Design colloidal particle morphology and self-assembly for coating applications

DOE PAGES

Jiang, Shan; Van Dyk, Antony; Maurice, Alvin; ...

2017-05-04

The progressive replacement of organic solvent-based coatings by waterborne latex polymer coatings has substantially renovated the coating industry, and generated huge environmental and health benefits. Today, on top of the continuing demand for higher performance and lower costs, the coating industry faces tighter regulation and higher sustainability standards. In addition, the new waterborne coatings have created unique opportunities and challenges in terms of fundamental understanding and research development. To address these challenges, polymer latex binders with diverse particle morphologies have been developed to improve coating performance. Furthermore, colloidal self-assembly has been utilized to help manufacturers make better paint with lessmore » cost. In this report, we review the recent progress in both fundamental study and industrial application in the context of developing new generation architectural coating materials. We introduce the basic concepts in coating materials and showcase several key technologies that have been implemented to improve coating performance. As a result, these technologies also represent the most important considerations in architectural coating design.« less

Understanding and representing natural language meaning

NASA Astrophysics Data System (ADS)

Waltz, D. L.; Maran, L. R.; Dorfman, M. H.; Dinitz, R.; Farwell, D.

1982-12-01

During this contract period the authors have: (1) continued investigation of events and actions by means of representation schemes called 'event shape diagrams'; (2) written a parsing program which selects appropriate word and sentence meanings by a parallel process know as activation and inhibition; (3) begun investigation of the point of a story or event by modeling the motivations and emotional behaviors of story characters; (4) started work on combining and translating two machine-readable dictionaries into a lexicon and knowledge base which will form an integral part of our natural language understanding programs; (5) made substantial progress toward a general model for the representation of cognitive relations by comparing English scene and event descriptions with similar descriptions in other languages; (6) constructed a general model for the representation of tense and aspect of verbs; (7) made progress toward the design of an integrated robotics system which accepts English requests, and uses visual and tactile inputs in making decisions and learning new tasks.

Refractory Pain Management in Amyloid-Associated Peripheral Neuropathy.

PubMed

Warner, Nafisseh S; Watson, James C; Bendel, Markus A; Moeschler, Susan M

2018-05-01

Systemic amyloidosis is a disease that often involves multiple organ systems, including the peripheral nervous system. Patients may present with severe, refractory neuropathic pain; however, the optimal treatment approach for pain for these patients remains unclear. A man with severe, refractory neuropathic pain in his bilateral upper and lower extremities and the trunk secondary to amyloid neuropathy is presented. Multiple medication trials, including neuropathic and opioid agents, produced considerable adverse effects and minimal relief. Scrambler therapy, a novel electrical stimulation modality, was used and was associated with substantial short-term but nonsustained benefit. Spinal cord stimulation was considered, but given his diffuse symptoms, it was deemed a less-than-optimal approach. Ultimately, an intrathecal drug delivery system was placed with infusion of hydromorphone, resulting in substantial pain reduction in all involved areas and with an improved adverse effect profile. This intervention resulted in immense improvement in the patient's quality of life, despite progression of his systemic amyloidosis. Severe pain in the setting of amyloid neuropathy is often difficult to treat. To our knowledge, this represents the first report of Scrambler therapy or an implanted intrathecal drug delivery system used for a patient with refractory amyloidosis-related neuropathic pain, resulting in substantial analgesic benefit and improved quality of life.

Distinguishing time-delayed causal interactions using convergent cross mapping

PubMed Central

Ye, Hao; Deyle, Ethan R.; Gilarranz, Luis J.; Sugihara, George

2015-01-01

An important problem across many scientific fields is the identification of causal effects from observational data alone. Recent methods (convergent cross mapping, CCM) have made substantial progress on this problem by applying the idea of nonlinear attractor reconstruction to time series data. Here, we expand upon the technique of CCM by explicitly considering time lags. Applying this extended method to representative examples (model simulations, a laboratory predator-prey experiment, temperature and greenhouse gas reconstructions from the Vostok ice core, and long-term ecological time series collected in the Southern California Bight), we demonstrate the ability to identify different time-delayed interactions, distinguish between synchrony induced by strong unidirectional-forcing and true bidirectional causality, and resolve transitive causal chains. PMID:26435402

Comparison of Solar Electric and Chemical Propulsion Missions

NASA Technical Reports Server (NTRS)

Freeh, Joshua E.; Burke, Laura M.; Sjauw, Waldy K.; McGuire, Melissa L.; Smith, Bryan K.

2015-01-01

Solar Electric Propulsion (SEP) offers fuel efficiency and mission robustness for spacecraft. The combination of solar power and electric propulsion engines is currently used for missions ranging from geostationary stationkeeping to deep space science because of these benefits. Both solar power and electric propulsion technologies have progressed to the point where higher electric power systems can be considered, making substantial cargo missions and potentially human missions viable. This paper evaluates and compares representative lunar, Mars, and Sun-Earth Langrangian point missions using SEP and chemical propulsion subsystems. The potential benefits and limitations are discussed along with technology gaps that need to be resolved for such missions to become possible. The connection to NASA's human architecture and technology development efforts will be discussed.

The place of SGML and HTML in building electronic patient records.

PubMed

Pitty, D; Gordon, C; Reeves, P; Capey, A; Vieyra, P; Rickards, T

1997-01-01

The authors are concerned that, although popular, SGML (Standard Generalized Markup Language) is only one approach to capturing, storing, viewing and exchanging healthcare information and does not provide a suitable paradigm for solving most of the problems associated with paper based patient record systems. Although a discussion of the relative merits of SGML, HTML (HyperText Markup Language) may be interesting, we feel such a discussion is avoiding the real issues associated with the most appropriate way to model, represent, and store electronic patient information in order to solve healthcare problems, and therefore the medical informatics community should firstly concern itself with these issues. The paper substantiates this viewpoint and concludes with some suggestions of how progress can be made.

Large Composite Structures Processing Technologies for Reusable Launch Vehicles

NASA Technical Reports Server (NTRS)

Clinton, R. G., Jr.; Vickers, J. H.; McMahon, W. M.; Hulcher, A. B.; Johnston, N. J.; Cano, R. J.; Belvin, H. L.; McIver, K.; Franklin, W.; Sidwell, D.

2001-01-01

Significant efforts have been devoted to establishing the technology foundation to enable the progression to large scale composite structures fabrication. We are not capable today of fabricating many of the composite structures envisioned for the second generation reusable launch vehicle (RLV). Conventional 'aerospace' manufacturing and processing methodologies (fiber placement, autoclave, tooling) will require substantial investment and lead time to scale-up. Out-of-autoclave process techniques will require aggressive efforts to mature the selected technologies and to scale up. Focused composite processing technology development and demonstration programs utilizing the building block approach are required to enable envisioned second generation RLV large composite structures applications. Government/industry partnerships have demonstrated success in this area and represent best combination of skills and capabilities to achieve this goal.

Psychobiologic correlates of treatment response in schizophrenia.

PubMed

Lieberman, J A; Alvir, J M; Koreen, A; Geisler, S; Chakos, M; Sheitman, B; Woerner, M

1996-03-01

In studies conducted on largely treatment naive patients in their first episode of psychosis, we have found that treatment outcome is quite good and that most patients recover or at least achieve a substantial degree of symptom remission. However, over the course of their illness and in the context of subsequent psychotic episodes, they may experience some decrease in their treatment response from illness progression. In addition, the heterogeneity of treatment outcome is associated with specific clinical (gender, primary negative symptoms of the deficit state, duration of psychosis) and biological variables (pHVA, ventricular volume). It is unclear whether these variables represent aspects of discrete subtypes of schizophrenia or dimensional measures of pathology within the broad context of a unitary disease entity.

Under the sea: microbial life in volcanic oceanic crust.

PubMed

Edwards, Katrina J; Wheat, C Geoffrey; Sylvan, Jason B

2011-09-06

Exploration of the microbiology in igneous, 'hard rock' oceanic crust represents a major scientific frontier. The igneous crust harbours the largest aquifer system on Earth, most of which is hydrologically active, resulting in a substantial exchange of fluids, chemicals and microorganisms between oceanic basins and crustal reservoirs. Study of the deep-subsurface biosphere in the igneous crust is technically challenging. However, technologies have improved over the past decade, providing exciting new opportunities for the study of deep-seated marine life, including in situ and cross-disciplinary experimentation in microbiology, geochemistry and hydrogeology. In this Progress article, we describe the recent advances, available technology and remaining challenges in the study of the marine intraterrestrial microbial life that is harboured in igneous oceanic crust.

Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFα and the Hormonal and Growth-Supporting Arms of the Tumor Microenvironment

PubMed Central

Weitzenfeld, Polina; Meron, Nurit; Leibovich-Rivkin, Tal; Meshel, Tsipi

2013-01-01

Breast cancer progression is strongly linked to inflammatory processes, aggravating disease course. The impacts of the inflammatory cytokine TNFα on breast malignancy are not fully substantiated, and they may be affected by cooperativity between TNFα and other protumoral mediators. Here, we show that together with representatives of other important arms of the tumor microenvironment, estrogen (hormonal) and EGF (growth-supporting), TNFα potently induced metastasis-related properties and functions in luminal breast tumor cells, representing the most common type of breast cancer. Jointly, TNFα + Estrogen + EGF had a stronger effect on breast cancer cells than each element alone, leading to the following: (1) extensive cell spreading and formation of FAK/paxillin-enriched cellular protrusions; (2) elevated proportion of tumor cells coexpressing high levels of CD44 and β1 and VLA6; (3) EMT and cell migration; (4) resistance to chemotherapy; (5) release of protumoral factors (CXCL8, CCL2, MMPs). Importantly, the tumor cells used in this study are known to be nonmetastatic under all conditions; nevertheless, they have acquired high metastasizing abilities in vivo in mice, following a brief stimulation by TNFα + Estrogen + EGF. These dramatic findings indicate that TNFα can turn into a strong prometastatic factor, suggesting a paradigm shift in which clinically approved inhibitors of TNFα would be applied in breast cancer therapy. PMID:24369447

Ventriculoperitoneal shunt infection in Haji Adam Malik Hospital, Medan

NASA Astrophysics Data System (ADS)

Dharmajaya, R.

2018-03-01

Installation of ventriculoperitoneal shunts (VP) represented a substantial progress in the neurosurgical management of hydrocephalus in children. However, infection is the most commonpostoperative complication of aventriculoperitoneal shunt. It is important because it is related to substantial morbidity and mortality, and exerts a negative impact on the quality of life of patients. We retrospectively analyzed all 20 cases of shunt infection from 2013 to 2016. The types of infections found were exposed shunts15 cases (75%), and 5 cases of ventriculitis (25%). Length of infection time which calculated from the beginning of surgery was 350.20 days or 11 months. The most common pathogen types are S. epidermidis followed by P. aeruginosa, E. coli, and A. baumanii. There were many risk factors for shunt infection, but the interesting fact was the level of pre-operative albumin. There was a significant difference between low albumin levels (<3.0) and normal albumin (≥3.0) levels against the risk of exposure shunt, p = 0.015. It means there is asignificant difference between low pre-operative albumin and normal level for the risk of theexposed shunt.

PACE Continuous Innovation Indicators-a novel tool to measure progress in cancer treatments.

PubMed

Paddock, Silvia; Brum, Lauren; Sorrow, Kathleen; Thomas, Samuel; Spence, Susan; Maulbecker-Armstrong, Catharina; Goodman, Clifford; Peake, Michael; McVie, Gordon; Geipel, Gary; Li, Rose

2015-01-01

Concerns about rising health care costs and the often incremental nature of improvements in health outcomes continue to fuel intense debates about 'progress' and 'value' in cancer research. In times of tightening fiscal constraints, it is increasingly important for patients and their representatives to define what constitutes 'value' to them. It is clear that diverse stakeholders have different priorities. Harmonisation of values may be neither possible nor desirable. Stakeholders lack tools to visualise or otherwise express these differences and to track progress in cancer treatments based on variable sets of values. The Patient Access to Cancer care Excellence (PACE) Continuous Innovation Indicators are novel, scientifically rigorous progress trackers that employ a three-step process to quantify progress in cancer treatments: 1) mine the literature to determine the strength of the evidence supporting each treatment; 2) allow users to weight the analysis according to their priorities and values; and 3) calculate Evidence Scores (E-Scores), a novel measure to track progress, based on the strength of the evidence weighted by the assigned value. We herein introduce a novel, flexible value model, show how the values from the model can be used to weight the evidence from the scientific literature to obtain E-Scores, and illustrate how assigning different values to new treatments influences the E-Scores. The Indicators allow users to learn how differing values lead to differing assessments of progress in cancer research and to check whether current incentives for innovation are aligned with their value model. By comparing E-Scores generated by this tool, users are able to visualise the relative pace of innovation across areas of cancer research and how stepwise innovation can contribute to substantial progress against cancer over time. Learning from experience and mapping current unmet needs will help to support a broad audience of stakeholders in their efforts to accelerate and maximise progress against cancer.

Early life programming and the risk of non-alcoholic fatty liver disease.

PubMed

Lynch, C; Chan, C S; Drake, A J

2017-06-01

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease and can be considered the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of disease, from the relatively benign simple steatosis to the more serious non-alcoholic steatohepatitis, which can progress to liver cirrhosis, hepatocellular carcinoma and end-stage liver failure, necessitating liver transplantation. Although the increasing prevalence of NAFLD in developed countries has substantial implications for public health, many of the precise mechanisms accounting for the development and progression of NAFLD are unclear. The environment in early life is an important determinant of cardiovascular disease risk in later life and studies suggest this also extends to NAFLD. Here we review data from animal models and human studies which suggest that fetal and early life exposure to maternal under- and overnutrition, excess glucocorticoids and environmental pollutants may confer an increased susceptibility to NAFLD development and progression in offspring and that such effects may be sex-specific. We also consider studies aimed at identifying potential dietary and pharmacological interventions aimed at reducing this risk. We suggest that further human epidemiological studies are needed to ensure that data from animal models are relevant to human health.

