having an effect independent of HIV/AIDS, consistent with micro-level studies of the influence of tobacco and diabetes on tuberculosis risks. Even after correcting for health system variables, initial child mortality, and tuberculosis diseases, we found that lower burdens of HIV/AIDS and NCDs were associated with much greater progress towards attainment of child mortality and tuberculosis MDGs than were gains in GDP. An estimated 1% lower HIV prevalence or 10% lower mortality rate from NCDs would have a similar impact on progress towards the tuberculosis MDG as an 80% or greater rise in GDP, corresponding to at least a decade of economic growth in low-income countries. Conclusions Unequal progress in health MDGs in low-income countries appears significantly related to burdens of HIV and NCDs in a population, after correcting for potentially confounding socioeconomic, disease burden, political, and health system variables. The common separation between NCDs, child mortality, and infectious syndromes among development programs may obscure interrelationships of illness affecting those living in poor households—whether economic (e.g., as money spent on tobacco is lost from child health expenditures) or biological (e.g., as diabetes or HIV enhance the risk of tuberculosis). Please see later in the article for the Editors' Summary PMID:20209000
Zhai, Shiyan; Song, Genxin; Qin, Yaochen; Ye, Xinyue; Lee, Jay
2017-01-01
This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.
Qin, Yaochen; Lee, Jay
2017-01-01
This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention. PMID:28950027
Barnabas, Ruanne V; Laukkanen, Päivi; Koskela, Pentti; Kontula, Osmo; Lehtinen, Matti; Garnett, Geoff P
2006-01-01
Background Candidate human papillomavirus (HPV) vaccines have demonstrated almost 90%-100% efficacy in preventing persistent, type-specific HPV infection over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention of precancerous lesions in phase III clinical trials, they will be licensed for public use in the near future. How these vaccines will be used in countries with national cervical cancer screening programmes is an important question. Methods and Findings We developed a transmission model of HPV 16 infection and progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence over time. The model was used to estimate the transmission probability of the virus, to look at the effect of changes in patterns of sexual behaviour and smoking on age-specific trends in cancer incidence, and to explore the impact of HPV 16 vaccination. We estimated a high per-partnership transmission probability of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour and smoking accounted, in part, for the increase seen in cervical cancer incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in opportunistic immunisation) and high (90% in a national immunisation programme) coverage of the adolescent population, vaccinating women and men had little benefit over vaccinating women alone. We estimate that vaccinating 90% of young women before sexual debut has the potential to decrease HPV type-specific (e.g., type 16) cervical cancer incidence by 91%. If older women are more likely to have persistent infections and progress to cancer, then vaccination with a duration of protection of less than 15 y could result in an older susceptible cohort and no decrease in cancer incidence. While vaccination has the potential to significantly reduce type-specific cancer incidence, its combination with screening further improves cancer prevention. Conclusions HPV vaccination has the potential to significantly decrease HPV type-specific cervical cancer incidence. High vaccine coverage of women alone, sustained over many decades, with a long duration of vaccine-conferred protection, would have the greatest impact on type-specific cancer incidence. This level of coverage could be achieved through national coordinated programmes, with surveillance to detect cancers caused by nonvaccine oncogenic HPV types. PMID:16573364
Padilla, Benita; Danovitch, Gabriel M; Lavee, Jacob
2013-11-01
We describe the parallel changes that have taken place in recent years in two countries, Israel and The Philippines, the former once an "exporter" of transplant tourists and the latter once an "importer" of transplant tourists. These changes were in response to progressive legislation in both countries under the influence of the Declaration of Istanbul. The annual number of Israeli patients who underwent kidney transplantation abroad decreased from a peak of 155 in 2006 to an all-time low of 35 in 2011 while in the Philippines the annual number of foreign transplant recipients fell from 531 in 2007 to two in 2011. The experience of these two countries provides a "natural experiment" on the potential impact of legal measures to prevent transplant tourism.
Marin, Deborah; Amaya, Karine; Casciano, Roman; Puder, Katherine L; Casciano, Julian; Chang, Sobin; Snyder, Edward H; Cheng, Isaac; Cuccia, Anthony J
2003-12-01
Alzheimer's disease (AD) places a significant burden on health care systems worldwide. As new treatments are developed, their cost-effectiveness is often assessed to help health care professionals make informed decisions. In addition to the more common practice of assessing direct medical costs, indirect costs, including time spent in caregiving, should be evaluated. This study examined the potential effects of the dual cholinesterase inhibitor rivastigmine (Exelon) on caregivers of patients with AD. Results from two 26-week, placebo-controlled trials have demonstrated the clinically relevant and statistically significant efficacy of rivastigmine (6-12 mg/day) compared to placebo, on cognition, activities of daily living, and global functioning. By delaying progression of AD, significant savings in caregiver burden are anticipated, as measured by time spent caregiving and its related costs. Data collected in a prospective, observational study of AD patients and their caregivers were used to establish the relationship between disease severity (based on Mini-Mental State Examination [MMSE] score) and time spent caregiving (according to the 5-item Caregivers Activity Survey score). A significant correlation was observed between the two scores (N = 43, r = -.56, p < .0001), demonstrating that more time for supervision from caregivers is required as the disease progresses. This finding was used to estimate the reduced caregiver burden resulting from the delay in disease progression that was demonstrated with use of rivastigmine. Over a 2-year period, the reduction in time spent in caregiving reached 691 hours for caregivers of patients with mild AD (MMSE score 21-30), resulting in a total savings of approximately 11,253 dollars. Treatment of patients with moderately severe AD was also evaluated. The trend was similar but the impact was less, suggesting an economic benefit to early therapy. Early diagnosis and a pharmacologic intervention that allows the patients to remain at home longer by delaying disease progression would have a beneficial impact on patients, caregivers, and payers, and should therefore be encouraged through initiatives designed to identify and treat patients early in the course of disease.
Defining the impact of non-native species.
Jeschke, Jonathan M; Bacher, Sven; Blackburn, Tim M; Dick, Jaimie T A; Essl, Franz; Evans, Thomas; Gaertner, Mirijam; Hulme, Philip E; Kühn, Ingolf; Mrugała, Agata; Pergl, Jan; Pyšek, Petr; Rabitsch, Wolfgang; Ricciardi, Anthony; Richardson, David M; Sendek, Agnieszka; Vilà, Montserrat; Winter, Marten; Kumschick, Sabrina
2014-10-01
Non-native species cause changes in the ecosystems to which they are introduced. These changes, or some of them, are usually termed impacts; they can be manifold and potentially damaging to ecosystems and biodiversity. However, the impacts of most non-native species are poorly understood, and a synthesis of available information is being hindered because authors often do not clearly define impact. We argue that explicitly defining the impact of non-native species will promote progress toward a better understanding of the implications of changes to biodiversity and ecosystems caused by non-native species; help disentangle which aspects of scientific debates about non-native species are due to disparate definitions and which represent true scientific discord; and improve communication between scientists from different research disciplines and between scientists, managers, and policy makers. For these reasons and based on examples from the literature, we devised seven key questions that fall into 4 categories: directionality, classification and measurement, ecological or socio-economic changes, and scale. These questions should help in formulating clear and practical definitions of impact to suit specific scientific, stakeholder, or legislative contexts. © 2014 The Authors. Conservation Biology published by Wiley Periodicals, Inc., on behalf of the Society for Conservation Biology.
Musa, Julian; Aynaud, Marie-Ming; Mirabeau, Olivier; Delattre, Olivier; Grünewald, Thomas GP
2017-01-01
Limitless cell proliferation, evasion from apoptosis, dedifferentiation, metastatic spread and therapy resistance: all these properties of a cancer cell contribute to its malignant phenotype and affect patient outcome. MYBL2 (alias B-Myb) is a transcription factor of the MYB transcription factor family and a physiological regulator of cell cycle progression, cell survival and cell differentiation. When deregulated in cancer cells, MYBL2 mediates the deregulation of these properties. In fact, MYBL2 is overexpressed and associated with poor patient outcome in numerous cancer entities. MYBL2 and players of its downstream transcriptional network can be used as prognostic and/or predictive biomarkers as well as potential therapeutic targets to offer less toxic and more specific anti-cancer therapies in future. In this review, we summarize current knowledge on the physiological roles of MYBL2 and highlight the impact of its deregulation on cancer initiation and progression. PMID:28640249
Erickson, Larry E.; Jennings, Merrisa
2017-01-01
The Paris Agreement on Climate Change has the potential to improve air quality and human health by encouraging the electrification of transportation and a transition from coal to sustainable energy. There will be human health benefits from reducing combustion emissions in all parts of the world. Solar powered charging infrastructure for electric vehicles adds renewable energy to generate electricity, shaded parking, and a needed charging infrastructure for electric vehicles that will reduce range anxiety. The costs of wind power, solar panels, and batteries are falling because of technological progress, magnitude of commercial activity, production experience, and competition associated with new trillion dollar markets. These energy and transportation transitions can have a very positive impact on health. The energy, transportation, air quality, climate change, health nexus may benefit from additional progress in developing solar powered charging infrastructure. PMID:29922702
The Role of Audiologic Evaluation in Progressive Audiologic Tinnitus Management
Henry, James A.; Zaugg, Tara L.; Myers, Paula J.; Schechter, Martin A.
2008-01-01
Progressive Audiologic Tinnitus Management (PATM) is based on the premise that tinnitus is managed most efficiently using a hierarchy of clinical services that address different levels of need. PATM includes five levels of management: (a) triage; (b) audiologic evaluation; (c) group education; (d) tinnitus evaluation; and (e) individualized management. This article provides an overview of PATM and focuses on the procedures that make up the Level 2 Audiologic Evaluation. The evaluation is conducted to assess the potential need for medical, audiologic (hearing loss, tinnitus, hyperacusis), and/or mental health services. The Tinnitus Handicap Inventory, Hearing Handicap Inventory, and Tinnitus and Hearing Survey are used to differentiate effects of tinnitus and hearing loss. If indicated, patients are interviewed with the Tinnitus-Impact Screening Interview. Patients requiring amplification receive hearing aids. Often, management of hearing loss at Level 2 addresses any problems that were attributed to the tinnitus, which obviates further tinnitus-specific intervention. PMID:18628281
Oxidative stress and adipocyte biology: focus on the role of AGEs.
Boyer, Florence; Vidot, Jennifer Baraka; Dubourg, Alexis Guerin; Rondeau, Philippe; Essop, M Faadiel; Bourdon, Emmanuel
2015-01-01
Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs) formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE). This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein) undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin) may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression.
The potential impact of plant biotechnology on the Millennium Development Goals.
Yuan, Dawei; Bassie, Ludovic; Sabalza, Maite; Miralpeix, Bruna; Dashevskaya, Svetlana; Farre, Gemma; Rivera, Sol M; Banakar, Raviraj; Bai, Chao; Sanahuja, Georgina; Arjó, Gemma; Avilla, Eva; Zorrilla-López, Uxue; Ugidos-Damboriena, Nerea; López, Alberto; Almacellas, David; Zhu, Changfu; Capell, Teresa; Hahne, Gunther; Twyman, Richard M; Christou, Paul
2011-03-01
The eight Millennium Development Goals (MDGs) are international development targets for the year 2015 that aim to achieve relative improvements in the standards of health, socioeconomic status and education in the world's poorest countries. Many of the challenges addressed by the MDGs reflect the direct or indirect consequences of subsistence agriculture in the developing world, and hence, plant biotechnology has an important role to play in helping to achieve MDG targets. In this opinion article, we discuss each of the MDGs in turn, provide examples to show how plant biotechnology may be able to accelerate progress towards the stated MDG objectives, and offer our opinion on the likelihood of such technology being implemented. In combination with other strategies, plant biotechnology can make a contribution towards sustainable development in the future although the extent to which progress can be made in today's political climate depends on how we deal with current barriers to adoption.
Nakamura, Kyohei; Kassem, Sahar; Cleynen, Alice; Chrétien, Marie-Lorraine; Guillerey, Camille; Putz, Eva Maria; Bald, Tobias; Förster, Irmgard; Vuckovic, Slavica; Hill, Geoffrey R; Masters, Seth L; Chesi, Marta; Bergsagel, P Leif; Avet-Loiseau, Hervé; Martinet, Ludovic; Smyth, Mark J
2018-04-09
Tumor-promoting inflammation and avoiding immune destruction are hallmarks of cancer. Here, we demonstrate that the pro-inflammatory cytokine interleukin (IL)-18 is critically involved in these hallmarks in multiple myeloma (MM). Mice deficient for IL-18 were remarkably protected from Vk ∗ MYC MM progression in a CD8 + T cell-dependent manner. The MM-niche-derived IL-18 drove generation of myeloid-derived suppressor cells (MDSCs), leading to accelerated disease progression. A global transcriptome analysis of the immune microenvironment in 73 MM patients strongly supported the negative impact of IL-18-driven MDSCs on T cell responses. Strikingly, high levels of bone marrow plasma IL-18 were associated with poor overall survival in MM patients. Furthermore, our preclinical studies suggested that IL-18 could be a potential therapeutic target in MM. Copyright © 2018 Elsevier Inc. All rights reserved.
The impact of mast cells on cardiovascular diseases.
Kritikou, Eva; Kuiper, Johan; Kovanen, Petri T; Bot, Ilze
2016-05-05
Mast cells comprise an innate immune cell population, which accumulates in tissues proximal to the outside environment and, upon activation, augments the progression of immunological reactions through the release and diffusion of either pre-formed or newly generated mediators. The released products of mast cells include histamine, proteases, as well as a variety of cytokines, chemokines and growth factors, which act on the surrounding microenvironment thereby shaping the immune responses triggered in various diseased states. Mast cells have also been detected in the arterial wall and are implicated in the onset and progression of numerous cardiovascular diseases. Notably, modulation of distinct mast cell actions using genetic and pharmacological approaches highlights the crucial role of this cell type in cardiovascular syndromes. The acquired evidence renders mast cells and their mediators as potential prognostic markers and therapeutic targets in a broad spectrum of pathophysiological conditions related to cardiovascular diseases. Copyright © 2015 Elsevier B.V. All rights reserved.
Synthetic Nanoelectronic Probes for Biological Cells and Tissue
2013-01-01
Research at the interface between nanoscience and biology has the potential to produce breakthroughs in fundamental science and lead to revolutionary technologies. In this review, we focus on nanoelectronic/biological interfaces. First, we discuss nanoscale field effect transistors (nanoFETs) as probes to study cellular systems, including the realization of nanoFET comparable in size to biological nanostructures involved in communication using synthesized nanowires. Second, we overview current progress in multiplexed extracellular sensing using planar nanoFET arrays. Third, we describe the design and implementation of three distinct nanoFETs used to realize the first intracellular electrical recording from single cells. Fourth, we present recent progress in merging electronic and biological systems at the 3D tissue level by using macroporous nanoelectronic scaffolds. Finally, we discuss future development in this research area, the unique challenges and opportunities, and the tremendous impact these nanoFET based technologies might have in advancing biology and medical sciences. PMID:23451719
Caffrey, Louise; Wyatt, David; Fudge, Nina; Mattingley, Helena; Williamson, Catherine; McKevitt, Christopher
2016-09-08
Gender inequity has persisted in academic medicine. Yet equity is vital for countries to achieve their full potential in terms of translational research and patient benefit. This study sought to understand how the gender equity programme, Athena SWAN, can be enabled and constrained by interactions between the programme and the context it is implemented into, and whether these interactions might produce unintended consequences. Multimethod qualitative case studies using a realist evaluation approach. 5 departments from a university medical school hosting a Translational Research Organisation. 25 hours of observations of gender equality committee meetings, 16 in-depth interviews with Heads of Departments, Committee Leads and key personnel involved in the initiative. 4 focus groups with 15 postdoctoral researchers, lecturers and senior lecturers. The implementation of Athena SWAN principles was reported to have created social space to address gender inequity and to have highlighted problematic practices to staff. However, a number of factors reduced the programme's potential to impact gender inequity. Gender inequity was reproduced in the programme's enactment as female staff was undertaking a disproportionate amount of Athena SWAN work, with potential negative impacts on individual women's career progression. Early career researchers experienced problems accessing Athena SWAN initiatives. Furthermore, the impact of the programme was perceived to be undermined by wider institutional practices, national policies and societal norms, which are beyond the programme's remit. Gender equity programmes have the potential to address inequity. However, paradoxically, they can also unintentionally reproduce and reinforce gender inequity through their enactment. Potential programme impacts may be undermined by barriers to staff availing of career development and training initiatives, and by wider institutional practices, national policies and societal norms. 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/
Andersen, Lotte Nygaard; Kohberg, Maria; Herborg, Lene Gram; Søgaard, Karen; Roessler, Kirsten Kaya
2014-08-01
Musculoskeletal pain impacts upon everyday life. A degree of chronicity may pose an increased risk of sickness absence. One of two rehabilitative interventions, "Tailored Physical Activity" or "Chronic Pain Self-Management Program", was offered to sick-listed citizens who experienced pain. The objectives of this paper were to: (1) Assess what factors are experienced as problematic for sick-listed citizens in everyday life with chronic pain, and (2) Evaluate the significance of two distinct rehabilitative interventions on the future everyday lives of sick-listed citizens. Seven semi-structured interviews with sick-listed citizens were analyzed using a phenomenological-hermeneutical approach. Results were discussed by applying the theoretical framework of Antonovsky's salutogenetic model and Yaloms principles for group psychology. The potential for development of citizen's coping is evaluated based on Roessler's notion of progression. The analysis revealed four main themes: (1) Living with pain and unemployment; (2) "Putting my foot down" and "asking for help"; (3) Significance of the group, including instructors, and; (4) Aspects significant to progression. Unemployment is a major life event that promotes stress and can be accompanied by problems related to depressed mood, acceptance of the life situation, feelings of not being useful, feelings of losing control and identity conflicts. Group characteristics that gave a significant basis for progression in the self-management program are both emotional and instrumental, while the physical training program offers a "here-and-now"-experience and motivation to participate. This study indicates that the self-management program could potentially improve coping while the physical activity program revealed one example of a means of progression. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.
Syrjänen, K
2011-01-01
Recent data indicate that persistent HR-HPV infections represent a significantly increased risk of developing incident high-grade CIN and cervical cancer. Accordingly, 6-month (6M+) or 12-month (12M+) type-specific persistence of HR-HPV have been proposed as powerful surrogates of progressive disease. Because of substantial practical impact in future HPV vaccine trials using non-HPV 16/18 vaccines, studies on HR-HPV persistence as a surrogate endpoint of progressive CIN have been subject to a comprehensive meta-analyses recently. The present communication was solicited to bring this important and timely topic to the awareness of the readers, in a format consisting of a review of the recent literature, supplemented with the author's own experience from different studies. Based on a large number of relevant studies, there remains little doubt that persistence of HR-HPV for 6+ or 12+ months is associated with a significantly increased risk of developing incident high-grade CIN. However, some data also disclosed several important issues that need to be carefully considered and/or adequately resolved before adopting 6M+ or 12M+ HR-HPV persistence as a surrogate of progressive disease. These include i) definitions of HPV persistence, ii) HPV detection techniques and iii) testing intervals and iv) length of follow-up, as well as v) diagnosis of the surrogate endpoints, and vi) other study characteristics, including vii) the type of reference category used in calculating the risk estimates. All these issues are critically discussed in the present communication. Of major impact seems to be the reference category used to calculate these risk estimates, as evident from the NIS-LAMS cohort. Taken together, it is suggested that in all future studies using the 6M+ or 12M+ HR-HPV persistence as a surrogate endpoint of progressive disease, a "gold standard" should be used in calculating the risk estimates. In addition to deciding, 1) whether to use 6M+ or 12M+ persistence criteria, and 2) cytological, histological or combined surrogate endpoints (SIL, CIN1, CIN2, CIN/SIL), one should 3) use exclusively the HPV negative reference group in calculating the risk estimates for viral persistence endpoints. This is supported by the data from the recent meta-analysis as well as from the author's combined NIS-LAMS cohort, both implicating that the most consistent association to progressive disease is obtained when women with persistent HR-HPV are compared with HPV-negative women. It is the conviction of this author that the two other reference categories (HPV transient and HPV mixed outcome) are far too heterogeneous and subject to potential misclassifications to give consistent and reproducible risk estimates for HR-HPV persistence as a surrogate endpoint of progressive CIN.
Domenighetti, Andrea A; Mathewson, Margie A; Pichika, Rajeswari; Sibley, Lydia A; Zhao, Leyna; Chambers, Henry G; Lieber, Richard L
2018-04-25
Cerebral palsy (CP) is the most common cause of pediatric neurodevelopmental and physical disability in the United States. It is defined as a group of motor disorders caused by a non-progressive perinatal insult to the brain. While the brain lesion is non-progressive, there is a progressive, lifelong impact on skeletal muscles, which are shorter, spastic, and may develop debilitating contractures. Satellite cells are resident muscle stem cells that are indispensable for postnatal growth and regeneration of skeletal muscles. Here we measured the myogenic potential of satellite cells isolated from contractured muscles in children with CP. When compared to typically developing (TD) children, satellite cell-derived myoblasts from CP differentiated more slowly (Slope: 0.013{plus minus}0.013 CP vs. 0.091{plus minus}0.024 TD over 24 hours, P<0.001) and fused less (Fusion Index: 21.3{plus minus}8.6 CP vs. 81.3{plus minus}7.7 TD after 48 hours, P<0.001) after exposure to low-serum conditions that stimulated myotube formation. This impairment was associated with downregulation of several markers important for myoblast fusion and myotube formation, including DNA methylation-dependent inhibition of pro-myogenic Integrin Beta 1D (ITGB1D) protein expression levels (-50% at 42 hours), and ~25% loss of integrin-mediated FAK kinase phosphorylation. The cytidine analog 5-Azacytidine (5-AZA), a demethylating agent, restored ITGB1D levels and promoted myogenesis in CP cultures. Our data demonstrate that muscle contractures in CP are associated with loss of satellite cell myogenic potential that is dependent on DNA methylation patterns affecting expression of genetic programs associated with muscle stem cell differentiation and muscle fiber formation.
An Argument for Formative Assessment with Science Learning Progressions
ERIC Educational Resources Information Center
Alonzo, Alicia C.
2018-01-01
Learning progressions--particularly as defined and operationalized in science education--have significant potential to inform teachers' formative assessment practices. In this overview article, I lay out an argument for this potential, starting from definitions for "formative assessment practices" and "learning progressions"…
Wu, Zhuangyuan; Zheng, Xinbiao; Luo, Yongming; Huo, Fei; Dong, Hong; Zhang, Guoting; Yu, Weihao; Tian, Fang; He, Liangjun; Chen, Jingbo
2015-12-01
The present study investigates the effects of five cryoprotectants (CPAs) and cryoprotectant combinations on the post-thaw total motility, progressive motility, viability, mitochondrial membrane potential and acrosome integrity in stallion spermatozoa. In Experiment 1, the objective was to compare the impact of different concentrations (2.5%, 3.5% and 5%) of a single CPA, including glycerol (Gly), ethylene glycol (EG), dimethyl sulphoxide (DMSO), methyl formamide (MF), and dimethylformamide (DMF) for stallion spermatozoa cryopreservation. In Experiment 2, two or more CPAs were used to assess whether this improved post-thaw spermatozoa quality. Gly, MF and DMF, were used to prepare seven combinations of freezing extender with different mixtures of cryoprotectant, and the 3.5% Gly, MF and DMF were used as a control group. The results show that post-thaw total motility, progressive motility, viability, and mitochondrial membrane potential for all concentrations of EG and DMSO were less than the 3.5% and 5% Gly and MF and 2.5% and 3.5% DMF (P<0.05). Use of the 3.5% concentration resulted in the greater post-thaw total motility and progressive motility than the 2.5% and 5% concentrations for all CPAs. The results for the use of different combinations of cryoprotectant indicate there are differences in progressive motility and viability. The viability with the use of Gly(2/3)+MF(1/3) was 44.65% and was greater than the Gly(1/3)+MF(1/3)+DMF(1/3) (30.96%), MF(2/3)+DMF(1/3) (35.05%), Gly (32.21%) and MF(33.76%) (P<0.05). The progressive motility with the use of the MF(2/3)+Gly(1/3) combination was 36.0% and was greater than in the DMF (25.0%) and MF(2/3)+DMF(1/3) (22.7%) (P<0.05). These results suggest that using the appropriate cryoprotectant combination instead of a single cryoprotectant can improve horse spermatozoa cryopreservation. Copyright © 2015 Elsevier B.V. All rights reserved.
Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11.
Bressler, Neil M; Bressler, Susan B; Congdon, Nathan G; Ferris, Frederick L; Friedman, David S; Klein, Ronald; Lindblad, Anne S; Milton, Roy C; Seddon, Johanna M
2003-11-01
To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States. The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS. An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced AMD and any associated vision loss during the next 5 years. If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.
Impact cratering experiments in Bingham materials and the morphology of craters on Mars and Ganymede
NASA Technical Reports Server (NTRS)
Fink, J. H.; Greeley, R.; Gault, D. E.
1982-01-01
Results from a series of laboratory impacts into clay slurry targets are compared with photographs of impact craters on Mars and Ganymede. The interior and ejecta lobe morphology of rampart-type craters, as well as the progression of crater forms seen with increasing diameter on both Mars and Ganymede, are equalitatively explained by a model for impact into Bingham materials. For increasing impact energies and constant target rheology, laboratory craters exhibit a morphologic progression from bowl-shaped forms that are typical of dry planetary surfaces to craters with ejecta flow lobes and decreasing interior relief, characteristic of more volatile-rich planets. A similar sequence is seen for uniform impact energy in slurries of decreasing yield strength. The planetary progressions are explained by assuming that volatile-rich or icy planetary surfaces behave locally in the same way as Bingham materials and produce ejecta slurries with yield strenghs and viscosities comparable to terrestrial debris flows. Hypothetical impact into Mars and Ganymede are compared, and it is concluded that less ejecta would be produced on Ganymede owing to its lower gravitational acceleration, surface temperature, and density of surface materials.
Kravchenko, Julia; Corsini, Emanuela; Williams, Marc A; Decker, William; Manjili, Masoud H; Otsuki, Takemi; Singh, Neetu; Al-Mulla, Faha; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A Ivana; Raju, Jayadev; Hamid, Roslida A; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K; Ryan, Elizabeth P; Brown, Dustin G; Bisson, William H; Lowe, Leroy; Lyerly, H Kim
2015-06-01
An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-β, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Cognitive impairment in COPD: should cognitive evaluation be part of respiratory assessment?
Gloeckl, Rainer; Vogiatzis, Ioannis; Kenn, Klaus
2017-01-01
Cognitive impairment is highly prevalent in patients with COPD and demonstrates multiple detrimental effects on many aspects of patient state and therapeutic outcomes. It is attributed to several overlapping pathophysiological factors, with the most common being the low level of oxygen saturation due to respiratory insufficiency. Despite the impact of cognitive impairment on clinical outcomes, the screening for coexisting cognitive deficits which may interfere with the successful progress of respiratory treatment is yet neglected. There is a special consideration that cognitive deficits should be taken into account when developing respiratory therapy plans. Cognitively impaired patients are likely to require more support and have need of an individualised respiratory care plan which can also be beneficial for their cognitive deficits. Pulmonary rehabilitation as a multidisciplinary approach could be prioritised for COPD patients with cognitive impairment. Educational aims To illustrate the common signs of cognitive impairment and define potential associations between lung and cognitive dysfunction. To illustrate the potential influence of cognitive deficits on the optimal progress of respiratory therapy. To illustrate the importance of cognitive evaluation as part of a comprehensive clinical assessment for patients suspected of suffering cognitive impairment. PMID:29184593
Wales, Michele; Cartier, Eddie
2015-01-01
One of the reasons that the United States is a leader in biotechnology is its strong and reliable patent system. However, the Supreme Court’s decision in Myriad potentially limits an inventor’s ability to protect her DNA-based inventions. Fortunately, with creativity, there are numerous ways in which to “claim around” Myriad, enabling inventors to fully protect their diagnostic or therapeutic inventions. Thus, under a proper reading of the holding, the potential negative effect of Myriad on the progress of biotechnology would be negligible. Unfortunately, the U.S. Patent and Trademark Office has promulgated revised examination procedures in the wake of Myriad that have the potential to greatly limit the patentability of all inventions based on products found in nature and create uncertainty that will not be resolved in the near future. PMID:26337114
Prioritizing Arctic Observations with Limited Resources
NASA Astrophysics Data System (ADS)
Kelly, B.; Starkweather, S.
2012-12-01
U.S. Federal agencies recently completed a five-year research plan for the Arctic including plans to enhance efforts toward an Arctic Observing Network (AON). Following on numerous national and international planning efforts, the five-year plan identifies nine priority areas including enhancing observing system design, assessing priorities of local residents, and improving data access. AON progress to date has been realized through bottom-up funding decisions and some top-down design optimization approaches, which have resulted in valuable yet ad hoc progress towards Arctic research imperatives. We suggest that advancing AON beyond theoretical design and ad hoc efforts with the engagement of multiple U.S. Federal agencies will require a structured, input-based planning approach to prioritization that recognizes budget realities. Completing a long list of worthy observing efforts appears to be unsustainable and inadequate in responding to the rapid changes taking place in the Arctic. Society would be better served by more rapid implementation of sustained, long-term observations focused on those climate feedbacks with the greatest potential negative impacts. Several emerging theoretical frameworks have pointed to the need to enhance iterative, capacity-building dialog between observationalists, modelers, and stakeholders as a way to identify these broadest potential benefits. We concur and suggest that those dialogs need to be facilitated and sustained over long periods. Efforts to isolate observational programs from process research are, we believe, impeding progress. At the same time, we note that bottom-up funding decisions, while useful for prioritizing process research, are less appropriate to building observing systems.
Pilutti, Lara A; Paulseth, John E; Dove, Carin; Jiang, Shucui; Rathbone, Michel P; Hicks, Audrey L
2016-01-01
Background: There is evidence of the benefits of exercise training in multiple sclerosis (MS); however, few studies have been conducted in individuals with progressive MS and severe mobility impairment. A potential exercise rehabilitation approach is total-body recumbent stepper training (TBRST). We evaluated the safety and participant-reported experience of TBRST in people with progressive MS and compared the efficacy of TBRST with that of body weight-supported treadmill training (BWSTT) on outcomes of function, fatigue, and health-related quality of life (HRQOL). Methods: Twelve participants with progressive MS (Expanded Disability Status Scale scores, 6.0-8.0) were randomized to receive TBRST or BWSTT. Participants completed three weekly sessions (30 minutes) of exercise training for 12 weeks. Primary outcomes included safety assessed as adverse events and patient-reported exercise experience assessed as postexercise response and evaluation of exercise equipment. Secondary outcomes included the Multiple Sclerosis Functional Composite, the Modified Fatigue Impact Scale, and the Multiple Sclerosis Quality of Life-54 questionnaire scores. Assessments were conducted at baseline and after 12 weeks. Results: Safety was confirmed in both exercise groups. Participants reported enjoying both exercise modalities; however, TBRST was reviewed more favorably. Both interventions reduced fatigue and improved HRQOL (P ≤ .05); there were no changes in function. Conclusions: Both TBRST and BWSTT seem to be safe, well tolerated, and enjoyable for participants with progressive MS with severe disability. Both interventions may also be efficacious for reducing fatigue and improving HRQOL. TBRST should be further explored as an exercise rehabilitation tool for patients with progressive MS.
Hong, Xiangchan; Chen, Qi; Ding, Lingyu; Liang, Ying; Zhou, Ningning; Fang, Wenfeng; Chen, Xinru; Wu, Haiying
2017-06-20
Although most patients with ALK-positive non-small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively. The impact of continued crizotinib therapy on the patients' PFS2 time was assessed after adjusting for potential confounding factors. With initial crizotinib therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33 patients were 63.6% and 8.6 months, respectively. With continued crizotinib therapy after documentation of PD, the median PFS2 for all 33 patients was 16 weeks, and in those with CNS progression but systemic disease control it was 30 weeks. Patients who received local therapy after disease progression had a significantly longer PFS2 compared with those who did not (P = 0.039). Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2. This study provides further evidence of the benefit of continuing crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC. Patients with a longer PFS1 and those who received local brain therapy would have a longer period of continuing crizotinib.
Current perspective of the impact of smoking on the progression and treatment of periodontitis.
Nociti, Francisco H; Casati, Marcio Z; Duarte, Poliana Mendes
2015-02-01
This literature review provides an overview of the current scenario regarding the impact of smoking on the progression and treatment of periodontitis; clinical, microbiological and immunological data from studies from our and other groups are presented. In general, preclinical and clinical data are unanimous in demonstrating that smokers present increased susceptibility, greater severity and faster progression of periodontal disease compared with nonsmokers. The evidence further demonstrates that smokers lose more teeth and have a less favorable response to therapy than do nonsmokers. Although it is well established that smoking significantly impacts on the onset, progression and outcome of periodontal disease, the mechanisms involved remain unclear. More importantly, some of the reported deleterious effects of smoking on periodontal tissues have been reported to be reversible upon participation in smoking-cessation programs. Therefore, clinicians should strongly advise smokers to enroll in cessation strategies, even temporarily, in order to improve the overall outcome. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
ERIC Educational Resources Information Center
Suhre, Cor J. M.; Jansen, Ellen P. W. A.; Torenbeek, M.
2013-01-01
Timely completion of university degree programmes is a topic of growing concern to higher education institutions and their students. This paper reports on a study about the impact of degree programme characteristics and student motivation on study progress. The setting for the study is a Dutch law school. Data on degree programme characteristics,…
Investigating the Impact of the Premier League Reading Stars Programme on Children's Attainment
ERIC Educational Resources Information Center
Pabion, Clémence
2014-01-01
The evaluation of the Premier League Reading Stars (PLRS) programme in 2013 has established that the intervention is having a positive impact on the attainment of participating children in reading and writing: Three out of four children made at least six months' progress in just ten weeks. One child in three made a year's progress or more. The…
ERIC Educational Resources Information Center
Webb, Oliver; Wyness, Lynne; Cotton, Debby
2017-01-01
This report presents a synthesis of literature--published since 2008--that demonstrates significant impact in each of the key student outcomes of access, retention, attainment, and progression. This builds on a number of key Higher Education Academy (HEA) publications or projects from the past five years that have addressed issues associated with…
Endocannabinoid system: potential novel targets for treatment of schizophrenia.
Saito, Atsushi; Ballinger, Michael D L; Pletnikov, Mikhail V; Wong, Dean F; Kamiya, Atsushi
2013-05-01
Accumulating epidemiological evidences suggest that cannabis use during adolescence is a potential environmental risk for the development of psychosis, including schizophrenia. Consistently, clinical and preclinical studies, using pharmacological approaches and genetically engineered animals to target endocannabinoid signaling, reveal the multiple varieties of endocannabinoid system-mediated human and animal behaviors, including cognition and emotion. Recently, there has been substantial progress in understanding the molecular mechanisms of the endocannabinoid system for synaptic communications in the central nervous system. Furthermore, the impact of endocannabinoid signaling on diverse cellular processes during brain development has emerged. Thus, although schizophrenia has etiological complexities, including genetic heterogeneities and multiple environmental factors, it now becomes crucial to explore molecular pathways of convergence of genetic risk factors and endocannabinoid signaling, which may provide us with clues to find novel targets for therapeutic intervention. In this review, epidemiological, clinical, and pathological evidences on the role of the endocannabinoid system in the pathophysiologies of schizophrenia will be presented. We will also make a brief overview of the recent progress in understanding molecular mechanisms of the endocannabinoid system for brain development and function, with particular focus on cannabinoid receptor type 1 (CB1R)-mediated cascade, the most well-characterized cannabinoid receptor. Lastly, we will discuss the potential of the endocannabinoid system in finding novel therapeutic targets for prevention and treatment of schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.
Arteca, Ellen M.; Newman, Jonathan A.
2017-01-01
D. suzukii is a relatively recent and destructive pest species to the North American soft-skinned fruit industry. Understanding this species’ potential to shift in abundance and range due to changing climate is an important part of an effective mitigation and management strategy. We parameterized a temperature-driven D. suzukii population dynamics model using temperature data derived from several Global Circulation Models (CMIP5) with a range of relative concentration pathway (RCP) predictions. Mean consensus between the models suggest that without adaptation to both higher prolonged temperatures and higher short-term temperature events D. suzukii population levels are likely to drop in currently higher-risk regions. The potential drop in population is evident both as time progresses and as the severity of the RCP scenario increases. Some regions, particularly in northern latitudes, may experience increased populations due to milder winter and more developmentally-ideal summer conditions, but many of these regions are not currently known for soft-skinned fruit production and so the effects of this population increase may not have a significant impact. PMID:28396828
Resistant starch: promise for improving human health.
Birt, Diane F; Boylston, Terri; Hendrich, Suzanne; Jane, Jay-Lin; Hollis, James; Li, Li; McClelland, John; Moore, Samuel; Phillips, Gregory J; Rowling, Matthew; Schalinske, Kevin; Scott, M Paul; Whitley, Elizabeth M
2013-11-01
Ongoing research to develop digestion-resistant starch for human health promotion integrates the disciplines of starch chemistry, agronomy, analytical chemistry, food science, nutrition, pathology, and microbiology. The objectives of this research include identifying components of starch structure that confer digestion resistance, developing novel plants and starches, and modifying foods to incorporate these starches. Furthermore, recent and ongoing studies address the impact of digestion-resistant starches on the prevention and control of chronic human diseases, including diabetes, colon cancer, and obesity. This review provides a transdisciplinary overview of this field, including a description of types of resistant starches; factors in plants that affect digestion resistance; methods for starch analysis; challenges in developing food products with resistant starches; mammalian intestinal and gut bacterial metabolism; potential effects on gut microbiota; and impacts and mechanisms for the prevention and control of colon cancer, diabetes, and obesity. Although this has been an active area of research and considerable progress has been made, many questions regarding how to best use digestion-resistant starches in human diets for disease prevention must be answered before the full potential of resistant starches can be realized.
Resistant Starch: Promise for Improving Human Health12
Birt, Diane F.; Boylston, Terri; Hendrich, Suzanne; Jane, Jay-Lin; Hollis, James; Li, Li; McClelland, John; Moore, Samuel; Phillips, Gregory J.; Rowling, Matthew; Schalinske, Kevin; Scott, M. Paul; Whitley, Elizabeth M.
2013-01-01
Ongoing research to develop digestion-resistant starch for human health promotion integrates the disciplines of starch chemistry, agronomy, analytical chemistry, food science, nutrition, pathology, and microbiology. The objectives of this research include identifying components of starch structure that confer digestion resistance, developing novel plants and starches, and modifying foods to incorporate these starches. Furthermore, recent and ongoing studies address the impact of digestion-resistant starches on the prevention and control of chronic human diseases, including diabetes, colon cancer, and obesity. This review provides a transdisciplinary overview of this field, including a description of types of resistant starches; factors in plants that affect digestion resistance; methods for starch analysis; challenges in developing food products with resistant starches; mammalian intestinal and gut bacterial metabolism; potential effects on gut microbiota; and impacts and mechanisms for the prevention and control of colon cancer, diabetes, and obesity. Although this has been an active area of research and considerable progress has been made, many questions regarding how to best use digestion-resistant starches in human diets for disease prevention must be answered before the full potential of resistant starches can be realized. PMID:24228189
Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects.
Vargas, Jose Ignacio; Arrese, Marco; Shah, Vijay H; Arab, Juan Pablo
2017-09-01
The purpose of this study is to analyze the current evidence regarding the use of statins in patients with chronic liver disease and cirrhosis. Chronic liver disease (CLD), cirrhosis, and its complications, including hepatocellular carcinoma (HCC), are significant public health problems. The use of statins in patients with CLD has been a matter of concern, and physicians are often reluctant to its prescription in these patients. This mainly relates to the potential occurrence of drug-induced liver injury. However, newer evidence from pre-clinical and clinical research has shown that statins are drugs with a potentially beneficial impact on the natural history of cirrhosis, on portal hypertension, and in HCC prevention. In this review, we summarize current evidence regarding the influence of statins in endothelial dysfunction in CLD, their ability to modulate hepatic fibrogenesis, and their vasoprotective effects in portal hypertension; we also focus on existing data about the impact of statins in cirrhosis development, progression, and complications and critically assess the current concerns about its use in patients with CLD.