31 CFR 341.8 - Payment or redemption during lifetime of owner.

Code of Federal Regulations, 2012 CFR

2012-07-01

... progressive. (5) Damage to the brain or brain abnormality which has resulted in severe loss of judgment... substantial, gainful activity: (1) Loss of use of two limbs. (2) Certain progressive diseases which have...

31 CFR 341.8 - Payment or redemption during lifetime of owner.

Code of Federal Regulations, 2011 CFR

2011-07-01

... progressive. (5) Damage to the brain or brain abnormality which has resulted in severe loss of judgment... substantial, gainful activity: (1) Loss of use of two limbs. (2) Certain progressive diseases which have...

31 CFR 341.8 - Payment or redemption during lifetime of owner.

Code of Federal Regulations, 2013 CFR

2013-07-01

... progressive. (5) Damage to the brain or brain abnormality which has resulted in severe loss of judgment... substantial, gainful activity: (1) Loss of use of two limbs. (2) Certain progressive diseases which have...

Intraobserver and Interobserver Agreement of Structural and Functional Software Programs for Measuring Glaucoma Progression.

PubMed

Moreno-Montañés, Javier; Antón, Vanesa; Antón, Alfonso; Larrosa, José M; Martinez-de-la-Casa, José María; Rebolleda, Gema; Ussa, Fernando; García-Granero, Marta

2017-04-01

It is important to evaluate intraobserver and interobserver agreement using visual field (VF) testing and optical coherence tomography (OCT) software in order to understand whether the use of this software is sufficient to detect glaucoma progression and to make decisions regarding its treatment. To evaluate agreement in VF and OCT software among 5 glaucoma specialists. The printout pages from VF progression software and OCT progression software from 100 patients were randomized, and the 5 glaucoma specialists subjectively and independently evaluated them for glaucoma. Each image was classified as having no progression, questionable progression, or progression. The principal investigator classified the patients previously as without variability (normal) or with high variability among tests (difficult). Using both software, the specialists also evaluated whether the glaucoma damage had progressed and if treatment change was needed. One month later, the same observers reevaluated the patients in a different order to determine intraobserver reproducibility. Intraobserver and interobserver agreement was estimated using κ statistics and Gwet second-order agreement coefficient. The agreement was compared with other factors. Of the 100 observed patients, half were male and all were white; the mean (SD) age was 69.7 (14.1) years. Intraobserver agreement was substantial to almost perfect for VF software (overall κ [95% CI], 0.59 [0.46-0.72] to 0.87 [0.79-0.96]) and similar for OCT software (overall κ [95% CI], 0.59 [0.46-0.71] to 0.85 [0.76-0.94]). Interobserver agreement among the 5 glaucoma specialists with the VF progression software was moderate (κ, 0.48; 95% CI, 0.41-0.55) and similar to OCT progression software (κ, 0.52; 95% CI, 0.44-0.59). Interobserver agreement was substantial in images classified as having no progression but only fair in those classified as having questionable glaucoma progression or glaucoma progression. Interobserver agreement was fair regarding questions about glaucoma progression (κ, 0.39; 95% CI, 0.32-0.48) and consideration about treatment changes (κ, 0.39; 95% CI, 0.32-0.48). The factors associated with agreement were the glaucoma stage and case difficulty. There was substantial intraobserver agreement but moderate interobserver agreement among glaucoma specialists using 2 glaucoma progression software packages. These data suggest that these glaucoma progression software packages are insufficient to obtain high interobserver agreement in both devices except in patients with no progression. The low agreement regarding progression or treatment changes suggests that both software programs used in isolation are insufficient for decision making.

PACE Continuous Innovation Indicators—a novel tool to measure progress in cancer treatments

PubMed Central

Paddock, Silvia; Brum, Lauren; Sorrow, Kathleen; Thomas, Samuel; Spence, Susan; Maulbecker-Armstrong, Catharina; Goodman, Clifford; Peake, Michael; McVie, Gordon; Geipel, Gary; Li, Rose

2015-01-01

Concerns about rising health care costs and the often incremental nature of improvements in health outcomes continue to fuel intense debates about ‘progress’ and ‘value’ in cancer research. In times of tightening fiscal constraints, it is increasingly important for patients and their representatives to define what constitutes ’value’ to them. It is clear that diverse stakeholders have different priorities. Harmonisation of values may be neither possible nor desirable. Stakeholders lack tools to visualise or otherwise express these differences and to track progress in cancer treatments based on variable sets of values. The Patient Access to Cancer care Excellence (PACE) Continuous Innovation Indicators are novel, scientifically rigorous progress trackers that employ a three-step process to quantify progress in cancer treatments: 1) mine the literature to determine the strength of the evidence supporting each treatment; 2) allow users to weight the analysis according to their priorities and values; and 3) calculate Evidence Scores (E-Scores), a novel measure to track progress, based on the strength of the evidence weighted by the assigned value. We herein introduce a novel, flexible value model, show how the values from the model can be used to weight the evidence from the scientific literature to obtain E-Scores, and illustrate how assigning different values to new treatments influences the E-Scores. The Indicators allow users to learn how differing values lead to differing assessments of progress in cancer research and to check whether current incentives for innovation are aligned with their value model. By comparing E-Scores generated by this tool, users are able to visualise the relative pace of innovation across areas of cancer research and how stepwise innovation can contribute to substantial progress against cancer over time. Learning from experience and mapping current unmet needs will help to support a broad audience of stakeholders in their efforts to accelerate and maximise progress against cancer. PMID:25624879

Moonshot Objectives: Catalyze New Scientific Breakthroughs-Proteogenomics.

PubMed

Rodland, Karin D; Piehowski, Paul; Smith, Richard D

Breaking down the silos between disciplines to accelerate the pace of cancer research is a key paradigm for the Cancer Moonshot. Molecular analyses of cancer biology have tended to segregate between a focus on nucleic acids-DNA, RNA, and their modifications-and a focus on proteins and protein function. Proteogenomics represents a fusion of those two approaches, leveraging the strengths of each to provide a more integrated vision of the flow of information from DNA to RNA to protein and eventually function at the molecular level. Proteogenomic studies have been incorporated into multiple activities associated with the Cancer Moonshot, demonstrating substantial added value. Innovative study designs integrating genomic, transcriptomic, and proteomic data, particularly those using clinically relevant samples and involving clinical trials, are poised to provide new insights regarding cancer risk, progression, and response to therapy.

Homelessness among a nationally representative sample of US veterans: prevalence, service utilization, and correlates.

PubMed

Tsai, Jack; Link, Bruce; Rosenheck, Robert A; Pietrzak, Robert H

2016-06-01

To examine the prevalence of lifetime homelessness among veterans and use of Veterans Affairs (VA) homeless services, as well as their association with sociodemographic and clinical characteristics. A nationally representative sample of 1533 US veterans was surveyed July-August 2015. Among all veterans, 8.5 % reported any lifetime homelessness in their adult life, but only 17.2 % of those reported using VA homeless services. Prevalence of homelessness and VA homeless service use did not significantly differ by gender. Being low income, aged 35-44, and having poor mental and physical health were each independently associated with lifetime homelessness. Veterans who were White or lived in rural areas were significantly less likely to have used VA homeless services. Homelessness remains a substantial problem across different generations of veterans. The low reported uptake of VA homeless services suggests there are barriers to care in this population, especially for veterans who live in rural areas. Governmental resources dedicated to veteran homelessness should be supported, and obtaining accurate prevalence estimates are important to tracking progress over time.

Who pays for healthcare in Bangladesh? An analysis of progressivity in health systems financing.

PubMed

Molla, Azaher Ali; Chi, Chunhuei

2017-09-06

The relationship between payments towards healthcare and ability to pay is a measure of financial fairness. Analysis of progressivity is important from an equity perspective as well as for macroeconomic and political analysis of healthcare systems. Bangladesh health systems financing is characterized by high out-of-pocket payments (63.3%), which is increasing. Hence, we aimed to see who pays what part of this high out-of-pocket expenditure. To our knowledge, this was the first progressivity analysis of health systems financing in Bangladesh. We used data from Bangladesh Household Income and Expenditure Survey, 2010. This was a cross sectional and nationally representative sample of 12,240 households consisting of 55,580 individuals. For quantification of progressivity, we adopted the 'ability-to-pay' principle developed by O'Donnell, van Doorslaer, Wagstaff, and Lindelow (2008). We used the Kakwani index to measure the magnitude of progressivity. Health systems financing in Bangladesh is regressive. Inequality increases due to healthcare payments. The differences between the Gini coefficient and the Kakwani index for all sources of finance are negative, which indicates regressivity, and that financing is more concentrated among the poor. Income inequality increases due to high out-of-pocket payments. The increase in income inequality caused by out-of-pocket payments is 89% due to negative vertical effect and 11% due to horizontal inequity. Our findings add substantial evidence of health systems financing impact on inequitable financial burden of healthcare and income. The heavy reliance on out-of-pocket payments may affect household living standards. If the government and people of Bangladesh are concerned about equitable financing burden, our study suggests that Bangladesh needs to reform the health systems financing scheme.

3 CFR - Improving Energy Security, American Competitiveness and Job Creation, and Environmental...

Code of Federal Regulations, 2011 CFR

2011-01-01

... source of fossil fuel consumption and greenhouse gas pollution. I therefore request that the... annual progress in reducing transportation sector emissions and fossil fuel consumption consistent with... substantial annual progress in reducing transportation sector greenhouse gas emissions and fossil fuel...

24 CFR 1006.430 - Corrective and remedial action.

Code of Federal Regulations, 2011 CFR

2011-04-01

... plan; (3) Made substantial progress in carrying out its program and achieving its quantifiable goals as... to submit progress schedules for completing activities or complying with the requirements of the Act... appropriate technical assistance using existing grant funds or other available resources to overcome the...

Omentum and bone marrow: how adipocyte-rich organs create tumour microenvironments conducive for metastatic progression

PubMed Central

Gusky, H. Chkourko; Diedrich, J.; MacDougald, O. A.; Podgorski, I.

2016-01-01

Summary A number of clinical studies have linked adiposity with increased cancer incidence, progression and metastasis, and adipose tissue is now being credited with both systemic and local effects on tumour development and survival. Adipocytes, a major component of benign adipose tissue, represent a significant source of lipids, cytokines and adipokines, and their presence in the tumour microenvironment substantially affects cellular trafficking, signalling and metabolism. Cancers that have a high predisposition to metastasize to the adipocyte-rich host organs are likely to be particularly affected by the presence of adipocytes. Although our understanding of how adipocytes influence tumour progression has grown significantly over the last several years, the mechanisms by which adipocytes regulate the meta-static niche are not well-understood. In this review, we focus on the omentum, a visceral white adipose tissue depot, and the bone, a depot for marrow adipose tissue, as two distinct adipocyte-rich organs that share common characteristic: they are both sites of significant metastatic growth. We highlight major differences in origin and function of each of these adipose depots and reveal potential common characteristics that make them environments that are attractive and conducive to secondary tumour growth. Special attention is given to how omental and marrow adipocytes modulate the tumour microenvironment by promoting angiogenesis, affecting immune cells and altering metabolism to support growth and survival of metastatic cancer cells. PMID:27432523

National quality improvement policies and strategies in European healthcare systems.

PubMed

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.

Climatology of Urban-regional Systems

NASA Technical Reports Server (NTRS)

Pease, R. W.

1971-01-01

Urbanized areas have come to be significant if not dominant components of many regional land surfaces. They represent perhaps the most dramatic recent change man has made in his environment - a change that may well burgeon in the foreseeable future as greater percentages of world populations crowd into metropolitan areas. The climate of urban-regional systems is involved because temperature, air, and pollutants added to the air are significant aspects of this change. During the past two years, substantial progress has been made in the application of remote sensing techniques to the study of urban climatology by programs jointly sponsored by NASA and the United States Geological Survey. The initial effort has endeavored with considerable success to map terrestrial radiation emission or the general thermal state of the land surface with the aid of imaging radiometers (mechanical-optical scanners).

Preface of the special issue: "Vertical coupling in the atmosphere-ionosphere system: Recent progress"

NASA Astrophysics Data System (ADS)

2018-06-01

This special issue of the Journal of Atmospheric and Solar-Terrestrial Physics comprises papers dealing with investigation of the coupling phenomena in the neutral Atmosphere-Ionosphere System of the Earth. The core of the special issue is formed by the recent results presented during the 6th IAGA/ICMA/SCOSTEP Workshop on the Vertical Coupling in the Neutral Atmosphere-Ionosphere System held in Taipei, Taiwan, July 2016. Workshops are organized with a substantial support of the scientific international bodies, such as the International Association of Geomagnetism and Aeronomy (IAGA), International Commission for the Middle Atmosphere (ICMA) and Committee on Solar-Terrestrial Physics (SCOSTEP). The special issue includes also recent results of other members of the aeronomic research community. Hence it represents the state-of-art knowledge in the associated research fields.

Pharmacologic inhibition of the menin-MLL interaction blocks progression of MLL leukemia in vivo

DOE PAGES

Borkin, Dmitry; He, Shihan; Miao, Hongzhi; ...

2015-03-26

Chromosomal translocations affecting mixed lineage leukemia gene ( MLL) result in acute leukemias resistant to therapy. The leukemogenic activity of MLL fusion proteins is dependent on their interaction with menin, providing basis for therapeutic intervention. In this paper, we report the development of highly potent and orally bioavailable small-molecule inhibitors of the menin-MLL interaction, MI-463 and MI-503, and show their profound effects in MLL leukemia cells and substantial survival benefit in mouse models of MLL leukemia. Finally, we demonstrate the efficacy of these compounds in primary samples derived from MLL leukemia patients. In conclusion, overall, we demonstrate that pharmacologic inhibitionmore » of the menin-MLL interaction represents an effective treatment for MLL leukemias in vivo and provide advanced molecular scaffold for clinical lead identification.« less

Does harm reduction programming make a difference in the lives of highly marginalized, at-risk drug users?

PubMed Central

Rogers, Susan J; Ruefli, Terry

2004-01-01

Harm reduction is a controversial model for treating drug users, with little formal research available on its operation and effectiveness. In order to advance the field, we first conducted participatory research of harm reduction with 120 clients using nominal-group technique to develop culturally relevant outcomes to measure progress. Second, we conducted focus group interviews with a different group of clients to help validate the outcomes. Third, we used the outcomes in an evaluation of the largest harm reduction program in New York City, which involved a representative sample of 261 and entailed baseline, post, and six follow-up assessments. The participatory research resulted in outcomes of 10 life areas important to drug users. Evaluation results showed that program participants made positive improvements across most outcomes, with the most substantial progress made in how clients dealt with drug-use problems. Along with their participation in the program, progress in some outcomes was also associated with clients' type of drug use (i.e., stable vs. chaotic), where more stable drug use was associated with better ways of making an income and types of housing. Surprisingly, progress was not associated with the kinds or numbers of services received or the length of time in the program. This was attributed to the service delivery model of harm reduction, in which clients are less inclined to associate their success with a single staff person or with a single service or intervention received than with the program as a whole. PMID:15171790

Syphilis. A tale of twisted treponemes.

PubMed Central

Flores, J L

1995-01-01

Despite the widespread availability of effective treatment, the incidence of primary and secondary syphilis in the United States is on the rise. In addition, syphilis is occurring in a substantial number of patients infected with the human immunodeficiency virus (HIV), thus adding to the complexities of diagnosis and treatment. Primary syphilis represents a disseminated infection, often accompanied by abnormalities of the cerebrospinal fluid, that may pass unrecognized and progress to the myriad manifestations of secondary syphilis. The diagnosis of syphilis in patients with mucosal or skin lesions may be made by darkfield examination; once lesions have resolved, serologic tests are required. Patients with latent syphilis may have asymptomatic neurosyphilis and risk progression to tertiary disease. The diagnosis of asymptomatic neurosyphilis is necessary to determine the optimal treatment of patients with latent disease. The diagnosis of active neurosyphilis generally requires an inflammatory cerebrospinal fluid profile and a reactive cerebrospinal fluid VDRL test. Syphilis is common in HIV-infected patients, who may have an altered antibody response to infection and an apparent increased incidence of neurologic complications. The preferred treatment at all stages is penicillin, which is also the only recommended therapy for neurosyphilis. The optimal treatment of syphilis in HIV-infected patients is unknown. Images Figure 1. PMID:8553639

Global Monitoring of Water Supply and Sanitation: History, Methods and Future Challenges

PubMed Central

Bartram, Jamie; Brocklehurst, Clarissa; Fisher, Michael B.; Luyendijk, Rolf; Hossain, Rifat; Wardlaw, Tessa; Gordon, Bruce

2014-01-01

International monitoring of drinking water and sanitation shapes awareness of countries’ needs and informs policy, implementation and research efforts to extend and improve services. The Millennium Development Goals established global targets for drinking water and sanitation access; progress towards these targets, facilitated by international monitoring, has contributed to reducing the global disease burden and increasing quality of life. The experiences of the MDG period generated important lessons about the strengths and limitations of current approaches to defining and monitoring access to drinking water and sanitation. The methods by which the Joint Monitoring Programme (JMP) of WHO and UNICEF tracks access and progress are based on analysis of data from household surveys and linear regression modelling of these results over time. These methods provide nationally-representative and internationally-comparable insights into the drinking water and sanitation facilities used by populations worldwide, but also have substantial limitations: current methods do not address water quality, equity of access, or extra-household services. Improved statistical methods are needed to better model temporal trends. This article describes and critically reviews JMP methods in detail for the first time. It also explores the impact of, and future directions for, international monitoring of drinking water and sanitation. PMID:25116635

Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

PubMed Central

Denkinger, Claudia M.; Kik, Sandra V.; Rangaka, Molebogeng X.; Zwerling, Alice; Oxlade, Olivia; Metcalfe, John Z.; Cattamanchi, Adithya; Dowdy, David W.; Dheda, Keertan; Banaei, Niaz

2014-01-01

SUMMARY Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-γ) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis. Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers. PMID:24396134

NASA's Space Launch System: Building a New Capability for Discovery

NASA Technical Reports Server (NTRS)

Creech, Stephen D.; Robinson, Kimberly F.

2015-01-01

Designed to enable human space exploration missions, including eventually landings on Mars, NASA's Space Launch System (SLS) represents a unique launch capability with a wide range of utilization opportunities, from delivering habitation systems into the lunar vicinity to high-energy transits through the outer solar system. Substantial progress has been made toward the first launch of the initial configuration of SLS, which will be able to deliver more than 70 metric tons of payload into low Earth orbit (LEO). The vehicle will then be evolved into more powerful configurations, culminating with the capability to deliver more than 130 metric tons to LEO. The initial configuration will be able to deliver greater mass to orbit than any contemporary launch vehicle, and the evolved configuration will have greater performance than the Saturn V rocket that enabled human landings on the moon. SLS will also be able to carry larger payload fairings than any contemporary launch vehicle, and will offer opportunities for co-manifested and secondary payloads. Because of its substantial mass-lift capability, SLS will also offer unrivaled departure energy, enabling mission profiles currently not possible. The basic capabilities of SLS have been driven by studies on the requirements of human deep-space exploration missions, and continue to be validated by maturing analysis of Mars mission options. Early collaboration with science teams planning future decadal-class missions have contributed to a greater understanding of the vehicle's potential range of utilization. As this paper will explain, SLS is making measurable progress toward becoming a global infrastructure asset for robotic and human scouts of all nations by providing the robust space launch capability to deliver sustainable solutions for exploration.

Lung disease in a global context. A call for public health action.

PubMed

Schluger, Neil W; Koppaka, Ram

2014-03-01

As described in a recently released report of the Forum of International Respiratory Societies, four of the leading causes of death in the world are chronic obstructive pulmonary disease, acute respiratory tract infections, lung cancer, and tuberculosis. A fifth, asthma, causes enormous global morbidity. Not enough progress has been made in introducing new therapies and reducing disease burden for these illnesses in the last few decades, despite generous investments and some notable progress in biomedical research. Four external and modifiable drivers are responsible for a substantial percentage of the disease burden represented by the major lung diseases: tobacco, outdoor air pollution, household air pollution, and occupational exposures to lung toxins. Especially in low- and middle-income countries, but in highly developed economies as well, pressures for economic development and lax regulation are contributing to the continued proliferation of these drivers. Public health approaches to the most common lung diseases could have enormous effects on reducing morbidity and mortality. There must be increased advocacy from and mobilization of civil society to bring attention to the drivers of lung diseases in the world. The World Health Organization should negotiate accords similar to the Framework Convention on Tobacco Control to address air pollution and occupational exposures. Large increases in funding by government agencies and nongovernmental organizations around the world are needed to identify technologies that will reduce health risks while allowing populations to enjoy the benefits of economic development. This paradigm, focused more on public health than on individual medical treatment, has the best chance of substantial reduction in the burden of lung disease around the world in the next several years.

A reverse genetic approach identifies an ancestral frameshift mutation in RP1 causing recessive progressive retinal degeneration in European cattle breeds.

PubMed

Michot, Pauline; Chahory, Sabine; Marete, Andrew; Grohs, Cécile; Dagios, Dimitri; Donzel, Elise; Aboukadiri, Abdelhak; Deloche, Marie-Christine; Allais-Bonnet, Aurélie; Chambrial, Matthieu; Barbey, Sarah; Genestout, Lucie; Boussaha, Mekki; Danchin-Burge, Coralie; Fritz, Sébastien; Boichard, Didier; Capitan, Aurélien

2016-08-10

Domestication and artificial selection have resulted in strong genetic drift, relaxation of purifying selection and accumulation of deleterious mutations. As a consequence, bovine breeds experience regular outbreaks of recessive genetic defects which might represent only the tip of the iceberg since their detection depends on the observation of affected animals with distinctive symptoms. Thus, recessive mutations resulting in embryonic mortality or in non-specific symptoms are likely to be missed. The increasing availability of whole-genome sequences has opened new research avenues such as reverse genetics for their investigation. Our aim was to characterize the genetic load of 15 European breeds using data from the 1000 bull genomes consortium and prove that widespread harmful mutations remain to be detected. We listed 2489 putative deleterious variants (in 1923 genes) segregating at a minimal frequency of 5 % in at least one of the breeds studied. Gene enrichment analysis showed major enrichment for genes related to nervous, visual and auditory systems, and moderate enrichment for genes related to cardiovascular and musculoskeletal systems. For verification purposes, we investigated the phenotypic consequences of a frameshift variant in the retinitis pigmentosa-1 gene segregating in several breeds and at a high frequency (27 %) in Normande cattle. As described in certain human patients, clinical and histological examination revealed that this mutation causes progressive degeneration of photoreceptors leading to complete blindness in homozygotes. We established that the deleterious allele was even more frequent in the Normande breed before 1975 (>40 %) and has been progressively counter-selected likely because of its associated negative effect on udder morphology. Finally, using identity-by-descent analysis we demonstrated that this mutation resulted from a unique ancestral event that dates back to ~2800 to 4000 years. We provide a list of mutations that likely represent a substantial part of the genetic load of domestication in European cattle. We demonstrate that they accumulated non-randomly and that genes related to cognition and sensory functions are particularly affected. Finally, we describe an ancestral deleterious variant segregating in different breeds causing progressive retinal degeneration and irreversible blindness in adult animals.

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…

Progress in Understanding Autism: 2007-2010

ERIC Educational Resources Information Center

Rutter, Michael L.

2011-01-01

Scientific progress is discussed in relation to clinical issues; genetic issues; environmental issues; and the state of play on psychological treatments. It is concluded that substantial gains in knowledge have been achieved during the last 3 years, and there have been some unexpected findings, but major puzzles remain. We should be hopeful of…

Transforming Performance Measurement for the 21st Century

ERIC Educational Resources Information Center

Hatry, Harry P.

2014-01-01

While substantial progress has been made in spreading performance measurement across the country and world, much of the information from performance measurement systems has been shallow. Modern technology and the considerable demand for information on progress in achieving the outcomes of public programs and policies are creating major…

THE DISADVANTAGED CHILDREN AND YOUTH OF AMERICA.

ERIC Educational Resources Information Center

OETTINGER, KATHERINE B.

PROGRESS IS BEING MADE TOWARD ERASING THE DISADVANTAGES OF THE MENTALLY RETARDED. MUCH PROGRESS HAS BEEN MADE IN RECOGNIZING THE HEALTH NEEDS OF THE RETARDED CHILD THROUGH SUBSTANTIAL LEGISLATION SPONSORED BY MANY BRANCHES OF GOVERNMENT, ACTION PROGRAMS STEMMING FROM BOTH PUBLIC AND VOLUNTARY SOURCES, AND A MOUNTING RESEARCH EFFORT. IN AN EFFORT…

Evaluating Test Validity: Reprise and Progress

ERIC Educational Resources Information Center

Shepard, Lorrie A.

2016-01-01

The AERA, APA, NCME Standards define validity as "the degree to which evidence and theory support the interpretations of test scores for proposed uses of tests". A century of disagreement about validity does not mean that there has not been substantial progress. This consensus definition brings together interpretations and use so that it…

Twenty Years of Progress on Global Ocean Tide: The Impact of Satellite Altimetry

NASA Astrophysics Data System (ADS)

Egbert, Gary D.; Ray, Richard D.

2013-09-01

At the dawn of the era of high-precision altimetry, before the launch of TOPEX/Poseidon, ocean tides were properly viewed as a source of noise-tidal variations in ocean height would represent a very substantial fraction of what the altimeter measures, and would have to be accurately predicted and subtracted if altimetry were to achieve its potential for ocean and climate studies. But to the extent that the altimetry could be severely contaminated by tides, it also represented an unprecedented global-scale tidal data set. These new data, together with research stimulated by the need for accurate tidal corrections, led to a renaissance in tidal studies in the oceanographic community. In this paper we review contributions of altimetry to tidal science over the past 20 years, emphasizing recent progress. Mapping of tides has now been extended from the early focus on major constituents in the open ocean to include minor constituents, (e.g., long-period tides; non-linear tides in shelf waters, and in the open ocean), and into shallow and coastal waters. Global and spatially local estimates of tidal energy balance have been refined, and the role of internal tide conversion in dissipating barotropic tidal energy is now well established through modeling, altimetry, and in situ observations. However, energy budgets for internal tides, and the role of tidal dissipation in vertical ocean mixing remain controversial topics. Altimetry may contribute to resolving some of these important questions through improved mapping of low-mode internal tides. This area has advanced significantly in recent years, with several global maps now available, and progress on constraining temporally incoherent components. For the future, new applications of altimetry (e.g., in the coastal ocean, where barotropic tidal models remain inadequate), and new mission concepts (studies of the sub-mesoscale with SWOT, which will require correction for internal tides) may bring us full circle, again pushing further development of tidal models as corrections.