Aerts, Céline; Sunyoto, Temmy; Tediosi, Fabrizio; Sicuri, Elisa
2017-07-01
Pharmaceutical companies are reluctant to invest in research and development (R&D) of products for neglected tropical diseases (NTDs) mainly due to the low ability-to-pay of health insurance systems and of potential consumers. The available preventive and curative interventions for NTDs mostly rely on old technologies and products that are often not adequate. Moreover, NTDs mostly affect populations living in remote rural areas and conflict zones, thereby hampering access to healthcare. The challenges posed by NTDs have led to the proliferation of a variety of public-private partnerships (PPPs) in the last decades. We conducted a systematic review to assess the functioning and impact of these partnerships on the development of and access to better technologies for NTDs. Our systematic review revealed a clear lack of empirical assessment of PPPs: we could not find any impact evaluation analyses, while these are crucial to realize the full potential of PPPs and to progress further towards NTDs elimination. Copyright © 2017 Elsevier B.V. All rights reserved.
The future impacts of non-targeted effects.
Bright, Scott; Kadhim, Munira
2018-04-11
Ionizing radiation was traditionally thought to exert its detrimental effects through interaction with sensitive cellular targets, nuclear DNA being of most importance. This theory has since merged with a more recently described radiation response called non-targeted effects (NTE). This review will briefly look at the various types of NTE and the potential implications they may have for radiobiology research and its applications. The most well-known NTE are genomic instability (GI) and bystander effects (BE). Other NTE include abscopal effects, which are similar to bystander effects but are generally based in a clinical environment with immune involvement as the defining feature. Currently, our understanding of NTE is limited to certain signaling pathways/molecules, and as yet there is no theory that describes or can accurately predict the occurrence or outcome of these NTE. There are numerous groups investigating these processes in vitro and in vivo, and thus steady progress is being made. Developing a deeper understanding of NTE has potential impacts for therapy and diagnosis, safer occupational exposures, space flight and our general understanding of radiation biology.
Lavie, Carl J; McAuley, Paul A; Church, Timothy S; Milani, Richard V; Blair, Steven N
2014-04-15
Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Wu, Feng; Zhang, Alice; Babbitt, Andrew; Ma, Qingyan; Eyal, Nir; Pan, Xin; Cai, Weiping; Hu, Fengyu; Cheng, Yu; Tucker, Joseph D
2017-11-17
Despite global progress in HIV stigma reduction, persistent HIV stigma thwarts effective HIV service delivery. Advances in HIV biomedical research toward a cure may shift perceptions of people living with HIV and HIV stigma. The purpose of this study was to examine how men who have sex with men (MSM) living with HIV in Guangzhou, China perceive HIV cure research and its potential impact on MSM and HIV stigma. We conducted in-depth interviews with 26 MSM living with HIV about their perceptions of HIV cure research and the potential impact of an HIV cure on their lives. Thematic coding was used to identify themes and structure the analysis. Two overarching themes emerged. First, participants stated that an HIV cure may have a limited impact on MSM-related stigma. Men noted that most stigma toward MSM was linked to stereotypes of promiscuity and high rates of sexual transmitted diseases in the MSM community and might persist even after a cure. Second, participants believed that an HIV cure could substantially reduce enacted, anticipated, and internalized stigma associated with HIV. These findings suggest that a biomedical cure alone would not remove the layered stigma facing MSM living with HIV. Comprehensive measures to reduce stigma are needed.
Zheng, Meixun; Bender, Daniel
2018-03-13
Computer-based testing (CBT) has made progress in health sciences education. In 2015, the authors led implementation of a CBT system (ExamSoft) at a dental school in the U.S. Guided by the Technology Acceptance Model (TAM), the purposes of this study were to (a) examine dental students' acceptance of ExamSoft; (b) understand factors impacting acceptance; and (c) evaluate the impact of ExamSoft on students' learning and exam performance. Survey and focus group data revealed that ExamSoft was well accepted by students as a testing tool and acknowledged by most for its potential to support learning. Regression analyses showed that perceived ease of use and perceived usefulness of ExamSoft significantly predicted student acceptance. Prior CBT experience and computer skills did not significantly predict acceptance of ExamSoft. Students reported that ExamSoft promoted learning in the first program year, primarily through timely and rich feedback on examination performance. t-Tests yielded mixed results on whether students performed better on computerized or paper examinations. The study contributes to the literature on CBT and the application of the TAM model in health sciences education. Findings also suggest ways in which health sciences institutions can implement CBT to maximize its potential as an assessment and learning tool.
High temperatures disrupt Artemia franciscana mating patterns and impact sexual selection intensity
NASA Astrophysics Data System (ADS)
Santos, Maria R.; Vieira, Natividade; Monteiro, Nuno M.
2018-07-01
Temperature plays a critical role in survival and reproduction, especially in ectotherms. Therefore, it is important to understand the mechanisms influencing life history traits and reproductive behaviours in order to predict climate change impacts on species' occurrence and performance. Here, we used the crustacean Artemia franciscana to investigate the potential impacts of temperature on life history traits, mating patterns and intensity of sexual selection. We reared A. franciscana at three temperatures 20 °C, 25 °C, and 30 °C and measured life history traits such as growth, mortality or development of sexual traits. Our observations confirmed a clear link between life history traits and temperature, with advanced sexual maturity and increased mortality rates following temperature rises. Also, we found that mating is size assortative close to the ideal developmental temperature. Nevertheless, when temperatures deviate from the optimum, mating patterns were altered. Although selection intensity for females remained similar at all tested temperatures, as males preferentially mated with the larger females, size assortative mating disappeared at the highest temperature. Overall, our results highlight the potential for a temperature-dependent disruption of A. franciscana mating patterns. This disruption is especially pronounced under high temperatures as reproduction becomes progressively more random, thus entailing a relaxation of sexual selection intensity.
Tonry, Claire; Armstrong, John; Pennington, Stephen
2017-01-01
Approximately one in six men are diagnosed with Prostate Cancer every year in the Western world. Although it can be well managed and non-life threatening in the early stages, over time many patients cease to respond to treatment and develop castrate resistant prostate cancer (CRPC). CRPC represents a clinically challenging and lethal form of prostate cancer. Progression of CRPC is, in part, driven by the ability of cancer cells to alter their metabolic profile during the course of tumourgenesis and metastasis so that they can survive in oxygen and nutrient-poor environments and even withstand treatment. This work was carried out as a continuation of a study aimed towards gaining greater mechanistic understanding of how conditions within the tumour microenvironment impact on both androgen sensitive (LNCaP) and androgen independent (LNCaP-abl and LNCaP-abl-Hof) prostate cancer cell lines. Here we have applied technically robust and reproducible label-free liquid chromatography mass spectrometry analysis for comprehensive proteomic profiling of prostate cancer cell lines under hypoxic conditions. This led to the identification of over 4,000 proteins – one of the largest protein datasets for prostate cancer cell lines established to date. The biological and clinical significance of proteins showing a significant change in expression as result of hypoxic conditions was established. Novel, intuitive workflows were subsequently implemented to enable robust, reproducible and high throughput verification of selected proteins of interest. Overall, these data suggest that this strategy supports identification of protein biomarkers of prostate cancer progression and potential therapeutic targets for CRPC. PMID:28410543
Du Four, Stephanie; Maenhout, Sarah K; Benteyn, Daphné; De Keersmaecker, Brenda; Duerinck, Johnny; Thielemans, Kris; Neyns, Bart; Aerts, Joeri L
2016-06-01
Recurrent glioblastoma is associated with a poor overall survival. Antiangiogenic therapy results in a high tumor response rate but has limited impact on survival. Immunotherapy has emerged as an efficient treatment modality for some cancers, and preclinical evidence indicates that anti-VEGF(R) therapy can counterbalance the immunosuppressive tumor microenvironment. We collected peripheral blood mononuclear cells (PBMC) of patients with recurrent glioblastoma treated in a randomized phase II clinical trial comparing the effect of axitinib with axitinib plus lomustine and analyzed the immunophenotype of PBMC, the production of cytokines and expression of inhibitory molecules by circulating T cells. PBMC of 18 patients were collected at baseline and at 6 weeks after initiation of study treatment. Axitinib increased the number of naïve CD8(+) T cells and central memory CD4(+) and CD8(+) T cells and reduced the TIM3 expression on CD4(+) and CD8(+) T cells. Patients diagnosed with progressive disease on axitinib had a significantly increased number of regulatory T cells and an increased level of PD-1 expression on CD4(+) and CD8(+) T cells. In addition, reduced numbers of cytokine-producing T cells were found in progressive patients as compared to patients responding to treatment. Our results suggest that axitinib treatment in patients with recurrent glioblastoma has a favorable impact on immune function. At the time of acquired resistance to axitinib, we documented further enhancement of a preexisting immunosuppression. Further investigations on the role of axitinib as potential combination partner with immunotherapy are necessary.
Liu, Jia; Shui, Sai-Lan
2016-12-28
The advent of site-specific nucleases, particularly CRISPR/Cas9, provides researchers with the unprecedented ability to manipulate genomic sequences. These nucleases are used to create model cell lines, engineer metabolic pathways, produce transgenic animals and plants, perform genome-wide functional screen and, most importantly, treat human diseases that are difficult to tackle by traditional medications. Considerable efforts have been devoted to improving the efficiency and specificity of nucleases for clinical applications. However, safe and efficient delivery methods remain the major obstacle for therapeutic gene editing. In this review, we summarize the recent progress on nuclease delivery methods, highlight their impact on the outcomes of gene editing and discuss the potential of different delivery approaches for therapeutic gene editing. Copyright © 2016 Elsevier B.V. All rights reserved.
Hazards to Early Development: The Biological Embedding of Early Life Adversity.
Nelson, Charles A
2017-10-11
The number of children under 18 years of age has increased worldwide over the past decade. This growth spurt is due, in part, to remarkable progress in child survival. Alas, surviving early hazards, like prematurity or infectious disease, does not guarantee that children's development will not be compromised by other hazards as they grow older. Throughout the world, children continue to be confronted with a large number of biological and psychosocial challenges that greatly limit their developmental potential. The focus of this article is how such adverse experiences impact the developing brain. Copyright © 2017 Elsevier Inc. All rights reserved.
Protein Arginine Methylation and Citrullination in Epigenetic Regulation
2015-01-01
The post-translational modification of arginine residues represents a key mechanism for the epigenetic control of gene expression. Aberrant levels of histone arginine modifications have been linked to the development of several diseases including cancer. In recent years, great progress has been made in understanding the physiological role of individual arginine modifications and their effects on chromatin function. The present review aims to summarize the structural and functional aspects of histone arginine modifying enzymes and their impact on gene transcription. We will discuss the potential for targeting these proteins with small molecules in a variety of disease states. PMID:26686581
The Nucleosome Remodeling and Deacetylase (NuRD) Complex in Development and Disease
Basta, Jeannine; Rauchman, Michael
2014-01-01
The Nucleosome Remodeling and Deacetylase (NuRD) complex is one of the major chromatin remodeling complexes found in cells. It plays an important role in regulating gene transcription, genome integrity and cell cycle progression. Through its impact on these basic cellular processes, increasing evidence indicates that alterations in the activity of this macromolecular complex can lead to developmental defects, oncogenesis and accelerated ageing. Recent genetic and biochemical studies have elucidated the mechanisms of NuRD action in modifying the chromatin landscape. These advances have the potential to lead to new therapeutic approaches to birth defects and cancer. PMID:24880148
The potential impact of the preparation rich in growth factors (PRGF) in different medical fields.
Anitua, Eduardo; Sánchez, Mikel; Orive, Gorka; Andía, Isabel
2007-11-01
Platelet-rich preparations constitute a relatively new biotechnology for the stimulation and acceleration of tissue healing and bone regeneration. The versatility and biocompatibility of this approach has stimulated its therapeutic use in numerous medical and scientific fields including dentistry, oral implantology, orthopaedics, ulcer treatment, tissue engineering among others. Here we discuss the important progress that has been accomplished in the field of platelet-rich preparations in the last few years. Some of the most interesting therapeutic applications of this technology are discussed as are some of the limitations, future challenges and directions in the field.
2012-01-01
Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy. Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies. Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals’ quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases. Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits. We call upon Europe’s policy-makers to coordinate actions and improve individual and public health in allergy by: Promoting awareness of the effectiveness of allergen specific immunotherapy Updating national healthcare policies to support allergen specific immunotherapy Prioritising funding for allergen specific immunotherapy research Monitoring the macroeconomic and health economic parameters of allergy Reinforcing allergy teaching in medical disciplines and specialties The effective implementation of the above policies has the potential for a major positive impact on European health and well-being in the next decade. PMID:23110958
Impact of stress on cancer metastasis
Moreno-Smith, Myrthala; Lutgendorf, Susan K; Sood, Anil K
2011-01-01
The influence of psychosocial factors on the development and progression of cancer has been a longstanding hypothesis since ancient times. In fact, epidemiological and clinical studies over the past 30 years have provided strong evidence for links between chronic stress, depression and social isolation and cancer progression. By contrast, there is only limited evidence for the role of these behavioral factors in cancer initiation. Recent cellular and molecular studies have identified specific signaling pathways that impact cancer growth and metastasis. This article provides an overview of the relationship between psychosocial factors, specifically chronic stress, and cancer progression. PMID:21142861
Clifford, Katie L.; Zaman, Muhammad H.
2016-01-01
The recent drafting of the Sustainable Development Goals challenges the research community to rethink the traditional approach to global health and provides the opportunity for science, technology, engineering, and mathematical (STEM) disciplines, particularly engineering, to demonstrate their benefit to the field. Higher education offers a platform for engineering to intersect with global health research through interdisciplinary partnerships among international universities that provide excellence in education, attract nontraditional STEM students, and foster a sense of innovation. However, a traditional lack of engineering–global health collaborations, as well as limited faculty and inadequate STEM research funding in low-income countries, has stifled progress. Still, the impact of higher education on development efforts holds great potential. This value will be realized in low-income countries through strengthening local capacity, supporting innovation through educational initiatives, and encouraging the inclusion of women and minorities in STEM programs. Current international university-level partnerships are working towards integrating engineering into global health research and strengthening STEM innovation among universities in low-income countries, but more can be done. Global health research informs sustainable development, and through integrating engineering into research efforts through university partnerships, we can accelerate progress and work towards a healthier future for all. PMID:26790462
McInerney, Mitchell P; Short, Jennifer L; Nicolazzo, Joseph A
2017-07-01
Despite a century of steady and incremental progress toward understanding the underlying biochemical mechanisms, Alzheimer's disease (AD) remains a complicated and enigmatic disease, and greater insight will be necessary before substantive clinical success is realised. Over the last decade in particular, a large body of work has highlighted the cerebral microvasculature as an anatomical region with an increasingly apparent role in the pathogenesis of AD. The causative interplay and temporal cascade that manifest between the brain vasculature and the wider disease progression of AD are not yet fully understood, and further inquiry is required to properly characterise these relationships. The purpose of this review is to highlight the recent advancements in research implicating neurovascular factors in AD, at both the molecular and anatomical levels. We begin with a brief introduction of the biochemical and genetic aspects of AD, before reviewing the essential concepts of the blood-brain barrier (BBB) and the neurovascular unit (NVU). In detail, we then examine the evidence demonstrating involvement of BBB dysfunction in AD pathogenesis, highlighting the importance of neurovascular components in AD. Lastly, we include within this review research that focuses on how altered properties of the BBB in AD impact upon CNS exposure of therapeutic agents and the potential clinical impact that this may have on people with this disease.
Sanz, Ana B; Sanchez-Niño, María Dolores; Martín-Cleary, Catalina; Ortiz, Alberto; Ramos, Adrián M
2013-07-01
Acute kidney injury (AKI) is a clinical syndrome characterized by the acute loss of kidney function. AKI is increasingly frequent and is associated with impaired survival and chronic kidney disease progression. Experimental AKI models have contributed to a better understanding of pathophysiological mechanisms but they have not yet resulted in routine clinical application of novel therapeutic approaches. The authors present the advances in experimental AKI models over the last decade. Furthermore, the authors review their current and expected impact on novel drug discovery. New AKI models have been developed in rodents and non-rodents. Non-rodents allow the evaluation of specific aspects of AKI in both bigger animals and simpler organisms such as drosophila and zebrafish. New rodent models have recently reproduced described clinical entities, such as aristolochic and warfarin nephropathies, and have also provided better models for old entities such as thrombotic microangiopathy-induced AKI. Several therapies identified in animal models are now undergoing clinical trials in human AKI, including p53 RNAi and bone-marrow derived mesenchymal stem cells. It is conceivable that further refinement of animal models in combination with ongoing trials and novel trials based on already identified potential targets will eventually yield effective therapies for clinical AKI.
Modelling of Damage Evolution in Braided Composites: Recent Developments
NASA Astrophysics Data System (ADS)
Wang, Chen; Roy, Anish; Silberschmidt, Vadim V.; Chen, Zhong
2017-12-01
Composites reinforced with woven or braided textiles exhibit high structural stability and excellent damage tolerance thanks to yarn interlacing. With their high stiffness-to-weight and strength-to-weight ratios, braided composites are attractive for aerospace and automotive components as well as sports protective equipment. In these potential applications, components are typically subjected to multi-directional static, impact and fatigue loadings. To enhance material analysis and design for such applications, understanding mechanical behaviour of braided composites and development of predictive capabilities becomes crucial. Significant progress has been made in recent years in development of new modelling techniques allowing elucidation of static and dynamic responses of braided composites. However, because of their unique interlacing geometric structure and complicated failure modes, prediction of damage initiation and its evolution in components is still a challenge. Therefore, a comprehensive literature analysis is presented in this work focused on a review of the state-of-the-art progressive damage analysis of braided composites with finite-element simulations. Recently models employed in the studies on mechanical behaviour, impact response and fatigue analyses of braided composites are presented systematically. This review highlights the importance, advantages and limitations of as-applied failure criteria and damage evolution laws for yarns and composite unit cells. In addition, this work provides a good reference for future research on FE simulations of braided composites.
7 CFR 3402.23 - Documentation of progress on funded projects.
Code of Federal Regulations, 2011 CFR
2011-01-01
... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...
7 CFR 3402.23 - Documentation of progress on funded projects.
Code of Federal Regulations, 2014 CFR
2014-01-01
... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...
7 CFR 3402.23 - Documentation of progress on funded projects.
Code of Federal Regulations, 2012 CFR
2012-01-01
... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...
7 CFR 3402.23 - Documentation of progress on funded projects.
Code of Federal Regulations, 2013 CFR
2013-01-01
... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...
Interactions between biomaterials and the sclera: Implications on myopia progression
NASA Astrophysics Data System (ADS)
Su, James
Myopia prevalence has steadily climbed worldwide in recent decades with the most dramatic impact in East Asian countries. Treatments such as eyeglasses, contact lenses, and laser surgery for the refractive error are widely available, but none cures the underlying cause. In progressive high myopia, invasive surgical procedures using a scleral buckle for mechanical support are performed since the patient is at risk of becoming blind. The treatment outcome is highly dependent on the surgeon's skills and the patient's myopia progression rate, with limited choices in buckling materials. This dissertation, in four main studies, represents efforts made to control high myopia progression through the exploration and development of biomaterials that influence scleral growth. First, mRNA expression levels of the chick scleral matrix metalloproteinases, tissue-inhibitor of matrix metalloproteinases, and transforming growth factor-beta 2 were assessed for temporal and defocus power effects. The first study elucidated the roles that these factors play in scleral growth regulation and suggested potential motifs that can be incorporated in future biomaterials design. Second, poly(vinyl-pyrrolidone) as injectable gels and poly(2-hydroxyethyl methacrylate) as solid strips were implanted in chicks to demonstrate the concept of posterior pole scleral reinforcements. This second study found that placing appropriate biomaterials at the posterior pole of the eye could directly influence scleral remodeling by interacting with the host cells. Both studies advanced the idea that scleral tissue remodeling could be potentially controlled by well-designed biomaterials. These findings led to the exploration of biomimetic hydrogels comprising enzymatically-degradable semi-interpenetrating polymer networks (edsIPNs) to determine their biocompatibility and effects on the chick posterior eye wall. This third study demonstrated the feasibility of stimulating scleral growth by applying biomimetic injectable materials. Fourth, the muscarinic antagonist drug, atropine, was encapsulated within the edsIPNs and delivered to the chick eye posterior pole to evaluate the local effect of atropine release. This fourth study offered an alternative method of ocular drug delivery for treatment of myopia, with the potential to elucidate the actual location of the inhibitive effect of atropine on myopia progression. In summary, this dissertation contributes to the design and use of biomaterials specific to myopia therapy and adds novel insights to scleral tissue engineering.
The progression rate of spinocerebellar ataxia type 2 changes with stage of disease.
Monte, Thais Lampert; Reckziegel, Estela da Rosa; Augustin, Marina Coutinho; Locks-Coelho, Lucas D; Santos, Amanda Senna P; Furtado, Gabriel Vasata; de Mattos, Eduardo Preusser; Pedroso, José Luiz; Barsottini, Orlando Póvoas; Vargas, Fernando Regla; Saraiva-Pereira, Maria-Luiza; Camey, Suzi Alves; Leotti, Vanessa Bielefeldt; Jardim, Laura Bannach
2018-01-25
Spinocerebellar ataxia type 2 (SCA2) affects several neurological structures, giving rise to multiple symptoms. However, only the natural history of ataxia is well known, as measured during the study duration. We aimed to describe the progression rate of ataxia, by the Scale for the Assessment and Rating of Ataxia (SARA), as well as the progression rate of the overall neurological picture, by the Neurological Examination Score for Spinocerebellar Ataxias (NESSCA), and not only during the study duration but also in a disease duration model. Comparisons between these models might allow us to explore whether progression is linear during the disease duration in SCA2; and to look for potential modifiers. Eighty-eight evaluations were prospectively done on 49 symptomatic subjects; on average (SD), study duration and disease duration models covered 13 (2.16) months and 14 (6.66) years of individuals' life, respectively. SARA progressed 1.75 (CI 95%: 0.92-2.57) versus 0.79 (95% CI 0.45 to 1.14) points/year in the study duration and disease duration models. NESSCA progressed 1.45 (CI 95%: 0.74-2.16) versus 0.41 (95% CI 0.24 to 0.59) points/year in the same models. In order to explain these discrepancies, the progression rates of the study duration model were plotted against disease duration. Then an acceleration was detected after 10 years of disease duration: SARA scores progressed 0.35 before and 2.45 points/year after this deadline (p = 0.013). Age at onset, mutation severity, and presence of amyotrophy, parkinsonism, dystonic manifestations and cognitive decline at baseline did not influence the rate of disease progression. NESSCA and SARA progression rates were not constant during disease duration in SCA2: early phases of disease were associated with slower progressions. Modelling of future clinical trials on SCA2 should take this phenomenon into account, since disease duration might impact on inclusion criteria, sample size, and study duration. Our database is available online and accessible to future studies aimed to compare the present data with other cohorts.
The Interaction Between Thyroid and Kidney Disease: An Overview of the Evidence
Rhee, Connie M.
2016-01-01
Purpose of Review Hypothyroidism is highly prevalent in chronic kidney disease (CKD) patients, including those receiving dialysis. This review examines potential mechanistic links between thyroid and kidney disease; current evidence for hypothyroidism as a risk factor for de novo CKD and CKD progression; and studies of thyroid functional disorders, cardiovascular disease, and death in the CKD population. Recent Findings Epidemiologic data have demonstrated an incrementally higher prevalence of hypothyroidism with increasing severity of kidney dysfunction. Various thyroid functional test abnormalities are also commonly observed in CKD, due to alterations in thyroid hormone synthesis, metabolism, and regulation. While the mechanistic link between thyroid and kidney disease remains unclear, observational studies suggest hypothyroidism is associated with abnormal kidney structure and function. Previously thought to be a physiologic adaptation, recent studies show that hypothyroidism is associated with higher risk of cardiovascular disease and death in CKD. Summary A growing body of evidence suggests that hypothyroidism is a risk factor for incident CKD, CKD progression, and higher death risk in kidney disease patients. Rigorous studies are needed to determine impact of thyroid hormone replacement upon kidney disease progression, cardiovascular disease, and mortality, which may shed light into the causal implications of hypothyroidism in CKD. PMID:27428519
Progress in Energy Storage Technologies: Models and Methods for Policy Analysis
NASA Astrophysics Data System (ADS)
Matteson, Schuyler W.
Climate change and other sustainability challenges have led to the development of new technologies that increase energy efficiency and reduce the utilization of finite resources. To promote the adoption of technologies with social benefits, governments often enact policies that provide financial incentives at the point of purchase. In their current form, these subsidies have the potential to increase the diffusion of emerging technologies; however, accounting for technological progress can improve program success while decreasing net public investment. This research develops novel methods using experience curves for the development of more efficient subsidy policies. By providing case studies in the field of automotive energy storage technologies, this dissertation also applies the methods to show the impacts of incorporating technological progress into energy policies. Specific findings include learning-dependent tapering subsidies for electric vehicles based on the lithium-ion battery experience curve, the effects of residual learning rates in lead-acid batteries on emerging technology cost competitiveness, and a cascading diffusion assessment of plug-in hybrid electric vehicle subsidy programs. Notably, the results show that considering learning rates in policy development can save billions of dollars in public funds, while also lending insight into the decision of whether or not to subsidize a given technology.
NASA Technical Reports Server (NTRS)
Crawford, D. A.; Schultz, P. H.
1993-01-01
The production of transient magnetic fields by hypervelocity meteoroid impact has been proposed to possibly explain the presence of paleomagnetic fields in certain lunar samples as well as across broader areas of the lunar surface. In an effort to understand the lunar magnetic record, continued experiments at the NASA Ames Vertical Gun Range allow characterizing magnetic fields produced by the 5 km/s impacts of 0.32-0.64 cm projectiles over a broad range of impact angles and projectile/target compositions. From such studies, another phenomenon has emerged, macroscopic electric charge separation, that may have importance for the magnetic state of solid-body surfaces. This phenomenon was observed during explosive cratering experiments, but the magnetic consequences of macroscopic electric charge separation (as opposed to plasma production) during explosion and impact cratering have not, to our knowledge, been explored before now. It is straightforward to show that magnetic field production due to this process may scale as a weakly increasing function of impactor kinetic energy, although more work is needed to precisely assess the scaling dependence. The original intent of our experiments was to assess the character of purely electrostatic signals for comparison with inferred electrostatic noise signals acquired by shielded magnetic sensors buried within particulate dolomite targets. The results demonstrated that electrostatic noise does affect the magnetic sensors but only at relatively short distances (less than 4 cm) from the impact point (our magnetic studies are generally performed at distances greater than approximately 5.5 cm). However, to assess models for magnetic field generation during impact, measurements are needed of the magnetic field as close to the impact point as possible; hence, work with an improved magnetic sensor design is in progress. In this paper, we focus on electric charge separation during hypervelocity impacts as a potential transient magnetic field production mechanism in its own right.
NASA Astrophysics Data System (ADS)
Irby, I.; Friedrichs, M. A. M.
2017-12-01
Human impacts on the Chesapeake Bay through increased nutrient run-off as a result of land-use change, urbanization, and industrialization, have resulted in a degradation of water quality over the last half-century. These direct impacts, compounded with human-induced climate changes such as warming, rising sea level, and changes in precipitation, have elevated the conversation surrounding the future of the Bay's water quality. As a result, in 2010, a Total Maximum Daily Load (TMDL) was established for the Chesapeake Bay that limited nutrient and sediment input in an effort to increase dissolved oxygen. This research utilizes a multiple model approach to evaluate confidence in the estuarine water quality modeling portion of the TMDL. One of the models is then used to assess the potential impact climate change may have on the success of currently mandated nutrient reduction levels in 2050. Results demonstrate that although the models examined differ structurally and in biogeochemical complexity, they project a similar attainment of regulatory water quality standards after nutrient reduction, while also establishing that meeting water quality standards is relatively independent of hydrologic conditions. By developing a Confidence Index, this research identifies the locations and causes of greatest uncertainty in modeled projections of water quality. Although there are specific locations and times where the models disagree, this research lends an increased degree of confidence in the appropriateness of the TMDL levels and in the general impact nutrient reductions will have on Chesapeake Bay water quality under current environmental conditions. However, when examining the potential impacts of climate change, this research shows that the combined impacts of increasing temperature, sea level, and river flow negatively affect dissolved oxygen throughout the Chesapeake Bay and impact progress towards meeting the water quality standards associated with the TMDL with increased temperature as the primary culprit. These results, having been continually shared with the regulatory TMDL modelers, will aid in the decision making for the 2017 TMDL Mid-Point Assessment.
The current and potential impact of genetics and genomics on neuropsychopharmacology.
Harrison, Paul J
2015-05-01
One justification for the major scientific and financial investments in genetic and genomic studies in medicine is their therapeutic potential, both for revealing novel targets for drugs which treat the disease process, as well as allowing for more effective and safe use of existing medications. This review considers the extent to which this promise has yet been realised within psychopharmacology, how things are likely to develop in the foreseeable future, and the key issues involved. It draws primarily on examples from schizophrenia and its treatments. One observation is that there is evidence for a range of genetic influences on different aspects of psychopharmacology in terms of discovery science, but far less evidence that meets the standards required before such discoveries impact upon clinical practice. One reason is that results reveal complex genetic influences that are hard to replicate and usually of very small effect. Similarly, the slow progress being made in revealing the genes that underlie the major psychiatric syndromes hampers attempts to apply the findings to identify novel drug targets. Nevertheless, there are some intriguing positive findings of various kinds, and clear potential for genetics and genomics to play an increasing and major role in psychiatric drug discovery. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.
NASA Astrophysics Data System (ADS)
Guzelbaeva, G. T.; Rakhmatullina, D. K.; Akhmetshina, E. R.
2017-12-01
Increase in the number of small businesses and the lack of effectiveness of existing support at local and regional level have led to curb the development of entrepreneurial activity. The article presents the methodological tools for assessing the effectiveness, which allows to identify existing municipalities in the advantages and disadvantages for the implementation of entrepreneurial potential, including the effectiveness of state and municipal support measures, as well as calculate the degree of progress in the implementation of entrepreneurial potential. In order to evaluate the implementation of the business potential of the Republic of Tatarstan and the impact of their public support at the regional level was calculated indexes of business activity in the municipal districts (MD) of the republic. It should be noted that a major breakthrough in share of small and medium-sized businesses is important to the whole ecosystem. The method of evaluation of the implementation of entrepreneurial potential which is presented in this paper can be used by every competent organization to analyze and form the effective programs of the economic and finance development.
Cha, Seungman
2017-01-01
ABSTRACT Background: As the Millennium Development Goals campaign (MDGs) came to a close, clear evidence was needed on the contribution of the worldwide MDG campaign. Objective: We seek to determine the degree of difference in the reduction rate between the pre-MDG and MDG campaign periods and its statistical significance by region. Design: Unlike the prevailing studies that measured progress in 1990–2010, this study explores by percentage how much MDG progress has been achieved during the MDG campaign period and quantifies the impact of the MDG campaign on the maternal and under-five child mortality reduction during the MDG era by comparing observed values with counterfactual values estimated on the basis of the historical trend. Results: The low accomplishment of sub-Saharan Africa toward the MDG target mainly resulted from the debilitated progress of mortality reduction during 1990–2000, which was not related to the worldwide MDG campaign. In contrast, the other regions had already achieved substantial progress before the Millennium Declaration was proclaimed. Sub-Saharan African countries have seen the most remarkable impact of the worldwide MDG campaign on maternal and child mortality reduction across all different measurements. In sub-Saharan Africa, the MDG campaign has advanced the progress of the declining maternal mortality ratio and under-five mortality rate, respectively, by 4.29 and 4.37 years. Conclusions: Sub-Saharan African countries were frequently labeled as ‘off-track’, ‘insufficient progress’, or ‘no progress’ even though the greatest progress was achieved here during the worldwide MDG campaign period and the impact of the worldwide MDG campaign was most pronounced in this region in all respects. It is time to learn from the success stories of the sub-Saharan African countries. Erroneous and biased measurement should be avoided for the sustainable development goals to progress. PMID:28168932
Molnar, Christoph; Scherer, Almut; Baraliakos, Xenofon; de Hooge, Manouk; Micheroli, Raphael; Exer, Pascale; Kissling, Rudolf O; Tamborrini, Giorgio; Wildi, Lukas M; Nissen, Michael J; Zufferey, Pascal; Bernhard, Jürg; Weber, Ulrich; Landewé, Robert B M; van der Heijde, Désirée; Ciurea, Adrian
2018-01-01
To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity. © 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.
Carlson, Josh J; Suh, Kangho; Orfanos, Panos; Wong, William
2018-04-01
The recently completed ALEX trial demonstrated that alectinib improved progression-free survival, and delayed time to central nervous system progression compared with crizotinib in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer. However, the long-term clinical and economic impact of using alectinib vs. crizotinib has not been evaluated. The objective of this study was to determine the potential cost utility of alectinib vs. crizotinib from a US payer perspective. A cost-utility model was developed using partition survival methods and three health states: progression-free, post-progression, and death. ALEX trial data informed the progression-free and overall survival estimates. Costs included drug treatments and supportive care (central nervous system and non-central nervous system). Utility values were obtained from trial data and literature. Sensitivity analyses included one-way and probabilistic sensitivity analyses. Treatment with alectinib vs. crizotinib resulted in a gain of 0.91 life-years, 0.87 quality-adjusted life-years, and incremental costs of US$34,151, resulting in an incremental cost-effectiveness ratio of US$39,312/quality-adjusted life-year. Drug costs and utilities in the progression-free health state were the main drivers of the model in the one-way sensitivity analysis. From the probabilistic sensitivity analysis, alectinib had a 64% probability of being cost effective at a willingness-to-pay threshold of US$100,000/quality adjusted life-year. Alectinib increased time in the progression-free state and quality-adjusted life-years vs. crizotinib. The marginal cost increase was reflective of longer treatment durations in the progression-free state. Central nervous system-related costs were considerably lower with alectinib. Our results suggest that compared with crizotinib, alectinib may be a cost-effective therapy for treatment-naïve patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer.
ERIC Educational Resources Information Center
Rawashdeh, Awni; Al-namlah, Lamia
2015-01-01
To examine the impact of the usage of fixed and mobile broadband on the progress of continuing professional education (CPE) from the perspective of chartered accountants in Saudi Arabia, an e-mail survey was conducted. A random sampling of chartered accountants in Saudi Arabia was investigated. This research was aimed to identify any correlation…
ERIC Educational Resources Information Center
Schagen, Ian; Shamsan, Yarim
2007-01-01
Private schooling in the third world is on the increase and in particular in one of the low-income areas of India, where a data analysis on Hyderabad has been carried out. The University of Newcastle has conducted an initiative research in Hyderabad on the impact on pupils' progress in Reading and Spelling tests. This initiative was called…
The catchment based approach using catchment system engineering
NASA Astrophysics Data System (ADS)
Jonczyk, Jennine; Quinn, Paul; Barber, Nicholas; Wilkinson, Mark
2015-04-01
The catchment based approach (CaBa) has been championed as a potential mechanism for delivery of environmental directives such as the Water Framework Directive in the UK. However, since its launch in 2013, there has been only limited progress towards achieving sustainable, holistic management, with only a few of examples of good practice ( e.g. from the Tyne Rivers trust). Common issues with developing catchment plans over a national scale include limited data and resources to identify issues and source of those issues, how to systematically identify suitable locations for measures or suites of measures that will have the biggest downstream impact and how to overcome barriers for implementing solutions. Catchment System Engineering (CSE) is an interventionist approach to altering the catchment scale runoff regime through the manipulation of hydrological flow pathways throughout the catchment. A significant component of the runoff generation can be managed by targeting hydrological flow pathways at source, such as overland flow, field drain and ditch function, greatly reducing erosive soil losses. Coupled with management of farm nutrients at source, many runoff attenuation features or measures can be co-located to achieve benefits for water quality and biodiversity. A catchment, community-led mitigation measures plan using the CSE approach will be presented from a catchment in Northumberland, Northern England that demonstrate a generic framework for identification of multi-purpose features that slow, store and filter runoff at strategic locations in the landscape. Measures include within-field barriers, edge of field traps and within-ditch measures. Progress on the implementation of measures will be reported alongside potential impacts on the runoff regime at both local and catchment scale and costs.
Hong, Xiangchan; Chen, Qi; Ding, Lingyu; Liang, Ying; Zhou, Ningning; Fang, Wenfeng; Chen, Xinru; Wu, Haiying
2017-01-01
Purpose Although most patients with ALK-positive non?small-cell lung cancer (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients may be beneficial. In this study, we investigated whether Chinese patients with advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are predictive of a longer post-initial progression-free survival time (PFS2). Materials and Methods Data on 33 patients with ALK-positive NSCLC who achieved disease control with crizotinib were analyzed retrospectively. The impact of continued crizotinib therapy on the patients’ PFS2 time was assessed after adjusting for potential confounding factors. Results With initial crizotinib therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33 patients were 63.6% and 8.6 months, respectively. With continued crizotinib therapy after documentation of PD, the median PFS2 for all 33 patients was 16 weeks, and in those with CNS progression but systemic disease control it was 30 weeks. Patients who received local therapy after disease progression had a significantly longer PFS2 compared with those who did not (P = 0.039). Multivariable Cox regression analysis showed that the PFS1 with initial crizotinib treatment and local therapy were independent predictors of PFS2. Discussion This study provides further evidence of the benefit of continuing crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC. Patients with a longer PFS1 and those who received local brain therapy would have a longer period of continuing crizotinib. PMID:28427213
NASA Technical Reports Server (NTRS)
Sanchez, Christopher M.
2011-01-01
NASA White Sands Test Facility (WSTF) is leading an evaluation effort in advanced destructive and nondestructive testing of composite pressure vessels and structures. WSTF is using progressive finite element analysis methods for test design and for confirmation of composite pressure vessel performance. Using composite finite element analysis models and failure theories tested in the World-Wide Failure Exercise, WSTF is able to estimate the static strength of composite pressure vessels. Additionally, test and evaluation on composites that have been impact damaged is in progress so that models can be developed to estimate damage tolerance and the degradation in static strength.
Byrne, Abbey; Hodge, Andrew; Jimenez-Soto, Eliana
2015-11-01
Many priority countries in the countdown to the millennium development goals deadline are lagging in progress towards maternal and child health (MCH) targets. Papua New Guinea (PNG) is one such country beset by challenges of geographical inaccessibility, inequity and health system weakness. Several countries, however, have made progress through focused initiatives which align with the burden of disease and overcome specific inequities. This study identifies the potential impact on maternal and child mortality through increased coverage of prioritised interventions within the PNG health system. The burden of disease and health system environment of PNG was documented to inform prioritised MCH interventions at community, outreach, and clinical levels. Potential reductions in maternal and child mortality through increased intervention coverage to close the geographical equity gap were estimated with the lives saved tool. A set community-level interventions, with highest feasibility, would yield significant reductions in newborn and child mortality. Adding the outreach group delivers gains for maternal mortality, particularly through family planning. The clinical services group of interventions demands greater investment but are essential to reach MCH targets. Cumulatively, the increased coverage is estimated to reduce the rates of under-five mortality by 19 %, neonatal mortality by 26 %, maternal mortality ratio by 10 % and maternal mortality by 33 %. Modest investments in health systems focused on disadvantaged populations can accelerate progress in maternal and child survival even in fragile health systems like PNG. The critical approach may be to target interventions and implementation appropriately to the sensitive context of lagging countries.
Poetry as Progress: Balancing Standards-Based Reforms with Aesthetic Inquiry
ERIC Educational Resources Information Center
Liu, Laura B.
2011-01-01
The meaning of "progress" in U.S. educational institutions has undergone much debate (Tyack & Cuban, 1995). Standards-driven practices have often promoted a search for "right" answers in place of critical and diverse thinking. Globalization and its impacts compel us to continue revising and articulating the meaning of progress for 21st century…
NASA Technical Reports Server (NTRS)
1975-01-01
Rapidly changing societal and individual values impact the course of man's future with accompanying conflict, tension and alienation. Conflict and fear over the impacts of science and technology may retard, or may hasten, societal progress. The broadening of the concept of equality of opportunity to an equality of outcome manifests itself by distributing the rewards of society based not on performance but simply on membership in the society. It is concluded that institutional failure caused by organizational and bureaucratic ineffectiveness inhibits change necessary for the solution of societal problems.
Proposed systems configurations for a satellite based ISDN
NASA Astrophysics Data System (ADS)
Capece, M.; Pavesi, B.; Tozzi, P.; Galligan, K. P.