Analysing post-apartheid gender and racial transformation in medical education in a South African province

PubMed Central

Khan, Taskeen; Thomas, Leena S.; Naidoo, Shan

2013-01-01

Introduction In light of global concerns about insufficient numbers of doctors, midwives, and nurses, the World Health Organization (WHO) has identified the scale-up of the production of medical professionals who are competent and responsive to community needs as urgent and necessary. Coincident with this imperative, South African medical schools have also had to consider redressing apartheid-era inequities in access to medical education and changing the racial and gender profile of medical graduates to be representative of the population. In this article, we explore progress and challenges with regard to transformation, defined as intentional and planned changes aimed at addressing historical disadvantages, in the Gauteng Province of South Africa. Methods A cross-sectional, descriptive analysis was conducted using data on medical school admissions and graduations from the Health and Education Departments for the period 1999–2011. Admission and graduation statistics of 1999, 2005, 2008, and 2011 were analysed according to race and gender. Results The results show that there has been progress in transforming the race and gender composition of medical students and graduates, in line with the transformation strategies of the South African government. In 1999, black African enrolments and graduates were conspicuously low in two of the three medical schools in the Gauteng province. By 2011, an almost six-fold increase in black African student enrolments was seen in one medical school that was previously designated as a white institution. In contrast, at the historically black medical school, whites only represented 0.40% of enrolments in 1999 and 7.4% in 2011. Since 1999, the number and proportion of female medical enrolments and graduates has also increased substantially. Conclusion While there has been progress with redressing historical disparities and inequities in terms of race and gender, further efforts are needed to ensure that student intakes and graduations are in line with the South African population profile. PMID:23364091

Twenty Years of Progress on Global Ocean Tides: The Impact of Satellite Altimetry

NASA Technical Reports Server (NTRS)

Egbert, Gary; Ray, Richard

2012-01-01

At the dawn of the era of high-precision altimetry, before the launch of TOPEX/Poseidon, ocean tides were properly viewed as a source of noise--tidal variations in ocean height would represent a very substantial fraction of what the altimeter measures, and would have to be accurately predicted and subtracted if altimetry were to achieve its potential for ocean and climate studies. But to the extent that the altimetry could be severely contaminated by tides, it also represented an unprecedented global-scale tidal data set. These new data, together with research stimulated by the need for accurate tidal corrections, led to a renaissance in tidal studies in the oceanographic community. In this paper we review contributions of altimetry to tidal science over the past 20 years, emphasizing recent progress. Mapping of tides has now been extended from the early focus on major constituents in the open ocean to include minor constituents, (e.g., long-period tides; non-linear tides in shelf waters, and in the open ocean), and into shallow and coastal waters. Global and spatially local estimates of tidal energy balance have been refined, and the role of internal tide conversion in dissipating barotropic tidal energy is now well established through modeling, altimetry, and in situ observations. However, energy budgets for internal tides, and the role of tidal dissipation in vertical ocean mixing remain controversial topics. Altimetry may contribute to resolving some of these important questions through improved mapping of low-mode internal tides. This area has advanced significantly in recent years, with several global maps now available, and progress on constraining temporally incoherent components. For the future, new applications of altimetry (e.g., in the coastal ocean, where barotropic tidal models remain inadequate), and new mission concepts (studies of the submesoscale with SWOT, which will require correction for internal tides) may bring us full circle, again pushing further development of tidal models as corrections.

Analysing post-apartheid gender and racial transformation in medical education in a South African province.

PubMed

Khan, Taskeen; Thomas, Leena S; Naidoo, Shan

2013-01-24

In light of global concerns about insufficient numbers of doctors, midwives, and nurses, the World Health Organization (WHO) has identified the scale-up of the production of medical professionals who are competent and responsive to community needs as urgent and necessary. Coincident with this imperative, South African medical schools have also had to consider redressing apartheid-era inequities in access to medical education and changing the racial and gender profile of medical graduates to be representative of the population. In this article, we explore progress and challenges with regard to transformation, defined as intentional and planned changes aimed at addressing historical disadvantages, in the Gauteng Province of South Africa. A cross-sectional, descriptive analysis was conducted using data on medical school admissions and graduations from the Health and Education Departments for the period 1999-2011. Admission and graduation statistics of 1999, 2005, 2008, and 2011 were analysed according to race and gender. The results show that there has been progress in transforming the race and gender composition of medical students and graduates, in line with the transformation strategies of the South African government. In 1999, black African enrolments and graduates were conspicuously low in two of the three medical schools in the Gauteng province. By 2011, an almost six-fold increase in black African student enrolments was seen in one medical school that was previously designated as a white institution. In contrast, at the historically black medical school, whites only represented 0.40% of enrolments in 1999 and 7.4% in 2011. Since 1999, the number and proportion of female medical enrolments and graduates has also increased substantially. While there has been progress with redressing historical disparities and inequities in terms of race and gender, further efforts are needed to ensure that student intakes and graduations are in line with the South African population profile.

Reinterpretation of Paleoproterozoic accretionary boundaries of the north-central United States based on a new aeromagnetic-geologic compilation

USGS Publications Warehouse

Holm, D.K.; Anderson, R.; Boerboom, Terrence; Cannon, W.F.; Chandler, V.; Jirsa, M.; Miller, J.; Schneider, D.A.; Schulz, K.J.; Van Schmus, W. R.

2007-01-01

The Paleoproterozoic crust in the north-central U.S. represents intact juvenile terranes accreted to the rifted Archean Superior craton. A new tectonic province map, based on the interpretation of a new aeromagnetic compilation, published geologic maps, and recent geochronologic data, shows progressive accretion of juvenile arc terranes from ca. 1900-1600 Ma. Contrary to earlier models, geon 18 Penokean-interval crust is primarily confined to a ???2100 Ma tectonic embayment of the rifted Superior craton. The newly defined Spirit Lake tectonic zone, characterized by a sharp magnetic discontinuity that marks the southern limit of Archean and Penokean-interval rocks, is here interpreted to represent an eastern analog of the Cheyenne belt suture zone in southern Wyoming. South of this boundary, geon 17 Yavapai-interval rocks form the basement upon which 1750 Ma rhyolite and succeeding quartzite sequences were deposited. Substantial portions of the Penokean and Yavapai terranes were subsequently deformed during the 1650-1630 Ma Mazatzal orogeny. The northern boundary of the Mazatzal terrane is obscured by abundant 1470-1430 Ma "anorogenic" plutons that stitched the suture with the older Yavapai terrane rocks. These data reveal a progressive tectonic younging to the south as the Laurentian craton grew southward and stabilized during the Proterozoic. Late Mesoproterozoic rift magmatism produced pronounced geophysical anomalies, indicating strong, but localized crustal modification. In comparison to the western U.S., little tectonism has occurred here in the last 1 billion years, providing a uniquely preserved record of the Precambrian evolution of the continental U.S. lithosphere. ?? 2007 Elsevier B.V. All rights reserved.

How does the size and shape of local populations in China compare to general anthropometric surveys currently used for product design?

PubMed

Daniell, Nathan; Fraysse, François; Paul, Gunther

2012-01-01

Anthropometry has long been used for a range of ergonomic applications & product design. Although products are often designed for specific cohorts, anthropometric data are typically sourced from large scale surveys representative of the general population. Additionally, few data are available for emerging markets like China and India. This study measured 80 Chinese males that were representative of a specific cohort targeted for the design of a new product. Thirteen anthropometric measurements were recorded and compared to two large databases that represented a general population, a Chinese database and a Western database. Substantial differences were identified between the Chinese males measured in this study and both databases. The subjects were substantially taller, heavier and broader than subjects in the older Chinese database. However, they were still substantially smaller, lighter and thinner than Western males. Data from current Western anthropometric surveys are unlikely to accurately represent the target population for product designers and manufacturers in emerging markets like China.

49 CFR 213.113 - Defective rails.

Code of Federal Regulations, 2010 CFR

2010-10-01

... smooth, bright, or dark, round or oval surface substantially at a right angle to the length of the rail... in the head of the rail as a smooth, bright, or dark surface progressing until substantially at a... head, and extending into or through it. A crack or rust streak may show under the head close to the web...

49 CFR 213.113 - Defective rails.

Code of Federal Regulations, 2011 CFR

2011-10-01

... smooth, bright, or dark, round or oval surface substantially at a right angle to the length of the rail... in the head of the rail as a smooth, bright, or dark surface progressing until substantially at a... head, and extending into or through it. A crack or rust streak may show under the head close to the web...

49 CFR 213.113 - Defective rails.

Code of Federal Regulations, 2012 CFR

2012-10-01

... smooth, bright, or dark, round or oval surface substantially at a right angle to the length of the rail... in the head of the rail as a smooth, bright, or dark surface progressing until substantially at a... head, and extending into or through it. A crack or rust streak may show under the head close to the web...

49 CFR 213.113 - Defective rails.

Code of Federal Regulations, 2013 CFR

2013-10-01

... smooth, bright, or dark, round or oval surface substantially at a right angle to the length of the rail... in the head of the rail as a smooth, bright, or dark surface progressing until substantially at a... head, and extending into or through it. A crack or rust streak may show under the head close to the web...

A Letter to White Women Teachers: An Urgent Plea for Change

ERIC Educational Resources Information Center

Baker, Laura

2017-01-01

The new Progressive Education Network mission says that Progressive Education "promotes diversity, equity, and justice." These goals cannot be met unless there are substantial changes in the way the majority of teachers in the United States, white women teachers, think and operate. This open letter to that audience from a white woman…

Finding the Right Mix: Teaching Methods as Predictors for Student Progress on Learning Objectives

ERIC Educational Resources Information Center

Glover, Jacob I.

2012-01-01

This study extends existing student ratings research by exploring how teaching methods, individually and collectively, influence a minimum standard of student achievement on learning objectives and how class size impacts this influence. Twenty teaching methods were used to predict substantial or exceptional progress on each of 12 learning…

Progressing batch hydrolysis process

DOEpatents

Wright, J.D.

1985-01-10

A progressive batch hydrolysis process is disclosed for producing sugar from a lignocellulosic feedstock. It comprises passing a stream of dilute acid serially through a plurality of percolation hydrolysis reactors charged with feed stock, at a flow rate, temperature and pressure sufficient to substantially convert all the cellulose component of the feed stock to glucose. The cooled dilute acid stream containing glucose, after exiting the last percolation hydrolysis reactor, serially fed through a plurality of pre-hydrolysis percolation reactors, charged with said feedstock, at a flow rate, temperature and pressure sufficient to substantially convert all the hemicellulose component of said feedstock to glucose. The dilute acid stream containing glucose is cooled after it exits the last prehydrolysis reactor.

Progressing batch hydrolysis process

DOEpatents

Wright, John D.

1986-01-01

A progressive batch hydrolysis process for producing sugar from a lignocellulosic feedstock, comprising passing a stream of dilute acid serially through a plurality of percolation hydrolysis reactors charged with said feedstock, at a flow rate, temperature and pressure sufficient to substantially convert all the cellulose component of the feedstock to glucose; cooling said dilute acid stream containing glucose, after exiting the last percolation hydrolysis reactor, then feeding said dilute acid stream serially through a plurality of prehydrolysis percolation reactors, charged with said feedstock, at a flow rate, temperature and pressure sufficient to substantially convert all the hemicellulose component of said feedstock to glucose; and cooling the dilute acid stream containing glucose after it exits the last prehydrolysis reactor.

Emodin and Its Role in Chronic Diseases.

PubMed

Monisha, B Anu; Kumar, Niraj; Tiku, Ashu Bhan

Diseases, such as heart disease, stroke, cancer, respiratory diseases, and diabetes, are by far the leading cause of mortality in the world, representing 60 % of all deaths. Although substantial medical advances have been made and many therapeutic approaches proposed yet traditional medicine and medicinal plants find an important place in therapy. They have been providing invaluable solutions to the various health problems. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a natural anthraquinone derivative found in various Chinese medicinal herbs. Traditionally, it has been used as an active constituent of many herbal laxatives. However, in the last few years, significant progress has been made in studying the biological effects of emodin at cellular and molecular levels and it is emerging as an important therapeutic agent. This review provides an overview of the modulatory effects of emodin in various diseases and cell signaling pathways, which may have important implications in its future clinical use.

Prescription of lipophilic statins to Alzheimer's disease patients: some controversies to consider.

PubMed

Biondi, Elisa

2011-04-01

Alzheimer's disease (AD) is the most common disorder causing cognitive decline in old age. It is a progressive and irreversible neuropathology with a diagnosis often missed or delayed. Cholesterol represents an important determinant of the physical state of biological membranes and in AD brains, specific changes in its membrane-ordering and Raft-organizing effects take place. A recent publication shows downregulation of Seladin-1 (selective Alzheimer's disease indicator, also called DHCR24), which catalyzes the last step of cholesterol biosynthesis in affected neurons in AD. Postmortem analysis of AD brains revealed a loss in membrane cholesterol content and this finding makes the therapeutical use of statins (especially the lipophilic ones) quite a lot controversial. Some clinical studies suggest that risk of Alzheimer's disease is substantially reduced in users of statins; however, because these studies are not randomized trials, they provide insufficient evidence to recommend statin family therapy.

Observations on autoregulation in skeletal muscle - The effects of arterial hypoxia

NASA Technical Reports Server (NTRS)

Pohost, G. M.; Newell, J. B.; Hamlin, N. P.; Powell, W. J., Jr.

1976-01-01

An experimental study was carried out on 25 mongrel dogs of both sexes to re-evaluate autoregulation of blood flow in skeletal muscle, with particular reference to the steady-state resistance and transient response in muscle blood flow following a square wave increase in arterial perfusion pressure and to the examination of the effect of arterial hypoxia on this transient response. The data emphasize the importance of considering the transient changes in blood flow in evaluating the autoregulatory response in skeletal muscle. For quantification purposes, a parameter termed alpha is introduced which represents the ratio between the increase in blood flow from baseline to peak and the return of blood flow from the peak to the new steady-state. Such a quantification of the transient response in flow with step increases in perfusion pressure demonstrates substantial transient responses under conditions of normal oxygenation and progressive attenuation of flow transients with increasing hypoxia.

The HIV-1 Tat protein modulates CD4 expression in human T cells through the induction of miR-222.