This paper summarizes concepts developed during a study for the ESA in which the evolution of ISDN capability and the impact in the satellite land mobile area are examined. Following the progressive steps of the expected ISDN implementation and the potential market penetration, a space based system capable of satisfying particular user services classes has been investigated. The approach used is to establish a comparison between the requirements of potential mobile users and the services already envisaged by ISDN, identifying the service subclasses that might be adopted in a mobile environment through a satellite system. Two system alternatives, with different ISDN compatibility, have been identified. The first option allows a partial compatibility, by providing the central stations of the earth segment with suitable interface units. The second option permits a full integration, operating on the satellite on-board capabilities.
Bish, Lawrence T; Yarchoan, Mark; Sleeper, Meg M; Gazzara, Jeffrey A; Morine, Kevin J; Acosta, Pedro; Barton, Elisabeth R; Sweeney, H Lee
2011-01-01
Duchenne muscular dystrophy (DMD) is a degenerative disorder affecting skeletal and cardiac muscle for which there is no effective therapy. Angiotension receptor blockade (ARB) has excellent therapeutic potential in DMD based on recent data demonstrating attenuation of skeletal muscle disease progression during 6-9 months of therapy in the mdx mouse model of DMD. Since cardiac-related death is major cause of mortality in DMD, it is important to evaluate the effect of any novel treatment on the heart. Therefore, we evaluated the long-term impact of ARB on both the skeletal muscle and cardiac phenotype of the mdx mouse. Mdx mice received either losartan (0.6 g/L) (n = 8) or standard drinking water (n = 9) for two years, after which echocardiography was performed to assess cardiac function. Skeletal muscle weight, morphology, and function were assessed. Fibrosis was evaluated in the diaphragm and heart by Trichrome stain and by determination of tissue hydroxyproline content. By the study endpoint, 88% of treated mice were alive compared to only 44% of untreated (p = 0.05). No difference in skeletal muscle morphology, function, or fibrosis was noted in losartan-treated animals. Cardiac function was significantly preserved with losartan treatment, with a trend towards reduction in cardiac fibrosis. We saw no impact on the skeletal muscle disease progression, suggesting that other pathways that trigger fibrosis dominate over angiotensin II in skeletal muscle long term, unlike the situation in the heart. Our study suggests that ARB may be an important prophylactic treatment for DMD-associated cardiomyopathy, but will not impact skeletal muscle disease.
Simulation-based planning of surgical interventions in pediatric cardiology
NASA Astrophysics Data System (ADS)
Marsden, Alison
2012-11-01
Hemodynamics plays an essential role in the progression and treatment of cardiovascular disease. This is particularly true in pediatric cardiology, due to the wide variation in anatomy observed in congenital heart disease patients. While medical imaging provides increasingly detailed anatomical information, clinicians currently have limited knowledge of important fluid mechanical parameters. Treatment decisions are therefore often made using anatomical information alone, despite the known links between fluid mechanics and disease progression. Patient-specific simulations now offer the means to provide this missing information, and, more importantly, to perform in-silico testing of new surgical designs at no risk to the patient. In this talk, we will outline the current state of the art in methods for cardiovascular blood flow simulation and virtual surgery. We will then present new methodology for coupling optimization with simulation and uncertainty quantification to customize treatments for individual patients. Finally, we will present examples in pediatric cardiology that illustrate the potential impact of these tools in the clinical setting.
Time to change the blind men and the elephant approach to Parkinson disease?
Racette, Brad A; Willis, Allison W
2015-07-14
Parkinson disease (PD) is a progressive neurodegenerative disease that is associated with substantial morbidity and early mortality. Disease-related costs exceed $10 billion, not including medications, out-of-pocket expenses, or societal costs. Symptomatic treatment with levodopa, which has been available for over 30 years, and advanced therapies such as deep brain stimulation improve outcomes. Yet most new medications for PD provide a therapeutic benefit that is relatively modest compared to the benefits from levodopa. Despite dozens of neuroprotective clinical trials, there are no medications proven to slow the progression of the disease. Given these limitations, we provide evidence of the potential public health impact of a research agenda that emphasizes identification of risk factors to reduce disease burden through exposure mitigation. In addition, we emphasize health care policy that focuses on increasing health care expenditures for neurologic evaluation and management services to increase access to specialists to improve disease outcomes and reduce costs through better disease management. © 2015 American Academy of Neurology.
Time to change the blind men and the elephant approach to Parkinson disease?
Willis, Allison W.
2015-01-01
Parkinson disease (PD) is a progressive neurodegenerative disease that is associated with substantial morbidity and early mortality. Disease-related costs exceed $10 billion, not including medications, out-of-pocket expenses, or societal costs. Symptomatic treatment with levodopa, which has been available for over 30 years, and advanced therapies such as deep brain stimulation improve outcomes. Yet most new medications for PD provide a therapeutic benefit that is relatively modest compared to the benefits from levodopa. Despite dozens of neuroprotective clinical trials, there are no medications proven to slow the progression of the disease. Given these limitations, we provide evidence of the potential public health impact of a research agenda that emphasizes identification of risk factors to reduce disease burden through exposure mitigation. In addition, we emphasize health care policy that focuses on increasing health care expenditures for neurologic evaluation and management services to increase access to specialists to improve disease outcomes and reduce costs through better disease management. PMID:26070339
Platelets Inhibit Migration of Canine Osteosarcoma Cells.
Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C
2017-01-01
The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.
Isocitrate dehydrogenase mutations in gliomas
Waitkus, Matthew S.; Diplas, Bill H.; Yan, Hai
2016-01-01
Over the last decade, extraordinary progress has been made in elucidating the underlying genetic causes of gliomas. In 2008, our understanding of glioma genetics was revolutionized when mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) were identified in the vast majority of progressive gliomas and secondary glioblastomas (GBMs). IDH enzymes normally catalyze the decarboxylation of isocitrate to generate α-ketoglutarate (αKG), but recurrent mutations at Arg132 of IDH1 and Arg172 of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of αKG into the putative oncometabolite D-2-hydroxyglutate (D2HG). D2HG inhibits αKG-dependent dioxygenases and is thought to create a cellular state permissive to malignant transformation by altering cellular epigenetics and blocking normal differentiation processes. Herein, we discuss the relevant literature on mechanistic studies of IDH1/2 mutations in gliomas, and we review the potential impact of IDH1/2 mutations on molecular classification and glioma therapy. PMID:26188014
High Throughput Sequencing for Detection of Foodborne Pathogens
Sekse, Camilla; Holst-Jensen, Arne; Dobrindt, Ulrich; Johannessen, Gro S.; Li, Weihua; Spilsberg, Bjørn; Shi, Jianxin
2017-01-01
High-throughput sequencing (HTS) is becoming the state-of-the-art technology for typing of microbial isolates, especially in clinical samples. Yet, its application is still in its infancy for monitoring and outbreak investigations of foods. Here we review the published literature, covering not only bacterial but also viral and Eukaryote food pathogens, to assess the status and potential of HTS implementation to inform stakeholders, improve food safety and reduce outbreak impacts. The developments in sequencing technology and bioinformatics have outpaced the capacity to analyze and interpret the sequence data. The influence of sample processing, nucleic acid extraction and purification, harmonized protocols for generation and interpretation of data, and properly annotated and curated reference databases including non-pathogenic “natural” strains are other major obstacles to the realization of the full potential of HTS in analytical food surveillance, epidemiological and outbreak investigations, and in complementing preventive approaches for the control and management of foodborne pathogens. Despite significant obstacles, the achieved progress in capacity and broadening of the application range over the last decade is impressive and unprecedented, as illustrated with the chosen examples from the literature. Large consortia, often with broad international participation, are making coordinated efforts to cope with many of the mentioned obstacles. Further rapid progress can therefore be prospected for the next decade. PMID:29104564
Wilson, Sarah M; Khanna, Rajesh
2015-04-01
The novel antiepileptic drug lacosamide (LCM; SPM927, Vimpat®) has been heralded as having a dual-mode of action through interactions with both the voltage-gated sodium channel and the neurite outgrowth-promoting collapsin response mediator protein 2 (CRMP2). Lacosamide's ability to dampen neuronal excitability through the voltage-gated sodium channel likely underlies its efficacy in attenuating the symptoms of epilepsy (i.e., seizures). While the role of CRMP2 in epilepsy has not been well studied, given the proposed involvement of circuit reorganization in epileptogenesis, the ability of lacosamide to alter CRMP2 function may prove disease modifying. Recently, however, the validity of lacosamide's interaction with CRMP2 has come under scrutiny. In this review, we address the contradictory reports concerning the binding of lacosamide to CRMP2 as well as the ability of lacosamide to directly impact CRMP2 function. Additionally, we address similarly the contradicting reports regarding the potential disease-modifying effect of lacosamide on the development and progression of epilepsy. As the vast majority of antiepileptic drugs influences only the symptoms of epilepsy, the ability to hinder disease progression would be a major breakthrough in efforts to cure or prevent this debilitating syndrome.
Wilson, Sarah M.; Khanna, Rajesh
2014-01-01
The novel anti-epileptic drug lacosamide (LCM; SPM927, Vimpat®) has been heralded as having a dual-mode of action through interactions with both the voltage-gated sodium channel and the neurite outgrowth-promoting collapsin response mediator protein 2 (CRMP2). Lacosamide’s ability to dampen neuronal excitability through the voltage-gated sodium channel likely underlies its efficacy in attenuating the symptoms of epilepsy (i.e. seizures). While the role of CRMP2 in epilepsy has not been well-studied, given the proposed involvement of circuit reorganization in epileptogenesis, the ability of lacosamide to alter CRMP2 function may prove disease-modifying. Recently, however, the validity of lacosamide’s interaction with CRMP2 has come under scrutiny. In this review, we address the contradictory reports concerning the binding of lacosamide to CRMP2, as well as, the ability of lacosamide to directly impact CRMP2 function. Additionally, we address similarly contradicting reports regarding the potential disease-modifying effect of lacosamide on the development and progression of epilepsy. As the vast majority of anti-epileptic drugs influence only the symptoms of epilepsy, the ability to hinder disease progression would be a major breakthrough in efforts to cure or prevent this debilitating syndrome. PMID:24944082
Progress on upwelling studies in the China seas
NASA Astrophysics Data System (ADS)
Hu, Jianyu; Wang, Xiao Hua
2016-09-01
East Asian marginal seas surrounding China exhibit rich ocean upwelling, mostly in response to the southwesterly summer monsoon. Upwelling in the China seas, namely, the South China Sea, the Taiwan Strait, the East China Sea, the Yellow Sea, and the Bohai Sea, has become increasingly important because the potential changes in the upwelling may have dramatic ecosystem, socioeconomic, and climate impacts. This paper reviews the progress of upwelling studies in the China seas since the year 2000, by presenting the principal characteristics and new understanding of 12 major upwelling regions in the China seas. Upwelling exhibits long-term variability at intraseasonal to multidecadal scales as well as short-term variability frequently caused by tropical cyclones. It is also associated with the El Niño-Southern Oscillation, local environmental variation, and biogeochemical factors. The coastal upwelling around Hainan Island and the upwelling or cold dome northeast of Taiwan Island are specifically highlighted because they have attracted great interest for decades. This paper summarizes upwelling mechanisms in terms of wind, topography, tide, stratification, and background flow, with applications mostly to the China seas. Finally, we propose some topics for future upwelling research, i.e., potential intensification of coastal upwelling under global climate change, downwelling, intrusion of upwelling into coastal embayments, and the influence of upwelling on fishery and biogeochemical processes.
Vascularisation to improve translational potential of tissue engineering systems for cardiac repair.
Dilley, Rodney J; Morrison, Wayne A
2014-11-01
Cardiac tissue engineering is developing as an alternative approach to heart transplantation for treating heart failure. Shortage of organ donors and complications arising after orthotopic transplant remain major challenges to the modern field of heart transplantation. Engineering functional myocardium de novo requires an abundant source of cardiomyocytes, a biocompatible scaffold material and a functional vasculature to sustain the high metabolism of the construct. Progress has been made on several fronts, with cardiac cell biology, stem cells and biomaterials research particularly promising for cardiac tissue engineering, however currently employed strategies for vascularisation have lagged behind and limit the volume of tissue formed. Over ten years we have developed an in vivo tissue engineering model to construct vascularised tissue from various cell and tissue sources, including cardiac tissue. In this article we review the progress made with this approach and others, together with their potential to support a volume of engineered tissue for cardiac tissue engineering where contractile mass impacts directly on functional outcomes in translation to the clinic. It is clear that a scaled-up cardiac tissue engineering solution required for clinical treatment of heart failure will include a robust vascular supply for successful translation. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. Copyright © 2014 Elsevier Ltd. All rights reserved.
Construction of a Cyber Attack Model for Nuclear Power Plants
DOE Office of Scientific and Technical Information (OSTI.GOV)
Varuttamaseni, Athi; Bari, Robert A.; Youngblood, Robert
The consideration of how one compromised digital equipment can impact neighboring equipment is critical to understanding the progression of cyber attacks. The degree of influence that one component may have on another depends on a variety of factors, including the sharing of resources such as network bandwidth or processing power, the level of trust between components, and the inclusion of segmentation devices such as firewalls. The interactions among components via mechanisms that are unique to the digital world are not usually considered in traditional PRA. This means potential sequences of events that may occur during an attack may be missedmore » if one were to only look at conventional accident sequences. This paper presents a method where, starting from the initial attack vector, the progression of a cyber attack can be modeled. The propagation of the attack is modeled by considering certain attributes of the digital components in the system. These attributes determine the potential vulnerability of a component to a class of attack and the capability gained by the attackers once they are in control of the equipment. The use of attributes allows similar components (components with the same set of attributes) to be modeled in the same way, thereby reducing the computing resources required for analysis of large systems.« less
Toss, M; Miligy, I; Thompson, A M; Khout, H; Green, A R; Ellis, I O; Rakha, E A
2017-10-01
The high proportion of ductal carcinoma in situ (DCIS) presented in mammographic screening and the relatively low risk of progression to invasive disease have raised questions related to overtreatment. Following a review of current DCIS management protocols a more conservative approach has been suggested. Clinical trials have been introduced to evaluate the option of avoiding surgical intervention in a proportion of patients with DCIS defined as "low-risk" using certain clinicopathological criteria. These trials can potentially provide evidence-based models of active surveillance (with or without endocrine therapy) as a future management approach. Despite the undisputable fact of our need to address the obvious overtreatment of screen-detected DCIS, some important questions need to be considered regarding these trials including the eligibility criteria and definition of risk, the proportion of patient eligible for inclusion, and the length of time required for proper analysis of the trials' outcome in view of the long-term natural history of DCIS progression particularly the low-risk group. These factors can potentially affect the practicality and future impact of such trials. This review provides critical analysis of current DCIS management trials and highlights critical issues related to their practicality and the expected outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.
The gut microbiota and the liver: implications for clinical practice.
Quigley, Eamonn M; Monsour, Howard P
2013-11-01
While a central role for the microbiota in the precipitation of infectious and non-infectious complications of liver disease has been long established, evidence for a more fundamental role in the etiology of several liver diseases continues to accumulate. However, though progress is rapidly occurring in this area, the definitive delineation of the precise relevance of changes in the microbiota to various forms and stages of liver disease is still far from complete. While high quality clinical evidence supports the use of antibiotic therapy, in the management of hepatic encephalopathy, spontaneous bacterial peritonitis and other infectious complications, how these interventions impact on the microbiota and microbiota-host interactions has not been clearly defined. Although probiotics and even, perhaps, fecal transplantation hold promise in the management of liver disease, and the potential impact of probiotics is supported by a considerable amount of laboratory data, high-quality clinical evidence is scanty.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hughes, Richard; Tyagi, Mayank; Radonjic, Mileva
This project is intended to demonstrate the technical and economic feasibility, and environmental and social attractiveness of a novel method of heat extraction from geothermal reservoirs. The emphasis is on assessing the potential for a heat extraction method that couples forced and free convection to maximize extraction efficiency. The heat extraction concept is enhanced by considering wellbore energy conversion, which may include only a boiler for a working fluid, or perhaps a complete boiler, turbine, and condenser cycle within the wellbore. The feasibility of this system depends on maintaining mechanical and hydraulic integrity of the wellbore, so the material propertiesmore » of the casing-cement system are examined both experimentally and with well design calculations. The attractiveness depends on mitigation of seismic and subsidence risks, economic performance, environmental impact, and social impact – all of which are assessed as components of this study.« less
Climate Change Impacts on Waterborne Diseases: Moving Toward Designing Interventions.
Levy, Karen; Smith, Shanon M; Carlton, Elizabeth J
2018-06-01
Climate change threatens progress achieved in global reductions of infectious disease rates over recent decades. This review summarizes literature on potential impacts of climate change on waterborne diseases, organized around a framework of questions that can be addressed depending on available data. A growing body of evidence suggests that climate change may alter the incidence of waterborne diseases, and diarrheal diseases in particular. Much of the existing work examines historical relationships between weather and diarrhea incidence, with a limited number of studies projecting future disease rates. Some studies take social and ecological factors into account in considerations of historical relationships, but few have done so in projecting future conditions. The field is at a point of transition, toward incorporating social and ecological factors into understanding the relationships between climatic factors and diarrheal diseases and using this information for future projections. The integration of these components helps identify vulnerable populations and prioritize adaptation strategies.
Health impact assessment in Australia: A review and directions for progress
DOE Office of Scientific and Technical Information (OSTI.GOV)
Harris, Patrick, E-mail: patrick.harris@unsw.edu.a; Spickett, Jeff, E-mail: J.Spickett@curtin.edu.a
2011-07-15
This article provides an overview of Health Impact Assessment (HIA) within Australia. We discuss the development and current position of HIA and offer some directions for HIA's progression. Since the early 1990s HIA activity in Australia has increased and diversified in application and practice. This article first highlights the emergent streams of HIA practice across environmental, policy and health equity foci, and how these have developed within Australia. The article then provides summaries of current practice provided by each Australian state and territory. We then offer some insight into current issues that require further progression or resolution if HIA ismore » to progress effectively in Australia. This progress rests both on developing broad system support for HIA across government, led by the health sector, and developing system capacity to undertake, commission or review HIAs. We argue that a unified and clear HIA approach is required as a prerequisite to gaining the understanding and support for HIA in the public and private sectors and the wider community.« less
Affordability Challenges to Value-Based Pricing: Mass Diseases, Orphan Diseases, and Cures.
Danzon, Patricia M
2018-03-01
To analyze how value-based pricing (VBP), which grounds the price paid for pharmaceuticals in their value, can manage "affordability" challenges, defined as drugs that meet cost-effectiveness thresholds but are "unaffordable" within the short-run budget. Three specific contexts are examined, drawing on recent experience. First, an effective new treatment for a chronic, progressive disease, such as hepatitis C, creates a budget spike that is transitory because initial prevalence is high, relative to current incidence. Second, "cures" that potentially provide lifetime benefits may claim abnormally high VBP prices, with high immediate budget impact potentially/partially offset by deferred cost savings. Third, although orphan drugs in principle target rare diseases, in aggregate they pose affordability concerns because of the growing number of orphan indications and increasingly high prices. For mass diseases, the transitory budget impact of treating the accumulated patient stock can be managed by stratified rollout that delays treatment of stable patients and prioritizes patients at high risk of deterioration. Delay spreads the budget impact and permits potential savings from launch of competing treatments. For cures, installment payments contingent on outcomes could align payment flows and appropriately shift risk to producers. This approach, however, entails high administrative and incentive costs, especially if applied across multiple payers in the United States. For orphan drugs, the available evidence on research and development trends and returns argues against the need for a higher VBP threshold to incentivize research and development in orphan drugs, given existing statutory benefits under orphan drug legislation. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
Chamarthi, Bindu; Gaziano, J. Michael; Blonde, Lawrence; Scranton, Richard E.; Ezrokhi, Michael; Rutty, Dean; Cincotta, Anthony H.
2015-01-01
Background. Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control may reduce long-term CVD risk. However, other risk factors such as elevated vascular sympathetic tone and/or endothelial dysfunction may be stronger potentiators of CVD. This study evaluated the impact of bromocriptine-QR, a sympatholytic dopamine D2 receptor agonist, on progression of metabolic disease and CVD in T2DM subjects in good glycemic control (HbA1c ≤7.0%). Methods. 1834 subjects (1219 bromocriptine-QR; 615 placebo) with baseline HbA1c ≤7.0% derived from the Cycloset Safety Trial (this trial is registered with ClinicalTrials.gov Identifier: NCT00377676), a 12-month, randomized, multicenter, placebo-controlled, double-blind study in T2DM, were evaluated. Treatment impact upon a prespecified composite CVD endpoint (first myocardial infarction, stroke, coronary revascularization, or hospitalization for angina/congestive heart failure) and the odds of losing glycemic control (HbA1c >7.0% after 52 weeks of therapy) were determined. Results. Bromocriptine-QR reduced the CVD endpoint by 48% (intention-to-treat; HR: 0.52 [0.28−0.98]) and 52% (on-treatment analysis; HR: 0.48 [0.24−0.95]). Bromocriptine-QR also reduced the odds of both losing glycemic control (OR: 0.63 (0.47−0.85), p = 0.002) and requiring treatment intensification to maintain HbA1c ≤7.0% (OR: 0.46 (0.31−0.69), p = 0.0002). Conclusions. Bromocriptine-QR therapy slowed the progression of CVD and metabolic disease in T2DM subjects in good glycemic control. PMID:26060823
Chamarthi, Bindu; Gaziano, J Michael; Blonde, Lawrence; Vinik, Aaron; Scranton, Richard E; Ezrokhi, Michael; Rutty, Dean; Cincotta, Anthony H
2015-01-01
Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control may reduce long-term CVD risk. However, other risk factors such as elevated vascular sympathetic tone and/or endothelial dysfunction may be stronger potentiators of CVD. This study evaluated the impact of bromocriptine-QR, a sympatholytic dopamine D2 receptor agonist, on progression of metabolic disease and CVD in T2DM subjects in good glycemic control (HbA1c ≤ 7.0%). 1834 subjects (1219 bromocriptine-QR; 615 placebo) with baseline HbA1c ≤ 7.0% derived from the Cycloset Safety Trial (this trial is registered with ClinicalTrials.gov Identifier: NCT00377676), a 12-month, randomized, multicenter, placebo-controlled, double-blind study in T2DM, were evaluated. Treatment impact upon a prespecified composite CVD endpoint (first myocardial infarction, stroke, coronary revascularization, or hospitalization for angina/congestive heart failure) and the odds of losing glycemic control (HbA1c >7.0% after 52 weeks of therapy) were determined. Bromocriptine-QR reduced the CVD endpoint by 48% (intention-to-treat; HR: 0.52 [0.28-0.98]) and 52% (on-treatment analysis; HR: 0.48 [0.24-0.95]). Bromocriptine-QR also reduced the odds of both losing glycemic control (OR: 0.63 (0.47-0.85), p = 0.002) and requiring treatment intensification to maintain HbA1c ≤ 7.0% (OR: 0.46 (0.31-0.69), p = 0.0002). Bromocriptine-QR therapy slowed the progression of CVD and metabolic disease in T2DM subjects in good glycemic control.
Marsh, Katherine M; Schipper, David; Ferng, Alice S; Johnson, Kitsie; Fisher, Julia; Knapp, Shannon; Dicken, Destiny; Khalpey, Zain
2017-08-01
Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease that predominantly affects women of childbearing age. Exogenous rapamycin (sirolimus) has been shown to improve clinical outcomes and was recently approved to treat LAM, whereas estrogen (E 2 ) is implicated in disease progression. No consistent metabolic model currently exists for LAM, therefore wild-type mouse embryonic fibroblasts (MEF +/+) and TSC2 knockout cells (MEF -/-) were used in this study as a model for LAM. Oxygen consumption rates (OCR) and redox potential were measured to determine metabolic state across control cells, MEF +/+ and -/- cells treated with rapamycin (Rapa), and MEF +/+ and -/- cells treated with E 2 . An XF96 extracellular flux analyzer from Seahorse Bioscience ® was used to measure OCR, and a RedoxSYS™ ORP was used to measure redox potential. OCR of MEF -/- cells treated with rapamycin (MEF -/- Rapa) versus MEF -/- control were significantly lower across all conditions. The static oxidation reduction potential of the MEF -/- Rapa group was also lower, approaching significance. The coupling efficiency and ratio of ATP-linked respiration to maximum respiration were statistically lower in MEF -/- Rapa compared to MEF +/+ Rapa. There were no significant metabolic findings across any of the MEF cells treated with E 2 . MEF -/- control cells versus MEF +/+ control cells were not found to significantly differ. MEF cells are thought to be a feasible metabolic model for LAM, which has implications for future pharmacologic and biologic testing.
The present and future role of microfluidics in biomedical research.
Sackmann, Eric K; Fulton, Anna L; Beebe, David J
2014-03-13
Microfluidics, a technology characterized by the engineered manipulation of fluids at the submillimetre scale, has shown considerable promise for improving diagnostics and biology research. Certain properties of microfluidic technologies, such as rapid sample processing and the precise control of fluids in an assay, have made them attractive candidates to replace traditional experimental approaches. Here we analyse the progress made by lab-on-a-chip microtechnologies in recent years, and discuss the clinical and research areas in which they have made the greatest impact. We also suggest directions that biologists, engineers and clinicians can take to help this technology live up to its potential.
Tissue mechanics and fibrosis.
Wells, Rebecca G
2013-07-01
Mechanical forces are essential to the development and progression of fibrosis, and are likely to be as important as soluble factors. These forces regulate the phenotype and proliferation of myofibroblasts and other cells in damaged tissues, the activation of growth factors, the structure and mechanics of the matrix, and, potentially, tissue patterning. Better understanding of the variety and magnitude of forces, the characteristics of those forces in biological tissues, and their impact on fibrosis in multiple tissues is needed and may lead to identification of important new therapeutic targets. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. Copyright © 2013 Elsevier B.V. All rights reserved.
Usefulness of Analytical Research: Rethinking Analytical R&D&T Strategies.
Valcárcel, Miguel
2017-11-07
This Perspective is intended to help foster true innovation in Research & Development & Transfer (R&D&T) in Analytical Chemistry in the form of advances that are primarily useful for analytical purposes rather than solely for publishing. Devising effective means to strengthen the crucial contribution of Analytical Chemistry to progress in Chemistry, Science & Technology, and Society requires carefully examining the present status of our discipline and also identifying internal and external driving forces with a potential adverse impact on its development. The diagnostic process should be followed by administration of an effective therapy and supported by adoption of a theragnostic strategy if Analytical Chemistry is to enjoy a better future.
Francis, Linda E; Colson, Paul W; Mizzi, Pamela
2002-04-01
Involvement of mental health service consumers in the provision of mental health services is a growing model in community mental health. It is, however, a complicated issue, made ever more so by the passage of the Americans with Disabilities Act. In this ethnographic case study, we seek to explore the changes one social services agency has made to adjust to the requirements of the ADA and the impact of these changes on their consumer employees. Our results indicate potential for positive progress as a result of the ADA, but also unexpected pitfalls as organizational cultures change as well.
A review on recent progress in observations, and health effects of bioaerosols.
Humbal, Charmi; Gautam, Sneha; Trivedi, Ujwalkumar
2018-06-06
Bioaerosol is a particulate mixture of solid and semi-solid matter combined with biotic matter like pollens, microbes and their fragments. The present review stresses on a cumulative understanding of sources, components, quantification and distribution of bioaerosols with respect to size, and its significant impacts on human health. The present review will be instrumental in devising strategies to understand and manage bioaerosols and reducing their human exposure and associated health hazards. The present review aims explore the relationship between particle and associated biological agents responsible for behaviours like dispersal, total potential health hazards and toxicology level during exposure to bioaerosol. Copyright © 2018. Published by Elsevier Ltd.
Wavefront shaping using a deformable mirror for focusing inside optical tissue phantoms
NASA Astrophysics Data System (ADS)
Gomes, Ricardo; Coelho, João. M. P.; Gabriel, Ana; Vieira, Pedro; Oliveira Silva, Catarina; Reis, Catarina
2014-08-01
Although light has long being used in medicine, scattering always hindered its use. This study intends to evolve into three different frontlines: development of methodologies to concentrate light inside biological tissues, development of an optical tissue phantom and development of multifunctional gold nanoparticles with therapeutic potential for targeting anticancer drug delivery. The impact of the scattering agent (milk) concentration in the measured wavefront and spot radius is analyzed. Wavefront correction proves to be efficient in overcoming the scattering effect in the different phantoms. Future studies for developing a photodynamic approach under near-infrared wavelength are now in progress and will be further presented.
InP (Indium Phosphide): Into the future
NASA Technical Reports Server (NTRS)
Brandhorst, Henry W., Jr.
1989-01-01
Major industry is beginning to be devoted to indium phosphide and its potential applications. Key to these applications are high speed and radiation tolerance; however the high cost of indium phosphide may be an inhibitor to progress. The broad applicability of indium phosphide to many devices will be discussed with an emphasis on photovoltaics. Major attention is devoted to radiation tolerance and means of reducing cost of devices. Some of the approaches applicable to solar cells may also be relevant to other devices. The intent is to display the impact of visionary leadership in the field and enable the directions and broad applicability of indium phosphide.
NASA Astrophysics Data System (ADS)
Källhammer, Jan-Erik; Pettersson, Håkan; Eriksson, Dick; Junique, Stéphane; Savage, Susan; Vieider, Christian; Andersson, Jan Y.; Franks, John; Van Nylen, Jan; Vercammen, Hans; Kvisterøy, Terje; Niklaus, Frank; Stemme, Göran
2006-04-01
Pedestrian fatalities are around 15% of the traffic fatalities in Europe. A proposed EU regulation requires the automotive industry to develop technologies that will substantially decrease the risk for Vulnerable Road Users when hit by a vehicle. Automatic Brake Assist systems, activated by a suitable sensor, will reduce the speed of the vehicle before the impact, independent of any driver interaction. Long Wavelength Infrared technology is an ideal candidate for such sensors, but requires a significant cost reduction. The target necessary for automotive serial applications are well below the cost of systems available today. Uncooled bolometer arrays are the most mature technology for Long Wave Infrared with low-cost potential. Analyses show that sensor size and production yield along with vacuum packaging and the optical components are the main cost drivers. A project has been started to design a new Long Wave Infrared system with a ten times cost reduction potential, optimized for the pedestrian protection requirement. It will take advantage of the progress in Micro Electro-Mechanical Systems and Long Wave Infrared optics to keep the cost down. Deployable and pre-impact braking systems can become effective alternatives to passive impact protection systems solutions fulfilling the EU pedestrian protection regulation. Low-cost Long Wave Infrared sensors will be an important enabler to make such systems cost competitive, allowing high market penetration.
Gülmezoglu, A Metin; Lawrie, Theresa A
2015-11-01
Although significant progress has been made towards Millennium Development Goal (MDG) 4 and 5 targets, maternal and neonatal mortality rates remain unacceptably high in low- and middle-income countries (LMICs). The potential for improvements in maternal and neonatal health outcomes with increased facility utilization in these countries is undermined by a lack of appropriate and timely treatment. Skilful emergency resuscitation can be the difference between life and death; therefore, training in emergency resuscitation is essential for health-care practitioners at all levels, with regular refresher sessions to ensure skill retention. Whilst there is little robust evidence on the impact of resuscitation training interventions on practitioner skills or patient outcomes, such training interventions are likely to have the greatest impact if integrated into a broader approach to improve the quality of care. Accelerated investments in training must go hand in hand with ensuring the availability of quality equipment and upgrading infrastructure to reduce the gap between current MDG status and what is achieved by the end of 2015; and to accelerate reductions in mortality rates beyond 2015 towards new Countdown targets. Copyright © 2015 Elsevier Ltd. All rights reserved.
Kfoury, Georgio; Raquez, Jean-Marie; Hassouna, Fatima; Odent, Jérémy; Toniazzo, Valérie; Ruch, David; Dubois, Philippe
2013-01-01
Due to its origin from renewable resources, its biodegradability, and recently, its industrial implementation at low costs, poly(lactide) (PLA) is considered as one of the most promising ecological, bio-sourced and biodegradable plastic materials to potentially and increasingly replace traditional petroleum derived polymers in many commodity and engineering applications. Beside its relatively high rigidity [high tensile strength and modulus compared with many common thermoplastics such as poly(ethylene terephthalate) (PET), high impact poly(styrene) (HIPS) and poly(propylene) (PP)], PLA suffers from an inherent brittleness, which can limit its applications especially where mechanical toughness such as plastic deformation at high impact rates or elongation is required. Therefore, the curve plotting stiffness vs. impact resistance and ductility must be shifted to higher values for PLA-based materials, while being preferably fully bio-based and biodegradable upon the application. This review aims to establish a state of the art focused on the recent progresses and preferably economically viable strategies developed in the literature for significantly improve the mechanical performances of PLA. A particular attention is given to plasticization as well as to impact resistance modification of PLA in the case of (reactive) blending PLA-based systems.
Kfoury, Georgio; Raquez, Jean-Marie; Hassouna, Fatima; Odent, Jérémy; Toniazzo, Valérie; Ruch, David; Dubois, Philippe
2013-01-01
Due to its origin from renewable resources, its biodegradability, and recently, its industrial implementation at low costs, poly(lactide) (PLA) is considered as one of the most promising ecological, bio-sourced and biodegradable plastic materials to potentially and increasingly replace traditional petroleum derived polymers in many commodity and engineering applications. Beside its relatively high rigidity [high tensile strength and modulus compared with many common thermoplastics such as poly(ethylene terephthalate) (PET), high impact poly(styrene) (HIPS) and poly(propylene) (PP)], PLA suffers from an inherent brittleness, which can limit its applications especially where mechanical toughness such as plastic deformation at high impact rates or elongation is required. Therefore, the curve plotting stiffness vs. impact resistance and ductility must be shifted to higher values for PLA-based materials, while being preferably fully bio-based and biodegradable upon the application. This review aims to establish a state of the art focused on the recent progresses and preferably economically viable strategies developed in the literature for significantly improve the mechanical performances of PLA. A particular attention is given to plasticization as well as to impact resistance modification of PLA in the case of (reactive) blending PLA-based systems. PMID:24790960
Obstructive Sleep Apnea and Surgery: Quality Improvement Imperatives and Opportunities
Goldman, Julie L.
2014-01-01
Obstructive sleep apnea (OSA) is more common in surgical candidates than in the general population and may increase susceptibility to perioperative complications that range from transient desaturation to catastrophic injuries. Understanding the potential impact of OSA on patients’ surgical risk profile is of particular interest to otolaryngologists, who routinely perform airway procedures—including surgical procedures for treatment of OSA. Whereas the effects of OSA on long-term health outcomes are well documented, the relationship between OSA and surgical risk is not collinear, and clear consensus on the nature of the association is lacking. Better guidelines for optimization of pain control, perioperative monitoring, and surgical decision making are potential areas for quality improvement efforts. Many interventions have been suggested to mitigate the risk of adverse events in surgical patients with OSA, but wide variations in clinical practice remain. We review the current literature, emphasizing recent progress in understanding the complex pathophysiologic interactions noted in OSA patients undergoing surgery and outlining potential strategies to decrease perioperative risks. PMID:25013745
MiR-29a: a potential therapeutic target and promising biomarker in tumors
Wang, Jin-yan; Zhang, Qian; Wang, Dan-dan; Yan, Wei; Sha, Huan-huan; Zhao, Jian-hua; Yang, Su-jin; Zhang, He-da; Hou, Jun-chen; Xu, Han-zi; He, Yun-jie; Hu, Jia-hua
2017-01-01
MiRNAs, small non-coding RNA molecules, were recognized to be associated with the incidence and development of diverse neoplasms. MiRNAs were small non-coding RNAs that could regulate post-transcriptional level by binding to 3′-UTR of target mRNAs. Amongst which, miR-29a was demonstrated that it had significant impact on oncogenicity in various neoplasms through binding to critical genes which enhanced or inhibited the progression of cancers. MiR-29a participated in kinds of physiological and pathological processes, including virus replication, cell proliferation, differentiation, apoptosis, fibrosis, angiogenesis, tumorigenicity, metastasis, drug-resistance, and so on. According to its sufficient sensitivity and specificity, many studies showed that miR-29a might serve as a potential therapeutic target and promising biomarker in various tumors. In this review, we discussed the functions of miR-29a and its potential application in the diagnosis, treatment and stages of carcinoma, which could provide additional insight to develop a novel therapeutic strategy. PMID:29217524
Yucca Mountain Biological Resources Monitoring Program. Progress report, January 1994--December 1994
DOE Office of Scientific and Technical Information (OSTI.GOV)
NONE
1995-07-01
The US Department of Energy (DOE) is required by the Nuclear Waste Policy Act of 1982 (as amended in 1987) to study and characterize the suitability of Yucca Mountain as a potential geological repository for high-level nuclear waste. During site characterization, the DOE will conduct a variety of geotechnical, geochemical, geological, and hydrological studies to determine the suitability of Yucca Mountain as a potential repository. To ensure that site characterization activities do not adversely affect the environment at Yucca Mountain, a program has been implemented to monitor and mitigate potential impacts and ensure activities comply with applicable environmental regulations. Thismore » report describes the activities and accomplishments of EG and G Energy Measurements, Inc. (EG and G/EM) from January 1994 through December 1994 for six program areas within the Terrestrial Ecosystem component of the environmental program for the Yucca Mountain Site Characterization Project (YMP): Site Characterization Effects, Desert Tortoises (Gopherus agassizii), Habitat Reclamation, Monitoring and Mitigation, Radiological Monitoring, and Biological Support.« less
Realizing the Promise of Chemical Glycobiology.
Wang, Lai-Xi; Davis, Benjamin G
2013-09-01
Chemical glycobiology is emerging as one of the most uniquely powerful sub-disciplines of chemical biology. The previous scarcity of chemical strategies and the unparalleled structural diversity have created a uniquely fertile ground that is both rich in challenges and potentially very profound in implications. Glycans (oligosaccharides, polysaccharides, and glycoconjugates) are everywhere in biological systems and yet remain disproportionately neglected - reviews highlighting this 'Cinderella status' abound. Yet, the last two decades have witnessed tremendous progress, notably in chemical and chemoenzymatic synthesis, 'sequencing' and arraying, metabolic engineering and imaging. These vital steps serve to highlight not only the great potential but just how much more remains to be done. The vast chemical and functional space of glycans remains to be truly explored. Top-down full-scale glycomic and glycoproteomic studies coupled with hypothesis-driven, bottom-up innovative chemical strategies will be required to properly realize the potential impact of glycoscience on human health, energy, and economy. In this review, we cherry-pick far-sighted advances and use these to identify possible challenges, opportunities and avenues in chemical glycobiology.
Progress Toward National Aeronautics Goals
NASA Technical Reports Server (NTRS)
Russo, Carlo J.; Sehra, Arun K.
1999-01-01
NASA has made definitive progress towards achieving several bold U.S. goals in aeronautics related to air breathing engines. The advanced technologies developed towards these goals span applications from general aviation to large subsonic and supersonic aircraft. The proof of successful technology development is demonstrated through successful technology transfer to U.S. industry and projected fleet impact. Specific examples of progress are discussed that quantifies the achievement towards these goals. In addition, a more detailed vision for NASA aeronautics is defined and key strategic issues are explored which invite international and national debate and involvement especially in reduced environmental impact for subsonic and supersonic aircraft, dramatic new capabilities in general aviation engines, and reduced development cycle time and costs.
Berndt, Nikolaus; Bulik, Sascha; Holzhütter, Hermann-Georg
2012-01-01
Reduced activity of brain α-ketoglutarate dehydrogenase complex (KGDHC) occurs in a number of neurodegenerative diseases like Parkinson's disease and Alzheimer's disease. In order to quantify the relation between diminished KGDHC activity and the mitochondrial ATP generation, redox state, transmembrane potential, and generation of reactive oxygen species (ROS) by the respiratory chain (RC), we developed a detailed kinetic model. Model simulations revealed a threshold-like decline of the ATP production rate at about 60% inhibition of KGDHC accompanied by a significant increase of the mitochondrial membrane potential. By contrast, progressive inhibition of the enzyme aconitase had only little impact on these mitochondrial parameters. As KGDHC is susceptible to ROS-dependent inactivation, we also investigated the reduction state of those sites of the RC proposed to be involved in ROS production. The reduction state of all sites except one decreased with increasing degree of KGDHC inhibition suggesting an ROS-reducing effect of KGDHC inhibition. Our model underpins the important role of reduced KGDHC activity in the energetic breakdown of neuronal cells during development of neurodegenerative diseases. PMID:22719765
Kelly, Adrian B.; Mason, W. Alex; Chmelka, Mary B.; Herrenkohl, Todd I.; Kim, Min Jung; Patton, George C.; Hemphill, Sheryl A.; Toumbourou, John W.; Catalano, Richard F.
2016-01-01
Adolescent depressed mood is related to the development of subsequent mental health problems, and family problems have been linked to adolescent depression. Longitudinal research on adolescent depressed mood is needed to establish the unique impact of family problems independent of other potential drivers. This study tested the extent to which family conflict exacerbates depressed mood during adolescence, independent of changes in depressed mood over time, academic performance, bullying victimization, negative cognitive style, and gender. Students (13 years old) participated in a three-wave bi-national study (n = 961 from Washington State, United States, n = 981 from Victoria, Australia, 98% retention, 51% females in each sample). The model was cross-lagged and controlled for the autocorrelation of depressed mood, negative cognitive style, academic failure, and bullying victimization. Family conflict partially predicted changes in depressed mood independent of changes in depressed mood over time and the other controls. There was also evidence that family conflict and adolescent depressed mood are reciprocally related over time. Findings were closely replicated across the two samples. The study identifies potential points of intervention to interrupt the progression of depressed mood in early to middle adolescence. PMID:26861643
Microbial physiology-based model of ethanol metabolism in subsurface sediments
NASA Astrophysics Data System (ADS)
Jin, Qusheng; Roden, Eric E.
2011-07-01
A biogeochemical reaction model was developed based on microbial physiology to simulate ethanol metabolism and its influence on the chemistry of anoxic subsurface environments. The model accounts for potential microbial metabolisms that degrade ethanol, including those that oxidize ethanol directly or syntrophically by reducing different electron acceptors. Out of the potential metabolisms, those that are active in the environment can be inferred by fitting the model to experimental observations. This approach was applied to a batch sediment slurry experiment that examined ethanol metabolism in uranium-contaminated aquifer sediments from Area 2 at the U.S. Department of Energy Field Research Center in Oak Ridge, TN. According to the simulation results, complete ethanol oxidation by denitrification, incomplete ethanol oxidation by ferric iron reduction, ethanol fermentation to acetate and H 2, hydrogenotrophic sulfate reduction, and acetoclastic methanogenesis: all contributed significantly to the degradation of ethanol in the aquifer sediments. The assemblage of the active metabolisms provides a frame work to explore how ethanol amendment impacts the chemistry of the environment, including the occurrence and levels of uranium. The results can also be applied to explore how diverse microbial metabolisms impact the progress and efficacy of bioremediation strategies.
Review of Tropical-Extratropical Teleconnections on Intraseasonal Time Scales
NASA Astrophysics Data System (ADS)
Stan, Cristiana; Straus, David M.; Frederiksen, Jorgen S.; Lin, Hai; Maloney, Eric D.; Schumacher, Courtney
2017-12-01
The interactions and teleconnections between the tropical and midlatitude regions on intraseasonal time scales are an important modulator of tropical and extratropical circulation anomalies and their associated weather patterns. These interactions arise due to the impact of the tropics on the extratropics, the impact of the midlatitudes on the tropics, and two-way interactions between the regions. Observational evidence, as well as theoretical studies with models of complexity ranging from the linear barotropic framework to intricate Earth system models, suggest the involvement of a myriad of processes and mechanisms in generating and maintaining these interconnections. At this stage, our understanding of these teleconnections is primarily a collection of concepts; a comprehensive theoretical framework has yet to be established. These intraseasonal teleconnections are increasingly recognized as an untapped source of potential subseasonal predictability. However, the complexity and diversity of mechanisms associated with these teleconnections, along with the lack of a conceptual framework to relate them, prevent this potential predictability from being translated into realized forecast skill. This review synthesizes our progress in understanding the observed characteristics of intraseasonal tropical-extratropical interactions and their associated mechanisms, identifies the significant gaps in this understanding, and recommends new research endeavors to address the remaining challenges.
NASA Astrophysics Data System (ADS)
Parisi, Alessandro; Fidelibus, Maria Dolores
2017-04-01
Physical extremes can be distinguished in "sudden physical extremes" (e.g. earthquakes, tsunami) and "progressive physical extremes" (e.g. drought, desertification, landslides). They differ for frequency, intensity, spatial extent, duration and timing of occurrence. If a physical extreme, by interacting with human systems, induces negative consequences, its outcome can be a "disaster". The disasters are, in both above cases, characterized by a few phases: physical extreme occurrence, emergency, response, and recovery. However, in the case of a progressive physical extreme, the disaster develops with an overlap in the time of the above-mentioned phases. When the events are repetitive, the emergency planning (which follows a cycle) succeeds with preparedness and mitigation with the intent of reducing the risk. Both the sudden and progressive physical extremes produce cascading effects of consequences on social, environmental and economic systems. Disasters consequent to sudden and progressive extremes show, however, some differences, mainly attributable to the "visibility" of the effects and to their time scale of evolution. As matter of fact, a disaster consequent to a progressive physical extreme produces "emerging signals" that are often invisible. Moreover, the emergency phase can arise with a time delay compared to the occurrence of the physical extreme, depending on the spatial scale of impacted system. The above differences allow defining "creeping disasters" the potential disasters related to progressive physical extremes. This study deals with some peculiar "cascading disasters" consequent to drought, which is the main "creeping disaster", namely the groundwater drought and the consequent salinization of coastal aquifers. In regional flow systems, their effects are invisible in the immediate to common people (and often even to managers) because of the concealed nature of groundwater; moreover, they are difficult to assess because of the shift over time of their evolution compared to the promptness of surface effects. The study area is the Salento coastal karstic aquifer (Apulia region, Southern Italy), where the groundwater flows according to a regional flow system. It has been subject to successive meteorological droughts between 1960 and 2010. The groundwater monitoring performed during this period, even with some gaps, allows identifying time lags between superficial effects and underground system response, potential tipping points, and emerging signals of the cascading disasters.
Rawat, Rahul; Faust, Elizabeth; Maluccio, John A; Kadiyala, Suneetha
2014-05-01
Although the last decade has seen increased access to antiretroviral therapy across the developing world, widespread food insecurity and undernutrition continue to compromise an effective response to the AIDS epidemic. Limited evidence exists on the potential benefit of food security and nutrition interventions to people living with HIV (PLHIV). We capitalized on an existing intervention to PLHIV in Uganda and conducted a prospective quasi-experimental study evaluating the impact of a monthly household food basket, provided to food insecure antiretroviral therapy-naive PLHIVs for 12 months. The outcomes of interest measured at baseline and follow-up were nutritional status [body mass index; mid-upper arm circumference and hemoglobin (Hb) concentrations], disease severity (CD4 count), and 2 measures of food security: diet quality (Individual Dietary Diversity Score) and food access (Household Food Insecurity Access Scale). We used difference-in-difference propensity score matching to examine the impact of food assistance. Over 12 months, food assistance significantly increased body mass index by 0.6 kg/m (P < 0.01) and mid-upper arm circumference by 6.7 mm (P < 0.05). We found no impact on CD4 count, Hb concentrations, or Individual Dietary Diversity Score. Restricting the analysis to individuals with CD4 counts of greater than 350 cells per microliter, there were significant impacts on Hb concentrations (1.0 g/dL; P < 0.05). At the household level, food assistance increased the Household Food Insecurity Access Scale, by 2.1 points (P < 0.01). This study demonstrates the potential for food assistance programming to be part of the standard of care for PLHIV in areas of widespread food insecurity.
Impact of metabolic syndrome on progression of aortic stenosis: influence of age and statin therapy.
Capoulade, Romain; Clavel, Marie-Annick; Dumesnil, Jean G; Chan, Kwan L; Teo, Koon K; Tam, James W; Côté, Nancy; Mathieu, Patrick; Després, Jean-Pierre; Pibarot, Philippe
2012-07-17
The aims of this study were to examine prospectively the relationship between metabolic syndrome (MetS) and aortic stenosis (AS) progression and to evaluate the effect of age and statin therapy on AS progression in patients with or without MetS. Despite the clear benefits of statin therapy in primary and secondary coronary heart disease prevention, several recent randomized trials have failed to demonstrate any significant effect of this class of drugs on the progression of AS. Previous retrospective studies have reported an association between MetS and faster AS progression. This predefined substudy included 243 of the 269 patients enrolled in the ASTRONOMER (AS Progression Observation: Measuring Effects of Rosuvastatin) trial. Follow-up was 3.4 ± 1.3 years. AS progression rate was measured by calculating the annualized increase in peak aortic jet velocity measured by Doppler echocardiography. Patients with MetS (27%) had faster stenosis progression (+0.25 ± 0.21 m/s/year vs. +0.19 ± 0.19 m/s/year, p = 0.03). Predictors of faster AS progression in multivariate analysis were older age (p = 0.01), higher degree of valve calcification (p = 0.01), higher peak aortic jet velocity at baseline (p = 0.007), and MetS (p = 0.005). Impact of MetS on AS progression was most significant in younger (< 57 years) patients (MetS: +0.24 ± 0.19 m/s/year vs. no MetS: +0.13 ± 0.18 m/s/year, p = 0.008) and among patients receiving statin therapy (+0.27 ± 0.23 m/s/year vs. +0.19 ± 0.18 m/s/year, p = 0.045). In multivariate analysis, the MetS-age interaction was significant (p = 0.01), but the MetS-statin use interaction was not. MetS was found to be a powerful and independent predictor of faster AS progression, with more pronounced impact in younger patients. These findings emphasize the importance of routinely identifying and treating MetS in AS patients. The apparent faster stenosis progression in the subset of normocholesterolemic patients with MetS receiving the statin will need to be confirmed by future studies. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Liver transplantation: Current status and challenges
Jadlowiec, Caroline C; Taner, Timucin
2016-01-01
Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death (DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function. PMID:27182155
Kamat, Ashish M; Cookson, Michael; Witjes, J Alfred; Stenzl, Arnulf; Grossman, H Barton
2016-04-27
Background: The International Bladder Cancer Group (IBCG) recently proposed a new definition of disease progression in non-muscle invasive bladder cancer (NMIBC), including change in T-stage, change to T2 or higher or change from low to high grade. Objective: To establish whether blue light cystoscopy with hexaminolevulinate (HAL) impacts the rate of progression and time to progression using the revised definition. Methods: An earlier long-term follow-up of a controlled Phase III study reported outcomes following blue light cystoscopy with HAL (255 patients) or white light (WL) cystoscopy (261 patients) in NMIBC patients. The data was re-analysed according to the new definition. Results: In the original analysis, after 4.5 years (median), eight HAL and 16 WL patients were deemed to have progressed (transition from NMIBC to muscle invasive bladder cancer, (T2-4)). According to the new definition, additional patients in both groups were found to have progressed: 31 (12.2%) HAL vs 46 (17.6%) WL ( p = 0.085) with four (1.6%) HAL and 11 (4.2%) WL patients progressing from Ta to CIS. Time to progression was longer in the HAL group ( p = 0.05). Conclusions: Applying the new IBCG definition there was a trend towards a lower rate of progression in HAL patients, particularly in those progressing from Ta to CIS. Time to progression was significantly prolonged. This suggests that patients should receive blue light cystoscopy with HAL rather than WL at resection. Adoption of the new definition could allow more patients at risk of progression to be treated appropriately earlier.
NASA Astrophysics Data System (ADS)
Le Bihan, Guillaume; Payrastre, Olivier; Gaume, Eric; Pons, Frederic; Moncoulon, David
2016-04-01
Hydrometeorological forecasting is an essential component of real-time flood management. The information it provides is of great help for crisis managers to anticipate the inundations and the associated risks. In the particular case of flash-floods, which may affect a large amount of small watersheds spread over the territory (up to 300 000 km of waterways considering a drained area of 5 km² minimum in France), appropriate flood forecasting systems are still under development. In France, highly distributed hydrological models have been implemented, enabling a real-time assessment of the potential intensity of flash-floods from the records of weather radars: AIGA-hydro system (Lavabre et al., 2005; Javelle et al., 2014), PreDiFlood project (Naulin et al., 2013). The approach presented here aims to go one step further by offering a direct assessment of the potential impacts of the simulated floods on inhabited areas. This approach is based on an a priori analysis of the study area in order (1) to evaluate with a simplified hydraulic approach (DTM treatment) the potentially flooded areas for different discharge levels, and (2) to identify the associated buildings and/or population at risk from geographic databases. This preliminary analysis enables to build an impact model (discharge-impact curve) on each river reach, which is then used to directly estimate the potentially affected assets based on a distributed rainfall runoff model. The overall principle of this approach was already presented at the 8th Hymex workshop. Therefore, the presentation will be here focused on the first validation results in terms of (1) accuracy of flooded areas simulated from DTM treatments, and (2) relevance of estimated impacts. The inundated areas simulated were compared to the European Directive cartography results (where available), showing an overall good correspondence in a large majority of cases, but also very significant errors for approximatively 10% of the river reaches incorporated in the model. The stage/discharge relations obtained at gauging stations were also compared to the real rating curves, showing a very different behavior of the method depending on the local configuration of the considered site. Some developments are now in progress in order to evaluate and validate, as far as possible, the results of the entire simulation chain at the event scale. This work relies on the comparison of simulation results (estimated flood impacts) with insurance losses data (provided by CCR) for several significant past flood events. The first results of this work will be presented.
Effect of blood pressure lowering on markers of kidney disease progression.
Udani, Suneel M; Koyner, Jay L
2009-10-01
Hypertension remains a common comorbidity and cause of chronic kidney disease (CKD). As the number of patients with CKD grows, so does the need to identify modifiable risk factors for CKD progression. Data on slowing progression of CKD or preventing end-stage renal disease with aggressive blood pressure control have not yielded definitive conclusions regarding ideal blood pressure targets. Shifting the focus of antihypertensive therapy to alternative markers of end-organ damage, specifically proteinuria, has yielded some promise in preventing the progression of CKD. Nevertheless, proteinuria and decline in estimated GFR may represent an irreversible degree of injury to the kidney that limits the impact of any therapy. The identification and use of novel markers of kidney injury to assess the impact of antihyper-tensive therapy may yield clearer direction with regard to optimal management of hypertension in the setting of CKD.
Szostak, Justyna; Martin, Florian; Talikka, Marja; Peitsch, Manuel C; Hoeng, Julia
2016-01-01
The cellular and molecular mechanisms behind the process of atherosclerotic plaque destabilization are complex, and molecular data from aortic plaques are difficult to interpret. Biological network models may overcome these difficulties and precisely quantify the molecular mechanisms impacted during disease progression. The atherosclerosis plaque destabilization biological network model was constructed with the semiautomated curation pipeline, BELIEF. Cellular and molecular mechanisms promoting plaque destabilization or rupture were captured in the network model. Public transcriptomic data sets were used to demonstrate the specificity of the network model and to capture the different mechanisms that were impacted in ApoE -/- mouse aorta at 6 and 32 weeks. We concluded that network models combined with the network perturbation amplitude algorithm provide a sensitive, quantitative method to follow disease progression at the molecular level. This approach can be used to investigate and quantify molecular mechanisms during plaque progression.
NASA Astrophysics Data System (ADS)
Jamison, David, IV
Low back pain is a large and costly problem in the United States. Several working populations, such as miners, construction workers, forklift operators, and military personnel, have an increased risk and prevalence of low back pain compared to the general population. This is due to exposure to repeated, transient impact shocks, particularly while operating vehicles or other machinery. These shocks typically do not cause acute injury, but rather lead to pain and injury over time. The major focus in low back pain is often the intervertebral disc, due to its role as the major primary load-bearing component along the spinal column. The formation of a reliable standard for human lumbar disc exposure to repeated transient shock could potentially reduce injury risk for these working populations. The objective of this project, therefore, is to characterize the mechanical response of the lumbar intervertebral disc subjected to sub-traumatic impact loading conditions using both cadaveric and computational models, and to investigate the possible implications of this type of loading environment for low back pain. Axial, compressive impact loading events on Naval high speed boats were simulated in the laboratory and applied to human cadaveric specimen. Disc stiffness was higher and hysteresis was lower than quasi-static loading conditions. This indicates a shift in mechanical response when the disc is under impact loads and this behavior could be contributing to long-term back pain. Interstitial fluid loss and disc height changes were shown to affect disc impact mechanics in a creep study. Neutral zone increased, while energy dissipation and low-strain region stiffness decreased. This suggests that the disc has greater clinical instability during impact loading with progressive creep and fluid loss, indicating that time of day should be considered for working populations subjected to impact loads. A finite element model was developed and validated against cadaver specimen subjected to impacts in the laboratory. Analysis showed greater total von Mises stress and pore pressure in the components of the disc under transient shocks compared to static or quasi-static loading. These findings support the idea that impact shocks cause a change in mechanical response and are potentially damaging to the disc in the long term.
Feeling bad about progress does not lead people want to change their health behaviour.
Reynolds, James P; Webb, Thomas L; Benn, Yael; Chang, Betty P I; Sheeran, Paschal
2018-02-01
When do people decide to do something about problematic health behaviours? Theoretical models and pragmatic considerations suggest that people should take action when they feel bad about their progress - in other words, when they experience negative progress-related affect. However, the impact of progress-related affect on goal striving has rarely been investigated. Study 1 (N = 744) adopted a cross-sectional design and examined the extent to which measures of progress-related affect were correlated with intentions to take action. Study 2 (N = 409) investigated the impact of manipulating progress-related affect on intentions and behaviour in an experimental design. Study 1 found that, while engaging in health behaviours had the expected affective consequences (e.g. people felt bad when they were not eating healthily, exercising regularly or limiting their alcohol consumption), it was feeling good rather than bad about progress that was associated with stronger intentions. Study 2 replicated these findings. Participants induced to feel good about their eating behaviour had marginally stronger intentions to eat healthily than participants led to feel bad about their eating behaviour. The findings have implications for interventions designed to promote changes in health behaviour, as well as theoretical frameworks for understanding self-regulation.
Watermeyer, Tamlyn J; Brown, Richard G; Sidle, Katie C L; Oliver, David J; Allen, Christopher; Karlsson, Joanna; Ellis, Cathy; Shaw, Christopher E; Al-Chalabi, Ammar; Goldstein, Laura H
2015-01-01
Up to 50% of patients with amyotrophic lateral sclerosis (ALS) show mild to moderate cognitive-behavioural change alongside their progressive functional impairment. This study examines the relative impact of patients' disease symptoms, behavioural change and current executive function and social cognition abilities on psychosocial outcomes in spouse caregivers of people with ALS. Thirty-five spouse caregivers rated their own levels of depression and anxiety, subjective burden and marital satisfaction. Caregivers also rated their partner's everyday behaviour. The patients were assessed for disease severity and cognitive function, with composite scores derived for executive function and social cognition. Regression analyses revealed that caregiver burden was predicted by the severity of patients' limb involvement and behavioural problems. Depression was predicted by patients' limb involvement, while behavioural problems and patient age predicted caregiver anxiety. Current marital satisfaction was predicted by patient behavioural problems beyond the level of pre-illness marital satisfaction. In conclusion, the study highlights the potential impact of ALS patients' functional impairment and behavioural change on ALS caregivers' psychosocial functioning. Clinical communication with ALS families should emphasise both physical and psychological challenges presented by the disease.
Honig, Aaron; LaPeyre, Megan K.; Supan, John
2014-01-01
Benthic intertidal bivalves play an essential role in estuarine ecosystems by contributing to habitat provision, water filtration, and host vegetation productivity. As such, ecosystem level changes that impact population distributions and persistence of local bivalve populations may have large ecosystem level consequences, making it important to better understand the population ecology of native bivalves. In order to determine potential impacts of shifting salinity and temperature regimes along the northern Gulf of Mexico, the seasonal timing of gametogenesis in the Gulf estuarine ribbed mussel, Geukensia granossisima, was examined across a salinity gradient in southeastern Louisiana, from July 2011 through October 2012. Ten mussels were randomly sampled monthly from low (~ 5) and high (~25) salinity marsh sites in southeastern Louisiana, and histologically processed to determine the seasonal progression of gametogenesis. Peak ripeness occurred at both sites between April and September, was positively correlated with temperature, and coincided with seasonal shifts in salinity. Mussels located in lower salinity waters demonstrated a shorter period of gametogenesis, and lower rates of ripeness indicating that changes in salinity regimes may impact long-term population dynamics.
Pertschuk, Mark; Pomeranz, Jennifer L; Aoki, Julie Ralston; Larkin, Michelle A; Paloma, Marjorie
2013-01-01
In the United States, state and local public health policies play a fundamental role in innovation and progress. Preemption, by which Congress or the state legislatures limit the authority of lower jurisdictions, can eliminate the benefits of state and local policy initiatives. Preemption can also have a negative impact on enforcement, civic engagement, and grassroots movement building.In June 2011, the Institute of Medicine published a groundbreaking report on policy and law that considered preemption as a crosscutting issue in public health. The Institute of Medicine recommended that federal and state policy makers "should set minimum standards...allowing states and localities to further protect the health and safety of their inhabitants," and "should avoid language that hinders public health action."The Preemption Framework is a tool to support effective decision making by helping the public health field anticipate, assess, and, if necessary, counter preemptive policy proposals. We review the consequences of preemption, including its potential impact on grassroots public health movements, and propose practical questions and considerations to assist decision makers in responding to preemptive proposals.
Monitoring road safety development at regional level: A case study in the ASEAN region.
Chen, Faan; Wang, Jianjun; Wu, Jiaorong; Chen, Xiaohong; Zegras, P Christopher
2017-09-01
Persistent monitoring of progress, evaluating the results of interventions and recalibrating to achieve continuous improvement over time is widely recognized as being crucial towards the successful development of road safety. In the ASEAN (Association of Southeast Asian Nations) region there is a lack of well-resourced teams that contain multidisciplinary safety professionals, and specialists in individual countries, who are able to carry out this work effectively. In this context, not only must the monitoring framework be effective, it must also be easy to use and adapt. This paper provides a case study that can be easily reproduced; based on an updated and refined Road Safety Development Index (RSDI), by means of the RSR (Rank-sum ratio)-based model, for monitoring/reporting road safety development at regional level. The case study was focused on the road safety achievements in eleven Southeast Asian countries; identifying the areas of poor performance, potential problems and delays. These countries are finally grouped into several classes based on an overview of their progress and achievements regarding to road safety. The results allow the policymakers to better understand their own road safety progress toward their desired impact; more importantly, these results enable necessary interventions to be made in a quick and timely manner. Keeping action plans on schedule if things are not progressing as desired. This would avoid 'reinventing the wheel' and trial and error approaches to road safety, making the implementation of action plans more effective. Copyright © 2017 Elsevier Ltd. All rights reserved.
Illusion or delusion--Lean management in the health sector.
McIntosh, Bryan; Sheppy, Bruce; Cohen, Ivan
2014-01-01
There has been considerable interest in the implementation of practices imported from manufacturing into healthcare as a solution to rising healthcare spending and disappointing patient safety indicators. One approach that has attracted particular interest is Lean management and the purpose of this paper is to engage with this topic. Secondary research. Despite widespread enthusiasm about the potential of Lean management processes, evidence about its contribution to higher organisational performance remains inconsistent. This paper engages with the major Lean concepts of operations management and human resource management, including just-in-time, total quality management, total productive maintenance and does not engage in-depth with concepts related to employee empowerment, and training This paper contributes to the organisational management literature in healthcare by showing that although Lean management seems to have the potential to improve organisational performance it is far from a panacea against under performing hospitals. It informs policy making by suggesting that a progressive managerial philosophy has a stronger impact on healthcare performance than the adoption of practices from any particular managerial approach. This paper provides a critical evaluation of the impact of Lean practices in informing healthcare policy. The paper contributes to the organisational management literature in healthcare by showing that even though Lean management in healthcare appears to have the potential to improve organisational performance; there remain problems with its application.
Ung, Timothy H; Madsen, Helen J; Hellwinkel, Justin E; Lencioni, Alex M; Graner, Michael W
2014-11-01
Exosomes are virus-sized, membrane-enclosed vesicles with origins in the cellular endosomal system, but are released extracellularly. As a population, these tiny vesicles carry relatively enormous amounts of information in their protein, lipid and nucleic acid content, and the vesicles can have profound impacts on recipient cells. This review employs publically-available data combined with gene ontology applications to propose a novel concept, that exosomes transport transcriptional and translational machinery that may have direct impacts on gene expression in recipient cells. Here, we examine the previously published proteomic contents of medulloblastoma-derived exosomes, focusing on transcriptional regulators; we found that there are numerous proteins that may have potential roles in transcriptional and translational regulation with putative influence on downstream, cancer-related pathways. We expanded this search to all of the proteins in the Vesiclepedia database; using gene ontology approaches, we see that these regulatory factors are implicated in many of the processes involved in cancer initiation and progression. This information suggests that some of the effects of exosomes on recipient cells may be due to the delivery of protein factors that can directly and fundamentally change the transcriptional landscape of the cells. Within a tumor environment, this has potential to tilt the advantage towards the cancer. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
Chiang, E-P; Wang, Y-C; Tang, F-Y
2007-04-01
The homozygous mutation (677TT) in the methylenetetrahydrofolate reductase (MTHFR) gene reduces enzyme activity and alters cellular folate composition. Previous epidemiological studies reported a potential protective effect of MTHFR677C --> T against acute lymphocytic leukemia and malignant lymphoma, but the mechanism remains to be determined. We investigated the biochemical impacts of MTHFR677C --> T on cellular S-adenosyl methionine (adoMet) synthesis, global DNA methylation, and de novo purine synthesis, all of which are potential regulatory pathways involved in tumorigenesis. Metabolic fluxes of homocysteine remethylation and de novo purine synthesis were compared between Epstein-Barr virus-transformed lymphoblasts expressing MTHFR 677C and MTHFR 677T using stable isotopic tracers and GCMS. MTHFR TT genotype significantly reduced folate-dependent remethylation under folate restriction, reflecting limited methylated folates under folate restriction. Data also suggested increased formylated folate pool and increased purine synthesis when folate is adequate. The impacts of MTHFR 677T polymorphism appeared closely related to folate status, and such alterations may modulate metabolic pathways involved in cancer onset/progression. The advantage of de novo purine synthesis found in the MTHFR TT genotype may account for the protective effect of MTHFR in hematological malignancies. These transformed cells are potential models for studying the consequences of human genetic variation and cancer pathogenesis.
Valproate inhibits MAP kinase signalling and cell cycle progression in S. cerevisiae.
Desfossés-Baron, Kristelle; Hammond-Martel, Ian; Simoneau, Antoine; Sellam, Adnane; Roberts, Stephen; Wurtele, Hugo
2016-10-26
The mechanism of action of valproate (VPA), a widely prescribed short chain fatty acid with anticonvulsant and anticancer properties, remains poorly understood. Here, the yeast Saccharomyces cerevisiae was used as model to investigate the biological consequences of VPA exposure. We found that low pH strongly potentiates VPA-induced growth inhibition. Transcriptional profiling revealed that under these conditions, VPA modulates the expression of genes involved in diverse cellular processes including protein folding, cell wall organisation, sexual reproduction, and cell cycle progression. We further investigated the impact of VPA on selected processes and found that this drug: i) activates markers of the unfolded protein stress response such as Hac1 mRNA splicing; ii) modulates the cell wall integrity pathway by inhibiting the activation of the Slt2 MAP kinase, and synergizes with cell wall stressors such as micafungin and calcofluor white in preventing yeast growth; iii) prevents activation of the Kss1 and Fus3 MAP kinases of the mating pheromone pathway, which in turn abolishes cellular responses to alpha factor; and iv) blocks cell cycle progression and DNA replication. Overall, our data identify heretofore unknown biological responses to VPA in budding yeast, and highlight the broad spectrum of cellular pathways influenced by this chemical in eukaryotes.
Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis.
Axelsson, Markus; Malmeström, Clas; Gunnarsson, Martin; Zetterberg, Henrik; Sundström, Peter; Lycke, Jan; Svenningsson, Anders
2014-01-01
In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.
Seizure clusters: characteristics and treatment.
Haut, Sheryl R
2015-04-01
Many patients with epilepsy experience 'clusters' or flurries of seizures, also termed acute repetitive seizures (ARS). Seizure clustering has a significant impact on health and quality of life. This review summarizes recent advances in the definition and neurophysiologic understanding of clustering, the epidemiology and risk factors for clustering and both inpatient and outpatient clinical implications. New treatments for seizure clustering/ARS are perhaps the area of greatest recent progress. Efforts have focused on creating a uniform definition of a seizure cluster. In neurophysiologic studies of refractory epilepsy, seizures within a cluster appear to be self-triggering. Clinical progress has been achieved towards a more precise prevalence of clustering, and consensus guidelines for epilepsy monitoring unit safety. The greatest recent advances are in the study of nonintravenous route of benzodiazepines as rescue medications for seizure clusters/ARS. Rectal benzodiazepines have been very effective but barriers to use exist. New data on buccal, intramuscular and intranasal preparations are anticipated to lead to a greater number of approved treatments. Progesterone may be effective for women who experience catamenial clusters. Seizure clustering is common, particularly in the setting of medically refractory epilepsy. Clustering worsens health and quality of life, and the field requires greater focus on clarifying of definition and clinical implications. Progress towards the development of nonintravenous routes of benzodiazepines has the potential to improve care in this area.
ERIC Educational Resources Information Center
Van Den Berg, M. N.; Hofman, W. H. A.
2005-01-01
This study focuses on the factors that determine study progress and numerical success rate in higher education. Study progress is influenced at three levels, namely the student level, course/institute level and government level. It is expected that various groups of economic, social, psychological and organisational factors will together influence…
USDA-ARS?s Scientific Manuscript database
Production and well-being of sheep and goats in many countries are harmfully impacted by small ruminant lentiviruses (SRLV) that cause incurable, progressive diseases. Susceptibility to ovine progressive pneumonia virus (OPPV), the North American form of SRLV, is influenced by variants of the ovine...
Cox, Louis Anthony Tony
2006-12-01
This article introduces an approach to estimating the uncertain potential effects on lung cancer risk of removing a particular constituent, cadmium (Cd), from cigarette smoke, given the useful but incomplete scientific information available about its modes of action. The approach considers normal cell proliferation; DNA repair inhibition in normal cells affected by initiating events; proliferation, promotion, and progression of initiated cells; and death or sparing of initiated and malignant cells as they are further transformed to become fully tumorigenic. Rather than estimating unmeasured model parameters by curve fitting to epidemiological or animal experimental tumor data, we attempt rough estimates of parameters based on their biological interpretations and comparison to corresponding genetic polymorphism data. The resulting parameter estimates are admittedly uncertain and approximate, but they suggest a portfolio approach to estimating impacts of removing Cd that gives usefully robust conclusions. This approach views Cd as creating a portfolio of uncertain health impacts that can be expressed as biologically independent relative risk factors having clear mechanistic interpretations. Because Cd can act through many distinct biological mechanisms, it appears likely (subjective probability greater than 40%) that removing Cd from cigarette smoke would reduce smoker risks of lung cancer by at least 10%, although it is possible (consistent with what is known) that the true effect could be much larger or smaller. Conservative estimates and assumptions made in this calculation suggest that the true impact could be greater for some smokers. This conclusion appears to be robust to many scientific uncertainties about Cd and smoking effects.
Kleinstreuer, Clement; Feng, Yu
2013-09-23
Inhaled toxic aerosols of conventional cigarette smoke may impact not only the health of smokers, but also those exposed to second-stream smoke, especially children. Thus, less harmful cigarettes (LHCs), also called potential reduced exposure products (PREPs), or modified risk tobacco products (MRTP) have been designed by tobacco manufacturers to focus on the reduction of the concentration of carcinogenic components and toxicants in tobacco. However, some studies have pointed out that the new cigarette products may be actually more harmful than the conventional ones due to variations in puffing or post-puffing behavior, different physical and chemical characteristics of inhaled toxic aerosols, and longer exposure conditions. In order to understand the toxicological impact of tobacco smoke, it is essential for scientists, engineers and manufacturers to develop experiments, clinical investigations, and predictive numerical models for tracking the intake and deposition of toxicants of both LHCs and conventional cigarettes. Furthermore, to link inhaled toxicants to lung and other diseases, it is necessary to determine the physical mechanisms and parameters that have significant impacts on droplet/vapor transport and deposition. Complex mechanisms include droplet coagulation, hygroscopic growth, condensation and evaporation, vapor formation and changes in composition. Of interest are also different puffing behavior, smoke inlet conditions, subject geometries, and mass transfer of deposited material into systemic regions. This review article is intended to serve as an overview of contributions mainly published between 2009 and 2013, focusing on the potential health risks of toxicants in cigarette smoke, progress made in different approaches of impact analyses for inhaled toxic aerosols, as well as challenges and future directions.
NASA Astrophysics Data System (ADS)
Keller, David P.; Lenton, Andrew; Scott, Vivian; Vaughan, Naomi E.; Bauer, Nico; Ji, Duoying; Jones, Chris D.; Kravitz, Ben; Muri, Helene; Zickfeld, Kirsten
2018-03-01
The recent IPCC reports state that continued anthropogenic greenhouse gas emissions are changing the climate, threatening severe, pervasive and irreversible
impacts. Slow progress in emissions reduction to mitigate climate change is resulting in increased attention to what is called geoengineering, climate engineering, or climate intervention - deliberate interventions to counter climate change that seek to either modify the Earth's radiation budget or remove greenhouse gases such as CO2 from the atmosphere. When focused on CO2, the latter of these categories is called carbon dioxide removal (CDR). Future emission scenarios that stay well below 2 °C, and all emission scenarios that do not exceed 1.5 °C warming by the year 2100, require some form of CDR. At present, there is little consensus on the climate impacts and atmospheric CO2 reduction efficacy of the different types of proposed CDR. To address this need, the Carbon Dioxide Removal Model Intercomparison Project (or CDRMIP) was initiated. This project brings together models of the Earth system in a common framework to explore the potential, impacts, and challenges of CDR. Here, we describe the first set of CDRMIP experiments, which are formally part of the 6th Coupled Model Intercomparison Project (CMIP6). These experiments are designed to address questions concerning CDR-induced climate reversibility
, the response of the Earth system to direct atmospheric CO2 removal (direct air capture and storage), and the CDR potential and impacts of afforestation and reforestation, as well as ocean alkalinization.>
DOE Office of Scientific and Technical Information (OSTI.GOV)
Keller, David P.; Lenton, Andrew; Scott, Vivian
The recent IPCC reports state that continued anthropogenic greenhouse gas emissions are changing the climate, threatening severe, pervasive and irreversible impacts. Slow progress in emissions reduction to mitigate climate change is resulting in increased attention to what is called geoengineering, climate engineering, or climate intervention – deliberate interventions to counter climate change that seek to either modify the Earth's radiation budget or remove greenhouse gases such as CO 2 from the atmosphere. When focused on CO 2, the latter of these categories is called carbon dioxide removal (CDR). Future emission scenarios that stay well below 2 °C, and all emissionmore » scenarios that do not exceed 1.5 °C warming by the year 2100, require some form of CDR. At present, there is little consensus on the climate impacts and atmospheric CO 2 reduction efficacy of the different types of proposed CDR. To address this need, the Carbon Dioxide Removal Model Intercomparison Project (or CDRMIP) was initiated. This project brings together models of the Earth system in a common framework to explore the potential, impacts, and challenges of CDR. Here, we describe the first set of CDRMIP experiments, which are formally part of the 6th Coupled Model Intercomparison Project (CMIP6). These experiments are designed to address questions concerning CDR-induced climate reversibility, the response of the Earth system to direct atmospheric CO 2 removal (direct air capture and storage), and the CDR potential and impacts of afforestation and reforestation, as well as ocean alkalinization.>« less
Chemoprevention of Barrett's Esophagus and Esophageal Adenocarcinoma.
Bresalier, Robert S
2018-06-12
Barrett's esophagus is common in Western countries, but progression to esophageal adenocarcinoma is uncommon. Chemoprevention therefore needs to consider whether benefits outweigh risks given an otherwise healthy population. This will depend on the particular population at risk and the relative safety of a potential preventive agent. Most evidence regarding the potential benefit of chemoprevention of Barrett's esophagus and prevention of progression to esophageal adenocarcinoma is based on observational studies such as case-control and cohort studies. Given the potential benefits and relatively low risks, patients with BE should receive once-daily PPI therapy, but routine use of twice-daily PPI is not recommended unless necessitated by poor control of reflux symptoms or esophagitis. Recent data suggest that the inverse associations between aspirin/NSAID use and esophageal adenocarcinoma may be the result of reducing neoplastic progression (from metaplasia to dysplasia and carcinoma) rather than initiation of Barrett's esophagus. While substantial associative data suggest a potential benefit of aspirin and nonaspirin NSAIDs in reducing the risk of progression of Barrett's esophagus, the low risk of progression and the potential risks (gastrointestinal bleeding, complicated ulcer disease, hemorrhagic stroke) do not warrant routine use, unless dictated by cardiovascular risk. Chemoprevention after mucosal ablation in those at highest risk of post-ablation recurrence (dysplastic Barrett's) is currently under investigation.
An interval kicking progression for return to soccer following lower extremity injury.
Arundale, Amelia; Silvers, Holly; Logerstedt, David; Rojas, Jaime; Snyder-Mackler, Lynn
2015-02-01
The majority of all soccer injuries affect the lower extremities. Regardless of whether the injured limb is an athlete's preferred kicking or stance leg, a lower extremity injury may affect their ability to impact the ball. Sport-specific biomechanical progressions to augment loading and gradually reintroduce a player to the demands of sport have been developed for upper extremity sports such as baseball, softball, tennis, and golf. Generalized return to soccer progressions have also been published in order to assist clinicians in safely returning athletes to sport; however, there are no specific progressions for the early stages of kicking designed to introduce stance leg loading and kicking leg impact. Thus, the purpose of this clinical commentary was to review the existing literature elucidating the biomechanics of kicking a soccer ball and propose a progressive kicking program to support clinicians in safely returning their soccer athletes to the demands of sport. The interval kicking program (IKP) describes clinical guidelines for readiness to begin a kicking program as well as possible readiness to return to sport measures. The program is performed on alternate days integrating therapeutic exercise and cardiovascular fitness. The IKP gradually introduces a player to the loading and impact of kicking. The progression increases kicking distance (using the markings of a soccer field as a guide), volume, and intensity and uses proposed soreness rules, effusion guidelines, and player feedback in order to assist clinicians in determining readiness for advancement though the stages. The IKP also recommends utility of specific tests and measures to determine readiness for return to sport. Gradual reintroduction to sport specific demands is essential for a safe return to soccer. This return to sport progression provides a framework integrating injury specific therapeutic exercise, cardiovascular fitness, and the return to kicking progression, to assist clinicians in initiating an athletes' return to soccer. Level 5.
Advanced organic composite materials for aircraft structures: Future program
NASA Technical Reports Server (NTRS)
1987-01-01
Revolutionary advances in structural materials have been responsible for revolutionary changes in all fields of engineering. These advances have had and are still having a significant impact on aircraft design and performance. Composites are engineered materials. Their properties are tailored through the use of a mix or blend of different constituents to maximize selected properties of strength and/or stiffness at reduced weights. More than 20 years have passed since the potentials of filamentary composite materials were identified. During the 1970s much lower cost carbon filaments became a reality and gradually designers turned from boron to carbon composites. Despite progress in this field, filamentary composites still have significant unfulfilled potential for increasing aircraft productivity; the rendering of advanced organic composite materials into production aircraft structures was disappointingly slow. Why this is and research and technology development actions that will assist in accelerating the application of advanced organic composites to production aircraft is discussed.
Regulation and Function of Adult Neurogenesis: From Genes to Cognition
Aimone, James B.; Li, Yan; Lee, Star W.; Clemenson, Gregory D.; Deng, Wei; Gage, Fred H.
2014-01-01
Adult neurogenesis in the hippocampus is a notable process due not only to its uniqueness and potential impact on cognition but also to its localized vertical integration of different scales of neuroscience, ranging from molecular and cellular biology to behavior. This review summarizes the recent research regarding the process of adult neurogenesis from these different perspectives, with particular emphasis on the differentiation and development of new neurons, the regulation of the process by extrinsic and intrinsic factors, and their ultimate function in the hippocampus circuit. Arising from a local neural stem cell population, new neurons progress through several stages of maturation, ultimately integrating into the adult dentate gyrus network. The increased appreciation of the full neurogenesis process, from genes and cells to behavior and cognition, makes neurogenesis both a unique case study for how scales in neuroscience can link together and suggests neurogenesis as a potential target for therapeutic intervention for a number of disorders. PMID:25287858
The Interaction between Epigenetics, Nutrition and the Development of Cancer
Bishop, Karen S.; Ferguson, Lynnette R.