PubMed

Orecchini, Elisa; Doria, Margherita; Michienzi, Alessandro; Giuliani, Erica; Vassena, Lia; Ciafrè, Silvia Anna; Farace, Maria Giulia; Galardi, Silvia

2014-01-01

Several cellular microRNAs show substantial changes in expression during HIV-1 infection and their active role in the viral life cycle is progressively emerging. In the present study, we found that HIV-1 infection of Jurkat T cells significantly induces the expression of miR-222. We show that this induction depends on HIV-1 Tat protein, which is able to increase the transcriptional activity of NFkB on miR-222 promoter. Moreover, we demonstrate that miR-222 directly targets CD4, a key receptor for HIV-1, thus reducing its expression. We propose that Tat, by inducing miR-222 expression, complements the CD4 downregulation activity exerted by other viral proteins (i.e., Nef, Vpu, and Env), and we suggest that this represents a novel mechanism through which HIV-1 efficiently represses CD4 expression in infected cells.

Bioresorbable Scaffolds: Current Evidences in the Treatment of Coronary Artery Disease

PubMed Central

2016-01-01

Percutaneous coronary revascularization strategies have gradually progressed over a period of last few decades. The advent of newer generation drug-eluting stents has significantly improved the outcomes of Percutaneous Coronary Intervention (PCI) by substantially reducing in-stent restenosis and stent thrombosis. However, vascular inflammation, restenosis, thrombosis, and neoatherosclerosis due to the permanent presence of a metallic foreign body within the artery limit their usage in complex Coronary Artery Disease (CAD). Bioresorbable Scaffolds (BRS) represent a novel approach in coronary stent technology. Complete resorption of the scaffold liberates the treated vessel from its cage and restores pulsatility, cyclical strain, physiological shear stress, and mechanotransduction. In this review article, we describe the advances in this rapidly evolving technology, present the evidence from the pre-clinical and clinical evaluation of these devices, and provide an overview of the ongoing clinical trials that were designed to examine the effectiveness of BRS in the clinical setting. PMID:27891384

Progress and challenges in implementing the research on ESKAPE pathogens.

PubMed

Rice, Louis B

2010-11-01

The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are responsible for a substantial percentage of nosocomial infections in the modern hospital and represent the vast majority of isolates whose resistance to antimicrobial agents presents serious therapeutic dilemmas for physicians. Over the years, improved molecular biology techniques have led to detailed information about individual resistance mechanisms in all these pathogens. However, there remains a lack of compelling data on the interplay between resistance mechanisms and between the bacteria themselves. In addition, data on the impact of clinical interventions to decrease the prevalence of resistance are also lacking. The difficulty in identifying novel antimicrobial agents with reliable activity against these pathogens argues for an augmentation of research in the basic and population science of resistance, as well as careful studies to identify optimal strategies for infection control and antimicrobial use.

The New US Preventive Services Task Force "C" Draft Recommendation for Prostate Cancer Screening.

PubMed

Cooperberg, Matthew R

2017-09-01

The US Preventive Services Task Force has issued a new draft guideline, with a "C" recommendation that men aged 55-69 yr should be informed about the benefits and harms of screening for prostate cancer, and offered prostate-specific antigen testing if they choose it. For men aged ≥70 yr, the recommendation remains "D", or "do not screen." This draft represents substantial progress in the right direction towards offering men a fair opportunity to discuss the risks and benefits of screening with their primary care providers. However, the evidence review underlying the draft remains fundamentally inadequate, leading to biased presentations of both benefits and harms of screening. The final guideline and future revisions should reflect formal engagement with subject matter experts to optimize the advise given to men and their physicians. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Text familiarity, word frequency, and sentential constraints in error detection.

PubMed

Pilotti, Maura; Chodorow, Martin; Schauss, Frances

2009-12-01

The present study examines whether the frequency of an error-bearing word and its predictability, arising from sentential constraints and text familiarity, either independently or jointly, would impair error detection by making proofreading driven by top-down processes. Prior to a proofreading task, participants were asked to read, copy, memorize, or paraphrase sentences, half of which contained errors. These tasks represented a continuum of progressively more demanding and time-consuming activities, which were thought to lead to comparable increases in text familiarity and thus predictability. Proofreading times were unaffected by whether the sentences had been encountered earlier. Proofreading was slower and less accurate for high-frequency words and for highly constrained sentences. Prior memorization produced divergent effects on accuracy depending on sentential constraints. The latter finding suggested that a substantial level of predictability, such as that produced by memorizing highly constrained sentences, can increase the probability of overlooking errors.

Vibration suppression and slewing control of a flexible structure

NASA Technical Reports Server (NTRS)

Inman, Daniel J.; Garcia, Ephrahim; Pokines, Brett

1991-01-01

Examined here are the effects of motor dynamics and secondary piezoceramic actuators on vibration suppression during the slewing of flexible structures. The approach focuses on the interaction between the structure, the actuators, and the choice of control law. The results presented here are all simulated, but are based on experimentally determined parameters for the motor, structure, piezoceramic actuators, and piezofilm sensors. The simulation results clearly illustrate that the choice of motor inertia relative to beam inertia makes a critical difference in the performance of the system. In addition, the use of secondary piezoelectric actuators reduces the load requirements on the motor and also reduces the overshoot of the tip deflection. The structures considered here are a beam and a frame. The majority of results are based on a Euler Bernoulli beam model. The slewing frame introduces substantial torsional modes and a more realistic model. The slewing frame results are incomplete and represent work in progress.

The HIV-1 Tat protein modulates CD4 expression in human T cells through the induction of miR-222

PubMed Central

Orecchini, Elisa; Doria, Margherita; Michienzi, Alessandro; Giuliani, Erica; Vassena, Lia; Ciafrè, Silvia Anna; Farace, Maria Giulia; Galardi, Silvia

2014-01-01

Several cellular microRNAs show substantial changes in expression during HIV-1 infection and their active role in the viral life cycle is progressively emerging. In the present study, we found that HIV-1 infection of Jurkat T cells significantly induces the expression of miR-222. We show that this induction depends on HIV-1 Tat protein, which is able to increase the transcriptional activity of NFkB on miR-222 promoter. Moreover, we demonstrate that miR-222 directly targets CD4, a key receptor for HIV-1, thus reducing its expression. We propose that Tat, by inducing miR-222 expression, complements the CD4 downregulation activity exerted by other viral proteins (i.e., Nef, Vpu, and Env), and we suggest that this represents a novel mechanism through which HIV-1 efficiently represses CD4 expression in infected cells. PMID:24717285

[Joubert syndrome and related disorders].

PubMed

Paprocka, Justyna; Jamroz, Ewa

2012-01-01

The cerebellum plays a role not only in motor control but also in motor learning and cognition. Joubert syndrome is a rare heterogeneous inherited genetic disorder characterized by ataxia, hypotonia, developmental delay, and at least one of the following features: neonatal respiratory disturbances or abnormal eye movement. The estimated frequency of Joubert syndrome in the United States is around 1 : 100 000. The term Joubert syndrome and related disorders (JSRD) has been recently coined to describe all disorders presenting with molar tooth sign on brain neuroimaging. Joubert syndrome is believed to be a representative of a new group of disorders named ciliopathies. The identification of seven causal genes (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67/MKS3, ARL13B, CC2D2A) has led to substantial progress in the understanding of the genetic basis of Joubert syndrome. The authors focus on clinical presentation of JSRD, differential diagnosis and molecular background.

Vemurafenib: a new treatment for BRAF-V600 mutated advanced melanoma

PubMed Central

Fisher, Rosalie; Larkin, James

2012-01-01

The BRAF inhibitor, vemurafenib, has demonstrated improved progression-free and overall survival compared with chemotherapy in a randomized trial, and represents a new standard of care in patients with advanced melanoma harboring a BRAF-V600 mutation. A BRAF-V600 mutation is identified in approximately half of patients with cutaneous melanoma, and is unequivocally a biomarker predictive of profound clinical benefit for these patients. However, acquired vemurafenib resistance is a major clinical challenge and therapy is not yet curative. A substantial body of translational research has been performed alongside clinical trials of vemurafenib, providing key insights into the molecular basis of response and resistance. This review summarizes the development of vemurafenib for the treatment of BRAF-V600 mutant melanoma and discusses how knowledge of critical signaling pathways will be applied for its optimal clinical use in future. PMID:22904646

Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases.

PubMed

Skeate, Joseph G; Woodham, Andrew W; Einstein, Mark H; Da Silva, Diane M; Kast, W Martin

2016-06-02

Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.

Engineering plant metabolism into microbes: from systems biology to synthetic biology.

PubMed

Xu, Peng; Bhan, Namita; Koffas, Mattheos A G

2013-04-01

Plant metabolism represents an enormous repository of compounds that are of pharmaceutical and biotechnological importance. Engineering plant metabolism into microbes will provide sustainable solutions to produce pharmaceutical and fuel molecules that could one day replace substantial portions of the current fossil-fuel based economy. Metabolic engineering entails targeted manipulation of biosynthetic pathways to maximize yields of desired products. Recent advances in Systems Biology and the emergence of Synthetic Biology have accelerated our ability to design, construct and optimize cell factories for metabolic engineering applications. Progress in predicting and modeling genome-scale metabolic networks, versatile gene assembly platforms and delicate synthetic pathway optimization strategies has provided us exciting opportunities to exploit the full potential of cell metabolism. In this review, we will discuss how systems and synthetic biology tools can be integrated to create tailor-made cell factories for efficient production of natural products and fuel molecules in microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia

PubMed Central

Gao, Kun; Swarup, Vivek; Versano, Revital; Dong, Hongmei; Jordan, Maria C

2017-01-01

Friedreich's ataxia (FRDA), the most common inherited ataxia, is caused by recessive mutations that reduce the levels of frataxin (FXN), a mitochondrial iron binding protein. We developed an inducible mouse model of Fxn deficiency that enabled us to control the onset and progression of disease phenotypes by the modulation of Fxn levels. Systemic knockdown of Fxn in adult mice led to multiple phenotypes paralleling those observed in human patients across multiple organ systems. By reversing knockdown after clinical features appear, we were able to determine to what extent observed phenotypes represent reversible cellular dysfunction. Remarkably, upon restoration of near wild-type FXN levels, we observed significant recovery of function, associated pathology and transcriptomic dysregulation even after substantial motor dysfunction and pathology were observed. This model will be of broad utility in therapeutic development and in refining our understanding of the relative contribution of reversible cellular dysfunction at different stages in disease. PMID:29257745

The current state of Bayesian methods in medical product development: survey results and recommendations from the DIA Bayesian Scientific Working Group.

PubMed

Natanegara, Fanni; Neuenschwander, Beat; Seaman, John W; Kinnersley, Nelson; Heilmann, Cory R; Ohlssen, David; Rochester, George

2014-01-01

Bayesian applications in medical product development have recently gained popularity. Despite many advances in Bayesian methodology and computations, increase in application across the various areas of medical product development has been modest. The DIA Bayesian Scientific Working Group (BSWG), which includes representatives from industry, regulatory agencies, and academia, has adopted the vision to ensure Bayesian methods are well understood, accepted more broadly, and appropriately utilized to improve decision making and enhance patient outcomes. As Bayesian applications in medical product development are wide ranging, several sub-teams were formed to focus on various topics such as patient safety, non-inferiority, prior specification, comparative effectiveness, joint modeling, program-wide decision making, analytical tools, and education. The focus of this paper is on the recent effort of the BSWG Education sub-team to administer a Bayesian survey to statisticians across 17 organizations involved in medical product development. We summarize results of this survey, from which we provide recommendations on how to accelerate progress in Bayesian applications throughout medical product development. The survey results support findings from the literature and provide additional insight on regulatory acceptance of Bayesian methods and information on the need for a Bayesian infrastructure within an organization. The survey findings support the claim that only modest progress in areas of education and implementation has been made recently, despite substantial progress in Bayesian statistical research and software availability. Copyright © 2013 John Wiley & Sons, Ltd.

Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death

PubMed Central

1996-01-01

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death under a variety of circumstances. However, despite a wealth of literature describing this phenomenon, very little is known about the mechanism of resistance. In the experiments described here, we show that bcl-2 gene expression can result in an inhibition of cell division cycle progression. These findings are based upon the analysis of cell cycle distribution, cell cycle kinetics, and relative phosphorylation of the retinoblastoma tumor suppressor protein, using primary tissues in vivo, ex vivo, and in vitro, as well as continuous cell lines. The effects of bcl-2 expression on cell cycle progression appear to be focused at the G1 to S phase transition, which is a critical control point in the decision between continued cell cycle progression or the induction programmed cell death. In all systems tested, bcl-2 expression resulted in a substantial 30-60% increase in the length of G1 phase; such an increase is very substantial in the context of other regulators of cell cycle progression. Based upon our findings, and the related findings of others, we propose a mechanism by which bcl-2 expression might exert its well known inhibition of programmed cell death by regulating the kinetics of cell cycle progression at a critical control point. PMID:8642331

Losses of ecosystem service values in the Taihu Lake Basin from 1979 to 2010

NASA Astrophysics Data System (ADS)

Zhang, Hui; Wang, Qiao; Li, Guangyu; Zhang, Hanpei; Zhang, Jue

2017-06-01

The Taihu Lake Basin, an east-coastal developed area, is one of the fastest-growing metropolitan areas in China. Ecosystem services in the Taihu Lake Basin have been overexploited and jeopardized. Based on land-use and land-cover change (LUCC) data from 1979, 1984, 2000, and 2010, in conjunction with the adjusted ecosystem service values (ESV), changes in ESV were analyzed in detail. Results revealed that LUCC resulted in a substantial decrease in total ESV from 3.92 billion in 1979 to 2.98 billion in 2010. The ESV of cropland decreased from 1.64 billion in 1979 to 1.34 billion in 2010, which represented a 20.28% reduction. The ESV of water areas decreased from 1.08 billion in 1979 to 0.36 billion in 2010, which represented a 65.62% reduction mainly because of a decline in water quality. In terms of annual change rate, cropland and water areas showed a sustained downward trend. Spatially, ESV declines were mainly observed in Suzhou, Wuxi, Changzhou, and Shanghai, probably due to a combination of economic progress, population growth, and rapid urbanization. The research results can be a useful reference for policymakers in mitigating ESV decline.