2015-01-01
Unlike the genome, the epigenome can be modified and hence some epigenetic risk markers have the potential to be reversed. Such modifications take place by means of drugs, diet or environmental exposures. It is widely accepted that epigenetic modifications take place during early embryonic and primordial cell development, but it is also important that we gain an understanding of the potential for such changes later in life. These “later life” epigenetic modifications in response to dietary intervention are the focus of this paper. The epigenetic modifications investigated include DNA methylation, histone modifications and the influence of microRNAs. The epigenotype could be used not only to predict susceptibility to certain cancers but also to assess the effectiveness of dietary modifications to reduce such risk. The influence of diet or dietary components on epigenetic modifications and the impact on cancer initiation or progression has been assessed herein. PMID:25647662
Leveraging of Open EMR Architecture for Clinical Trial Accrual
Afrin, Lawrence B.; Oates, James C.; Boyd, Caroline K.; Daniels, Mark S.
2003-01-01
Accrual to clinical trials is a major bottleneck in scientific progress in clinical medicine. Many methods for identifying potential subjects and improving accrual have been pursued; few have succeeded, and none have proven generally reproducible or scalable. We leveraged the open architecture of the core clinical data repository of our electronic medical record system to prototype a solution for this problem in a manner consistent with contemporary regulations and research ethics. We piloted the solution with a local investigator-initiated trial for which candidate identification was expected to be difficult. Key results in the eleven months of experience to date include automated screening of 7,296,708 lab results from 69,288 patients, detection of 1,768 screening tests of interest, identification of 70 potential candidates who met all further automated criteria, and accrual of three candidates to the trial. Hypotheses for this disappointing impact on accrual, and directions for future research, are discussed. PMID:14728125
Semi-automated identification of cones in the human retina using circle Hough transform
Bukowska, Danuta M.; Chew, Avenell L.; Huynh, Emily; Kashani, Irwin; Wan, Sue Ling; Wan, Pak Ming; Chen, Fred K
2015-01-01
A large number of human retinal diseases are characterized by a progressive loss of cones, the photoreceptors critical for visual acuity and color perception. Adaptive Optics (AO) imaging presents a potential method to study these cells in vivo. However, AO imaging in ophthalmology is a relatively new phenomenon and quantitative analysis of these images remains difficult and tedious using manual methods. This paper illustrates a novel semi-automated quantitative technique enabling registration of AO images to macular landmarks, cone counting and its radius quantification at specified distances from the foveal center. The new cone counting approach employs the circle Hough transform (cHT) and is compared to automated counting methods, as well as arbitrated manual cone identification. We explore the impact of varying the circle detection parameter on the validity of cHT cone counting and discuss the potential role of using this algorithm in detecting both cones and rods separately. PMID:26713186
NASA Astrophysics Data System (ADS)
Gandy, Yuridia Patricia Peralta De
Studies were conducted to investigate the use of spectral reflectance by foliage of common sunflower as a potential indicator of arsenic contamination of soil. Germination method was developed for sunflower seeds, and cohorts of sunflower seedlings in hydroponic tanks were established. The cohorts were exposed to 0 ppm, 5 ppm, 7.5 ppm, and 10 ppm treatments of As (V) and reflectance measurements of foliage were collected using a spectroradiometer during two experiments. Results demonstrated the feasibility of using spectral reflectance by foliage of common sunflower as a potential indicator of arsenic contamination. In both experiments, arsenic concentrations in leaf tissues were directly proportional to arsenic concentrations in hydroponic solutions in which such plants were grown. Although the effect(s) of arsenic accumulation had minimal impact on reflectance of visible wavelengths, the effects on NIR reflectance were substantial and resulted in a progressive decrease in reflectance as arsenic concentrations in foliage increased.
Potential crashworthiness benefits to general aviation from Indianapolis Motor Speedway technology.
Jennings, R T; Mohler, S R
1988-01-01
General aviation crashworthiness can potentially benefit from certain advances being accomplished by the automobile industry. Progressive improvements in crash protection technology, as documented by a dramatic reduction in crash injuries and fatalities at the Indianapolis Motor Speedway, reflect improved crashworthiness. The speeds of survivable general aviation aircraft impacts are in the range of the Indianapolis Motor Speedway crashes (200-220 mph). This paper relates the declining crash death rates at Indy by decade versus the increase in speeds. The continuous rise in speeds has prompted the development of new crashworthy designs and driver protection equipment. Crashworthiness improvements include crushable surrounding structures, high-grade restraint systems, protective head gear, fire resistant clothing, break-away structural components, and a "protective cocoon" concept. Adaptation of selected advances in crashworthiness design and operations accomplished at the Indianapolis Motor Speedway to the next generation of general aviation aircraft should provide significant dividends in survival of air crashes.
Experiment K-313: Rat and quail ontogenesis
NASA Technical Reports Server (NTRS)
Keefe, J. R.
1981-01-01
The potential effects of spaceflight on the processes of mammalian fertilizaton, implantation and embryonic development are investigated. Five female and two male rats were placed together on Day 2 of the flight. By R+17, it was determined that both flight and synchronous females were not carrying normal pregnancies and three of the flight animals were laparotomized. The uterus and ovaries were processed for microscopic analyses. The two remaining flight females were allowed to recover from the exploratory operation, rebred with flight males and delivered normal litters. As a control for potential transplacental effects that might be interpreted as direct spaceflight effects, a series of fertilized Japanese quail (Coturnix japonica) eggs was flown on Cosmos 1129. Although all of the eggs were adversely impacted by an inflight failure of the incubator humidifier on flight Day 13, several embryos were able to progress to a developmental stage equivalent to that of a control 10-12 Day embryo.
Bead-based screening in chemical biology and drug discovery.
Komnatnyy, Vitaly V; Nielsen, Thomas E; Qvortrup, Katrine
2018-06-11
High-throughput screening is an important component of the drug discovery process. The screening of libraries containing hundreds of thousands of compounds requires assays amenable to miniaturisation and automization. Combinatorial chemistry holds a unique promise to deliver structurally diverse libraries for early drug discovery. Among the various library forms, the one-bead-one-compound (OBOC) library, where each bead carries many copies of a single compound, holds the greatest potential for the rapid identification of novel hits against emerging drug targets. However, this potential has not yet been fully realized due to a number of technical obstacles. In this feature article, we review the progress that has been made in bead-based library screening and its application to the discovery of bioactive compounds. We identify the key challenges of this approach and highlight key steps needed for making a greater impact in the field.
The impact of nitric oxide in cardiovascular medicine: untapped potential utility.
Pepine, Carl J
2009-05-01
The structural integrity and functional activity of the endothelium play an important role in atherogenesis and related adverse outcomes. Cardiovascular disease risk conditions contribute to oxidative stress, which causes a disruption in the balance between nitric oxide (NO) and reactive oxygen species, with a resulting relative decrease in bioavailable NO and/or the NO-soluble guanylate cyclase cascade in blood vessels. This leads to endothelial and vascular smooth muscle cell dysfunction, resulting in increased tone and alterations in cell growth and gene expression that create a prothrombotic, proinflammatory environment. This leads to formation, progression, and destabilization of atherosclerotic plaques which may result in myocardial infarction, stroke, and cardiovascular death. NO clearly has a critical role in the maintenance and repair of the vasculature, and a decrease in bioavailable NO is linked to adverse outcomes. This background provides the rationale for exploring the potential therapeutic role for NO-donating agents in the prevention of adverse cardiovascular outcomes.
NASA Astrophysics Data System (ADS)
Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew
2016-10-01
Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.
Genome-editing technologies and their potential application in horticultural crop breeding
Xiong, Jin-Song; Ding, Jing; Li, Yi
2015-01-01
Plant breeding, one of the oldest agricultural activities, parallels human civilization. Many crops have been domesticated to satisfy human's food and aesthetical needs, including numerous specialty horticultural crops such as fruits, vegetables, ornamental flowers, shrubs, and trees. Crop varieties originated through selection during early human civilization. Other technologies, such as various forms of hybridization, mutation, and transgenics, have also been invented and applied to crop breeding over the past centuries. The progress made in these breeding technologies, especially the modern biotechnology-based breeding technologies, has had a great impact on crop breeding as well as on our lives. Here, we first review the developmental process and applications of these technologies in horticultural crop breeding. Then, we mainly describe the principles of the latest genome-editing technologies and discuss their potential applications in the genetic improvement of horticultural crops. The advantages and challenges of genome-editing technologies in horticultural crop breeding are also discussed. PMID:26504570
Outdoor Ambient Air Pollution and Neurodegenerative Diseases: the Neuroinflammation Hypothesis.
Jayaraj, Richard L; Rodriguez, Eric A; Wang, Yi; Block, Michelle L
2017-06-01
Accumulating research indicates that ambient outdoor air pollution impacts the brain and may affect neurodegenerative diseases, yet the potential underlying mechanisms are poorly understood. The neuroinflammation hypothesis holds that elevation of cytokines and reactive oxygen species in the brain mediates the deleterious effects of urban air pollution on the central nervous system (CNS). Studies in human and animal research document that neuroinflammation occurs in response to several inhaled pollutants. Microglia are a prominent source of cytokines and reactive oxygen species in the brain, implicated in the progressive neuron damage in diverse neurodegenerative diseases, and activated by inhaled components of urban air pollution through both direct and indirect pathways. The MAC1-NOX2 pathway has been identified as a mechanism through which microglia respond to different forms of air pollution, suggesting a potential common deleterious pathway. Multiple direct and indirect pathways in response to air pollution exposure likely interact in concert to exert CNS effects.
Implications of pharmacogenomics for drug development and clinical practice.
Ginsburg, Geoffrey S; Konstance, Richard P; Allsbrook, Jennifer S; Schulman, Kevin A
2005-11-14
Pharmacogenomics is likely to be among the first clinical applications of the Human Genome Project and is certain to have an enormous impact on the clinical practice of medicine. Herein, we discuss the potential implications of pharmacogenomics on the drug development process, including drug safety, productivity, market segmentation, market expansion, differentiation, and personalized health care. We also review 3 challenges facing the translation of pharmacogenomics into clinical practice: dependence on information technology, limited health care financing, and the scientific uncertainty surrounding validation of specific applications of the technology. To our knowledge, there is currently no formal agenda to promote and cultivate innovation, to develop progressive information technology, or to obtain the financing that would be required to advance the use of pharmacogenomic technologies in patient care. Although the potential of these technologies is driving change in the development of clinical sciences, it remains to be seen which health care systems level needs will be addressed.
Pappas, Katherine
2016-01-01
In this review, we provide a historical perspective on marijuana, and survey contemporary research investigating its potential negative effects on the brain. We discuss the evidence regarding cannabis dependence, driving under the influence of cannabis, underachievement, inducing (or worsening) certain psychiatric conditions, and the potential for progression to use of more dangerous drugs—summarized by the acronym DDUMB, a cognitive tool that may help healthcare providers in their risk/benefit discussions with patients who use cannabis. We also review and discuss the impact of marijuana use on target populations, including adolescents (who are at increased risk of harm); heavy users; and people suffering from—or at high risk of— mental illness. While cannabis presents certain subjective, healthrelated, and pecuniary benefits to users, growers, and other entities, it is also associated with several brainbased risks. Understanding these risks aids clinicians and their patients in making informed and balanced decisions regarding the initiation or continuance of marijuana use. PMID:27354924
Rahmani, Arshad H; shabrmi, Fahad M Al; Aly, Salah M
2014-01-01
The current mode of treatment based on synthetic drugs is expensive and also causes genetic and metabolic alterations. However, safe and sound mode of treatment is needed to control the diseases development and progression. In this regards, medicinal plant and its constituents play an important role in diseases management via modulation of biological activities. Ginger, the rhizome of the Zingiber officinale, has shown therapeutic role in the health management since ancient time and considered as potential chemopreventive agent. Numerous studies based on clinical trials and animal model has shown that ginger and its constituents shows significant role in the prevention of diseases via modulation of genetic and metabolic activities. In this review, we focused on the therapeutics effects of ginger and its constituents in the diseases management, and its impact on genetic and metabolic activities. PMID:25057339
The economic impact of NASA R and D spending: Executive summary
NASA Technical Reports Server (NTRS)
Evans, M. K.
1976-01-01
An evaluation of the economic impact of NASA research and development programs is made. The methodology and the results revolve around the interrelationships existing between the demand and supply effects of increased research and development spending, in particular, NASA research and development spending. The INFORUM Inter-Industry Forecasing Model is used to measure the short-run economic impact of alternative levels of NASA expenditures for 1975. An aggregate production function approach is used to develop the data series necessary to measure the impact of NASA research and development spending, and other determinants of technological progress, on the rate of growth in productivity of the U. S. economy. The measured relationship between NASA research and development spending and technological progress is simulated in the Chase Macroeconometric Model to measure the immediate, intermediate, and long-run economic impact of increased NASA research and development spending over a sustained period.
Research on environmental impacts of tourism in China: progress and prospect.
Zhong, Linsheng; Deng, Jinyang; Song, Zengwen; Ding, Peiyi
2011-11-01
With the rapid development of tourism industry in China since 1980, the country has experienced an increasing use of its natural and cultural environment for tourism, resulting in tourism resources being adversely impacted in many tourism destinations. This paper described the research progress in tourism impacts on the environment in the context of China through a review of the growing literature in this field. Specifically, research on tourism impacts on the biophysical and socio-cultural environments, tourism carrying capacity, environmental quality assessment, and measures for the protection and management of tourism resources was reviewed. The review found that the majority of research was qualitative and descriptive in nature, and there was a lack of case studies and theoretical development. Future research should focus on the evaluation of environmental impacts, particularly those gradual cumulative impacts on the tourism environment; examination of the quantitative relationship between the impact and the level of tourism use for different activities; development of methods to estimate the carrying capacity; and understanding of positive impacts of tourism. Copyright © 2011. Published by Elsevier Ltd.
Neglected tropical diseases: now more than just 'other diseases'--the post-2015 agenda.
Molyneux, David H
2014-09-01
Neglected tropical diseases (NTDs) have become recognised as important health problems facing at least a billion people in the low-income countries and the poorest communities in middle-income countries. WHO plays a leading role in developing strategies to address these diseases, pharmaceutical companies provide drug donations to treat or control the NTDs and many partners from different constituencies have become increasingly committed to their control or elimination. This review looks to the post-2015 agenda and emphasises that despite the progress made over recent years, if the targets established are to be achieved, then not only will additional financial resources be required to up-scale treatments and increase access, but increased applied and operational research will be necessary to address problems and human capacity in NTD skills will need to be strengthened. Continuing advocacy for the relevance of control or elimination of NTDs must be placed in the context of universal health coverage and access to donated essential medicines for the poor as a right. The evidence that investment in NTD interventions are cost-effective and impact not only on health, but also to enhance socio-economic development, must be refined and promulgated. The global burden of disease attributable to NTDs requires reassessment to appropriately define the true burden, while the potential for unexpected events, political, climatic, environmental as well as biological, have the potential to reduce future progress towards the agreed post-2015 targets. NTD progress towards the WHO Roadmap targets and the fulfilment of the World Health Assembly Resolution 66.12 of 2013 demand continued commitment from all partner constituencies when challenges emerge. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Würth, Roberto; Bajetto, Adriana; Harrison, Jeffrey K; Barbieri, Federica; Florio, Tullio
2014-01-01
Chemokines are crucial autocrine and paracrine players in tumor development. In particular, CXCL12, through its receptors CXCR4 and CXCR7, affects tumor progression by controlling cancer cell survival, proliferation and migration, and, indirectly, via angiogenesis or recruiting immune cells. Glioblastoma (GBM) is the most prevalent primary malignant brain tumor in adults and despite current multimodal therapies it remains almost incurable. The aggressive and recurrent phenotype of GBM is ascribed to high growth rate, invasiveness to normal brain, marked angiogenesis, ability to escape the immune system and resistance to standard of care therapies. Tumor molecular and cellular heterogeneity severely hinders GBM therapeutic improvement. In particular, a subpopulation of chemo- and radio-therapy resistant tumorigenic cancer stem-like cells (CSCs) is believed to be the main responsible for tumor cell dissemination to the brain. GBM cells display heterogeneous expression levels of CXCR4 and CXCR7 that are overexpressed in CSCs, representing a molecular correlate for the invasive potential of GBM. The microenvironment contribution in GBM development is increasingly emphasized. An interplay exists between CSCs, differentiated GBM cells, and the microenvironment, mainly through secreted chemokines (e.g., CXCL12) causing recruitment of fibroblasts, endothelial, mesenchymal and inflammatory cells to the tumor, via specific receptors such as CXCR4. This review covers recent developments on the role of CXCL12/CXCR4-CXCR7 networks in GBM progression and the potential translational impact of their targeting. The biological and molecular understanding of the heterogeneous GBM cell behavior, phenotype and signaling is still limited. Progress in the identification of chemokine-dependent mechanisms that affect GBM cell survival, trafficking and chemo-attractive functions, opens new perspectives for development of more specific therapeutic approaches that include chemokine-based drugs.
Proxemy Research Grant NAG5-10263 Closeout Report
NASA Technical Reports Server (NTRS)
Stofan, Ellen R.
2002-01-01
Proxemy Research had a grant from NASA to perform science research of upwelling and volcanism on Venus. This was a 5 year Presidential Early Career Award to E. Stofan, entitled "Upwelling and volcanism: Constraints from regional studies and geologic mapping." Here we summarize the scientific progress and accomplishments of this grant. Scientific publications and abstracts of presentations are indicated in the final section. This was a very productive grant and the progress that was made is summarized. Attention is drawn to the publications, abstracts, and talks given in each year. Volcanism and tectonism are the dominant geological processes that have shaped the surface of Venus, as revealed by the Magellan data. However, the development of a global geologic history for Venus has caused considerable debate (e.g., Head and Basilevsky, 1996; Guest and Stofan, 1999). The lack of global time horizons on Venus, such as that provided by impact craters on most bodies and the fossil record on Earth, make developing global stratigraphies for Venus difficult, if not impossible, with current datasets. Before the geologic history of Venus can be determined and used as a constraint on potential lithospheric thickness variations through time, it is necessary to perform detailed stratigraphic studies on a local to regional scale. In addition, detailed studies of specific types of venusian features and terrains, such as coronae, volcanic rises, and large lava flow fields, may help to constrain the lithospheric thickness and its potential variations in time and space. This report describes progress made during the five year award under a Presidential Early Career Award for Scientists and Engineers which allows researchers freedom to explore new areas of research.
Impact of the level of state tax code progressivity on children's health outcomes.
Granruth, Laura Brierton; Shields, Joseph J
2011-08-01
This research study examines the impact of the level of state tax code progressivity on selected children's health outcomes. Specifically, it examines the degree to which a state's tax code ranking along the progressive-regressive continuum relates to percentage of low birthweight babies, infant and child mortality rates, and percentage of uninsured children. Using data merged from a number of public data sets, the authors find that the level of state tax code progressivity is a factor in state rates of infant and child mortality. States with lower median incomes and regressive tax policies have the highest rates of infant and child mortality.With regard to the percentage of children 17 years of age and below who lack health insurance, it is found that larger states with regressive tax policies have the largest percentage of uninsured children. In general, more heavily populated states with more progressive tax codes have healthier children. The implications of these findings are discussed in terms of tax policy and the well-being of children as well as for social work education, social work practice, and social work research.
Analysis of Restricted Natural Gas Supply Cases
2004-01-01
The four cases examined in this study have progressively greater impacts on overall natural gas consumption, prices, and supply. Compared to the Annual Energy Outlook 2004 reference case, the no Alaska pipeline case has the least impact; the low liquefied natural gas case has more impact; the low unconventional gas recovery case has even more impact; and the combined case has the most impact.
Key Role of Sulfonylurea Receptor 1 in Progressive Secondary Hemorrhage after Brain Contusion
Kilbourne, Michael; Tsymbalyuk, Orest; Tosun, Cigdem; Caridi, John; Ivanova, Svetlana; Keledjian, Kaspar; Bochicchio, Grant; Gerzanich, Volodymyr
2009-01-01
Abstract An important but poorly understood feature of traumatic brain injury (TBI) is the clinically serious problem of spatiotemporal progression (“blossoming”) of a hemorrhagic contusion, a phenomenon we term progressive secondary hemorrhage (PSH). Molecular mechanisms of PSH are unknown and efforts to reduce it by promoting coagulation have met with equivocal results. We hypothesized that PSH might be due to upregulation and activation of sulfonylurea receptor 1 (SUR1)-regulated NCCa-ATP channels in capillary endothelial cells, predisposing to oncotic death of endothelial cells and catastrophic failure of capillary integrity. Anesthetized adult male rats underwent left parietal craniectomy for induction of a focal cortical contusion. The regulatory subunit of the channel, SUR1, was prominently upregulated in capillaries of penumbral tissues surrounding the contusion. In untreated rats, PSH was characterized by progressive enlargement of the contusion deep into the site of cortical impact, including corpus callosum, hippocampus, and thalamus, by progressive accumulation of extravasated blood, with a doubling of the volume during the first 12 h after injury, and by capillary fragmentation in penumbral tissues. Block of SUR1 using low-dose (non-hypoglycemogenic) glibenclamide largely eliminated PSH and capillary fragmentation, and was associated with a significant reduction in the size of the necrotic lesion and in preservation of neurobehavioral function. Antisense oligodeoxynucleotide against SUR1, administered after injury, reduced both SUR1 expression and PSH, consistent with a requirement for transcriptional upregulation of SUR1. Our findings provide novel insights into molecular mechanisms responsible for PSH associated with hemorrhagic contusions, and point to SUR1 as a potential therapeutic target in TBI. PMID:19604096
Kreuter, Michael; Spagnolo, Paolo; Wuyts, Wim; Renzoni, Elisabetta; Koschel, Dirk; Bonella, Francesco; Maher, Toby M; Kolb, Martin; Weycker, Derek; Kirchgässler, Klaus-Uwe; Costabel, Ulrich
2017-01-01
Gastroesophageal reflux disease is a potential risk factor for idiopathic pulmonary fibrosis (IPF) progression; however, the impact of antacid therapy (AAT) is under debate. To evaluate the effect of AAT on IPF progression in pirfenidone-treated patients. This post hoc analysis included patients with IPF who received pirfenidone in 3 trials (CAPACITY [PIPF-004/PIPF-006] and ASCEND [PIPF-016]). Pulmonary function, exercise tolerance, survival, hospitalizations, and adverse events (AEs) over 52 weeks were analyzed by baseline AAT use. Disease progression was defined as a decrease in forced vital capacity (FVC) of ≥10%, a decrease in 6-min walking distance of ≥50 m, or death over 1 year. Of 623 patients, 44% received AAT. No significant differences were found at 52 weeks (AAT versus non-AAT, respectively) in disease progression (24.9 vs. 30.6%; p = 0.12), all-cause mortality rate (2.9 vs. 4.0%; p = 0.47), IPF-related mortality rate (1.1 vs. 2.0%; p = 0.37), all-cause hospitalization rate (16.1 vs. 18.3%; p = 0.48), or mean change in percent FVC (-2.7 vs. -3.1%; p = 0.44). A relative, but not absolute, FVC decline of ≥10% favored AAT (15 vs. 22%; p = 0.03). Severe gastrointestinal AEs (3.7 vs. 0.9%; p = 0.015) and severe pulmonary infections (3.7 vs. 1.1%; p = 0.035) were more frequent with AAT. AAT and pirfenidone had outcomes comparable to those of pirfenidone alone in patients with IPF, underscoring the need for prospective trials to elucidate the role of AAT with or without antifibrotic drugs as a treatment for IPF. © 2017 The Author(s) Published by S. Karger AG, Basel.
Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M
2017-09-01
There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43-0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39-0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53-1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50-0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss.
Sermier Dessemontet, Rachel; Bless, Gérard
2013-03-01
This study aimed at assessing the impact of including children with intellectual disability (ID) in general education classrooms with support on the academic achievement of their low-, average-, and high-achieving peers without disability. A quasi-experimental study was conducted with an experimental group of 202 pupils from classrooms with an included child with mild or moderate ID, and a control group of 202 pupils from classrooms with no included children with special educational needs (matched pairs sample). The progress of these 2 groups in their academic achievement was compared over a period of 1 school year. No significant difference was found in the progress of the low-, average-, or high-achieving pupils from classrooms with or without inclusion. The results suggest that including children with ID in primary general education classrooms with support does not have a negative impact on the progress of pupils without disability.
Improvement of Progressive Damage Model to Predicting Crashworthy Composite Corrugated Plate
NASA Astrophysics Data System (ADS)
Ren, Yiru; Jiang, Hongyong; Ji, Wenyuan; Zhang, Hanyu; Xiang, Jinwu; Yuan, Fuh-Gwo
2018-02-01
To predict the crashworthy composite corrugated plate, different single and stacked shell models are evaluated and compared, and a stacked shell progressive damage model combined with continuum damage mechanics is proposed and investigated. To simulate and predict the failure behavior, both of the intra- and inter- laminar failure behavior are considered. The tiebreak contact method, 1D spot weld element and cohesive element are adopted in stacked shell model, and a surface-based cohesive behavior is used to capture delamination in the proposed model. The impact load and failure behavior of purposed and conventional progressive damage models are demonstrated. Results show that the single shell could simulate the impact load curve without the delamination simulation ability. The general stacked shell model could simulate the interlaminar failure behavior. The improved stacked shell model with continuum damage mechanics and cohesive element not only agree well with the impact load, but also capture the fiber, matrix debonding, and interlaminar failure of composite structure.
Estimating the National Carbon Abatement Potential of City Policies: A Data-Driven Approach
DOE Office of Scientific and Technical Information (OSTI.GOV)
O'Shaughnessy, Eric; Heeter, Jenny; Keyser, David
Cities are increasingly taking actions such as building code enforcement, urban planning, and public transit expansion to reduce emissions of carbon dioxide in their communities and municipal operations. However, many cities lack the quantitative information needed to estimate policy impacts and prioritize city actions in terms of carbon abatement potential and cost effectiveness. This report fills this research gap by providing methodologies to assess the carbon abatement potential of a variety of city actions. The methodologies are applied to an energy use data set of 23,458 cities compiled for the U.S. Department of Energy City Energy Profile tool. The analysismore » develops a national estimate of the carbon abatement potential of realizable city actions in six specific policy areas encompassing the most commonly implemented city actions. The results of this analysis suggest that, in aggregate, cities could reduce nationwide carbon emissions by about 210 million metric tons of carbon dioxide (MMT CO2) per year in a 'moderate abatement scenario' by 2035 and 480 MMT CO2/year in a 'high abatement scenario' by 2035 through these common actions typically within a city's control in the six policy areas. The aggregate carbon abatement potential of these specific areas equates to a reduction of 3%-7% relative to 2013 U.S. emissions. At the city level, the results suggest the average city could reduce carbon emissions by 7% (moderate) to 19% (high) relative to current city-level emissions. In the context of U.S. climate commitments under the 21st session of the Conference of the Parties (COP21), the estimated national abatement potential of the city actions analyzed in this report equates to about 15%-35% of the remaining carbon abatement necessary to achieve the U.S. COP21 target. Additional city actions outside the scope of this report, such as community choice aggregation (city-level purchasing of renewable energy), zero energy districts, and multi-level governance strategies, could significantly augment the carbon abatement contributions of city actions toward national climate targets. The results suggest that cities may play a pivotal role in progress toward national climate targets. In addition to providing carbon and emissions estimates, this report estimates the national net economic impacts of policies for which cost and benefit data are available. Impact metrics include employment, worker earnings, and gross domestic product (GDP). For the policy areas studied, the economic analysis demonstrates that city carbon abatement may be achieved with only minimal and generally slightly positive economic impacts. Employment impacts range from 0.04% to 0.13% of U.S, employment during implementation and zero to 0.1% thereafter. GDP estimates show net impacts of 0.02% to 0.07% of GDP during implementation and impacts from -0.02% to zero thereafter. This report quantitatively demonstrates the material impact of a limited set of local policy areas on national carbon abatement potential. The magnitude of estimated carbon reductions from city policies, 3%-7% of national emissions by 2035, suggests an important role for city-led actions in reaching U.S. climate goals. Multi-level governance at the city, state, and national levels could augment the carbon abatement potential of city actions and make cities a key component of long-term U.S. climate strategies.« less
Design for inadvertent damage in composite laminates
NASA Technical Reports Server (NTRS)
Singhal, Surendra N.; Chamis, Christos C.
1992-01-01
Simplified predictive methods and models to computationally simulate durability and damage in polymer matrix composite materials/structures are described. The models include (1) progressive fracture, (2) progressively damaged structural behavior, (3) progressive fracture in aggressive environments, (4) stress concentrations, and (5) impact resistance. Several examples are included to illustrate applications of the models and to identify significant parameters and sensitivities. Comparisons with limited experimental data are made.
Late accretion to the Moon recorded in zircon (U-Th)/He thermochronometry
NASA Astrophysics Data System (ADS)
Kelly, Nigel M.; Flowers, Rebecca M.; Metcalf, James R.; Mojzsis, Stephen J.
2018-01-01
We conducted zircon (U-Th)/He (ZHe) analysis of lunar impact-melt breccia 14311 with the aim of leveraging radiation damage accumulated in zircon over extended intervals to detect low-temperature or short-lived impact events that have previously eluded traditional isotopic dating techniques. Our ZHe data record a coherent date vs. effective Uranium concentration (eU) trend characterized by >3500 Ma dates from low (≤75 ppm) eU zircon grains, and ca. 110 Ma dates for high (≥100 ppm) eU grains. A progression between these date populations is apparent for intermediate (75-100 ppm) eU grains. Thermal history modeling constrains permissible temperatures and cooling rates during and following impacts. Modeling shows that the data are most simply explained by impact events at ca. 3950 Ma and ca. 110 Ma, and limits allowable temperatures of heating events between 3950-110 Ma. Modeling of solar cycling thermal effects at the lunar surface precludes this as the explanation for the ca. 110 Ma ZHe dates. We propose a sample history characterized by zircon resetting during the ca. 3950 Ma Imbrium impact event, with subsequent heating during an impact at ca. 110 Ma that ejected the sample to the vicinity of its collection site. Our data show that zircon has the potential to retain 4He over immense timescales (≥3950 Myrs), thus providing a valuable new thermochronometer for probing the impact histories of lunar samples, and martian or asteroidal meteorites.
NASA Astrophysics Data System (ADS)
Heatwole, K. K.; McCray, J.; Lowe, K.
2005-12-01
Individual sewage disposal systems (ISDS) have demonstrated the capability to be an effective method of treatment for domestic wastewater. They also are advantageous from a water resources standpoint because there is little water leaving the local hydrologic system. However, if unfavorable settings exist, ISDS can have a detrimental effect on local water-quality. This presentation will focus on assessing the potential impacts of a large housing development to area water quality. The residential development plans to utilize ISDS to accommodate all domestic wastewater generated within the development. The area of interest is located just west of Brighton, Colorado, on the northwestern margin of the Denver Basin. Efforts of this research will focus on impacts of ISDS to local groundwater and surface water systems. The Arapahoe Aquifer, which exists at relatively shallow depths in the area of proposed development, is suspected to be vulnerable to contamination from ISDS. Additionally, the local water quality of the Arapahoe Aquifer was not well known at the start of the study. As a result, nitrate was selected as a fo-cus water quality parameter because it is easily produced through nitrification of septic tank effluent and because of the previous agricultural practices that could be another potential source of nitrate. Several different predictive tools were used to attempt to predict the potential impacts of ISDS to water quality in the Arapahoe Aquifer. The objectives of these tools were to 1) assess the vulnerability of the Arapahoe Aquifer to ni-trate contamination, 2) predict the nitrate load to the aquifer, and 3) determine the sensitivity of different parameter inputs and the overall prediction uncertainty. These predictive tools began with very simple mass-loading calcula-tions and progressed to more complex, vadose-zone numerical contaminant transport modeling.
NASA Astrophysics Data System (ADS)
Dunning, C.; Black, E.; Allan, R. P.
2017-12-01
The seasonality of rainfall over Africa plays a key role in determining socio-economic impacts for agricultural stakeholders, influences energy supply from hydropower, affects the length of the malaria transmission season and impacts surface water supplies. Hence, failure or delays of these rains can lead to significant socio-economic impacts. Diagnosing and interpreting interannual variability and long-term trends in seasonality, and analysing the physical driving mechanisms, requires a robust definition of African precipitation seasonality, applicable to both observational datasets and model simulations. Here we present a methodology for objectively determining the onset and cessation of multiple wet seasons across the whole of Africa. Compatibility with known physical drivers of African rainfall, consistency with indigenous methods, and generally strong agreement between satellite-based rainfall data sets confirm that the method is capturing the correct seasonal progression of African rainfall. Application of this method to observational datasets reveals that over East Africa cessation of the short rains is 5 days earlier in La Nina years, and the failure of the rains and subsequent humanitarian disaster is associated with shorter as well as weaker rainy seasons over this region. The method is used to examine the representation of the seasonality of African precipitation in CMIP5 model simulations. Overall, atmosphere-only and fully coupled CMIP5 historical simulations represent essential aspects of the seasonal cycle; patterns of seasonal progression of the rainy season are captured, for the most part mean model onset/ cessation dates agree with mean observational dates to within 18 days. However, unlike the atmosphere-only simulations, the coupled simulations do not capture the biannual regime over the southern West African coastline, linked to errors in Gulf of Guinea Sea Surface Temperature. Application to both observational and climate model datasets, and good agreement with agricultural onset methods, indicates the potential applicability of this method to a variety of meteorological and climate impact studies.
Velocity visualization in gaseous flows
NASA Technical Reports Server (NTRS)
Hanson, R. K.; Hiller, B.; Hassa, C.; Booman, R. A.
1984-01-01
Techniques yielding simultaneous, multiple-point measurements of velocity in reacting or nonreacting flow fields have the potential to significantly impact basic and applied studies of fluid mechanics. This research program is aimed at investigating several candidate schemes which could provide such measurement capability. The concepts under study have in common the use of a laser source (to illuminate a column, a grid, a plane or a volume in the flow) and the collection of light at right angles (from Mie scattering, fluorescence, phosphorescence or chemiluminescence) using a multi-element solid-state camera (100 x 100 array of photodiodes). The work will include an overview and a status report of work in progress with particular emphasis on the method of Doppler-modulated absorption.
NASA Technical Reports Server (NTRS)
Britcher, Colin P.
1997-01-01
This paper will briefly review previous work in wind tunnel Magnetic Suspension and Balance Systems (MSBS) and will examine the handful of systems around the world currently known to be in operational condition or undergoing recommissioning. Technical developments emerging from research programs at NASA and elsewhere will be reviewed briefly, where there is potential impact on large-scale MSBSS. The likely aerodynamic applications for large MSBSs will be addressed, since these applications should properly drive system designs. A recently proposed application to ultra-high Reynolds number testing will then be addressed in some detail. Finally, some opinions on the technical feasibility and usefulness of a large MSBS will be given.
Data Sharing: Convert Challenges into Opportunities.
Figueiredo, Ana Sofia
2017-01-01
Initiatives for sharing research data are opportunities to increase the pace of knowledge discovery and scientific progress. The reuse of research data has the potential to avoid the duplication of data sets and to bring new views from multiple analysis of the same data set. For example, the study of genomic variations associated with cancer profits from the universal collection of such data and helps in selecting the most appropriate therapy for a specific patient. However, data sharing poses challenges to the scientific community. These challenges are of ethical, cultural, legal, financial, or technical nature. This article reviews the impact that data sharing has in science and society and presents guidelines to improve the efficient sharing of research data.
Data Sharing: Convert Challenges into Opportunities
Figueiredo, Ana Sofia
2017-01-01
Initiatives for sharing research data are opportunities to increase the pace of knowledge discovery and scientific progress. The reuse of research data has the potential to avoid the duplication of data sets and to bring new views from multiple analysis of the same data set. For example, the study of genomic variations associated with cancer profits from the universal collection of such data and helps in selecting the most appropriate therapy for a specific patient. However, data sharing poses challenges to the scientific community. These challenges are of ethical, cultural, legal, financial, or technical nature. This article reviews the impact that data sharing has in science and society and presents guidelines to improve the efficient sharing of research data. PMID:29270401
Webb-Vargas, Yenny; Chen, Shaojie; Fisher, Aaron; Mejia, Amanda; Xu, Yuting; Crainiceanu, Ciprian; Caffo, Brian; Lindquist, Martin A
2017-12-01
Big Data are of increasing importance in a variety of areas, especially in the biosciences. There is an emerging critical need for Big Data tools and methods, because of the potential impact of advancements in these areas. Importantly, statisticians and statistical thinking have a major role to play in creating meaningful progress in this arena. We would like to emphasize this point in this special issue, as it highlights both the dramatic need for statistical input for Big Data analysis and for a greater number of statisticians working on Big Data problems. We use the field of statistical neuroimaging to demonstrate these points. As such, this paper covers several applications and novel methodological developments of Big Data tools applied to neuroimaging data.
Offshore Wind Market and Economic Analysis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hamilton, Bruce Duncan
2014-08-27
This report is the third annual assessment of the U.S. offshore wind market. It includes the following major sections: Section 1: key data on developments in the offshore wind technology sector and the global development of offshore wind projects, with a particular focus on progress in the United States; Section 2: analysis of policy developments at the federal and state levels that have been effective in advancing offshore wind deployment in the United States; Section 3: analysis of actual and projected economic impact, including regional development and job creation; Section 4: analysis of developments in relevant sectors of the economymore » with the potential to affect offshore wind deployment in the United States« less
Zinger, Anna; Latham, Sharissa L; Combes, Valery; Byrne, Scott; Barnett, Michael H; Hawke, Simon; Grau, Georges E
2016-12-01
No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier. To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production. In non-treated MS patients compared to healthy and fingolimod-treated patients, endothelial microparticles were higher, while B-cell-microparticle numbers were lower. Fingolimod dramatically reduced tumour necrosis factor (TNF)-induced endothelial microparticle release in vitro. Fingolimod restored dysregulated endothelial and B-cell-microparticle numbers, which could serve as a biomarker in MS. © The Author(s), 2016.
Applications of diatoms as potential microalgae in nanobiotechnology.
Jamali, Ali Akbar; Akbari, Fariba; Ghorakhlu, Mohamad Moradi; de la Guardia, Miguel; Yari Khosroushahi, Ahmad
2012-01-01
Diatoms are single cell eukaryotic microalgae, which present in nearly every water habitat make them ideal tools for a wide range of applications such as oil explora-tion, forensic examination, environmental indication, biosilica pattern generation, toxicity testing and eutrophication of aqueous ecosystems. Essential information on diatoms were reviewed and discussed towards impacts of diatoms on biosynthesis and bioremediation. In this review, we present the recent progress in this century on the application of diatoms in waste degradation, synthesis of biomaterial, biomineraliza-tion, toxicity and toxic effects of mineral elements evaluations. Diatoms can be considered as metal toxicity bioindicators and they can be applied for biomineralization, synthesis of biomaterials, and degradation of wastes.
Progress on bioinspired, biomimetic, and bioreplication routes to harvest solar energy
NASA Astrophysics Data System (ADS)
Martín-Palma, Raúl J.; Lakhtakia, Akhlesh
2017-06-01
Although humans have long been imitating biological structures to serve their particular purposes, only a few decades ago engineered biomimicry began to be considered a technoscientific discipline with a great problem-solving potential. The three methodologies of engineered biomimicry-viz., bioinspiration, biomimetic, and bioreplication-employ and impact numerous technoscientific fields. For producing fuels and electricity by artificial photosynthesis, both processes and porous surfaces inspired by plants and certain marine animals are under active investigation. Biomimetically textured surfaces on the subwavelength scale have been shown to reduce the reflectance of photovoltaic solar cells over the visible and the near-infrared regimes. Lenticular compound lenses bioreplicated from insect eyes by an industrially scalable technique offer a similar promise.
Ho, Allen L; Koch, Matthew J; Tanaka, Shota; Eichler, April F; Batchelor, Tracy T; Tanboon, Jantima; Louis, David N; Cahill, Daniel P; Chi, Andrew S; Curry, William T
2016-09-01
Progression of anaplastic glioma (World Health Organization [WHO] grade III) is typically determined radiographically, and transformation to glioblastoma (GB) (WHO grade IV) is often presumed at that time. However, the frequency of actual histopathologic transformation of anaplastic glioma and the subsequent clinical impact is unclear. To determine these associations, we retrospectively reviewed all anaplastic glioma patients who underwent surgery at our center at first radiographic progression, and we examined the effects of histological diagnosis, clinical history, and molecular factors on transformation rate and survival. We identified 85 anaplastic glioma (39 astrocytoma, 24 oligodendroglioma, 22 oligoastrocytoma), of which 38.8% transformed to GB. Transformation was associated with shorter overall survival (OS) from the time of diagnosis (3.4 vs. 10.9years, p=0.0005) and second surgery (1.0 vs. 3.5years, p<0.0001). Original histologic subtype did not significantly impact the risk of transformation or OS. No other factors, including surgery, adjuvant therapy or molecular markers, significantly affected the risk of transformation. However, mutations in isocitrate dehydrogenase 1 (IDH1) was associated with longer time to progression (median 4.6 vs. 1.4years, p=0.008) and OS (median 10.0 vs. 4.2years, p=0.046). At radiographic progression, tissue diagnosis may be warranted as histologic grade may provide valuable prognostic information and affect therapeutic clinical trial selection criteria for this patient population. Copyright © 2016 Elsevier Ltd. All rights reserved.
Terrorism involving cyanide: the prospect of improving preparedness in the prehospital setting.
Keim, Mark E
2006-01-01
The potential for domestic or international terrorism involving cyanide has not diminished and in fact may have increased in recent years. This paper discusses cyanide as a terrorist weapon and the current state of readiness for a cyanide attack in the United States. Many of the factors that render cyanide appealing to terrorists are difficult to modify sufficiently to decrease the probability of a cyanide attack. For example, the relative ease with which cyanide can be used as a weapon without special training, its versatile means of delivery to intended victims, and to a large degree, its ready availability cannot be significantly modified through preparedness efforts. On the other hand, the impact of an attack can be mitigated through preparedness measures designed to minimize the physical, psychological, and social consequences of cyanide exposure. Although the nation remains ill-equipped to manage a cyanide disaster, significant progress is being realized in some aspects of preparedness. Hydroxocobalamin-a cyanide antidote that may be appropriate for use in the prehospital setting for presumptive cases of cyanide poisoning-currently is under development for potential introduction in the US. If it becomes available in the US, hydroxocobalamin could enhance the role of the prehospital emergency responder in providing care to victims of a cyanide disaster. Additional progress is required in the areas of ensuring local and regional availability of antidotal treatment and supportive interventions, educating emergency healthcare providers about cyanide poisoning and its management, and raising public awareness of the potential for a cyanide attack and how to respond.
Alao, John P; Sjölander, Johanna J; Baar, Juliane; Özbaki-Yagan, Nejla; Kakoschky, Bianca; Sunnerhagen, Per
2014-01-01
Cdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in a Rad3-dependent manner. Caffeine is believed to override activation of the replication and DNA damage checkpoints by inhibiting Rad3-related proteins in both S chizosaccharomyces pombe and mammalian cells. In this study, we have investigated the impact of caffeine on Cdc25 stability, cell cycle progression and checkpoint override. Caffeine induced Cdc25 accumulation in S . pombe independently of Rad3. Caffeine delayed cell cycle progression under normal conditions but advanced mitosis in cells treated with replication inhibitors and DNA-damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin. Caffeine induces Cdc25 accumulation in S . pombe by suppressing its degradation independently of Rad3. The induction of Cdc25 accumulation was not associated with accelerated progression through mitosis, but rather with delayed progression through cytokinesis. Caffeine-induced Cdc25 accumulation appears to underlie its ability to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest that caffeine overrides checkpoint enforcement by inducing the inappropriate nuclear localization of Cdc25. PMID:24666325
What Does It Take for Practitioners to Use Data to Change Behavior in Collective Impact?
ERIC Educational Resources Information Center
Raderstrong, Jeff; Nazaire, JaNay Queen
2017-01-01
The use of data to track and manage progress is critical to a collective impact initiative achieving results or understanding impact. Yet, little research has been done to determine how collective impact practitioners can effectively use data. This article--including a literature review, semistructured interviews with experts on performance…
Impact analysis of composite aircraft structures
NASA Technical Reports Server (NTRS)
Pifko, Allan B.; Kushner, Alan S.
1993-01-01
The impact analysis of composite aircraft structures is discussed. Topics discussed include: background remarks on aircraft crashworthiness; comments on modeling strategies for crashworthiness simulation; initial study of simulation of progressive failure of an aircraft component constructed of composite material; and research direction in composite characterization for impact analysis.
Preliminary safety evaluation of an aircraft impact on a near-surface radioactive waste repository
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lo Frano, R.; Forasassi, G.; Pugliese, G.
2013-07-01
The aircraft impact accident has become very significant in the design of a nuclear facilities, particularly, after the tragic September 2001 event, that raised the public concern about the potential damaging effects that the impact of a large civilian airplane could bring in safety relevant structures. The aim of this study is therefore to preliminarily evaluate the global response and the structural effects induced by the impact of a military or commercial airplane (actually considered as a 'beyond design basis' event) into a near surface radioactive waste (RWs) disposal facility. The safety evaluation was carried out according to the Internationalmore » safety and design guidelines and in agreement with the stress tests requirements for the security track. To achieve the purpose, a lay out and a scheme of a possible near surface repository, like for example those of the El Cabril one, were taken into account. In order to preliminarily perform a reliable analysis of such a large-scale structure and to determine the structural effects induced by such a types of impulsive loads, a realistic, but still operable, numerical model with suitable materials characteristics was implemented by means of FEM codes. In the carried out structural analyses, the RWs repository was considered a 'robust' target, due to its thicker walls and main constitutive materials (steel and reinforced concrete). In addition to adequately represent the dynamic response of repository under crashing, relevant physical phenomena (i.e. penetration, spalling, etc.) were simulated and analysed. The preliminary assessment of the effects induced by the dynamic/impulsive loads allowed generally to verify the residual strength capability of the repository considered. The obtained preliminary results highlighted a remarkable potential to withstand the impact of military/large commercial aircraft, even in presence of ongoing concrete progressive failure (some penetration and spalling of the concrete wall) of the impacted area. (authors)« less
Surface Modeling to Support Small-Body Spacecraft Exploration and Proximity Operations
NASA Technical Reports Server (NTRS)
Riedel, Joseph E.; Mastrodemos, Nickolaos; Gaskell, Robert W.
2011-01-01
In order to simulate physically plausible surfaces that represent geologically evolved surfaces, demonstrating demanding surface-relative guidance navigation and control (GN&C) actions, such surfaces must be made to mimic the geological processes themselves. A report describes how, using software and algorithms to model body surfaces as a series of digital terrain maps, a series of processes was put in place that evolve the surface from some assumed nominal starting condition. The physical processes modeled in this algorithmic technique include fractal regolith substrate texturing, fractally textured rocks (of empirically derived size and distribution power laws), cratering, and regolith migration under potential energy gradient. Starting with a global model that may be determined observationally or created ad hoc, the surface evolution is begun. First, material of some assumed strength is layered on the global model in a fractally random pattern. Then, rocks are distributed according to power laws measured on the Moon. Cratering then takes place in a temporal fashion, including modeling of ejecta blankets and taking into account the gravity of the object (which determines how much of the ejecta blanket falls back to the surface), and causing the observed phenomena of older craters being progressively buried by the ejecta of earlier impacts. Finally, regolith migration occurs which stratifies finer materials from coarser, as the fine material progressively migrates to regions of lower potential energy.
Plant based dietary supplement increases urinary pH
Berardi, John M; Logan, Alan C; Rao, A Venket
2008-01-01
Background Research has demonstrated that the net acid load of the typical Western diet has the potential to influence many aspects of human health, including osteoporosis risk/progression; obesity; cardiovascular disease risk/progression; and overall well-being. As urinary pH provides a reliable surrogate measure for dietary acid load, this study examined whether a plant-based dietary supplement, one marketed to increase alkalinity, impacts urinary pH as advertised. Methods Using pH test strips, the urinary pH of 34 healthy men and women (33.9 +/- 1.57 y, 79.3 +/- 3.1 kg) was measured for seven days to establish a baseline urinary pH without supplementation. After this initial baseline period, urinary pH was measured for an additional 14 days while participants ingested the plant-based nutritional supplement. At the end of the investigation, pH values at baseline and during the treatment period were compared to determine the efficacy of the supplement. Results Mean urinary pH statistically increased (p = 0.03) with the plant-based dietary supplement. Mean urinary pH was 6.07 +/- 0.04 during the baseline period and increased to 6.21 +/- 0.03 during the first week of treatment and to 6.27 +/- 0.06 during the second week of treatment. Conclusion Supplementation with a plant-based dietary product for at least seven days increases urinary pH, potentially increasing the alkalinity of the body. PMID:18990209
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.
2015-03-01
Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively activemore » Notch1 transgene (Notch{sup ICN-TG}). Following exposure of adult Notch{sup ICN-TG} mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch{sup ICN-TG} offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch{sup ICN-TG} offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch-induced thymoma was different in offspring exposed to TCDD developmentally. • Developmental AHR activation attenuates later-life Notch1-dependent impacts on T cell differentiation.« less
Schadendorf, Dirk; Amonkar, Mayur M; Stroyakovskiy, Daniil; Levchenko, Evgeny; Gogas, Helen; de Braud, Filippo; Grob, Jean-Jacques; Bondarenko, Igor; Garbe, Claus; Lebbe, Celeste; Larkin, James; Chiarion-Sileni, Vanna; Millward, Michael; Arance, Ana; Mandalà, Mario; Flaherty, Keith T; Nathan, Paul; Ribas, Antoni; Robert, Caroline; Casey, Michelle; DeMarini, Douglas J; Irani, Jhangir G; Aktan, Gursel; Long, Georgina V
2015-05-01
To present the impact of treatments on health-related quality of life (HRQoL) from the double-blind, randomised phase III COMBI-d study that investigated the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600E/K-mutant metastatic melanoma. COMBI-d showed significantly prolonged progression-free survival for the combination. HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, a generic cancer questionnaire (completed at baseline, during study treatment, at progression and post progression) assessing various dimensions (global health/QoL, functional status, and symptom impact). A mixed-model, repeated-measures analyses of covariance evaluated differences between arms. Questionnaire completion rates were >95% at baseline, >85% to week 40 and >70% at disease progression. Baseline scores across both arms were comparable for all dimensions. Global health dimension scores were significantly better at weeks 8, 16 and 24 for patients receiving the combination during treatment and at progression. The majority of functional dimension scores (physical, social, role, emotional and cognitive functioning) trended in favour of the combination. Pain scores were significantly improved and clinically meaningful (6-13 point difference) for patients receiving the combination for all follow-up assessments versus those receiving dabrafenib monotherapy. For other symptom dimensions (nausea and vomiting, diarrhoea, dyspnoea, and constipation), scores trended in favour of dabrafenib monotherapy. This analysis demonstrates that the combination of dabrafenib and trametinib provides better preservation of HRQoL and pain improvements versus dabrafenib monotherapy while also delaying progression. (Clinicaltrials.gov registration number: NCT01584648). Copyright © 2015 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Ji, Zhaojie; Guan, Zhidong; Li, Zengshan
2017-10-01
In this paper, a progressive damage model was established on the basis of ABAQUS software for predicting permanent indentation and impact damage in composite laminates. Intralaminar and interlaminar damage was modelled based on the continuum damage mechanics (CDM) in the finite element model. For the verification of the model, low-velocity impact tests of quasi-isotropic laminates with material system of T300/5228A were conducted. Permanent indentation and impact damage of the laminates were simulated and the numerical results agree well with the experiments. It can be concluded that an obvious knee point can be identified on the curve of the indentation depth versus impact energy. Matrix cracking and delamination develops rapidly with the increasing impact energy, while considerable amount of fiber breakage only occurs when the impact energy exceeds the energy corresponding to the knee point. Predicted indentation depth after the knee point is very sensitive to the parameter μ which is proposed in this paper, and the acceptable value of this parameter is in range from 0.9 to 1.0.
Scientific and Technological Progress: Problems for the West.
ERIC Educational Resources Information Center
de Rose, Francois
1978-01-01
Discusses the impact of science and technology on major social problems confronting the Western world. Topics include pollution and ecology, military impact, computer science, and the benefits of science and technology. (Author/MA)
Ramos-Jorge, Joana; Alencar, Bruna Mota; Pordeus, Isabela Almeida; Soares, Maria Eliza da Consolação; Marques, Leandro Silva; Ramos-Jorge, Maria Letícia; Paiva, Saul Martins
2015-04-01
The aim of this cross-sectional study was to evaluate the impact of dental caries on the quality of life of preschool children and their parents/caretakers, with an emphasis on the type of tooth and stage of progression. A randomly selected sample of preschool children, 3-5 yrs of age, underwent an oral examination for the assessment of dental caries using the International Caries Detection and Assessment System II (ICDAS II) criteria. Parents/caretakers answered two questionnaires, one on the oral health-related quality of life (OHRQoL) of the child [the Early Childhood Oral Health Impact Scale (ECOHIS)], and the other on the socio-economic characteristics of the family. Statistical analyses were performed using the chi-square test, Kruskal-Wallis test, Mann-Whitney U-test, and Poisson regression. A total of 451 preschool children participated in the study. The majority of carious lesions exhibited severe decay (60.6%) and were found in both anterior (incisors/canines) and posterior (molars) teeth. The final Poisson model revealed negative impacts on quality of life from more advanced stages of dental caries, both in incisors/canines and molars. Child's age and household income were also associated with impact on quality of life. Carious lesions in more advanced stages of progression in anterior and posterior teeth were associated with a negative impact on the quality of life of preschool children. © 2014 Eur J Oral Sci.
Challenges and Opportunities of Airborne Metagenomics
Behzad, Hayedeh; Gojobori, Takashi; Mineta, Katsuhiko
2015-01-01
Recent metagenomic studies of environments, such as marine and soil, have significantly enhanced our understanding of the diverse microbial communities living in these habitats and their essential roles in sustaining vast ecosystems. The increase in the number of publications related to soil and marine metagenomics is in sharp contrast to those of air, yet airborne microbes are thought to have significant impacts on many aspects of our lives from their potential roles in atmospheric events such as cloud formation, precipitation, and atmospheric chemistry to their major impact on human health. In this review, we will discuss the current progress in airborne metagenomics, with a special focus on exploring the challenges and opportunities of undertaking such studies. The main challenges of conducting metagenomic studies of airborne microbes are as follows: 1) Low density of microorganisms in the air, 2) efficient retrieval of microorganisms from the air, 3) variability in airborne microbial community composition, 4) the lack of standardized protocols and methodologies, and 5) DNA sequencing and bioinformatics-related challenges. Overcoming these challenges could provide the groundwork for comprehensive analysis of airborne microbes and their potential impact on the atmosphere, global climate, and our health. Metagenomic studies offer a unique opportunity to examine viral and bacterial diversity in the air and monitor their spread locally or across the globe, including threats from pathogenic microorganisms. Airborne metagenomic studies could also lead to discoveries of novel genes and metabolic pathways relevant to meteorological and industrial applications, environmental bioremediation, and biogeochemical cycles. PMID:25953766
NASA Astrophysics Data System (ADS)
Morrow, Cherilynn A.
1993-11-01
The visceral appeal of space science and exploration is a very powerful emotional connection to a very large and diverse collection of people, most of whom have little or no perspective about what it means to do science and engineering. Therein lies the potential of space for a substantially enhanced positive impact on culture through education. This essay suggests that through engaging more of the space research and development community in enabling unique and 'meaningful educational experiences' for educators and students at the pre-collegiate levels, space science and exploration can amplify its positive feedback on society and act as an important medium for cultural transformation to greater science literacy. I discuss the impact of space achievements on people and define what is meant by a 'meaningful educational experience,' all of which points to the need for educators and students to be closer to the practice of real science. I offer descriptions of two nascent science education programs associated with NASA which have the needed characteristics for providing meaningful experiences that can cultivate greater science literacy. Expansion of these efforts and others like it will be needed to have the desired impact on culture, but I suggest that the potential for the needed resources is there in the scientific research communities. A society in which more people appreciate and understand science and science methods would be especially conducive to human progress in space and on Earth.
NASA Technical Reports Server (NTRS)
Morrow, Cherilynn A.
1993-01-01
The visceral appeal of space science and exploration is a very powerful emotional connection to a very large and diverse collection of people, most of whom have little or no perspective about what it means to do science and engineering. Therein lies the potential of space for a substantially enhanced positive impact on culture through education. This essay suggests that through engaging more of the space research and development community in enabling unique and 'meaningful educational experiences' for educators and students at the pre-collegiate levels, space science and exploration can amplify its positive feedback on society and act as an important medium for cultural transformation to greater science literacy. I discuss the impact of space achievements on people and define what is meant by a 'meaningful educational experience,' all of which points to the need for educators and students to be closer to the practice of real science. I offer descriptions of two nascent science education programs associated with NASA which have the needed characteristics for providing meaningful experiences that can cultivate greater science literacy. Expansion of these efforts and others like it will be needed to have the desired impact on culture, but I suggest that the potential for the needed resources is there in the scientific research communities. A society in which more people appreciate and understand science and science methods would be especially conducive to human progress in space and on Earth.
Chen, Tingting; Yang, Shizhou; Huang, Yongjie; Hong, Die; Li, Yang; Chen, Xiaojing; Wang, Xinyu; Cheng, Xiaodong; Lu, Weiguo; Xie, Xing
2016-01-01
Human papillomavirus (HPV) infects cervical epithelial cells through cellular membrane receptors, and then induces the initiation and progression of cervical cancer. Single nucleotide polymorphisms (SNPs) may impact the susceptibility and outcome of diseases, but it's still unknown whether variant in HPV receptor and associated genes is associated with type-specific HPV infection and cervical lesion progression. We examined 96 SNPs in 8 genes which may participate in the HPV infection process in 875 samples with HPV negative or single HPV16, 18, 52, 58 positive from 3299 cervical exfoliated cell samples, by Illumina BeadXpress VeraCode platform, and analyzed the correlation between the SNPs and type-specific HPV infection and cervical lesions progression. We found rs28384376 in EGFR and rs12034979 in HSPG2 significantly correlated to HPV16 infection; rs2575738, rs2575712, rs2575735 in SDC2 and rs6697265 in HSPG2 significantly correlated to HPV18 infection; rs10510097 in FGFR2, rs12718946 in EGFR significantly correlated to HPV52 infection; rs4947972 in EGFR, rs2981451 in FGFR2, rs2575735 in SDC2 significantly correlated to HPV58 infection. And rs3135772, rs1047057 and rs2556537 in FGFR2, rs12034979 in HSPG2, rs16894821 in SDC2 significantly correlated to cervical lesion progression induced by HPV16 infection; rs6697265 and rs6680566 in HSPG2, rs16860426 in ITGA6 by HPV18 infection; rs878949 in HSPG2, rs12718946 and rs12668175 in EGFR by HPV52 infection; no SNP by HPV58 infection. Our findings suggest that HPV receptor and associated gene variants may influence the susceptibilities to HPV type-specific infection and cervical lesion progression, which might have a potential application value in cervical cancer screening and therapy. PMID:27223085
A Possible Buried Impact Structure Near Bow City, Alberta
NASA Astrophysics Data System (ADS)
Xie, W.; Glombick, P.; Schmitt, D. R.; Bown, T. D.
2012-12-01
In recent years, improved exploration techniques have resulted in the serendipitous discoveries of increasing numbers of extraterrestrial impact structures in sedimentary basins around the world. Following in this tradition, a new potential impact structure centered near 50.4°N, 112.35°N in SE Alberta has been identified. The first indications of this structure appeared in careful systematic mapping of Cretaceous age sediments using public domain well log information that showed overturned and missing components in what regionally is a simple layered stratigraphy. This motivated the examination of legacy 2D seismic profiles over the area that confirmed the stratigraphic anomalies and provided new details that further supported interpretation of a potential impact structure. Further, the existence of unexpected faults through the Cretaceous Bearpaw formation had been noted as early as the 1940's in the limited outcrop available in coulees, and these as well as other complex fault structures along the Bow River outcrops were confirmed in recent field visits to the site. The 2D seismic data displays a number of listric and rose-petal faulting consistent with late stage collapse of the impact crater. Further, a seismically transparent central uplift peak is visible. Based on the results, the structure is recognized as a complex crater with a diameter of approximately 8 kilometers and, today, bottoming at a depth of 900 meters from the current surface. Currently, the age of the feature is grossly estimated to be less than 70 my on the basis of underlying undisturbed seismic reflectors. The structure may be somewhat unique in that weak coals surrounding the feature are clearly thickened indicating outward lateral sliding along shear planes through weaker layers. Work in progress includes acquisition of a high resolution seismic profile and detailed mapping of the magnetic and gravity potential fields. More detailed mapping will include searches for shock metamorphism and melt although it is not likely that this will be seen in the current outcrop. Drilling may be necessary to confirm details of the structure.
Passey, Samantha L; Hansen, Michelle J; Bozinovski, Steven; McDonald, Christine F; Holland, Anne E; Vlahos, Ross
2016-10-01
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that constitutes a major global health burden. A significant proportion of patients experience skeletal muscle wasting and loss of strength as a comorbidity of their COPD, a condition that severely impacts on their quality of life and survival. At present, the lung pathology is considered to be largely irreversible; however, the inherent adaptability of muscle tissue offers therapeutic opportunities to tackle muscle wasting and potentially reverse or delay the progression of this aspect of the disease, to improve patients' quality of life. Muscle wasting in COPD is complex, with contributions from a number of factors including inflammatory cytokines, oxidative stress, growth and anabolic hormones, nutritional status, and physical activity. In this review, we discuss current and emerging therapeutic approaches to treat muscle wasting in COPD, including a number of pharmacological therapies that are in development for muscle atrophy in other pathological states that could be of relevance for treating muscle wasting in COPD patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Wang, Hou; Wu, Yan; Yuan, Xingzhong; Zeng, Guangming; Zhou, Jin; Wang, Xin; Chew, Jia Wei
2018-03-01
MXene, an important and increasingly popular category of postgraphene 2D nanomaterials, has been rigorously investigated since early 2011 because of advantages including flexible tunability in element composition, hydrophobicity, metallic nature, unique in-plane anisotropic structure, high charge-carrier mobility, tunable band gap, and favorable optical and mechanical properties. To fully exploit these potentials and further expand beyond the existing boundaries, novel functional nanostructures spanning monolayer, multilayer, nanoparticles, and composites have been developed by means of intercalation, delamination, functionalization, hybridization, among others. Undeniably, the cutting-edge developments and applications of clay-inspired 2D MXene platform as electrochemical electrode or photo-electrocatalyst have conferred superior performance and have made significant impact in the field of energy and advanced catalysis. This review provides an overview of the fundamental properties and synthesis routes of pure MXene, functionalized MXene and their hybrids, highlights the state-of-the-art progresses of MXene-based applications with respect to supercapacitors, batteries, electrocatalysis and photocatalysis, and presents the challenges and prospects in the burgeoning field. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
BACE1 inhibition more effectively suppresses initiation than progression of β-amyloid pathology.
Peters, Finn; Salihoglu, Hazal; Rodrigues, Eva; Herzog, Etienne; Blume, Tanja; Filser, Severin; Dorostkar, Mario; Shimshek, Derya R; Brose, Nils; Neumann, Ulf; Herms, Jochen
2018-05-01
BACE1 is the rate-limiting protease in the production of synaptotoxic β-amyloid (Aβ) species and hence one of the prime drug targets for potential therapy of Alzheimer's disease (AD). However, so far pharmacological BACE1 inhibition failed to rescue the cognitive decline in mild-to-moderate AD patients, which indicates that treatment at the symptomatic stage might be too late. In the current study, chronic in vivo two-photon microscopy was performed in a transgenic AD model to monitor the impact of pharmacological BACE1 inhibition on early β-amyloid pathology. The longitudinal approach allowed to assess the kinetics of individual plaques and associated presynaptic pathology, before and throughout treatment. BACE1 inhibition could not halt but slow down progressive β-amyloid deposition and associated synaptic pathology. Notably, the data revealed that the initial process of plaque formation, rather than the subsequent phase of gradual plaque growth, is most sensitive to BACE1 inhibition. This finding of particular susceptibility of plaque formation has profound implications to achieve optimal therapeutic efficacy for the prospective treatment of AD.
Technologies for Controlled, Local Delivery of siRNA
Sarett, Samantha M.; Nelson, Christopher E.; Duvall, Craig L.
2015-01-01
The discovery of RNAi in the late 1990s unlocked a new realm of therapeutic possibilities by enabling potent and specific silencing of theoretically any desired genetic target. Better elucidation of the mechanism of action, the impact of chemical modifications that stabilize and reduce nonspecific effects of siRNA molecules, and the key design considerations for effective delivery systems has spurred progress toward developing clinically-successful siRNA therapies. A logical aim for initial siRNA translation is local therapies, as delivering siRNA directly to its site of action helps to ensure that a sufficient dose reaches the target tissue, lessens the potential for off-target side effects, and circumvents the substantial systemic delivery barriers. While topical siRNA delivery has progressed into numerous clinical trials, an enormous opportunity also exists to develop sustained-release, local delivery systems that enable both spatial and temporal control of gene silencing. This review focuses on material platforms that establish both localized and controlled gene silencing, with emphasis on the systems that show most promise for clinical translation. PMID:26476177
Cao, Hui; Wang, Ming
2016-11-25
Gastrointestinal stromal tumor(GIST) is the most common mesenchymal tumor in the gastrointestinal tract. Due to the occult onset, GIST may present as local advanced or with metastatic disease at diagnosis. Imatinib mesylate (IM) has effectively improved the prognosis of GIST patients and has been established as principle therapy in metastatic GIST. The role of IM as an adjunction to surgery in the management of high-risk and local advanced GIST is also highly regarded. The role of surgery in metastatic or recurrent GIST is still a controversial clinic problem. For local advanced GIST or GIST in the unfavorable anatomic site(e.g. esophagogastric junction, duodenum, and rectum), based on the limited evidence, surgery may have potential benefits as conversion therapy. Surgery may have a limited favorable impact on progression-free survival and overall survival for those patients whose disease is responding to imatinib or those with limited focal progression. Patients with extensive advanced relapse metastatic GIST or imatinib-resistant disease should not undergo surgery unless emergency situation or complication occurs, where palliative intervention may be justified.
Tsunami Forecasting and Monitoring in New Zealand
NASA Astrophysics Data System (ADS)
Power, William; Gale, Nora
2011-06-01
New Zealand is exposed to tsunami threats from several sources that vary significantly in their potential impact and travel time. One route for reducing the risk from these tsunami sources is to provide advance warning based on forecasting and monitoring of events in progress. In this paper the National Tsunami Warning System framework, including the responsibilities of key organisations and the procedures that they follow in the event of a tsunami threatening New Zealand, are summarised. A method for forecasting threat-levels based on tsunami models is presented, similar in many respects to that developed for Australia by Allen and Greenslade (Nat Hazards 46:35-52, 2008), and a simple system for easy access to the threat-level forecasts using a clickable pdf file is presented. Once a tsunami enters or initiates within New Zealand waters, its progress and evolution can be monitored in real-time using a newly established network of online tsunami gauge sensors placed at strategic locations around the New Zealand coasts and offshore islands. Information from these gauges can be used to validate and revise forecasts, and assist in making the all-clear decision.
Freitag, Nancy; Otto, Teresa; Thijssen, Victor L. J. L.; Moschansky, Petra; von Kwiatkowski, Petra; Klapp, Burghard F.; Winterhager, Elke; Bauersachs, Stefan; Blois, Sandra M.
2012-01-01
Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression. PMID:23056436
Tirado-González, Irene; González, Irene Tirado; Barrientos, Gabriela; Freitag, Nancy; Otto, Teresa; Thijssen, Victor L J L; Moschansky, Petra; von Kwiatkowski, Petra; Klapp, Burghard F; Winterhager, Elke; Bauersachs, Stefan; Blois, Sandra M
2012-01-01
Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression.
Allegra, Alessandro; Innao, Vanessa; Gerace, Demetrio; Allegra, Andrea Gaetano; Vaddinelli, Doriana; Bianco, Oriana; Musolino, Caterina
2018-07-01
In addition to its capacity to store lipids the adipose tissue is now identified as a real organ with both endocrine and metabolic roles. Preclinical results indicate that modifying adipose tissue and bone marrow adipose tissue (BMAT) could be a successful multiple myeloma (MM) therapy. BMAT interrelates with bone marrow cells and other immune cells, and may influence MM disease progression. The BM adipocytes may have a role in MM progression, bone homing, chemoresistance, and relapse, due to local endocrine, paracrine, or metabolic factors. BM adipocytes isolated from MM subjects have been shown to increase myeloma growth in vitro and may preserve cells from chemotherapy-induced apoptosis. By producing free fatty acids and emitting signaling molecules such as growth factors and adipokines, BM adipocytes are both an energy font and an endocrine signaling factory. This review should suggest future research approaches toward developing novel treatments to target MM by targeting BMAT and its products. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Measuring the Interdisciplinary Impact of Using Geospatial Data with Remote Sensing Data
NASA Astrophysics Data System (ADS)
Downs, R. R.; Chen, R. S.; Schumacher, J.
2017-12-01
Various disciplines offer benefits to society by contributing to the scientific progress that informs the knowledge and decisions that improve the lives, safety, and conditions of people around the globe. In addition to disciplines within the natural sciences, other disciplines, including those in the social, health, and computer sciences, provide benefits to society by collecting, preparing, and analyzing data in the process of conducting research. Preparing geospatial environmental and socioeconomic data together with remote sensing data from satellite-based instruments for wider use by heterogeneous communities of users increases the potential impact of these data by enabling their use in different application areas and sectors of society. Furthermore, enabling wider use of scientific data can bring to bear resources and expertise that will improve reproducibility, quality, methodological transparency, interoperability, and improved understanding by diverse communities of users. In line with its commitment to open data, the NASA Socioeconomic Data and Applications Center (SEDAC), which focuses on human interactions in the environment, curates and disseminates freely and publicly available geospatial data for use across many disciplines and societal benefit areas. We describe efforts to broaden the use of SEDAC data and to publicly document their impact, assess the interdisciplinary impact of the use of SEDAC data with remote sensing data, and characterize these impacts in terms of their influence across disciplines by analyzing citations of geospatial data with remote sensing data within scientific journals.
NASA Technical Reports Server (NTRS)
Lin, Shih-Yung; Splinter, Scott C.; Tarkenton, Chris; Paddock, David A.; Smeltzer, Stanley S.; Ghose, Sayata; Guzman, Juan C.; Stukus, Donald J.; McCarville, Douglas A.
2013-01-01
The development of durable bonded joint technology for assembling composite structures is an essential component of future space technologies. While NASA is working toward providing an entirely new capability for human space exploration beyond low Earth orbit, the objective of this project is to design, fabricate, analyze, and test a NASA patented durable redundant joint (DRJ) and a NASA/Boeing co-designed fluted-core joint (FCJ). The potential applications include a wide range of sandwich structures for NASA's future launch vehicles. Three types of joints were studied -- splice joint (SJ, as baseline), DRJ, and FCJ. Tests included tension, after-impact tension, and compression. Teflon strips were used at the joint area to increase failure strength by shifting stress concentration to a less sensitive area. Test results were compared to those of pristine coupons fabricated utilizing the same methods. Tensile test results indicated that the DRJ design was stiffer, stronger, and more impact resistant than other designs. The drawbacks of the DRJ design were extra mass and complex fabrication processes. The FCJ was lighter than the DRJ but less impact resistant. With barely visible but detectable impact damages, all three joints showed no sign of tensile strength reduction. No compression test was conducted on any impact-damaged sample due to limited scope and resource. Failure modes and damage propagation were also studied to support progressive damage modeling of the SJ and the DRJ.
Dimitrov, Dobromir T; Kiem, Hans-Peter; Jerome, Keith R; Johnston, Christine; Schiffer, Joshua T
2016-02-24
HIV curative strategies currently under development aim to eradicate latent provirus, or prevent viral replication, progression to AIDS, and transmission. The impact of implementing curative programs on HIV epidemics has not been considered. We developed a mathematical model of heterosexual HIV transmission to evaluate the independent and synergistic impact of ART, HIV prevention interventions and cure on HIV prevalence and incidence. The basic reproduction number was calculated to study the potential for the epidemic to be eliminated. We explored scenarios with and without the assumption that patients enrolled into HIV cure programs need to be on antiretroviral treatment (ART). In our simulations, curative regimes had limited impact on HIV incidence if only ART patients were eligible for cure. Cure implementation had a significant impact on HIV incidence if ART-untreated patients were enrolled directly into cure programs. Concurrent HIV prevention programs moderately decreased the percent of ART treated or cured patients needed to achieve elimination. We project that widespread implementation of HIV cure would decrease HIV prevalence under all scenarios but would only lower rate of new infections if ART-untreated patients were targeted. Current efforts to identify untreated HIV patients will gain even further relevance upon availability of an HIV cure.
Lifestyle modification and progressive renal failure.
Ritz, Eberhard; Schwenger, Vedat
2005-08-01
There is increasing evidence that lifestyle factors impact on the risk of developing chronic kidney disease (CKD) and the risk of progression of CKD. Equally important is the consideration that patients with CKD are more likely to die from cardiovascular disease than to reach the stage of end-stage renal failure. It is advantageous that manoeuvres that interfere with progression at the same time also reduce the risk of cardiovascular events. Lifestyle factors that aggravate progression include, among others, smoking, obesity and dietary salt intake. Alcohol consumption, according to some preliminary information, has a bimodal relationship to cardiovascular risk and progression, with moderate consumption being protective.
Do Age and Anticoagulants Affect the Natural History of Acute Subdural Hematomas?
Lucke-Wold, Brandon P; Turner, Ryan C; Josiah, Darnell; Knotts, Chelsea; Bhatia, Sanjay
2016-01-01
Acute subdural hematoma is a serious complication following traumatic brain injury. Large volume hematomas or those with underlying brain injury can cause mass effect, midline shift, and eventually herniation of the brain. Acute subdural hematomas in the young are associated with high-energy trauma and often have underlying contusions, while acute subdural hematomas in the elderly are associated with minor trauma and an absence of underlying contusions, even though the elderly are more likely to be on anticoagulants or anti-platelet therapy. In the young patients with high impact injuries the hematomas tend to be small and the underlying brain injury and swelling is responsible for the increased intracranial pressure and midline shift. In the elderly, the injuries are low impact (e.g fall from standing), the underlying brain is intact, and the volume of the hematoma itself produces symptoms. In addition the use of anticoagulants and antiplatelet agents in the elderly population has been thought to be a poor prognostic indicator and is considered to be responsible for larger hematomas and poor outcome. When managed conservatively, acute subdural hematomas can sometimes progress to chronic subdural hematoma formation, further enlargement, seizures, and progressive midline shift. Another potential difference in the young and the elderly is brain atrophy, which increases the potential space to accommodate a larger hematoma. It is not known if these two groups differ in other ways that might have implications for treatment or prognosis. In this paper, we investigate the clinical course of 80 patients admitted to our institution with acute subdural hematomas, to identify differences in patients above or below the age of 65 years. The natural progression/resolution of acute subdural hematomas was mapped by measuring volume expansion/regression over time. In this retrospective chart review, we investigated clinical baseline metrics and subsequent volumetric expansion outcomes between patients < 65 years old (N=44) and those > 65 years old (N=36). Volume was estimated by the ABC/2 method. We observed a statistically significant difference between groups in use of anticoagulants χ 2 =40.305 with p < 0.001, corrective platelet administration χ 2 =19.380 with p < 0.001, gender χ 2 =14.573 with p < 0.001, and Glasgow Coma Scale with χ 2 =23.125 (p=0.026). Overall outcomes were similar in the two groups. Younger patients on average had worse presenting GCS scores, but recovered comparable to older patients. No significant difference in rate of volume expansion, resolution time, or need for surgical treatment was seen between these two groups. We conclude that the initial volume, size, and severity of subdural hematoma determined by the Glasgow Coma Scale score is more likely to predict surgery or future expansion than age of the patient. Patients on oral anti-coagulants that are given appropriate medical reversal agents early do quite well and no impact on the eventual outcome could be demonstrated. Further work is needed to establish better predictors of future volume expansion, and progression to chronic subdural hematoma based on improved severity scales.
Do Age and Anticoagulants Affect the Natural History of Acute Subdural Hematomas?
Lucke-Wold, Brandon P.; Turner, Ryan C.; Josiah, Darnell; Knotts, Chelsea; Bhatia, Sanjay
2016-01-01
Acute subdural hematoma is a serious complication following traumatic brain injury. Large volume hematomas or those with underlying brain injury can cause mass effect, midline shift, and eventually herniation of the brain. Acute subdural hematomas in the young are associated with high-energy trauma and often have underlying contusions, while acute subdural hematomas in the elderly are associated with minor trauma and an absence of underlying contusions, even though the elderly are more likely to be on anticoagulants or anti-platelet therapy. In the young patients with high impact injuries the hematomas tend to be small and the underlying brain injury and swelling is responsible for the increased intracranial pressure and midline shift. In the elderly, the injuries are low impact (e.g fall from standing), the underlying brain is intact, and the volume of the hematoma itself produces symptoms. In addition the use of anticoagulants and antiplatelet agents in the elderly population has been thought to be a poor prognostic indicator and is considered to be responsible for larger hematomas and poor outcome. When managed conservatively, acute subdural hematomas can sometimes progress to chronic subdural hematoma formation, further enlargement, seizures, and progressive midline shift. Another potential difference in the young and the elderly is brain atrophy, which increases the potential space to accommodate a larger hematoma. It is not known if these two groups differ in other ways that might have implications for treatment or prognosis. In this paper, we investigate the clinical course of 80 patients admitted to our institution with acute subdural hematomas, to identify differences in patients above or below the age of 65 years. The natural progression/resolution of acute subdural hematomas was mapped by measuring volume expansion/regression over time. In this retrospective chart review, we investigated clinical baseline metrics and subsequent volumetric expansion outcomes between patients < 65 years old (N=44) and those > 65 years old (N=36). Volume was estimated by the ABC/2 method. We observed a statistically significant difference between groups in use of anticoagulants χ2 =40.305 with p < 0.001, corrective platelet administration χ2 =19.380 with p < 0.001, gender χ2 =14.573 with p < 0.001, and Glasgow Coma Scale with χ2 =23.125 (p=0.026). Overall outcomes were similar in the two groups. Younger patients on average had worse presenting GCS scores, but recovered comparable to older patients. No significant difference in rate of volume expansion, resolution time, or need for surgical treatment was seen between these two groups. We conclude that the initial volume, size, and severity of subdural hematoma determined by the Glasgow Coma Scale score is more likely to predict surgery or future expansion than age of the patient. Patients on oral anti-coagulants that are given appropriate medical reversal agents early do quite well and no impact on the eventual outcome could be demonstrated. Further work is needed to establish better predictors of future volume expansion, and progression to chronic subdural hematoma based on improved severity scales. PMID:27857999
Social defeat models in animal science: What we have learned from rodent models.
Toyoda, Atsushi
2017-07-01
Studies on stress and its impacts on animals are very important in many fields of science, including animal science, because various stresses influence animal production and animal welfare. In particular, the social stresses within animal groups have profound impact on animals, with the potential to induce abnormal behaviors and health problems. In humans, social stress induces several health problems, including psychiatric disorders. In animal stress models, social defeat models are well characterized and used in various research fields, particularly in studies concerning mental disorders. Recently, we have focused on behavior, nutrition and metabolism in rodent models of social defeat to elucidate how social stresses affect animals. In this review, recent significant progress in studies related to animal social defeat models are described. In the field of animal science, these stress models may contribute to advances in the development of functional foods and in the management of animal welfare. © 2017 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.
Wildlife health implications of sewage disposal in wetlands
Friend, M.; Godfrey, P.J.; Kaynor, E.R.; Pelczarski, S.
1985-01-01
Wildlife health concerns associated with disposal of sewage effluent in wetlands are of three primary types: (1) introduction of pathogens, (2) introduction of pollutants that adversely impact on host body defense mechanisms, and (3) changes in the physical and chemical properties of wetlands that favor the development and maintenance of disease problems. Unlike the situation with human health concerns, introduction of pathogens is not the major concern regarding wildlife health. Instead, the focus of attention needs to be directed at environmental changes likely to take place as a result of effluent discharges into different types of wetlands. Unless these changes are adequately addressed from a disease perspective, marshes utilized for sewage disposal could become disease incubators and wildlife death traps. This result would be unfortunate because the backlash would likely negate the potentially beneficial aspects of the use of sewage wastewater for the creation of new wetlands and have a severe impact on progress being made towards evaluation of the compatibility of wildlife and sewage effluents.