Improvement attributes in healthcare: implications for integrated care.

PubMed

Harnett, Patrick John

2018-04-16

Purpose Healthcare quality improvement is a key concern for policy makers, regulators, carers and service users. Despite a contemporary consensus among policy makers that integrated care represents a means to substantially improve service outcomes, progress has been slow. Difficulties achieving sustained improvement at scale imply that methods employed are not sufficient and that healthcare improvement attributes may be different when compared to prior reference domains. The purpose of this paper is to examine and synthesise key improvement attributes relevant to a complex healthcare change process, specifically integrated care. Design/methodology/approach This study is based on an integrative literature review on systemic improvement in healthcare. Findings A central theme emerging from the literature review indicates that implementing systemic change needs to address the relationship between vision, methods and participant social dynamics. Practical implications Accommodating personal and professional network dynamics is required for systemic improvement, especially among high autonomy individuals. This reinforces the need to recognise the change process as taking place in a complex adaptive system where personal/professional purpose/meaning is central to the process. Originality/value Shared personal/professional narratives are insufficiently recognised as a powerful change force, under-represented in linear and rational empirical improvement approaches.

One‐Dimensional Earth‐Abundant Nanomaterials for Water‐Splitting Electrocatalysts

PubMed Central

Li, Jun

2016-01-01

Hydrogen fuel acquisition based on electrochemical or photoelectrochemical water splitting represents one of the most promising means for the fast increase of global energy need, capable of offering a clean and sustainable energy resource with zero carbon footprints in the environment. The key to the success of this goal is the realization of robust earth‐abundant materials and cost‐effective reaction processes that can catalyze both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), with high efficiency and stability. In the past decade, one‐dimensional (1D) nanomaterials and nanostructures have been substantially investigated for their potential in serving as these electrocatalysts for reducing overpotentials and increasing catalytic activity, due to their high electrochemically active surface area, fast charge transport, efficient mass transport of reactant species, and effective release of gas produced. In this review, we summarize the recent progress in developing new 1D nanomaterials as catalysts for HER, OER, as well as bifunctional electrocatalysts for both half reactions. Different categories of earth‐abundant materials including metal‐based and metal‐free catalysts are introduced, with their representative results presented. The challenges and perspectives in this field are also discussed. PMID:28331791

System integration of wind and solar power in integrated assessment models: A cross-model evaluation of new approaches

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

Pietzcker, Robert C.; Ueckerdt, Falko; Carrara, Samuel

Mitigation-Process Integrated Assessment Models (MP-IAMs) are used to analyze long-term transformation pathways of the energy system required to achieve stringent climate change mitigation targets. Due to their substantial temporal and spatial aggregation, IAMs cannot explicitly represent all detailed challenges of integrating the variable renewable energies (VRE) wind and solar in power systems, but rather rely on parameterized modeling approaches. In the ADVANCE project, six international modeling teams have developed new approaches to improve the representation of power sector dynamics and VRE integration in IAMs. In this study, we qualitatively and quantitatively evaluate the last years' modeling progress and study themore » impact of VRE integration modeling on VRE deployment in IAM scenarios. For a comprehensive and transparent qualitative evaluation, we first develop a framework of 18 features of power sector dynamics and VRE integration. We then apply this framework to the newly-developed modeling approaches to derive a detailed map of strengths and limitations of the different approaches. For the quantitative evaluation, we compare the IAMs to the detailed hourly-resolution power sector model REMIX. We find that the new modeling approaches manage to represent a large number of features of the power sector, and the numerical results are in reasonable agreement with those derived from the detailed power sector model. Updating the power sector representation and the cost and resources of wind and solar substantially increased wind and solar shares across models: Under a carbon price of 30$/tCO2 in 2020 (increasing by 5% per year), the model-average cost-minimizing VRE share over the period 2050-2100 is 62% of electricity generation, 24%-points higher than with the old model version.« less

Flaws in the LNT single-hit model for cancer risk: An historical assessment.

PubMed

Calabrese, Edward J

2017-10-01

The LNT single-hit model was derived from the Nobel Prize-winning research of Herman J. Muller who showed that x-rays could induce gene mutations in Drosophila and that the dose response for these so-called mutational events was linear. Lewis J. Stadler, another well-known and respected geneticist at the time, strongly disagreed with and challenged Muller's claims. Detailed evaluations by Stadler over a prolonged series of investigations revealed that Muller's experiments had induced gross heritable chromosomal damage instead of specific gene mutations as had been claimed by Muller at his Nobel Lecture. These X-ray-induced alterations became progressively more frequent and were of larger magnitude (more destructive) with increasing doses. Thus, Muller's claim of having induced discrete gene mutations represented a substantial speculative overreach and was, in fact, without proof. The post hoc arguments of Muller to support his gene mutation hypothesis were significantly challenged and weakened by a series of new findings in the areas of cytogenetics, reverse mutation, adaptive and repair processes, and modern molecular methods for estimating induced genetic damage. These findings represented critical and substantial limitations to Muller's hypothesis of X-ray-induced gene mutations. Furthermore, they challenged the scientific foundations used in support of the LNT single-hit model by severing the logical nexus between Muller's data on radiation-induced inheritable alterations and the LNT single-hit model. These findings exposed fundamental scientific flaws that undermined not only the seminal recommendation of the 1956 BEAR I Genetics Panel to adopt the LNT single-hit Model for risk assessment but also any rationale for its continued use in the present day. Copyright © 2017 Elsevier Inc. All rights reserved.

Compartments, Customers, or Convergence?: Evolving Challenges to IT Progress

ERIC Educational Resources Information Center

Jackson, Gregory A.

2007-01-01

For most of the past decade, IT leaders in higher education felt on top of things. Challenges were usually comprehensible and addressable, doing reasonable things yielded reasonable results, and for the most part, IT was a substantial contributor to institutional progress. But these days, IT leaders rarely feel on top of things. Instead, some days…

The Global Nutrition Report 2014: Actions and Accountability to Accelerate the World’s Progress on Nutrition1–4

PubMed Central

Haddad, Lawrence; Achadi, Endang; Bendech, Mohamed Ag; Ahuja, Arti; Bhatia, Komal; Bhutta, Zulfiqar; Blössner, Monika; Borghi, Elaine; Colecraft, Esi; de Onis, Mercedes; Eriksen, Kamilla; Fanzo, Jessica; Flores-Ayala, Rafael; Fracassi, Patrizia; Kimani-Murage, Elizabeth; Koukoubou, Eunice Nago; Krasevec, Julia; Newby, Holly; Nugent, Rachel; Oenema, Stineke; Martin-Prével, Yves; Randel, Judith; Requejo, Jennifer; Shyam, Tara; Udomkesmalee, Emorn; Reddy, K Srinath

2016-01-01

In 2013, the Nutrition for Growth Summit called for a Global Nutrition Report (GNR) to strengthen accountability in nutrition so that progress in reducing malnutrition could be accelerated. This article summarizes the results of the first GNR. By focusing on undernutrition and overweight, the GNR puts malnutrition in a new light. Nearly every country in the world is affected by malnutrition, and multiple malnutrition burdens are the “new normal.” Unfortunately, the world is off track to meet the 2025 World Health Assembly (WHA) targets for nutrition. Many countries are, however, making good progress on WHA indicators, providing inspiration and guidance for others. Beyond the WHA goals, nutrition needs to be more strongly represented in the Sustainable Development Goal (SDG) framework. At present, it is only explicitly mentioned in 1 of 169 SDG targets despite the many contributions improved nutritional status will make to their attainment. To achieve improvements in nutrition status, it is vital to scale up nutrition programs. We identify bottlenecks in the scale-up of nutrition-specific and nutrition-sensitive approaches and highlight actions to accelerate coverage and reach. Holding stakeholders to account for delivery on nutrition actions requires a well-functioning accountability infrastructure, which is lacking in nutrition. New accountability mechanisms need piloting and evaluation, financial resource flows to nutrition need to be made explicit, nutrition spending targets should be established, and some key data gaps need to be filled. For example, many UN member states cannot report on their WHA progress and those that can often rely on data >5 y old. The world can accelerate malnutrition reduction substantially, but this will require stronger accountability mechanisms to hold all stakeholders to account. PMID:25740908

Scheduling Earth Observing Fleets Using Evolutionary Algorithms: Problem Description and Approach

NASA Technical Reports Server (NTRS)

Globus, Al; Crawford, James; Lohn, Jason; Morris, Robert; Clancy, Daniel (Technical Monitor)

2002-01-01

We describe work in progress concerning multi-instrument, multi-satellite scheduling. Most, although not all, Earth observing instruments currently in orbit are unique. In the relatively near future, however, we expect to see fleets of Earth observing spacecraft, many carrying nearly identical instruments. This presents a substantially new scheduling challenge. Inspired by successful commercial applications of evolutionary algorithms in scheduling domains, this paper presents work in progress regarding the use of evolutionary algorithms to solve a set of Earth observing related model problems. Both the model problems and the software are described. Since the larger problems will require substantial computation and evolutionary algorithms are embarrassingly parallel, we discuss our parallelization techniques using dedicated and cycle-scavenged workstations.

Do scheduled caste and scheduled tribe women legislators mean lower gender-caste gaps in primary schooling in India?

PubMed

Halim, Nafisa; Yount, Kathryn M; Cunningham, Solveig

2016-07-01

Despite India's substantial investments in primary schooling, gaps in schooling persist across gender and caste-with scheduled caste and scheduled tribe (SC/ST) girls being particularly disadvantaged. The representation of SC/ST women in state legislatures may help to mitigate this disadvantage. Specifically, because of her intersecting gender and caste/tribe identities, a SC/ST woman legislator might maintain a strong sense of solidarity especially with SC/ST girls and women, and support legislative policies benefitting SC/ST girls. Consequently, for this reason, we expect that living in a district where SC/ST women represent in state legislatures in a higher proportion may increase SC/ST girls' primary school completion, progression and performance. We tested this hypothesis using district-level data between 2000 and 2004 from the Indian Election Commission, the 2004/5 India Human Development Survey, and the Indian Census of 2001. As expected, the representation of SC/ST women in state legislatures was positively associated with SC/ST girls' grade completion and age-appropriate grade progression but was apparent not SC/ST girls' primary-school performance. SC/ST women's representation in state legislatures may reduce gender-caste gaps in primary-school attainment in India. Copyright © 2016. Published by Elsevier Inc.

Vaccines licensed and in clinical trials for the prevention of dengue.

PubMed

Torresi, J; Ebert, G; Pellegrini, M

2017-05-04

Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1-80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans.

Current perspectives and the future of domestication studies

PubMed Central

Larson, Greger; Piperno, Dolores R.; Allaby, Robin G.; Purugganan, Michael D.; Andersson, Leif; Arroyo-Kalin, Manuel; Barton, Loukas; Climer Vigueira, Cynthia; Denham, Tim; Dobney, Keith; Doust, Andrew N.; Gepts, Paul; Gilbert, M. Thomas P.; Gremillion, Kristen J.; Lucas, Leilani; Lukens, Lewis; Marshall, Fiona B.; Olsen, Kenneth M.; Pires, J. Chris; Richerson, Peter J.; Rubio de Casas, Rafael; Sanjur, Oris I.; Thomas, Mark G.; Fuller, Dorian Q.

2014-01-01

It is difficult to overstate the cultural and biological impacts that the domestication of plants and animals has had on our species. Fundamental questions regarding where, when, and how many times domestication took place have been of primary interest within a wide range of academic disciplines. Within the last two decades, the advent of new archaeological and genetic techniques has revolutionized our understanding of the pattern and process of domestication and agricultural origins that led to our modern way of life. In the spring of 2011, 25 scholars with a central interest in domestication representing the fields of genetics, archaeobotany, zooarchaeology, geoarchaeology, and archaeology met at the National Evolutionary Synthesis Center to discuss recent domestication research progress and identify challenges for the future. In this introduction to the resulting Special Feature, we present the state of the art in the field by discussing what is known about the spatial and temporal patterns of domestication, and controversies surrounding the speed, intentionality, and evolutionary aspects of the domestication process. We then highlight three key challenges for future research. We conclude by arguing that although recent progress has been impressive, the next decade will yield even more substantial insights not only into how domestication took place, but also when and where it did, and where and why it did not. PMID:24757054

Do scheduled caste and scheduled tribe women legislators mean lower gender-caste gaps in primary schooling in India?

PubMed Central

Halim, Nafisa; Yount, Kathryn M.; Cunningham, Solveig

2017-01-01

Despite India’s substantial investments in primary schooling, gaps in schooling persist across gender and caste—with scheduled caste and scheduled tribe (SC/ST) girls being particularly disadvantaged. The representation of SC/ST women in state legislatures may help to mitigate this disadvantage. Specifically, because of her intersecting gender and caste/tribe identities, a SC/ST woman legislator might maintain a strong sense of solidarity especially with SC/ST girls and women, and support legislative policies benefitting SC/ST girls. Consequently, for this reason, we expect that living in a district where SC/ST women represent in state legislatures in a higher proportion may increase SC/ST girls’ primary school completion, progression and performance. We tested this hypothesis using district-level data between 2000 and 2004 from the Indian Election Commission, the 2004/5 India Human Development Survey, and the Indian Census of 2001. As expected, the representation of SC/ST women in state legislatures was positively associated with SC/ST girls’ grade completion and age-appropriate grade progression but was apparent not SC/ST girls’ primary-school performance. SC/ST women’s representation in state legislatures may reduce gender-caste gaps in primary-school attainment in India. PMID:27194655

Vaccines licensed and in clinical trials for the prevention of dengue

PubMed Central

Torresi, J.; Ebert, G.; Pellegrini, M.