Police must join the fast track to end AIDS by 2030.
Crofts, Nick; Patterson, David
2016-01-01
World leaders have committed to ending AIDS by 2030, but stigma and discrimination remain significant obstacles. In particular, police are critical, front-line determinants of risk for many people living with HIV (PLHIV) and members of other key affected populations (KAPs). The negative impact of adverse police behaviours and practices on HIV risk is well documented, and these risks undermine global efforts to end AIDS. Far less well documented, and less common, are attempts to ameliorate this impact by working to change police behaviours. This Special Issue seeks to help redress this imbalance by presenting a selection of original, provocative and important interventions from academics, police officers and other stakeholders concerned with documenting the potential for constructive, progressive and evidence-based approaches to the reduction of HIV risk. We recommend urgent boosting of efforts and funding to engage police in the HIV response. Among other strategies, this needs sustainable funding of programmes and their evaluation, and increased and continuing advocacy and education at all levels to match policy and law reform.
New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling
DOE Office of Scientific and Technical Information (OSTI.GOV)
Erickson, Keesha E.; Rukhlenko, Oleksii S.; Posner, Richard G.
RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisitionmore » of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers.« less
Bernardo, Theresa M; Malinowski, Robert P
2005-01-01
In this article, advances in the application of medical media to education, clinical care, and research are explored and illustrated with examples, and their future potential is discussed. Impact is framed in terms of the Sloan Consortium's five pillars of quality education: access; student and faculty satisfaction; learning effectiveness; and cost effectiveness. (Hiltz SR, Zhang Y, Turoff M. Studies of effectiveness of learning networks. In Bourne J, Moore J, ed. Elements of Quality Online Education. Needham, MA: Sloan-Consortium, 2002:15-45). The alternatives for converting analog media (text, photos, graphics, sound, video, animations, radiographs) to digital media and direct digital capture are covered, as are options for storing, manipulating, retrieving, and sharing digital collections. Diagnostic imaging is given particular attention, clarifying the difference between computerized radiography and digital radiography and explaining the accepted standard (DICOM) and the advantages of Web PACS. Some novel research applications of medical media are presented.
New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling
Erickson, Keesha E.; Rukhlenko, Oleksii S.; Posner, Richard G.; ...
2018-03-05
RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisitionmore » of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers.« less
Yang, Lawrence H; Singla, Daisy R
2011-11-01
Indigenous interpretations of mental illness might negatively impact treatment adherence. However, psychiatric "labeling" potentially leads to stigma among Chinese groups, thus encouraging the use of indigenous idioms. We examined how relatives' use of indigenous labeling varied with the consumers' experience of illness and whether indigenous labeling protected relatives from internalized and experienced forms of stigma. Forty-nine relatives of Chinese-immigrant consumers with psychosis were sampled. Although consumers had progressed to the middle stages of psychosis, 39% of relatives used indigenous idioms to label psychosis. Indigenous labeling decreased when illness duration increased and when visual hallucinations were present. Indigenous labeling further predicted lower internalized stigma among relatives. Relatives who used indigenous labeling also reported fewer indirect stigma experiences, although not after controlling for illness severity. The frequency of direct discrimination among relatives did not differ by labeling. These forms of felt stigma might be embedded into relatives' psychoeducation programs to mitigate adverse consequences of psychiatric labeling.
Implications of dual practice for universal health coverage.
McPake, Barbara; Russo, Giuliano; Hipgrave, David; Hort, Krishna; Campbell, James
2016-02-01
Making progress towards universal health coverage (UHC) requires that health workers are adequate in numbers, prepared for their jobs and motivated to perform. In establishing the best ways to develop the health workforce, relatively little attention has been paid to the trends and implications of dual practice - concurrent employment in public and private sectors. We review recent research on dual practice for its potential to guide staffing policies in relation to UHC. Many studies describe the characteristics and correlates of dual practice and speculate about impacts, but there is very little evidence that is directly relevant to policy-makers. No studies have evaluated the impact of policies on the characteristics of dual practice or implications for UHC. We address this lack and call for case studies of policy interventions on dual practice in different contexts. Such research requires investment in better data collection and greater determination on the part of researchers, research funding bodies and national research councils to overcome the difficulties of researching sensitive topics of health systems functions.
New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling.
Erickson, Keesha E; Rukhlenko, Oleksii S; Posner, Richard G; Hlavacek, William S; Kholodenko, Boris N
2018-03-05
RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisition of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers. Copyright © 2018 Elsevier Ltd. All rights reserved.
Interest Group Conflict Over Medicaid Expansion: The Surprising Impact of Public Advocates.
Callaghan, Timothy; Jacobs, Lawrence R
2016-02-01
We examined the potential economic, policy, and political influences on the decisions of the 50 US states to expand Medicaid under the Affordable Care Act. We related a measure of relative state progress toward Medicaid expansion updated to 2015 to each state's economic circumstances, established policy frameworks in states, partisan control of state government, and lobbyists for businesses, medical professionals, unions, and public interest organizations. The 9201 lobbyists working on health care reform in state capitols exerted a strong and significant impact on Medicaid expansion. Controlling for confounding factors (including partisanship and existing policy frameworks), we found that business and professional lobbyists exerted a negative effect on state Medicaid expansion and, unexpectedly, that public interest advocates exerted a positive effect. There are 3.1 million adults who lack coverage because they live in the 20 states that refused to expand Medicaid. Although political party and lobbyists for private interests present significant barriers in these states, legislative lobbying on behalf of the uninsured appears likely to be effective.
The "Century of Biology" and the Evolving Role of Medicinal Chemists in Neuroscience.
Doller, Dario
2017-01-18
Society expects that the wave of contemporary new discoveries in biological sciences will soon lead to novel treatments for human diseases, including many devastating brain disorders. Historically, medicinal chemists have contributed to drug discovery teams in ways that synergize with those from their partner sciences, and help transform new knowledge into the ultimate tangible asset: a new drug. The optimal balance of resources and the right strategy to minimize the risk of late clinical failure may differ for different therapeutic indications. Recent progress in the oncology and neuroscience therapeutic areas is compared and contrasted, in particular looking at the biological target space and functional attributes of recently FDA-approved drugs and those in the late clinical pipeline. Medicinal chemists are poised to have major influence in neuroscience drug research, and examples of areas of potential impact are presented, together with a discussion of the soft skills they bring to their project teams and why they have been so impactful.
Analysis of progressive damage in thin circular laminates due to static-equivalent impact loads
NASA Technical Reports Server (NTRS)
Shivakumar, K. N.; Elber, W.; Illg, W.
1983-01-01
Clamped circular graphite/epoxy plates (25.4, 38.1, and 50.8 mm radii) with an 8-ply quasi-isotropic layup were analyzed for static-equivalent impact loads using the minimum-total-potential-energy method and the von Karman strain-displacement equations. A step-by-step incremental transverse displacement procedure was used to calculate plate load and ply stresses. The ply failure region was calculated using the Tsai-Wu criterion. The corresponding failure modes (splitting and fiber failure) were determined using the maximum stress criteria. The first-failure mode was splitting and initiated first in the bottom ply. The splitting-failure thresholds were relatively low and tended to be lower for larger plates than for small plates. The splitting-damage region in each ply was elongated in its fiber direction; the bottom ply had the largest damage region. The calculated damage region for the 25.4-mm-radius plate agreed with limited static test results from the literature.
Bhanji, Rahima A; Carey, Elizabeth J; Yang, Liu; Watt, Kymberly D
2017-10-01
Frailty and sarcopenia are common complications of cirrhosis. Frailty has been described as an increased susceptibility to stressors secondary to a cumulative decline in physiologic reserve; this decline occurs with aging or is a result of the disease process, across multiple organ systems. Sarcopenia, a key component of frailty, is defined as progressive and generalized loss of skeletal muscle mass and strength. The presence of either of these complications is associated with increased morbidity and mortality, as these are tightly linked to decompensation and increased complication rates. Recognition of these entities is critical. Studies have shown improvement in muscle strength and function lead to reduced mortality, suggesting both frailty and sarcopenia are modifiable risk factors. In this review we outline the prevalence of frailty and sarcopenia in cirrhosis and the impact on clinical outcomes such as decompensation, hospitalization, and mortality. Existing and potential novel therapeutic approaches for frailty and sarcopenia are also reviewed. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.
CO2 Reduction: From the Electrochemical to Photochemical Approach
Wu, Jinghua; Huang, Yang; Ye, Wen
2017-01-01
Abstract Increasing CO2 concentration in the atmosphere is believed to have a profound impact on the global climate. To reverse the impact would necessitate not only curbing the reliance on fossil fuels but also developing effective strategies capture and utilize CO2 from the atmosphere. Among several available strategies, CO2 reduction via the electrochemical or photochemical approach is particularly attractive since the required energy input can be potentially supplied from renewable sources such as solar energy. In this Review, an overview on these two different but inherently connected approaches is provided and recent progress on the development, engineering, and understanding of CO2 reduction electrocatalysts and photocatalysts is summarized. First, the basic principles that govern electrocatalytic or photocatalytic CO2 reduction and their important performance metrics are discussed. Then, a detailed discussion on different CO2 reduction electrocatalysts and photocatalysts as well as their generally designing strategies is provided. At the end of this Review, perspectives on the opportunities and possible directions for future development of this field are presented. PMID:29201614
Phenological Indicators of Vegetation Recovery in Wetland Ecosystems
NASA Astrophysics Data System (ADS)
Taddeo, S.; Dronova, I.
2017-12-01
Landscape phenology is increasingly used to measure the impacts of climatic and environmental disturbances on plant communities. As plants show rapid phenological responses to environmental changes, variation in site phenology can help characterize vegetation recovery following restoration treatments and qualify their resistance to environmental fluctuations. By leveraging free remote sensing datasets, a phenology-based analysis of vegetation dynamics could offer a cost-effective assessment of restoration progress in wetland ecosystems. To fulfill this objective, we analyze 20 years of free remote sensing data from NASA's Landsat archive to offer a landscape-scale synthesis of wetland restoration efforts in the Sacramento-San Joaquin Delta of California, USA. Through an analysis of spatio-temporal changes in plant phenology and greenness, we assess how 25 restored wetlands across the Delta have responded to restoration treatments, time, and landscape context. We use a spline smoothing approach to generate both site-wide and pixel-specific phenological curves and identify key phenological events. Preliminary results reveal a greater variability in greenness and growing season length during the initial post-restoration years and a significant impact of landscape context in the time needed to reach phenological stability. Well-connected sites seem to benefit from an increased availability of propagules enabling them to reach peak greenness and maximum growing season length more rapidly. These results demonstrate the potential of phenological analyses to measure restoration progress and detect factors promoting wetland recovery. A thorough understanding of wetland phenology is key to the quantification of ecosystem processes including carbon sequestration and habitat provisioning.
Langer, Corey J; Obasaju, Coleman; Bunn, Paul; Bonomi, Philip; Gandara, David; Hirsch, Fred R; Kim, Edward S; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Socinski, Mark A; Spigel, David R; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick
2016-12-01
Squamous cell lung cancer (sqCLC) is an aggressive form of cancer that poses many therapeutic challenges. Patients tend to be older, present at a later stage, and have a high incidence of comorbidities, which can compromise treatment delivery and exacerbate toxicity. In addition, certain agents routinely available for nonsquamous cell histologic subtypes, such as bevacizumab and pemetrexed, are contraindicated or lack efficacy in sqCLC. Therapeutic progress has been much slower for advanced sqCLC, with median survival times of approximately 9 to 11 months in most studies. Herein, we discuss the current therapeutic landscape for patients with sqCLC versus with nonsquamous NSCLC. Current evidence indicates that new targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab can provide survival prolongation, although the benefits are still relatively modest. These incremental improvements, all realized since 2012, in aggregate, will very likely have a clinically meaningful impact for patients with sqCLC. We also discuss recent genomic studies of sqCLC that have identified potentially actionable molecular targets, as well as the relevant targeted agents in clinical development. Finally, we discuss the magnitude of survival benefit and the risk-to-benefit ratio that would prove clinically meaningful in this underserved patient population with unmet needs. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Shaikhouni, Ammar; Elder, J Bradley
2012-11-01
At the turn of the twentieth century, the only computational device used in neurosurgical procedures was the brain of the surgeon. Today, most neurosurgical procedures rely at least in part on the use of a computer to help perform surgeries accurately and safely. The techniques that revolutionized neurosurgery were mostly developed after the 1950s. Just before that era, the transistor was invented in the late 1940s, and the integrated circuit was invented in the late 1950s. During this time, the first automated, programmable computational machines were introduced. The rapid progress in the field of neurosurgery not only occurred hand in hand with the development of modern computers, but one also can state that modern neurosurgery would not exist without computers. The focus of this article is the impact modern computers have had on the practice of neurosurgery. Neuroimaging, neuronavigation, and neuromodulation are examples of tools in the armamentarium of the modern neurosurgeon that owe each step in their evolution to progress made in computer technology. Advances in computer technology central to innovations in these fields are highlighted, with particular attention to neuroimaging. Developments over the last 10 years in areas of sensors and robotics that promise to transform the practice of neurosurgery further are discussed. Potential impacts of advances in computers related to neurosurgery in developing countries and underserved regions are also discussed. As this article illustrates, the computer, with its underlying and related technologies, is central to advances in neurosurgery over the last half century. Copyright © 2012 Elsevier Inc. All rights reserved.
Kappos, Ludwig; De Stefano, Nicola; Freedman, Mark S; Cree, Bruce Ac; Radue, Ernst-Wilhelm; Sprenger, Till; Sormani, Maria Pia; Smith, Terence; Häring, Dieter A; Piani Meier, Daniela; Tomic, Davorka
2016-09-01
'No evidence of disease activity' (NEDA), defined as absence of magnetic resonance imaging activity (T2 and/or gadolinium-enhanced T1 lesions), relapses and disability progression ('NEDA-3'), is used as a comprehensive measure of treatment response in relapsing multiple sclerosis (RMS), but is weighted towards inflammatory activity. Accelerated brain volume loss (BVL) occurs in RMS and is an objective measure of disease worsening and progression. To assess the contribution of individual components of NEDA-3 and the impact of adding BVL to NEDA-3 ('NEDA-4') METHODS: We analysed data pooled from two placebo-controlled phase 3 fingolimod trials in RMS and assessed NEDA-4 using different annual BVL mean rate thresholds (0.2%-1.2%). At 2 years, 31.0% (217/700) of patients receiving fingolimod 0.5 mg achieved NEDA-3 versus 9.9% (71/715) on placebo (odds ratio (OR) 4.07; p < 0.0001). Adding BVL (threshold of 0.4%), the respective proportions of patients achieving NEDA-4 were 19.7% (139/706) and 5.3% (38/721; OR 4.41; p < 0.0001). NEDA-4 status favoured fingolimod across all BVL thresholds tested (OR 4.01-4.41; p < 0.0001). NEDA-4 has the potential to capture the impact of therapies on both inflammation and neurodegeneration, and deserves further evaluation across different compounds and in long-term studies. © The Author(s), 2015.
Gassiot, Susanna; Motlló, Cristina; Llombart, Inuska; Morgades, Mireia; González, Yolanda; Garcia-Caro, Montse; Ribera, Josep-Maria; Oriol, Albert
2017-06-01
Clinical trials for patients with multiple myeloma (MM) using novel agent (NA)-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS); however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potential impact of initial induction on the feasibility and outcome of subsequent treatment lines in a real clinical practice setting. Patients with consecutive MM <70 years of age diagnosed between 1999 and 2009 were prospectively registered and classified as having received conventional chemotherapy induction regimens with new agents available at relapse (CC cohort, 89 patients) or as treated with NAs upfront (NA cohort, 65 patients). Patients in the NA cohort demonstrated a superior median PFS (2.8 years vs 1.6 years, P=.03) and also a median PFS from diagnosis to second progression (5.2 years vs 2.7 years, P=.003). After a median follow-up of 7 years, clear differences in OS were observed (7.97 years in NA cohort compared to 3.35 years in CC cohort, P<.001). New agent-based first-line induction treatments provide benefits in both PFS and beyond that point, contributing to a significant improvement in OS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Cross-scale interactions affect tree growth and intrinsic water ...
1. We investigated the potential of cross-scale interactions to affect the outcome of density reduction in a large-scale silvicultural experiment. 2. We measured tree growth and intrinsic water-use efficiency (iWUE) based on stable carbon isotopes (13C) to investigate the impacts of thinning across a range of progressively finer spatial scales: site, stand, hillslope position, and neighborhood position. In particular, we focused on the influence of thinning beyond the boundaries of thinned stands to include impacts on downslope and neighboring stands across sites varying in soil moisture. 3. Trees at the wet site responded to thinning with increased growth when compared with trees at the dry site. Additionally, trees in thinned stands at the dry site responded with increased iWUE while trees in thinned stands at the wet site showed no difference in iWUE compared to unthinned stands. 4. We hypothesized that water is not the primary limiting factor for growth at our sites, but that thinning released other resources, such as growing space or nutrients to drive the growth response. At progressively finer spatial scales we found that the responses of trees was not driven by hillslope location (i.e., downslope of thinning) but to changes in local neighborhood tree density. 5. The results of this study demonstrated that water can be viewed as an “agent” that allows us to investigate cross-scale interactions as it links coarse to finer spatial scales and vice ver
2015-01-01
Strengthening capacity in poorer countries to generate multi-disciplinary health research and to utilise research findings, is one of the most effective ways of advancing the countries' health and development. This paper explores current knowledge about how to design health research capacity strengthening (RCS) programmes and how to measure their progress and impact. It describes a systematic, evidence-based approach for designing such programmes and highlights some of the key challenges that will be faced in the next 10 years. These include designing and implementing common frameworks to facilitate comparisons among capacity strengthening projects, and developing monitoring indicators that can capture their interactions with knowledge users and their impact on changes in health systems. PMID:28281707
NASA Astrophysics Data System (ADS)
Ishin, Artem; Voeykov, Sergey; Perevalova, Natalia; Khakhinov, Vitaliy
2017-12-01
As a part of the Plasma-Progress and Radar-Progress space experiments conducted from 2006 to 2014, effects of the Progress spacecraft engines on the ionosphere have been studied using data from Global Navigation Satellite System (GNSS) receivers. 72 experiments have been carried out. All these experiments were based on data from the International GNSS Service (IGS) to record ionospheric plasma irregularities caused by engine operation. 35 experiments used data from the ISTP SB RAS network SibNet. The analysis of the spatio-temporal structure of total electron content (TEC) variations has shown that the problem of identifying the TEC response to engine operation is complicated by a number of factors: 1) the engine effect on ionospheric plasma is strongly localized in space and has a relatively low intensity; 2) a small number of satellite-receiver radio rays due to the limited number of GNSS stations, particularly before 2013; 3) a potential TEC response is masked with background ionospheric disturbances of various intensities. However, TEC responses are identified with certainty when a satellite-receiver radio ray crosses a disturbed region within minutes after the impact. TEC responses have been registered in 7 experiments (10 % of cases). The amplitude of ionospheric response (0.3-0.16 TECU) exceeded the background TEC variations (~0.25 TECU) several times. The TEC data indicate that the ionospheric irregularity lifetime is from 4 to 10 minutes. According to the estimates we made, the transverse size of irregularities is from 12 to 30 km.
Blockade of sarcolemmal TRPV2 accumulation inhibits progression of dilated cardiomyopathy.
Iwata, Yuko; Ohtake, Hitomi; Suzuki, Osamu; Matsuda, Junichiro; Komamura, Kazuo; Wakabayashi, Shigeo
2013-09-01
Dilated cardiomyopathy (DCM) is a severe disorder defined by ventricular dilation and contractile dysfunction. Abnormal Ca(2+) handling is hypothesized to play a critical pathological role in DCM progression. The transient receptor potential vanilloid 2 (TRPV2) has been previously suggested as a candidate pathway for enhanced Ca(2+) entry. Here, we examined the sarcolemmal accumulation of TRPV2 in various heart-failure model animals and DCM patients, and assessed whether presently available inhibitory tools against TRPV2 ameliorate DCM symptoms. Immunological and cell physiological analyses revealed that TRPV2 is highly concentrated and activated in the ventricular sarcolemma of DCM patients and three animal models-δ-sarcoglycan-deficient hamsters (J2N-k), transgenic mice over-expressing sialytransferase (4C30), and doxorubicin (DOX)-induced DCM mice. Over-expression of the amino-terminal (NT) domain of TRPV2 could block the plasma membrane accumulation and influx of Ca(2+) via TRPV2. Transgenic (Tg) or adenoviral expression of the NT domain in DCM animals caused effective removal of sarcolemmal TRPV2 along with reduction in the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and reactive oxygen species (ROS) production, which were activated in DCM; further, it prevented ventricular dilation and fibrosis, ameliorated contractile dysfunction in DCM, and improved survival of the affected animals. The TRPV2 inhibitor tranilast markedly suppressed DCM progression. Sarcolemmal TRPV2 accumulation appears to have considerable pathological impact on DCM progression, and blockade of this channel may be a promising therapeutic strategy for treating advanced heart failure.
Potential future impact of a partially effective HIV vaccine in a southern African setting.
Phillips, Andrew N; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Lundgren, Jens D; Roset-Bahmanyar, Edith; Roman, François; Van Effelterre, Thierry
2014-01-01
It is important for public health and within the HIV vaccine development field to understand the potential population level impact of an HIV vaccine of partial efficacy--both in preventing infection and in reducing viral load in vaccinated individuals who become infected--in the context of a realistic future implementation scenario in resource limited settings. An individual level model of HIV transmission, progression and the effect of antiretroviral therapy was used to predict the outcome to 2060 of introduction in 2025 of a partially effective vaccine with various combinations of efficacy characteristics, in the context of continued ART roll-out in southern Africa. In the context of our base case epidemic (in 2015 HIV prevalence 28% and incidence 1.7 per 100 person years), a vaccine with only 30% preventative efficacy could make a substantial difference in the rate with which HIV incidence declines; the impact on incidence in relative terms is projected to increase over time, with a projected 67% lower HIV incidence in 2060 compared with no vaccine introduction. The projected mean decline in the general adult population death rate 2040-2060 is 11%. A vaccine with no prevention efficacy but which reduces viral load by 1 log is predicted to result in a modest (14%) reduction in HIV incidence and an 8% reduction in death rate in the general adult population (mean 2040-2060). These effects were broadly similar in multivariable uncertainty analysis. Introduction of a partially effective preventive HIV vaccine would make a substantial long-term impact on HIV epidemics in southern Africa, in addition to the effects of ART. Development of an HIV vaccine, even of relatively low apparent efficacy at the individual level, remains a critical global public health goal.
Kleinstreuer, Clement; Feng, Yu
2013-01-01
Inhaled toxic aerosols of conventional cigarette smoke may impact not only the health of smokers, but also those exposed to second-stream smoke, especially children. Thus, less harmful cigarettes (LHCs), also called potential reduced exposure products (PREPs), or modified risk tobacco products (MRTP) have been designed by tobacco manufacturers to focus on the reduction of the concentration of carcinogenic components and toxicants in tobacco. However, some studies have pointed out that the new cigarette products may be actually more harmful than the conventional ones due to variations in puffing or post-puffing behavior, different physical and chemical characteristics of inhaled toxic aerosols, and longer exposure conditions. In order to understand the toxicological impact of tobacco smoke, it is essential for scientists, engineers and manufacturers to develop experiments, clinical investigations, and predictive numerical models for tracking the intake and deposition of toxicants of both LHCs and conventional cigarettes. Furthermore, to link inhaled toxicants to lung and other diseases, it is necessary to determine the physical mechanisms and parameters that have significant impacts on droplet/vapor transport and deposition. Complex mechanisms include droplet coagulation, hygroscopic growth, condensation and evaporation, vapor formation and changes in composition. Of interest are also different puffing behavior, smoke inlet conditions, subject geometries, and mass transfer of deposited material into systemic regions. This review article is intended to serve as an overview of contributions mainly published between 2009 and 2013, focusing on the potential health risks of toxicants in cigarette smoke, progress made in different approaches of impact analyses for inhaled toxic aerosols, as well as challenges and future directions. PMID:24065038
Tabachnick, W J
2010-03-15
Vector-borne pathogens cause enormous suffering to humans and animals. Many are expanding their range into new areas. Dengue, West Nile and Chikungunya have recently caused substantial human epidemics. Arthropod-borne animal diseases like Bluetongue, Rift Valley fever and African horse sickness pose substantial threats to livestock economies around the world. Climate change can impact the vector-borne disease epidemiology. Changes in climate will influence arthropod vectors, their life cycles and life histories, resulting in changes in both vector and pathogen distribution and changes in the ability of arthropods to transmit pathogens. Climate can affect the way pathogens interact with both the arthropod vector and the human or animal host. Predicting and mitigating the effects of future changes in the environment like climate change on the complex arthropod-pathogen-host epidemiological cycle requires understanding of a variety of complex mechanisms from the molecular to the population level. Although there has been substantial progress on many fronts the challenges to effectively understand and mitigate the impact of potential changes in the environment on vector-borne pathogens are formidable and at an early stage of development. The challenges will be explored using several arthropod-borne pathogen systems as illustration, and potential avenues to meet the challenges will be presented.
Kelly, Adrian B; Mason, W Alex; Chmelka, Mary B; Herrenkohl, Todd I; Kim, Min Jung; Patton, George C; Hemphill, Sheryl A; Toumbourou, John W; Catalano, Richard F
2016-08-01
Adolescent depressed mood is related to the development of subsequent mental health problems, and family problems have been linked to adolescent depression. Longitudinal research on adolescent depressed mood is needed to establish the unique impact of family problems independent of other potential drivers. This study tested the extent to which family conflict exacerbates depressed mood during adolescence, independent of changes in depressed mood over time, academic performance, bullying victimization, negative cognitive style, and gender. Students (13 years old) participated in a three-wave bi-national study (n = 961 from the State of Washington, United States, n = 981 from Victoria, Australia; 98 % retention, 51 % female in each sample). The model was cross-lagged and controlled for the autocorrelation of depressed mood, negative cognitive style, academic failure, and bullying victimization. Family conflict partially predicted changes in depressed mood independent of changes in depressed mood over time and the other controls. There was also evidence that family conflict and adolescent depressed mood are reciprocally related over time. The findings were closely replicated across the two samples. The study identifies potential points of intervention to interrupt the progression of depressed mood in early to middle adolescence.
Jenkins, Frank J.; Van Houten, Bennett; Bovbjerg, Dana H.
2014-01-01
Considerable research effort in the past several decades has focused on the impact of psychological stress, and stress hormones, on cancer progression. Numerous studies have reported that stress hormone treatment or in vivo stress exposure can enhance the growth of tumor cell lines in vitro, as well as tumors in animal models, and have begun to explore molecular mechanisms. Comparatively little research has focused on the impact of psychological stress and stress hormones on cancer initiation, in part due to inherent methodological challenges, but also because potential underlying biological mechanisms have remained obscure. In this review, we present a testable theoretical model of pathways by which stress may result in cellular transformation and tumorigenesis. This model supports our overarching hypothesis that psychological stress, acting through increased levels of catecholamines and/or cortisol, can increase DNA damage and/or reduce repair mechanisms, resulting in increased risk of DNA mutations leading to carcinogenesis. A better understanding of molecular pathways by which psychological stress can increase the risk of cancer initiation would open new avenues of translational research, bringing together psychologists, neuroscientists, and molecular biologists, potentially resulting in the development of novel approaches for cancer risk reduction at the population level. PMID:24891812
Ćwiklińska, Agnieska; Cackowska, Monika; Wieczorek, Ewa; Król, Ewa; Kowalski, Robert; Kuchta, Agnieszka; Kortas-Stempak, Barbara; Gliwińska, Anna; Dąbkowski, Kamil; Zielińska, Justyna; Dębska-Ślizień, Alicja; Jankowski, Maciej
2018-06-15
Hypertriglyceridaemia (HTG) and reduction and dysfunction of high density lipoprotein (HDL) are common lipid disturbances in chronic kidney disease (CKD). HTG in CKD is caused mainly by the decreased efficiency of lipoprotein lipase (LPL)-mediated very low density lipoprotein triglyceride (VLDL-TG) lipolysis. It has not been clarified whether HDL dysfunction in CKD contributes directly to HTG development; thus, the aim of this study was to assess the impact of CKD progression on the ability of HDL to enhance LPL-mediated VLDL-TG lipolysis efficiency. VLDL was isolated from non-dialysis patients in CKD stages 3 and 4 and from non-CKD patients. The VLDL was incubated with LPL at the constant LPL:VLDL-TG ratio, in the absence or presence of HDL. After incubation, the VLDL was separated and the percentage (%) of hydrolyzed TG was calculated. HDL presence increased the lipolysis efficiency of VLDL isolated from CKD and non-CKD patients, for the VLDL-TG> 50 mg/dl. Its effect was dependent on the VLDL-TG and HDL-cholesterol concentrations in the reaction mixtures: the higher the concentrations of VLDL-TG and HDL-cholesterol, the greater the effect. The positive impact of HDL on VLDL lipolysis was modified by CKD progression: the percentage of lipolyzed VLDL-TG in the presence of HDL decreased with a reduction in eGFR (r=0.43, p=0.009), and for patients with stage 4 CKD, no positive impact of HDL on lipolysis was observed. The percentage of lipolyzed TG correlated negatively with apoE and apoCs content in VLDL, and positively with HDL-apoCII, as well as with VLDL and HDL apoCII/ apoCIII ratios. The progression of CKD was associated with unfavourable changes in VLDL and HDL composition; apoE and apoCs levels increased in VLDL with a decrease in eGFR whereas the HDL-cholesterol level decreased. The progression of CKD affects lipoprotein composition and properties, and modulates the positive impact of HDL on VLDL lipolysis efficiency. In CKD patients, HDL deficiency and dysfunction can directly affect hypertriglyceridaemia development. © 2018 The Author(s). Published by S. Karger AG, Basel.
Weinmann, Tobias; Gerlich, Jessica; Heinrich, Sabine; Nowak, Dennis; Gerdes, Jennifer; Schlichtiger, Jenny; von Mutius, Erika; Schaub, Bianca; Vogelberg, Christian; Roller, Diana; Radon, Katja
2015-12-04
Atopic diseases are a major burden of disease on a global scale. Regarding their aetiology, the early years of life are assumed to play a crucial role. In addition, there is growing evidence that elucidating the impact of cross-generational effects and epigenetic mechanisms such as DNA methylation can substantially widen the scientific knowledge of the occurrence and progression of these diseases. We are thus aiming at following the course of asthma, allergies, and potential risk factors for their occurrence across three generations by establishing a birth cohort in the offspring of an existing population-based cohort. 2051 young adults who have been recruited in 1995 for Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC) and who have subsequently been followed-up by the Study on Occupational Allergy Risks (SOLAR) are asked bi-annually since 2009 if they conceived a child in the meantime. If parenthood is reported, parents are invited to enrol along with their children in the ACROSSOLAR cohort. Participation involves completing a questionnaire assessing general and health-related information about the course of the pregnancy and the first year of life of their children. Subsequently, the children are followed up until primary school age when asthma and allergies can be diagnosed reliably. In addition, DNA for epigenetic analysis will be collected and analysed. Longitudinal data analysis techniques will then be used to assess potential associations between early-life exposures and onset of childhood asthma and allergies taking into account epigenetics. Birth cohorts are especially suited to elucidate the impact of genetic predisposition, epigenetics, exposures during the first years of life, and gene-environment interactions on the occurrence and progression of asthma and allergies. By building upon an existing cohort, ACROSSOLAR offers a unique and cost-effective opportunity to investigate the aetiology of atopic disease in a prospective and cross-generational way.
Stefanko, D P; Shah, V D; Yamasaki, W K; Petzinger, G M; Jakowec, M W
2017-09-01
Depression, cognitive impairments, and other neuropsychiatric disturbances are common during the prodromal phase of Huntington's disease (HD) well before the onset of classical motor symptoms of this degenerative disorder. The purpose of this study was to examine the potential impact of physical activity in the form of exercise on a motorized treadmill on non-motor behavioral features including depression-like behavior and cognition in the CAG 140 knock-in (KI) mouse model of HD. The CAG 140 KI mouse model has a long lifespan compared to other HD rodent models with HD motor deficits emerging after 12months of age and thus provides the opportunity to investigate early life interventions such as exercise on disease progression. Motorized treadmill running was initiated at 4weeks of age (1h per session, 3 times per week) and continued for 6months. Non-motor behaviors were assessed up to 6months of age and included analysis of depression-like behavior (using the tail-suspension and forced-swim tests) and cognition (using the T-maze and object recognition tests). At both 4 and 6months of age, CAG 140 KI mice displayed significant depression-like behavior in the forced swim and tail suspension tests and cognitive impairment by deficits in reversal relearning in the T-maze test. These deficits were not evident in mice engaged in treadmill running. In addition, exercise restored striatal dopamine D2 receptor expression and dopamine neurotransmitter levels both reduced in sedentary HD mice. Finally, we examined the pattern of striatal expression of mutant huntingtin (mHTT) protein and showed that the number and intensity of immunohistochemical staining patterns of intranuclear aggregates were significantly reduced with exercise. Altogether these findings begin to address the potential impact of lifestyle and early intervention such as exercise on modifying HD progression. Copyright © 2017 Elsevier Inc. All rights reserved.
Jerusalem, Guy; Rorive, Andree; Collignon, Joelle
2014-01-01
Many systemic treatment options are available for advanced breast cancer, including endocrine therapy, chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, and other targeted agents. Recently, everolimus, a mammalian target of rapamycin (mTOR) inhibitor, combined with exemestane, an aromatase inhibitor, has been approved in Europe and the USA for patients suffering from estrogen receptor-positive, HER2-negative advanced breast cancer previously treated by a nonsteroidal aromatase inhibitor, based on the results of BOLERO-2 (Breast cancer trials of OraL EveROlimus). This study showed a statistically significant and clinically meaningful improvement in median progression-free survival. Results concerning the impact on overall survival are expected in the near future. This clinically oriented review focuses on the use of mTOR inhibitors in breast cancer. Results reported with first-generation mTOR inhibitors (ridaforolimus, temsirolimus, everolimus) are discussed. The current and potential role of mTOR inhibitors is reported according to breast cancer subtype (estrogen receptor-positive HER2-negative, triple-negative, and HER2-positive ER-positive/negative disease). Everolimus is currently being evaluated in the adjuvant setting in high-risk estrogen receptor-positive, HER2-negative early breast cancer. Continuing mTOR inhibition or alternatively administering other drugs targeting the phosphatidylinositol-3-kinase/protein kinase B-mTOR pathway after progression on treatments including an mTOR inhibitor is under evaluation. Potential biomarkers to select patients showing a more pronounced benefit are reviewed, but we are not currently using these biomarkers in routine practice. Subgroup analysis of BOLERO 2 has shown that the benefit is consistent in all subgroups and that it is impossible to select patients not benefiting from addition of everolimus to exemestane. Side effects and impact on quality of life are other important issues discussed in this review. Second-generation mTOR inhibitors and dual mTOR-phosphatidylinositol-3-kinase inhibitors are currently being evaluated in clinical trials. PMID:24833916
NASA Technical Reports Server (NTRS)
Wright, C. C.; Baker, D. J.
1980-01-01
This report describes the third phase of work, the objective of which was to overcome the excessive brittleness of the previously developed UH-1 helicopter tail rotor drive shaft design which demonstrated a shaft train weight savings of 53.1% over the current 2024-T3 aluminum shaft train. A materials impact program demonstrated exceptionally noteworthy performance of two woven constructions containing E-glass and PRD 49-III (designation later changed to KEVLAR 49) fibers in an epoxy resin matrix. Thermoplastic matrices and PRD 49-III fiber provided impact resistance at low weight which was superior to composites having the same fiber in a thermoset resin matrix. A design, fabrication, and test program showed that shaft impact resistance could be improved over the previously developed graphite composite design at a cost in shaft train rate savings. The shaft train weight savings of the most impact tolerant construction was 4.0% over the current aluminum shaft train. Alternating plies of graphite and glass appear to provide substantially greater tube impact durability than that provided by hybridization of the two fibers into one tape wound to a ply design equivalent in strength and stiffness to that of the alternating ply design. Recommendations were made to continue research work to exploit the potential for more impact-durable structures through the use of KEVLAR 49 fiber, woven structures, thermoplastic matrices and THORNEL 50-S/KEVLAR 49 blends with thermoset matrices.
The Role of Plant Water Storage on Water Fluxes within the Coupled Soil-Plant-Atmosphere System
NASA Astrophysics Data System (ADS)
Huang, C. W.; Duman, T.; Parolari, A.; Katul, G. G.
2015-12-01
Plant water storage (PWS) contributes to whole-plant transpiration (up to 50%), especially in large trees and during severe drought conditions. PWS also can impact water-carbon economy as well as the degree of resistance to drought. A 1-D porous media model is employed to accommodate transient water flow through the plant hydraulic system. This model provides a mechanistic representation of biophysical processes constraining water transport, accounting for plant hydraulic architecture and the nonlinear relation between stomatal aperture and leaf water potential when limited by soil water availability. Water transport within the vascular system from the stem base to the leaf-lamina is modeled using Richards's equation, parameterized with the hydraulic properties of the plant tissues. For simplicity, the conducting flow in the radial direction is not considered here and the capacitance at the leaf-lamina is assumed to be independent of leaf water potential. The water mass balance in the leaf lamina sets the upper boundary condition for the flow system, which links the leaf-level transpiration to the leaf water potential. Thus, the leaf-level gas exchange can be impacted by soil water availability through the water potential gradient from the leaf lamina to the soil, and vice versa. The root water uptake is modeled by a multi-layered macroscopic scheme to account for possible hydraulic redistribution (HR) in certain conditions. The main findings from the model calculations are that (1) HR can be diminished by the residual water potential gradient from roots to leaves at night due to aboveground capacitance, tree height, nocturnal transpiration or the combination of the three. The degree of reduction depends on the magnitude of residual water potential gradient; (2) nocturnal refilling to PWS elevates the leaf water potential that subsequently delays the onset of drought stress at the leaf; (3) Lifting water into the PWS instead of HR can be an advantageous strategy for overstory species especially when drought progresses in the presence of competing understory species.
Selection bias in rheumatic disease research.
Choi, Hyon K; Nguyen, Uyen-Sa; Niu, Jingbo; Danaei, Goodarz; Zhang, Yuqing
2014-07-01
The identification of modifiable risk factors for the development of rheumatic conditions and their sequelae is crucial for reducing the substantial worldwide burden of these diseases. However, the validity of such research can be threatened by sources of bias, including confounding, measurement and selection biases. In this Review, we discuss potentially major issues of selection bias--a type of bias frequently overshadowed by other bias and feasibility issues, despite being equally or more problematic--in key areas of rheumatic disease research. We present index event bias (a type of selection bias) as one of the potentially unifying reasons behind some unexpected findings, such as the 'risk factor paradox'--a phenomenon exemplified by the discrepant effects of certain risk factors on the development versus the progression of osteoarthritis (OA) or rheumatoid arthritis (RA). We also discuss potential selection biases owing to differential loss to follow-up in RA and OA research, as well as those due to the depletion of susceptibles (prevalent user bias) and immortal time bias. The lesson remains that selection bias can be ubiquitous and, therefore, has the potential to lead the field astray. Thus, we conclude with suggestions to help investigators avoid such issues and limit the impact on future rheumatology research.