2017-01-01

ABSTRACT Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1–80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans. PMID:28281864

Progress in Application of the Neurosciences to an Understanding of Human Learning: The Challenge of Finding a Middle-Ground Neuroeducational Theory

ERIC Educational Resources Information Center

Anderson, O. Roger

2014-01-01

Modern neuroscientific research has substantially enhanced our understanding of the human brain. However, many challenges remain in developing a strong, brain-based theory of human learning, especially in complex environments such as educational settings. Some of the current issues and challenges in our progress toward developing comprehensive…

Progress and Challenges in Subseasonal Prediction

NASA Technical Reports Server (NTRS)

Schubert, Siegfried

2003-01-01

While substantial advances have occurred over the last few decades in both weather and seasonal prediction, progress in improving predictions on subseasonal time scales (approximately 2 weeks to 2 months) has been slow. In this talk I will highlight some of the recent progress that has been made to improve forecasts on subseasonal time scales and outline the challenges that we face both from an observational and modeling perspective. The talk will be based primarily on the results and conclusions of a recent NASA-sponsored workshop that focused on the subseasonal prediction problem. One of the key conclusions of that workshop was that there is compelling evidence for predictability at forecast lead times substantially longer than two weeks, and that much of that predictability is currently untapped. Tropical diabatic heating and soil wetness were singled out as particularly important processes affecting predictability on these time scales. Predictability was also linked to various low-frequency atmospheric phenomena such as the annular modes in high latitudes (including their connections to the stratosphere), the Pacific/North American pattern, and the Madden-Julian Oscillation. I will end the talk by summarizing the recommendations and plans that have been put forward for accelerating progress on the subseasonal prediction problem.

Wildland fire as a self-regulating mechanism: the role of previous burns and weather in limiting fire progression.

PubMed

Parks, Sean A; Holsinger, Lisa M; Miller, Carol; Nelson, Cara R

2015-09-01

Theory suggests that natural fire regimes can result in landscapes that are both self-regulating and resilient to fire. For example, because fires consume fuel, they may create barriers to the spread of future fires, thereby regulating fire size. Top-down controls such as weather, however, can weaken this effect. While empirical examples demonstrating this pattern-process feedback between vegetation and fire exist, they have been geographically limited or did not consider the influence of time between fires and weather. The availability of remotely sensed data identifying fire activity over the last four decades provides an opportunity to explicitly quantify-the ability of wildland fire to limit the progression of subsequent fire. Furthermore, advances in fire progression mapping now allow an evaluation of how daily weather as a top-down control modifies this effect. In this study, we evaluated the ability of wildland fire to create barriers that limit the spread of subsequent fire along a gradient representing time between fires in four large study areas in the western United States. Using fire progression maps in conjunction with weather station data, we also evaluated the influence of daily weather. Results indicate that wildland fire does limit subsequent fire spread in all four study areas, but this effect decays over time; wildland fire no longer limits subsequent fire spread 6-18 years after fire, depending on the study area. We also found that the ability of fire to regulate, subsequent fire progression was substantially reduced under extreme conditions compared to moderate weather conditions in all four study areas. This study increases understanding of the spatial feedbacks that can lead to self-regulating landscapes as well as the effects of top-down controls, such as weather, on these feedbacks. Our results will be useful to managers who seek to restore natural fire regimes or to exploit recent burns when managing fire.

Vision in a phase 3 trial of natalizumab for multiple sclerosis: relation to disability and quality of life.

PubMed

Chahin, Salim; Balcer, Laura J; Miller, Deborah M; Zhang, Annie; Galetta, Steven L

2015-03-01

Low-contrast visual acuity (LCVA), a sensitive measure of visual function in multiple sclerosis (MS), demonstrated treatment effects as a secondary outcome measure in the Phase 3 trial of natalizumab, AFFIRM. In these posttrial analyses, we studied the relation of visual function to quality of life (QOL), magnetic resonance imaging (MRI) measures, and Expanded Disability Status Scale (EDSS) scores. At baseline and at 52 and 104 weeks in AFFIRM, patients underwent binocular testing of LCVA (1.25% and 2.5% contrast) and high-contrast visual acuity (HCVA). Vision-specific QOL was assessed by the Impact of Visual Impairment Scale (IVIS), whereas the SF-36 Health Survey and Visual Analog Scale were administered as generic QOL measures and the EDSS as a measure of neurologic impairment. Among QOL measures, IVIS scores showed the most significant correlations with visual dysfunction at all time points in the trial (r= -0.25 to -0.45, P < 0.0001 for LCVA and HCVA). Higher MRI T1- and T2-lesion volumes were also associated with worse vision scores at all time points (P < 0.0001). Clinically meaningful worsening (progression) of LCVA was noted in substantial proportions of patients in AFFIRM and was prevalent even among those without EDSS progression over 2 years (21.9% with LCVA progression at 2.5% contrast; 26.2% at 1.25% contrast). HCVA worsened in only 3.7% of patients without EDSS progression. Loss of visual function, particularly as measured by LCVA, was common in AFFIRM, occurring in >20% of patients. Both LCVA and HCVA scores reflect vision-specific aspects of QOL, but LCVA provides information about disability progression not entirely captured by the EDSS. Vision represents a key dimension of outcome assessment for MS and adds valuable information on disability and QOL that can be useful to clinicians.

Primary progressive aphasia: a clinical approach.

PubMed

Marshall, Charles R; Hardy, Chris J D; Volkmer, Anna; Russell, Lucy L; Bond, Rebecca L; Fletcher, Phillip D; Clark, Camilla N; Mummery, Catherine J; Schott, Jonathan M; Rossor, Martin N; Fox, Nick C; Crutch, Sebastian J; Rohrer, Jonathan D; Warren, Jason D

2018-06-01

The primary progressive aphasias are a heterogeneous group of focal 'language-led' dementias that pose substantial challenges for diagnosis and management. Here we present a clinical approach to the progressive aphasias, based on our experience of these disorders and directed at non-specialists. We first outline a framework for assessing language, tailored to the common presentations of progressive aphasia. We then consider the defining features of the canonical progressive nonfluent, semantic and logopenic aphasic syndromes, including 'clinical pearls' that we have found diagnostically useful and neuroanatomical and other key associations of each syndrome. We review potential diagnostic pitfalls and problematic presentations not well captured by conventional classifications and propose a diagnostic 'roadmap'. After outlining principles of management, we conclude with a prospect for future progress in these diseases, emphasising generic information processing deficits and novel pathophysiological biomarkers.

Micronutrients, N-Acetyl Cysteine, Probiotics and Prebiotics, a Review of Effectiveness in Reducing HIV Progression

PubMed Central

Hummelen, Ruben; Hemsworth, Jaimie; Reid, Gregor

2010-01-01

Low serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical trials of these interventions on the progression of HIV. Vitamin B, C, E, and folic acid have been shown to delay the progression of HIV. Supplementation with selenium, N-acetyl cysteine, probiotics, and prebiotics has considerable potential, but the evidence needs to be further substantiated. Vitamin A, iron, and zinc have been associated with adverse effects and caution is warranted for their use. PMID:22254046

Early Rockets

NASA Image and Video Library

2004-04-15

Dr. Robert H. Goddard loading a 1918 version of the Bazooka of World War II. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets, which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

The Unfulfilled Promise of Special Education: The Transition from Education to Work for Young Adults with Disabilities

ERIC Educational Resources Information Center

Rusch, Frank R.; Loomis, Frederick D.

2005-01-01

During the past quarter century, federal legislation has resulted in fundamental changes in the way youth with special needs are educated. Despite legal mandates and substantial funding support, only minimal progress has been made in the rate at which exceptional children progress through school to the world of work. During the past 30 years,…

Designing Unmanned Systems with Greater Autonomy: Using a Federated, Partially Open Systems Architecture Approach

DTIC Science & Technology

2014-01-01

system UAV unmanned aircraft vehicle UCI User -Computer Interface UCS UAS control segment Abbreviations xxix UGS unmanned ground system UGV unmanned ...made substantial progress in the deployment of more capable sensors, unmanned aircraft systems (UAS), and other unmanned systems (UxS). Innovative...progress in fielding more, and more capable unmanned aircraft systems (UAS) to meet the needs of warfighters

Programmatic Research to Develop and Disseminate Improved Instructional Technology for Handicapped Children. Project MORE Quarterly Progress Report, September 1 to December 1, 1972.

ERIC Educational Resources Information Center

Schiefelbusch, Richard L.; Lent, James R.

During the past reporting period the curriculum development staff of Project MORE (Mediated Operational Research for Education) has made substantial progress in attaining its program objectives. Design and development phases have proceeded on schedule. Four programs are currently in the field-testing stage, and four others are under development.…

Maternal and neonatal tetanus

PubMed Central

Thwaites, C Louise; Beeching, Nicholas J; Newton, Charles R

2017-01-01

Maternal and neonatal tetanus is still a substantial but preventable cause of mortality in many developing countries. Case fatality from these diseases remains high and treatment is limited by scarcity of resources and effective drug treatments. The Maternal and Neonatal Tetanus Elimination Initiative, launched by WHO and its partners, has made substantial progress in eliminating maternal and neonatal tetanus. Sustained emphasis on improvement of vaccination coverage, birth hygiene, and surveillance, with specific approaches in high-risk areas, has meant that the incidence of the disease continues to fall. Despite this progress, an estimated 58 000 neonates and an unknown number of mothers die every year from tetanus. As of June, 2014, 24 countries are still to eliminate the disease. Maintenance of elimination needs ongoing vaccination programmes and improved public health infrastructure. PMID:25149223

Solid-state optical refrigeration to sub-100 Kelvin regime

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

Melgaard, Seth D.; Albrecht, Alexander R.; Hehlen, Markus P.

We report that since the first demonstration of net cooling twenty years ago, optical refrigeration of solids has progressed to outperform all other solid-state cooling processes. It has become the first and only solid-state refrigerator capable of reaching cryogenic temperatures, and now the first solid-state cooling below 100 K. Such substantial progress required a multi-disciplinary approach of pump laser absorption enhancement, material characterization and purification, and thermal management. Here we present the culmination of two decades of progress, the record cooling to ≈91K from room temperature.

Solid-state optical refrigeration to sub-100 Kelvin regime

DOE PAGES

Melgaard, Seth D.; Albrecht, Alexander R.; Hehlen, Markus P.; ...

2016-02-05

We report that since the first demonstration of net cooling twenty years ago, optical refrigeration of solids has progressed to outperform all other solid-state cooling processes. It has become the first and only solid-state refrigerator capable of reaching cryogenic temperatures, and now the first solid-state cooling below 100 K. Such substantial progress required a multi-disciplinary approach of pump laser absorption enhancement, material characterization and purification, and thermal management. Here we present the culmination of two decades of progress, the record cooling to ≈91K from room temperature.

Extended-range tiltable micromirror

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

Allen, James J; Wiens, Gloria J; Bronson, Jessica R

A tiltable micromirror device is disclosed in which a micromirror is suspended by a progressive linkage with an electrostatic actuator (e.g. a vertical comb actuator or a capacitive plate electrostatic actuator) being located beneath the micromirror. The progressive linkage includes a pair of torsion springs which are connected together to operate similar to a four-bar linkage with spring joints. The progressive linkage provides a non-linear spring constant which can allow the micromirror to be tilted at any angle within its range substantially free from any electrostatic instability or hysteretic behavior.

Solid-state optical refrigeration to sub-100 Kelvin regime

PubMed Central

Melgaard, Seth D.; Albrecht, Alexander R.; Hehlen, Markus P.; Sheik-Bahae, Mansoor

2016-01-01

Since the first demonstration of net cooling twenty years ago, optical refrigeration of solids has progressed to outperform all other solid-state cooling processes. It has become the first and only solid-state refrigerator capable of reaching cryogenic temperatures, and now the first solid-state cooling below 100 K. Such substantial progress required a multi-disciplinary approach of pump laser absorption enhancement, material characterization and purification, and thermal management. Here we present the culmination of two decades of progress, the record cooling to ≈ 91 K from room temperature. PMID:26847703

Artificial intelligence and deep learning - Radiology's next frontier?

PubMed

Mayo, Ray Cody; Leung, Jessica

Tracing the use of computers in the radiology department from administrative functions through image acquisition, storage, and reporting, to early attempts at improved diagnosis, we begin to imagine possible new frontiers for their use in exam interpretation. Given their initially slow but ultimately substantial progress in the noninterpretive areas, we are left desiring and even expecting more in the interpretation realm. New technological advances may provide the next wave of progress and radiologists should be early adopters. Several potential applications are discussed and hopefully will serve to inspire future progress. Published by Elsevier Inc.

FOXA1 promotes tumor progression in prostate cancer and represents a novel hallmark of castration-resistant prostate cancer.

PubMed

Gerhardt, Josefine; Montani, Matteo; Wild, Peter; Beer, Marc; Huber, Fabian; Hermanns, Thomas; Müntener, Michael; Kristiansen, Glen

2012-02-01

Forkhead box protein A1 (FOXA1) modulates the transactivation of steroid hormone receptors and thus may influence tumor growth and hormone responsiveness in prostate cancer. We therefore investigated the correlation of FOXA1 expression with clinical parameters, prostate-specific antigen (PSA) relapse-free survival, and hormone receptor expression in a large cohort of prostate cancer patients at different disease stages. FOXA1 expression did not differ significantly between benign glands from the peripheral zone and primary peripheral zone prostate carcinomas. However, FOXA1 was overexpressed in metastases and particularly in castration-resistant cases, but was expressed at lower levels in both normal and neoplastic transitional zone tissues. FOXA1 levels correlated with higher pT stages and Gleason scores, as well as with androgen (AR) and estrogen receptor expression. Moreover, FOXA1 overexpression was associated with faster biochemical disease progression, which was pronounced in patients with low AR levels. Finally, siRNA-based knockdown of FOXA1 induced decreased cell proliferation and migration. Moreover, in vitro tumorigenicity was inducible by ARs only in the presence of FOXA1, substantiating a functional cooperation between FOXA1 and AR. In conclusion, FOXA1 expression is associated with tumor progression, dedifferentiation of prostate cancer cells, and poorer prognosis, as well as with cellular proliferation and migration and with AR signaling. These findings suggest FOXA1 overexpression as a novel mechanism inducing castration resistance in prostate cancer. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease.