Selection bias in rheumatic disease research
Choi, Hyon K.; Nguyen, Uyen-Sa; Niu, Jingbo; Danaei, Goodarz; Zhang, Yuqing
2014-01-01
The identification of modifiable risk factors for the development of rheumatic conditions and their sequelae is crucial for reducing the substantial worldwide burden of these diseases. However, the validity of such research can be threatened by sources of bias, including confounding, measurement and selection biases. In this Review, we discuss potentially major issues of selection bias—a type of bias frequently overshadowed by other bias and feasibility issues, despite being equally or more problematic—in key areas of rheumatic disease research. We present index event bias (a type of selection bias) as one of the potentially unifying reasons behind some unexpected findings, such as the ‘risk factor paradox’—a phenomenon exemplified by the discrepant effects of certain risk factors on the development versus the progression of osteoarthritis (OA) or rheumatoid arthritis (RA). We also discuss potential selection biases owing to differential loss to follow-up in RA and OA research, as well as those due to the depletion of susceptibles (prevalent user bias) and immortal time bias. The lesson remains that selection bias can be ubiquitous and, therefore, has the potential to lead the field astray. Thus, we conclude with suggestions to help investigators avoid such issues and limit the impact on future rheumatology research. PMID:24686510
NASA Research Center Contributions to Space Shuttle Return to Flight (SSRTF)
NASA Technical Reports Server (NTRS)
Cockrell, Charles E., Jr.; Barnes, Robert S.; Belvin, Harry L.; Allmen, John; Otero, Angel
2005-01-01
Contributions provided by the NASA Research Centers to key Space Shuttle return-to-flight milestones, with an emphasis on debris and Thermal Protection System (TPS) damage characterization, are described herein. Several CAIB recommendations and Space Shuttle Program directives deal with the mitigation of external tank foam insulation as a debris source, including material characterization as well as potential design changes, and an understanding of Orbiter TPS material characteristics, damage scenarios, and repair options. Ames, Glenn, and Langley Research Centers have performed analytic studies, conducted experimental testing, and developed new technologies, analysis tools, and hardware to contribute to each of these recommendations. For the External Tank (ET), these include studies of spray-on foam insulation (SOFI), investigations of potential design changes, and applications of advanced non-destructive evaluation (NDE) technologies to understand ET TPS shedding during liftoff and ascent. The end-to-end debris assessment included transport analysis to determine the probabilities of impact for various debris sources. For the Orbiter, methods were developed, and validated through experimental testing, to determine thresholds for potential damage of Orbiter TPS components. Analysis tools were developed and validated for on-orbit TPS damage assessments, especially in the area of aerothermal environments. Advanced NDE technologies were also applied to the Orbiter TPS components, including sensor technologies to detect wing leading edge impacts during liftoff and ascent. Work is continuing to develop certified TPS repair options and to develop improved methodologies for reinforced carbon-carbon (RCC) damage progression to assist in on-orbit repair decision philosophy.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Love, A H
Science-based decision making required robust and high-fidelity mechanistic data about the system dynamics and impacts of system changes. Alkaloid cyanotoxins have the characteristics to warrant consideration for their potential threat. Since insufficient information is available to construct a systems model for the alkaloid cyanotoxins, saxitoxins, anatoxins, and anatoxin-a(S), an accurate assessments of these toxins as a potential threat for use for intentional contamination is not possible. Alkaloid cyanotoxin research that contributed to such a model has numerous areas of overlap for natural and intentional health effects issues that generates dual improvements to the state of the science. The use ofmore » sensitivity analyses of systems models can identify parameters that, when determined, result in the greatest impact to the overall system and may help to direct the most efficient use of research funding. This type of modeling-assisted experimentation may allow rapid progress for overall system understanding compared to observational or disciplinary research agendas. Assessment and management of risk from intentional contamination can be performed with greater confidence when mechanisms are known and the relationships between different components are validated. This level of understanding allows high-fidelity assessments that do not hamper legitimate possession of these toxins for research purposes, while preventing intentional contamination that would affect public health. It also allows for appropriate response to an intentional contamination event, even if the specific contamination had not been previous considered. Development of science-based decision making tools will only improve our ability to address the new requirements addressing potential threats to our nation.« less
Smith, J; Ward, D; Michaelides, M; Moore, A T; Simpson, S
2015-09-01
The horizon scanning review aimed to identify new and emerging technologies in development that have the potential to slow or stop disease progression and/or reverse sight loss in people with inherited retinal diseases (IRDs). Potential treatments were identified using recognized horizon scanning methods. These included a combination of online searches using predetermined search terms, suggestions from clinical experts and patient and carer focus groups, and contact with commercial developers. Twenty-nine relevant technologies were identified. These included 9 gene therapeutic approaches, 10 medical devices, 5 pharmacological agents, and 5 regenerative and cell therapies. A further 11 technologies were identified in very early phases of development (typically phase I or pre-clinical) and were included in the final report to give a complete picture of developments 'on the horizon'. Clinical experts and patient and carer focus groups provided helpful information and insights, such as the availability of specialised services for patients, the potential impacts of individual technologies on people with IRDs and their families, and helped to identify additional relevant technologies. This engagement ensured that important areas of innovation were not missed. Most of the health technologies identified are still at an early stage of development and it is difficult to estimate when treatments might be available. Further, well designed trials that generate data on efficacy, applicability, acceptability, and costs of the technologies, as well as the long-term impacts for various conditions are required before these can be considered for adoption into routine clinical practice.
Dressler, L
1998-04-01
Genetic testing for the BRCA1 gene is available commercially and clinically. The information gained from this test impacts not only on the individual tested, but on family members as well. The test can offer an individual and their family the opportunity to gain valuable information about their risks of developing certain forms of inherited breast cancer and other inherited cancers. In addition to its emotional and psychological impact, this information is associated with significant social and economic issues. This includes the potential for denial, loss, or increased rates for health insurance as well as denial and loss of employment based on genetic test information. The risk for such discrimination can lead to fear of seeking testing and can discourage participation in and potential benefit from prevention, screening, and treatment programs. Therefore, misuse of this information carries significant risk for the individual being tested and for their family members. It is imperative that the potential benefits of genetic testing and genetic information be afforded to all without this risk and fear. In addition to protecting all individuals from genetic discrimination, there is a need to protect the confidentiality of genetic information and an individual's right to privacy. This article discusses protection currently available through legislation at the federal and state level, focusing on the experience in North Carolina in developing and passing a genetic antidiscrimination bill. Although progress has been made, troublesome issues still remain.
Morgan, Gareth J; Gregory, Walter M; Davies, Faith E; Bell, Sue E; Szubert, Alexander J; Brown, Julia M; Coy, Nuria N; Cook, Gordon; Russell, Nigel H; Rudin, Claudius; Roddie, Huw; Drayson, Mark T; Owen, Roger G; Ross, Fiona M; Jackson, Graham H; Child, J Anthony
2012-01-05
Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.
Minireview: SLCO and ABC Transporters: A Role for Steroid Transport in Prostate Cancer Progression
Cho, Eunpi; Montgomery, R. Bruce
2014-01-01
Androgens play a critical role in the development and progression of prostate cancer (PCa), and androgen deprivation therapy via surgical or medical castration is front-line therapy for patients with advanced PCa. However, intratumoral testosterone levels are elevated in metastases from patients with castration-resistant disease, and residual intratumoral androgens have been implicated in mediating ligand-dependent mechanisms of androgen receptor activation. The source of residual tissue androgens present despite castration has not been fully elucidated, but proposed mechanisms include uptake and conversion of adrenal androgens, such as dehdroepiandrosterone to testosterone and dihydrotestosterone, or de novo androgen synthesis from cholesterol or progesterone precursors. In this minireview, we discuss the emerging evidence that suggests a role for specific transporters in mediating transport of steroids into or out of prostate cells, thereby influencing intratumoral androgen levels and PCa development and progression. We focus on the solute carrier and ATP binding cassette gene families, which have the most published data for a role in PCa-related steroid transport, and review the potential impact of genetic variation on steroid transport activity and PCa outcomes. Continued assessment of transport activity in PCa models and human tumor tissue is needed to better delineate the different roles these transporters play in physiologic and neoplastic settings, and in order to determine whether targeting the uptake of steroid substrates by specific transporters may be a clinically feasible therapeutic strategy. PMID:25147980
National quality improvement policies and strategies in European healthcare systems.
Spencer, E; Walshe, K
2009-02-01
This survey provides an overview of the development of policies and strategies for quality improvement in European healthcare systems, by mapping quality improvement policies and strategies, progress in their implementation, and early indications of their impact. A survey of quality improvement policies and strategies in healthcare systems of the European Union was conducted in 2005 for the first phase of the Methods of Assessing Response to Quality Improvement Strategies (MARQuIS) project. The survey, completed by 68 key experts in quality improvement from 24 European Union member states, represents their views and accounts of quality improvement policies and strategies in their healthcare systems. There are substantial international and intra-national variations in the development of healthcare quality improvement. Legal requirements for quality improvement strategies are an important driver of progress, along with the activities of national governments and professional associations and societies. Patient and service user organisations appear to have less influence on quality improvement. Wide variation in voluntary and mandatory coverage of quality improvement policies and strategies across sectors can potentially lead to varying levels of progress in implementation. Many healthcare organisations lack basic infrastructure for quality improvement. Some convergence can be observed in policies on quality improvement in healthcare. Nevertheless, the growth of patient mobility across borders, along with the implications of free market provisions for the organisation and funding of healthcare systems in European Union member states, require policies for cooperation and learning transfer.
Progress on DCLL Blanket Concept
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wong, Clement; Abdou, M.; Katoh, Yutai
2013-09-01
Under the US Fusion Nuclear Science and Technology Development program, we have selected the Dual Coolant Lead Lithium concept (DCLL) as a reference blanket, which has the potential to be a high performance DEMO blanket design with a projected thermal efficiency of >40%. Reduced activation ferritic/martensitic (RAF/M) steel is used as the structural material. The self-cooled breeder PbLi is circulated for power conversion and for tritium breeding. A SiC-based flow channel insert (FCI) is used as a means for magnetohydrodynamic pressure drop reduction from the circulating liquid PbLi and as a thermal insulator to separate the high-temperature PbLi (~700°C) frommore » the helium-cooled RAF/M steel structure. We are making progress on related R&D needs to address critical Fusion Nuclear Science and Facility (FNSF) and DEMO blanket development issues. When performing the function as the Interface Coordinator for the DCLL blanket concept, we had been developing the mechanical design and performing neutronics, structural and thermal hydraulics analyses of the DCLL TBM module. We had estimated the necessary ancillary equipment that will be needed at the ITER site and a detailed safety impact report has been prepared. This provided additional understanding of the DCLL blanket concept in preparation for the FNSF and DEMO. This paper will be a summary report on the progress of the DCLL TBM design and R&Ds for the DCLL blanket concept.« less
Private Pay Progression. Research Brief. Edition 6
ERIC Educational Resources Information Center
Anders, Jake
2015-01-01
While the issue of access to the professions is relatively well understood, there is limited understanding of the impact of entrants' backgrounds on success once in graduate employment. The research looks at the way social background continues to influence graduate pay and career progression once in professional employment. Key findings include:…
The Mixed Economic Progress of Immigrants.
ERIC Educational Resources Information Center
Schoeni, Robert F.; And Others
This report examines whether the economic well-being of male immigrants to the United States improves substantially over time, details differences in economic progress of immigrants from different countries of origin, and assesses the impact of educational attainment on immigrants' earnings. Analyses are based on Public Use Micro Samples of the…
22 CFR 201.24 - Progress and advance payments.
Code of Federal Regulations, 2010 CFR
2010-04-01
... are payments to a supplier prior to, and in anticipation of, performance under a procurement contract. They are not based on actual performance or actual costs incurred. (b) Progress payments—(1) Conditions... predelivery costs that may have a material impact on a suppliers's working capital; (iii) The total FAS...
The Impact of the Measures of Academic Progress (MAP) Program on Student Reading Achievement
ERIC Educational Resources Information Center
Cordray, David S.; Pion, Georgine M.; Brandt, Chris; Molefe, Ayrin
2013-01-01
One of the most widely used commercially available systems incorporating benchmark assessment and training in differentiated instruction is the Northwest Evaluation Association's (NWEA) Measures of Academic Progress (MAP) program. The MAP program involves two components: (1) computer-adaptive assessments administered to students three to four…
Thielen, Marc; Speck, Thomas; Seidel, Robin
2015-01-01
Pomelos (Citrus maxima) are known for their thick peel which—inter alia—serves as energy dissipator when fruits impact on the ground after being shed. It protects the fruit from splitting open and thus enables the contained seeds to stay germinable and to potentially be dispersed by animal vectors. The main part of the peel consists of a parenchymatous tissue that can be interpreted from a materials point of view as open pored foam whose struts are pressurized and filled with liquid. In order to investigate the influence of the water content on the energy dissipation capacity, drop weight tests were conducted with fresh and with freeze-dried peel samples. Based on the coefficient of restitution it was found that freeze-drying markedly reduces the relative energy dissipation capacity of the peel. Measuring the transmitted force during impact furthermore indicated a transition from a uniform collapse of the foam-like tissue to a progressive collapse due to water extraction. Representing the peel by a Maxwell model illustrates that freeze-drying not only drastically reduces the damping function of the dashpots but also stiffens the springs of the model. PMID:26543566
Wilmer, Henry H.; Sherman, Lauren E.; Chein, Jason M.
2017-01-01
While smartphones and related mobile technologies are recognized as flexible and powerful tools that, when used prudently, can augment human cognition, there is also a growing perception that habitual involvement with these devices may have a negative and lasting impact on users’ ability to think, remember, pay attention, and regulate emotion. The present review considers an intensifying, though still limited, area of research exploring the potential cognitive impacts of smartphone-related habits, and seeks to determine in which domains of functioning there is accruing evidence of a significant relationship between smartphone technology and cognitive performance, and in which domains the scientific literature is not yet mature enough to endorse any firm conclusions. We focus our review primarily on three facets of cognition that are clearly implicated in public discourse regarding the impacts of mobile technology – attention, memory, and delay of gratification – and then consider evidence regarding the broader relationships between smartphone habits and everyday cognitive functioning. Along the way, we highlight compelling findings, discuss limitations with respect to empirical methodology and interpretation, and offer suggestions for how the field might progress toward a more coherent and robust area of scientific inquiry. PMID:28487665
Broekhuijse, M L W J; Gaustad, A H; Bolarin Guillén, A; Knol, E F
2015-07-01
Diluting semen from high fertile breeding boars, and by that inseminating many sows, is the core business for artificial insemination (AI) companies worldwide. Knowledge about fertility results is the reason by which an AI company can lower the concentration of a dose. Efficient use of AI boars with high genetic merit by decreasing the number of sperm cells per insemination dose is important to maximize dissemination of the genetic progress made in the breeding nucleus. However, a potential decrease in fertility performance in the field should be weighed against the added value of improved genetics and, in general, is not tolerated in commercial production. This overview provides some important aspects that influence the impact of low-dose AI on fertility: (i) the importance of monitoring field fertility, (ii) the need for accurate and precise semen assessment, (iii) the parameters that are taken into account, (iv) the application of information from genetic and genomic selection and (v) the optimization when using different AI techniques. Efficient semen production, processing and insemination in combination with increasing use of genetic and genomic applications result in maximum impact of genetic trend. © 2015 Blackwell Verlag GmbH.
The development of an ecological approach to manage the pollution risk from highway runoff.
Crabtree, B; Dempsey, P; Johnson, I; Whitehead, M
2009-01-01
In the UK, the Highways Agency is responsible for operating, maintaining and improving the strategic road network in England. One focus of the Highways Agency's ongoing research into the nature and impact of highway runoff is aimed at ensuring that the Highways Agency will meet the requirements of the EU Water Framework Directive. A research programme, undertaken in partnership with the Environment Agency, is in progress to develop a better understanding of pollutants in highway runoff and their ecological impact. The paper presents the outcome of a study to: (1) monitor pollutants in highway runoff under different climate and traffic conditions; (2) develop standards to assess potential ecological risks from soluble pollutants in highway runoff; and (3) develop a model to predict pollutant concentrations in highway runoff. The model has been embedded in a design tool incorporating risk assessment procedures and receiving water standards for soluble and insoluble pollutants--the latter has been developed elsewhere in another project within the research programme. The design tool will be used to support improved guidance on where, and to what level, treatment of runoff is required for highway designers to manage the risk of ecological impact from highway runoff.
Genetic diversity, inbreeding and cancer.
Ujvari, Beata; Klaassen, Marcel; Raven, Nynke; Russell, Tracey; Vittecoq, Marion; Hamede, Rodrigo; Thomas, Frédéric; Madsen, Thomas
2018-03-28
Genetic diversity is essential for adaptive capacities, providing organisms with the potential of successfully responding to intrinsic and extrinsic challenges. Although a clear reciprocal link between genetic diversity and resistance to parasites and pathogens has been established across taxa, the impact of loss of genetic diversity by inbreeding on the emergence and progression of non-communicable diseases, such as cancer, has been overlooked. Here we provide an overview of such associations and show that low genetic diversity and inbreeding associate with an increased risk of cancer in both humans and animals. Cancer being a multifaceted disease, loss of genetic diversity can directly (via accumulation of oncogenic homozygous mutations) and indirectly (via increased susceptibility to oncogenic pathogens) impact abnormal cell emergence and escape of immune surveillance. The observed link between reduced genetic diversity and cancer in wildlife may further imperil the long-term survival of numerous endangered species, highlighting the need to consider the impact of cancer in conservation biology. Finally, the somewhat incongruent data originating from human studies suggest that the association between genetic diversity and cancer development is multifactorial and may be tumour specific. Further studies are therefore crucial in order to elucidate the underpinnings of the interactions between genetic diversity, inbreeding and cancer. © 2018 The Author(s).
Genetic diversity, inbreeding and cancer
Klaassen, Marcel; Raven, Nynke; Russell, Tracey; Vittecoq, Marion; Hamede, Rodrigo; Thomas, Frédéric
2018-01-01
Genetic diversity is essential for adaptive capacities, providing organisms with the potential of successfully responding to intrinsic and extrinsic challenges. Although a clear reciprocal link between genetic diversity and resistance to parasites and pathogens has been established across taxa, the impact of loss of genetic diversity by inbreeding on the emergence and progression of non-communicable diseases, such as cancer, has been overlooked. Here we provide an overview of such associations and show that low genetic diversity and inbreeding associate with an increased risk of cancer in both humans and animals. Cancer being a multifaceted disease, loss of genetic diversity can directly (via accumulation of oncogenic homozygous mutations) and indirectly (via increased susceptibility to oncogenic pathogens) impact abnormal cell emergence and escape of immune surveillance. The observed link between reduced genetic diversity and cancer in wildlife may further imperil the long-term survival of numerous endangered species, highlighting the need to consider the impact of cancer in conservation biology. Finally, the somewhat incongruent data originating from human studies suggest that the association between genetic diversity and cancer development is multifactorial and may be tumour specific. Further studies are therefore crucial in order to elucidate the underpinnings of the interactions between genetic diversity, inbreeding and cancer. PMID:29563261
Tsagalioti, Eftyhia; Trifonos, Christina; Morari, Aggeliki; Vadikolias, Konstantinos; Giaginis, Constantinos
2018-04-01
Neurodegenerative diseases constitute a major problem of public health that is associated with an increased risk of mortality and poor quality of life. Malnutrition is considered as a major problem that worsens the prognosis of patients suffering from neurodegenerative diseases. In this aspect, the present review is aimed to critically collect and summarize all the available existing clinical data regarding the clinical impact of nutritional assessment in neurodegenerative diseases, highlighting on the crucial role of nutritional status in disease progression and management. According to the currently available clinical data, the nutritional status of patients seems to play a very important role in the development and progression of neurodegenerative diseases. A correct nutritional evaluation of neurodegenerative disease patients and a right nutrition intervention is essential in monitoring their disease.
NASA Astrophysics Data System (ADS)
Schaub, Y.; Huggel, C.; Serraino, M.; Haeberli, W.
2012-04-01
The changes in high-mountain environments are increasingly fast and complex. GIS-based models of the Swiss Alps show that numerous topographic overdeepenings are likely to appear on progressively exposed glacier beds, which are considered as potential sites of future lake formation. In many cases these newly forming lakes will be situated in an over-steepened and destabilized high-mountain environment and are, therefore, prone to impact waves from landslides. The risk of glacier lake outburst floods, endangering infrastructure, residential areas and persons further downvalley, is increasing with further lake formation and glacier recession. This risk may persist for many decades if not centuries. Future-oriented hazard assessments have to be integrative and must deal with all possible process chains. Reference studies and methodologies are still scarce, however. We present an approach to compare risks resulting from high-mountain lakes in the Swiss Alps amongst each other. Already existing lakes are thereby as much included in the analysis as future ones. The presented risk assessment approach integrates the envisaged high-mountain hazard process chain with present and future socio-economic conditions. Applying the concept of integral risk management, the hazard and damage potentials have to be analyzed. The areas that feature the topographic potential for rock/iceavalanches to reach a lake were analyzed regarding their susceptibility to slope failure including the factors slope inclination, permafrost occurrence, glacier recession and bedrock lithology. Together with the analysis of the lakes (volume and runout path of potential outburst floods), the hazard analysis of the process chain was completed. As an example, high long-term hazard potentials in the Swiss Alps have, for instance, to be expected in the area of the Great Aletsch glacier. A methodology for the assessment of the damage potential was elaborated and will be presented. In order to estimate the location of the largest damage potentials, driving forces of different spatial development scenarios for the Swiss Alps will be implemented in a land allocation model for the Swiss Alps. By bringing together hazard, exposure and vulnerability analyses, a risk assessment for the entire Swiss Alps regarding lake-outburst floods triggered by impacts of rock/ice avalanches can be conducted for today, the middle of the century and even beyond.
Diniz, Luan Pereira; Tortelli, Vanessa; Matias, Isadora; Morgado, Juliana; Bérgamo Araujo, Ana Paula; Melo, Helen M; Seixas da Silva, Gisele S; Alves-Leon, Soniza V; de Souza, Jorge M; Ferreira, Sergio T; De Felice, Fernanda G; Gomes, Flávia Carvalho Alcantara
2017-07-12
Alzheimer's disease (AD) is characterized by progressive cognitive decline, increasingly attributed to neuronal dysfunction induced by amyloid-β oligomers (AβOs). Although the impact of AβOs on neurons has been extensively studied, only recently have the possible effects of AβOs on astrocytes begun to be investigated. Given the key roles of astrocytes in synapse formation, plasticity, and function, we sought to investigate the impact of AβOs on astrocytes, and to determine whether this impact is related to the deleterious actions of AβOs on synapses. We found that AβOs interact with astrocytes, cause astrocyte activation and trigger abnormal generation of reactive oxygen species, which is accompanied by impairment of astrocyte neuroprotective potential in vitro We further show that both murine and human astrocyte conditioned media (CM) increase synapse density, reduce AβOs binding, and prevent AβO-induced synapse loss in cultured hippocampal neurons. Both a neutralizing anti-transforming growth factor-β1 (TGF-β1) antibody and siRNA-mediated knockdown of TGF-β1, previously identified as an important synaptogenic factor secreted by astrocytes, abrogated the protective action of astrocyte CM against AβO-induced synapse loss. Notably, TGF-β1 prevented hippocampal dendritic spine loss and memory impairment in mice that received an intracerebroventricular infusion of AβOs. Results suggest that astrocyte-derived TGF-β1 is part of an endogenous mechanism that protects synapses against AβOs. By demonstrating that AβOs decrease astrocyte ability to protect synapses, our results unravel a new mechanism underlying the synaptotoxic action of AβOs in AD. SIGNIFICANCE STATEMENT Alzheimer's disease is characterized by progressive cognitive decline, mainly attributed to synaptotoxicity of the amyloid-β oligomers (AβOs). Here, we investigated the impact of AβOs in astrocytes, a less known subject. We show that astrocytes prevent synapse loss induced by AβOs, via production of transforming growth factor-β1 (TGF-β1). We found that AβOs trigger morphological and functional alterations in astrocytes, and impair their neuroprotective potential. Notably, TGF-β1 reduced hippocampal dendritic spine loss and memory impairment in mice that received intracerebroventricular infusions of AβOs. Our results describe a new mechanism underlying the toxicity of AβOs and indicate novel therapeutic targets for Alzheimer's disease, mainly focused on TGF-β1 and astrocytes. Copyright © 2017 the authors 0270-6474/17/376798-13$15.00/0.
Ost, John A; Newton, Paul W; Neilson, Duncan R; Cioffi, Joseph A; Wackym, P Ashley; Perkins, R Serene
2017-02-01
The Legacy Biorepository is a College of American Pathologists-accredited biorepository operating within a seven-hospital healthcare system, with a decade's experience in specimen accrual, storage, and distribution. While standardization of our practices through accreditation remains a priority, we along with others face challenges with regard to sustainability. Purposeful changes in our consent process, which we term "progressive consent," are expected to improve sustainability and operational flexibility while increasing our scientific impact. Until 2015, informed consent was performed primarily by biorepository staff at an estimated time of 1 hour per case. After a process improvement exercise, we successfully changed our informed consent process to a modified front-door model, with use of material and data for research as an opt-in or opt-out selection on the institutional patient informed consent form provided to surgery patients in the healthcare system. Successful implementation of this change required the engagement and participation of multiple stakeholders in healthcare system leadership, hospital administration, research, legal, regulatory, and patient care levels. A modified front-door consent enabled us to collect an additional 38 specimens in the first two quarters of 2016, with a time commitment of 15.75 hours, a time savings per specimen increasing in Q2 over Q1. We estimate a potential savings of 43 hours in 2016. This progressive model allowed us to maintain our frozen sample collection while increasing the availability of paraffin-embedded tissue and bodily fluids. Augmenting our tissue collection added little expense per case (approximately half that of each frozen tissue aliquot) and increased the range of biospecimens collected. Biorepository financial sustainability is a critical issue. Thorough evaluation and modification of existing procedures and collection models, as well as cost recovery initiatives, can translate into savings. Sustainability, process improvement, and scientific impact broadly overlap and continue to require operational critique and implementation of strategic changes.
Likhvantseva, V G; Sokolov, V A; Levanova, O N; Kovelenova, I V
2018-01-01
Prediction of the clinical course of primary open-angle glaucoma (POAG) is one of the main directions in solving the problem of vision loss prevention and stabilization of the pathological process. Simple statistical methods of correlation analysis show the extent of each risk factor's impact, but do not indicate the total impact of these factors in personalized combinations. The relationships between the risk factors is subject to correlation and regression analysis. The regression equation represents the dependence of the mathematical expectation of the resulting sign on the combination of factor signs. To develop a technique for predicting the probability of development and progression of primary open-angle glaucoma based on a personalized combination of risk factors by linear multivariate regression analysis. The study included 66 patients (23 female and 43 male; 132 eyes) with newly diagnosed primary open-angle glaucoma. The control group consisted of 14 patients (8 male and 6 female). Standard ophthalmic examination was supplemented with biochemical study of lacrimal fluid. Concentration of matrix metalloproteinase MMP-2 and MMP-9 in tear fluid in both eyes was determined using 'sandwich' enzyme-linked immunosorbent assay (ELISA) method. The study resulted in the development of regression equations and step-by-step multivariate logistic models that can help calculate the risk of development and progression of POAG. Those models are based on expert evaluation of clinical and instrumental indicators of hydrodynamic disturbances (coefficient of outflow ease - C, volume of intraocular fluid secretion - F, fluctuation of intraocular pressure), as well as personalized morphometric parameters of the retina (central retinal thickness in the macular area) and concentration of MMP-2 and MMP-9 in the tear film. The newly developed regression equations are highly informative and can be a reliable tool for studying of the influence vector and assessment of pathogenic potential of the independent risk factors in specific personalized combinations.
Kluding, Patricia M; Singleton, J Robinson; Pasnoor, Mamatha; Dimachkie, Mazen M; Barohn, Richard J; Smith, A Gordon; Marcus, Robin L
2017-01-01
Half of all patients with diabetes develop diabetic peripheral neuropathy (DPN), a complication leading to reduced mobility and quality of life. Although there are no proven pharmacologic approaches to reduce DPN risk or slow its progression, evidence suggests that physical activity may improve symptoms and enhance peripheral nerve regeneration. The aim of the study will be to determine the impact of an intense lifestyle intervention on neuropathy progression and quality of life in individuals with DPN. The study will be a randomized controlled trial. The study will be conducted at 2 academic medical centers. The participants will be 140 individuals with type 2 diabetes and mild to moderate DPN. The intervention group will receive 18 months of supervised exercise training, actigraphy-based counseling to reduce sedentary behavior, and individualized dietary counseling. Control group participants will receive diet and activity counseling at baseline and at 9 months. The primary outcomes are neuropathy progression as measured by intraepidermal nerve fiber density in a distal thigh skin biopsy and the Norfolk Quality of Life-Diabetic Neuropathy score. Secondary outcomes include pain, gait, balance, and mobility measures. Due to the combined intervention approach, this protocol will not be able to determine which intervention components influence outcomes. There also may be difficulty with participant attrition during the 18-month study intervention. The Activity for Diabetic Polyneuropathy (ADAPT) protocol resulted from a collaboration between physical therapists and neurologist researchers that includes as primary outcomes both a quality-of-life measure (NQOL-DN) and a physiologic biomarker (IENFD). It has the potential to demonstrate that an intensive lifestyle intervention may be a sustainable, clinically effective approach for people with DPN that improves patient outcomes and can have an immediate impact on patient care and future clinical trials. © 2017 American Physical Therapy Association
Mihajlović, Jovan; Pechlivanoglou, Petros; Sabo, Ana; Tomić, Zdenko; Postma, Maarten J
2013-12-01
New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had progressed on sunitinib and/or sorafenib. The only targeted therapy for mRCC currently reimbursed in Serbia is sunitinib. The aim of this study was to estimate the cost-effectiveness and the budget impact of the introduction of everolimus in Serbia in comparison to best supportive care, for mRCC patients refractory to sunitinib. A Markov model was designed corresponding with Serbian treatment protocols. A health care payer perspective was taken, including direct costs only. Treated and untreated cohorts were followed up over 18 cycles, each cycle lasting 8 weeks, which covered the lifetime horizon of mRCC patients refractory to the first-line treatment. Annual discounted rates of 1.5% for effectiveness and 3% for costs were applied. Transitions between health states were modeled by time-dependent probabilities extracted from published Kaplan-Meier curves of PFS and overall survival (OS). Utility values were obtained from the appraisals of other mRCC treatments. One-way and probabilistic sensitivity analyses were done to test the robustness and uncertainty of the base-case estimate. Lastly, the potential impacts of everolimus on the overall health care expenditures on annual and 4-year bases were estimated in the budget-impact analysis. The incremental cost-effectiveness ratio for everolimus was estimated at €86,978 per quality-adjusted life-year. Sensitivity analysis identified the hazard multiplier, a statistical approximator of OS gain, as the main driver of everolimus cost-effectiveness. Furthermore, probabilistic sensitivity analyses revealed a wide 95% CI around the base-case incremental cost-effectiveness ratio estimate (€32,594-€425,258 per quality-adjusted life-year). Finally, an average annual budgetary impact of everolimus in first 4 years after its potential reimbursement would be around €270,000, contributing to <1% of the total budget in Serbian oncology. Everolimus as a second-line treatment of mRCC is not likely to be a cost-effective option under the present conditions in Serbia, with a relatively limited impact on its budget in oncology. A major constraint on the estimation of the cost-effectiveness of everolimus relates to the uncertainty around the everolimus effect on extending OS. However, prior to a final decision on the acceptance/rejection of everolimus, reassessment of the whole therapeutic group might be needed to construct an economically rational treatment strategy within the mRCC field. © 2013 Elsevier HS Journals, Inc. All rights reserved.
Before the Deep Impact Collision
2011-02-18
This series of images shows the area where NASA Deep Impact probe collided with the surface of comet Tempel 1 in 2005. The view zooms in as the images progress from top left to right, and then bottom left to right.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Baalman, R.W.; Dotson, C.W.
1980-02-01
Part 5 of the 1979 Annual Report to the Department of Energy Assistant Secretary for the Environment presents Pacific Northwest Laboratory's progress on work performed for the Office of Technology Impacts, the Office of Environmental Compliance and Overview, and the Office of Health and Environmental Research. The report is in four sections, corresponding to the program elements: technology impacts, environmental control engineering, operational and environmental compliance, and human health studies. In each section, articles describe progress made during FY 1979 on individual projects.
Pearl, John E; Das, Mrinal; Cooper, Andrea M
2018-03-01
Accurate prediction of which patient will progress from a sub-clinical Mycobacterium tuberculosis infection to active tuberculosis represents an elusive, yet critical, clinical research objective. From the individual perspective, progression can be considered to be the product of a series of unfortunate events or even a run of bad luck. Here, we identify the subtle physiological relationships that can influence the odds of progression to active TB and how this progression may reflect directed dysbiosis in a number of interrelated systems. Most infected individuals who progress to disease have apparently good immune responses, but these responses are, at times, compromised by either local or systemic environmental factors. Obvious disease promoting processes, such as tissue-damaging granulomata, usually manifest in the lung, but illness is systemic. This apparent dichotomy between local and systemic reflects a clear need to define the factors that promote progression to active disease within the context of the body as a physiological whole. We discuss aspects of the host environment that can impact expression of immunity, including the microbiome, glucocorticoid-mediated regulation, catecholamines and interaction between the gut, liver and lung. We suggest the importance of integrating precision medicine into our analyses of experimental outcomes such that apparently conflicting results are not contentious, but rather reflect the impact of these subtle relationships with our environment and microbiota.
Asif, Irfan M; Price, David; Fisher, Leslee A; Zakrajsek, Rebecca A; Larsen, Leslie K; Raabe, Johannes J; Bejar, Matthew P; Rao, Ashwin L; Harmon, Kimberly G; Drezner, Jonathan A
2015-01-01
Sudden cardiac death (SCD) in sports is a tragic event. Pre-participation cardiovascular screening is required before participation in high school and college athletic programs and is universally endorsed by major medical societies. The medical impact of a diagnosis may be life-saving; however, the detection of disease should not be the sole endpoint of care. Physicians have an obligation to attend to both the medical and psychological well-being of their patients. To determine the psychological impact of being diagnosed with cardiac disease in young competitive athletes. Athletes diagnosed with cardiac conditions were recruited to participate in a semi-structured interview, which was analyzed by sport psychology experts using qualitative research. Individuals shared reactions and experiences regarding diagnosis, lifestyle implications, coping strategies, major concerns, and overall impact on psychosocial functioning. Young competitive athletes from across the United States. 25 athletes (52% male, 80% Caucasian, median age 17.7) participated. Diagnoses included: 5 hypertrophic cardiomyopathy, 8 Wolff Parkinson White, 4 long QT syndrome, 3 atrial septal defect, 2 supraventricular tachycardia, and 3 other. Interviews were analyzed using consensual qualitative research (CQR) to identify domains, categories, and core ideas. Athletes progressed through 4 stages of psychological impact including: 1) immediate reactions and challenge to athlete identity, 2) grief/coping, 3) adaptation, and 4) acceptance. Risk factors for increased psychological morbidity included: higher level of competition, permanent disqualification from sports, persistent reminders (e.g. daily medication, monitoring heart rate during activity), and unanticipated outcomes (e.g. failed procedures). Those undergoing simple corrective procedures came to terms with their diagnosis quickly with little impact on daily life. Few athletes described emotional support mechanisms provided by medical programs. Diagnosis often led to new goals such as mentoring or coaching. All athletes diagnosed through advanced cardiovascular screening stated they would repeat the process. Athletes diagnosed with cardiac disease represent an emotionally vulnerable population and experience 4 stages of psychological adjustment not previously described. This proposed model of psychological impact should be used to develop improved support mechanisms, awareness, and education to assist athletes diagnosed with serious or potentially lethal cardiac disease. Copyright © 2015 Elsevier Inc. All rights reserved.
The influence of child sexual abuse on the self from adult narrative perspectives.
Krayer, Anne; Seddon, Diane; Robinson, Catherine A; Gwilym, Hefin
2015-01-01
The impact of child sexual abuse on the adult self is not yet clearly understood. We explored adult perspectives through the use of narrative interviews (N = 30). Three key themes or views of self were identified in all narratives to varying degrees: the worthless self, the self as unknown, and the potential/developing self. Ambivalence and tension were present in all narratives. Individuals were challenged to integrate the sexual abuse experience in a constructive way and develop a more coherent perception of the self. The narrative method highlighted the dynamic nature of peoples' experiences at the same time recognizing that the narratives themselves are in progress. Reactions to disclosure, social support, and interpersonal connections are crucial at every turn.
The Genetic and Environmental Factors Underlying Hypospadias
Pask, Andrew; Heloury, Yves; Sinclair, Andrew H.
2016-01-01
Hypospadias results from a failure of urethral closure in the male phallus and affects 1 in 200–300 boys. It is thought to be due to a combination of genetic and environmental factors. The development of the penis progresses in 2 stages: an initial hormone-independent phase and a secondary hormone-dependent phase. Here, we review the molecular pathways that contribute to each of these stages, drawing on studies from both human and mouse models. Hypospadias can occur when normal development of the phallus is disrupted, and we provide evidence that mutations in genes underlying this developmental process are causative. Finally, we discuss the environmental factors that may contribute to hypospadias and their potential immediate and transgen erational epigenetic impacts. PMID:26613581
Regulation of the Rhythmic Emission of Plant Volatiles by the Circadian Clock.
Zeng, Lanting; Wang, Xiaoqin; Kang, Ming; Dong, Fang; Yang, Ziyin
2017-11-13
Like other organisms, plants have endogenous biological clocks that enable them to organize their metabolic, physiological, and developmental processes. The representative biological clock is the circadian system that regulates daily (24-h) rhythms. Circadian-regulated changes in growth have been observed in numerous plants. Evidence from many recent studies indicates that the circadian clock regulates a multitude of factors that affect plant metabolites, especially emitted volatiles that have important ecological functions. Here, we review recent progress in research on plant volatiles showing rhythmic emission under the regulation of the circadian clock, and on how the circadian clock controls the rhythmic emission of plant volatiles. We also discuss the potential impact of other factors on the circadian rhythmic emission of plant volatiles.
NASA Technical Reports Server (NTRS)
1980-01-01
An updated program plan is presented showing the task descriptions depicting the work, progress, achievements, and the cause of any deviations from the original plan (SC-1), and how this impacted on the original schedule of the program. In addition there is an update documenting all design alterations made during the pre-production phase and a complete up to date set of engineering and manufacturing documentation (CM-1). The purpose of the work in the original plan was to explore, design, develop, test, and deliver 1000 watts of prototype flat plate, photovoltaic modules appropriate for use in applications in the 20 to 500 kilowatt range and which show potential for meeting the 1986 cost goals.
Recent Progress on Sonic Boom Research at NASA
NASA Technical Reports Server (NTRS)
Loubeau, Alexandra
2012-01-01
Sonic boom research conducted at NASA through the Supersonics Project of the Fundamental Aeronautics Program is oriented toward understanding the potential impact of sonic boom noise on communities from new low-boom supersonic aircraft designs. Encompassing research in atmospheric propagation, structural response, and human response, NASA research contributes to knowledge in key areas needed to support development of a new noise-based standard for supersonic aircraft certification. Partnerships with several industry, government, and academic institutions have enabled the recent execution of several acoustic field studies on sonic booms. An overview of recent activities funded by NASA includes: focus boom model development and experimental validation, field experiments of structural transmission of sonic booms into large buildings, and low boom community response testing.
Aging of the endocrine system and its potential impact on sarcopenia.
Vitale, Giovanni; Cesari, Matteo; Mari, Daniela
2016-11-01
Sarcopenia, occurring as a primary consequence of aging, is a progressive generalized decline of skeletal muscle mass, strength and function. The pathophysiology of sarcopenia is complex and multifactorial. One major cause of muscle mass and strength loss with aging appears to be the alteration in hormonal networks involved in the inflammatory processes, muscle regeneration and protein synthesis. This review describes the recent findings concerning the role of the aging on the endocrine system in the development of sarcopenia. We also report the benefits and safety of hormone replacement therapy in elderly subjects and discuss future perspectives in the therapy and prevention of skeletal muscle aging. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing
Yang, Haitao; Jaeger, MariaLynn; Walker, Averi; Wei, Daniel; Leiker, Katie; Weitao, Tao
2018-01-01
Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of breast cancer. This review intends to delineate the impact of the CRSPR/Cas-mediated genome editing in identification and validation of these anticancer biomarkers. It reviews the progress in three aspects of CRISPR/Cas9-mediated editing of the breast cancer genomes: Somatic genome editing, transcription and protein degradation addictions. PMID:29344267
Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing.
Yang, Haitao; Jaeger, MariaLynn; Walker, Averi; Wei, Daniel; Leiker, Katie; Weitao, Tao
2018-01-01
Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of breast cancer. This review intends to delineate the impact of the CRSPR/Cas-mediated genome editing in identification and validation of these anticancer biomarkers. It reviews the progress in three aspects of CRISPR/Cas9-mediated editing of the breast cancer genomes: Somatic genome editing, transcription and protein degradation addictions.