PubMed

Levey, Allan; Lah, James; Goldstein, Felicia; Steenland, Kyle; Bliwise, Donald

2006-07-01

There is increasing evidence that subtle losses in cognitive function may be symptomatic of a transition to early Alzheimer's disease (AD). Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to AD. Of the MCI subtypes, patients with amnestic MCI (a-MCI) are at greatest risk. The objectives of this article were to review the relationship between MCI, normal aging, and AD, and to summarize recent research on the diagnosis and potential treatment of MCI. Relevant articles were identified through searches of MEDLINE and EMBASE using the terms mild cognitive impairment; cognitive impairment, no dementia; and dementia prodrome, with no restrictions as to year. Additional papers of interest were identified from the reference lists of the identified articles. The search was current as of February 2006. Guidelines and recommendations are being developed to assist physicians in diagnosing MCI, identifying its subtype and etiology, understanding the risks for conversion to AD, and managing disease progression. Given the existence of a subset of individuals with a-MCI, who are at greatest risk for progression to AD but still have high levels of cognition and function, the ability to improve symptoms and delay progression to AD would be particularly beneficial. In a 3-year, randomized, double-blind, placebo-controlled study in 769 patients with a-MCI, treatment with the cholinesterase inhibitor donepezil was associated with a significantly lower rate of progression to AD compared with placebo during the first 12 months of treatment (hazard ratio=0.42; 95% CI, 0.24-0.76; P=0.004) but not at later time points. Of other types of agents that have been investigated (antioxidants, estrogen replacement therapy, cyclooxygenase-2-selective inhibitors), none have shown significant beneficial effects in delaying cognitive decline or progression to AD. New drugs such as secretase inhibitors, small molecules that disrupt amyloid aggregation, and immunotherapies are in preclinical development. MCI involves more substantial cognitive and memory decline than normal aging and represents a significant risk factor for the development of dementia. Further research is needed into treatments to delay the conversion from MCI to AD.

Visualizing global properties of a molecular dynamics trajectory.

PubMed

Zhou, Hao; Li, Shangyang; Makowski, Lee

2016-01-01

Molecular dynamics (MD) trajectories are very large data sets that contain substantial information about the dynamic behavior of a protein. Condensing these data into a form that can provide intuitively useful understanding of the molecular behavior during the trajectory is a substantial challenge that has received relatively little attention. Here, we introduce the sigma-r plot, a plot of the standard deviation of intermolecular distances as a function of that distance. This representation of global dynamics contains within a single, one-dimensional plot, the average range of motion between pairs of atoms within a macromolecule. Comparison of sigma-r plots calculated from 10 ns trajectories of proteins representing the four major SCOP fold classes indicates diversity of dynamic behaviors which are recognizably different among the four classes. Differences in domain structure and molecular weight also produce recognizable features in sigma-r plots, reflective of differences in global dynamics. Plots generated from trajectories with progressively increasing simulation time reflect the increased sampling of the structural ensemble as a function of time. Single amino acid replacements can give rise to changes in global dynamics detectable through comparison of sigma-r plots. Dynamic behavior of substructures can be monitored by careful choice of interatomic vectors included in the calculation. These examples provide demonstrations of the utility of the sigma-r plot to provide a simple measure of the global dynamics of a macromolecule. © 2015 Wiley Periodicals, Inc.

Checkpoints to Progression: Qualitative Analysis of the Personal and Contextual Factors That Influence Selection of Upper Extremity Reconstruction Among Patients With Tetraplegia.

PubMed

Harris, Chelsea A; Muller, John-Michael; Shauver, Melissa J; Chung, Kevin C

2017-07-01

Patients with tetraplegia consistently rank better use of the upper extremity as their top functional priority. Multiple case series have demonstrated that upper extremity reconstruction (UER) is well-tolerated and can produce substantial functional improvements for appropriate candidates; however, UER remains critically underutilized. The mechanisms that drive differences in provider practice and referral patterns have been studied, but comprehensive examination of the patient factors that influence UER decisions has not been performed for American patients. Nineteen patients with C4-8 cervical spinal injuries were selected using purposive sampling: 9 patients had undergone UER, 10 had not undergone UER. Semistructured interviews were conducted and transcripts evaluated using grounded theory methodology. Our study yielded a conceptual model that describes the characteristics common to all patients who undergo UER. Patients who selected reconstruction proceeded stepwise through a shared sequence of steps: (1) functional dissatisfaction, (2) awareness of UER, and (3) acceptance of surgery. Patients' ability to meet these criteria was determined by 3 checkpoints: how well they coped, their access to information, and the acceptability of surgery. Extremely positive or negative coping prevented patients from moving from the Coping to the Information Checkpoint; thus, they remained unaware of UER and did not undergo surgery. A lack of knowledge regarding reconstruction was the strongest barrier to surgery among our participants. We built a conceptual model that outlines how patients' personal and contextual factors drive their progression to UER. Moving from functional dissatisfaction to understanding that they were candidates for UER was a substantial barrier for participants, particularly those with very high and very low coping skills. To improve utilization for all patients, interventions are needed to increase UER awareness. Standardizing introduction to UER during the rehabilitation process or improving e-content may represent key awareness access points. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

30 CFR 18.61 - Final inspection of complete machine.

Code of Federal Regulations, 2011 CFR

2011-07-01

... substantially modified design of a previously approved one shall be inspected by a qualified representative(s... requirements of this part with respect to joints, lead entrances, and other pertinent features. (2) Wiring...

A Learning Progression for Elementary Students' Functional Thinking

ERIC Educational Resources Information Center

Stephens, Ana C.; Fonger, Nicole; Strachota, Susanne; Isler, Isil; Blanton, Maria; Knuth, Eric; Murphy Gardiner, Angela

2017-01-01

In this article we advance characterizations of and supports for elementary students' progress in generalizing and representing functional relationships as part of a comprehensive approach to early algebra. Our learning progressions approach to early algebra research involves the coordination of a curricular framework and progression, an…

Pluripotent stem cell derived hepatocyte like cells and their potential in toxicity screening.

PubMed

Greenhough, Sebastian; Medine, Claire N; Hay, David C

2010-12-30

Despite considerable progress in modelling human liver toxicity, the requirement still exists for efficient, predictive and cost effective in vitro models to reduce attrition during drug development. Thousands of compounds fail in this process, with hepatotoxicity being one of the significant causes of failure. The cost of clinical studies is substantial, therefore it is essential that toxicological screening is performed early on in the drug development process. Human hepatocytes represent the gold standard model for evaluating drug toxicity, but are a limited resource. Current alternative models are based on immortalised cell lines and animal tissue, but these are limited by poor function, exhibit species variability and show instability in culture. Pluripotent stem cells are an attractive alternative as they are capable of self-renewal and differentiation to all three germ layers, and thereby represent a potentially inexhaustible source of somatic cells. The differentiation of human embryonic stem cells and induced pluripotent stem cells to functional hepatocyte like cells has recently been reported. Further development of this technology could lead to the scalable production of hepatocyte like cells for liver toxicity screening and clinical therapies. Additionally, induced pluripotent stem cell derived hepatocyte like cells may permit in vitro modelling of gene polymorphisms and genetic diseases. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Uremic Solutes in Chronic Kidney Disease and Their Role in Progression.

PubMed

van den Brand, Jan A J G; Mutsaers, Henricus A M; van Zuilen, Arjan D; Blankestijn, Peter J; van den Broek, Petra H; Russel, Frans G M; Masereeuw, Rosalinde; Wetzels, Jack F M

2016-01-01

To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated. Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year) or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated. In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time. Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated.

Dr. Goddard and a 1918 version of 'Bazooka'

NASA Technical Reports Server (NTRS)

2004-01-01

Dr. Robert H. Goddard loading a 1918 version of the Bazooka of World War II. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets, which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

42 CFR 422.254 - Submission of bids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... part or may choose not to renew the contract. (4) Substantial differences between bids. An MA organization's bid submissions must reflect differences in benefit packages or plan costs that CMS determines to represent substantial differences relative to a sponsor's other bid submissions. (5) CMS may...

42 CFR 422.254 - Submission of bids.

Code of Federal Regulations, 2012 CFR

2012-10-01

... this part or may choose not to renew the contract. (4) Substantial differences between bids. An MA organization's bid submissions must reflect differences in benefit packages or plan costs that CMS determines to represent substantial differences relative to a sponsor's other bid submissions. (5) CMS may...

42 CFR 422.254 - Submission of bids.

Code of Federal Regulations, 2013 CFR

2013-10-01

... this part or may choose not to renew the contract. (4) Substantial differences between bids. An MA organization's bid submissions must reflect differences in benefit packages or plan costs that CMS determines to represent substantial differences relative to a sponsor's other bid submissions. (5) CMS may...

Immunotherapy in ovarian, endometrial and cervical cancer: State of the art and future perspectives.

PubMed

Ventriglia, Jole; Paciolla, Immacolata; Pisano, Carmela; Cecere, Sabrina Chiara; Di Napoli, Marilena; Tambaro, Rosa; Califano, Daniela; Losito, Simona; Scognamiglio, Giosuè; Setola, Sergio Venanzio; Arenare, Laura; Pignata, Sandro; Della Pepa, Chiara

2017-09-01

The tumors of the female genital tract represent a leading cause of morbidity and mortality among women worldwide. Substantial progresses have been made in ovarian cancer, with the increasing knowledge about BRCA mutated tumors and the recent development of PARP inhibitors, and in cervical cancer, thanks to extensive screening and widespread of vaccination against Human Papilloma Virus. Nevertheless many needs remain unmet, advanced stage diseases are still incurable and cervical and endometrial carcinoma, as well as platinum-resistant ovarian carcinoma, can certainly be classifiable among the cancers with poor sensitivity to conventional chemotherapy. Immunotherapy, including a number of approaches, checkpoint inhibitors, adoptive cellular transfer, vaccines, has experienced a remarkable growth in the last few years and it is already an available option in melanoma, lung and renal malignancies. We reviewed the main findings about the immune microenvironment in ovarian, endometrial and cervical cancer with a special focus on the clinical data, the therapeutic implications and the most promising novel agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Big data to smart data in Alzheimer's disease: Real-world examples of advanced modeling and simulation.

PubMed

Haas, Magali; Stephenson, Diane; Romero, Klaus; Gordon, Mark Forrest; Zach, Neta; Geerts, Hugo

2016-09-01

Many disease-modifying clinical development programs in Alzheimer's disease (AD) have failed to date, and development of new and advanced preclinical models that generate actionable knowledge is desperately needed. This review reports on computer-based modeling and simulation approach as a powerful tool in AD research. Statistical data-analysis techniques can identify associations between certain data and phenotypes, such as diagnosis or disease progression. Other approaches integrate domain expertise in a formalized mathematical way to understand how specific components of pathology integrate into complex brain networks. Private-public partnerships focused on data sharing, causal inference and pathway-based analysis, crowdsourcing, and mechanism-based quantitative systems modeling represent successful real-world modeling examples with substantial impact on CNS diseases. Similar to other disease indications, successful real-world examples of advanced simulation can generate actionable support of drug discovery and development in AD, illustrating the value that can be generated for different stakeholders. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Advancing pluripotent stem cell culture: it is a matter of setting the standard.

PubMed

Sartipy, Peter

2013-04-15

Human pluripotent stem cells (hPSCs), defined by their ability to proliferate indefinitely and the capacity to differentiate into all tissue cell types of the adult, represent a platform for the realization of breakthrough technologies for industrial and regenerative medicine applications. We have witnessed tremendous developments over the last decade related to methods for establishment, maintenance, differentiation, and applications of hPSCs and their derivatives. Despite all progress made in the hPSC field, there are still fundamental issues yet to be resolved. For example, our understanding of the pluripotent state remains limited, which in turn may have substantial consequences on how we interpret and communicate scientific data concerning hPSCs. This brief commentary aims to highlight recent important findings that demonstrate additional levels of complexity to the current assessment of pluripotent stem cell cultures. In addition, these data may help to provide some explanations for the challenges in reproducing hPSC differentiation protocols across laboratories.

Strategy for earth explorers in global earth sciences

NASA Technical Reports Server (NTRS)

1988-01-01

The goal of the current NASA Earth System Science initiative is to obtain a comprehensive scientific understanding of the Earth as an integrated, dynamic system. The centerpiece of the Earth System Science initiative will be a set of instruments carried on polar orbiting platforms under the Earth Observing System program. An Earth Explorer program can open new vistas in the earth sciences, encourage innovation, and solve critical scientific problems. Specific missions must be rigorously shaped by the demands and opportunities of high quality science and must complement the Earth Observing System and the Mission to Planet Earth. The committee believes that the proposed Earth Explorer program provides a substantial opportunity for progress in the earth sciences, both through independent missions and through missions designed to complement the large scale platforms and international research programs that represent important national commitments. The strategy presented is intended to help ensure the success of the Earth Explorer program as a vital stimulant to the study of the planet.

Disentangling the heterogeneity of autism spectrum disorder through genetic findings

PubMed Central

Jeste, Shafali S.; Geschwind, Daniel H.

2014-01-01

Autism spectrum disorder (ASD) represents a heterogeneous group of disorders, which presents a substantial challenge to diagnosis and treatment. Over the past decade, considerable progress has been made in the identification of genetic risk factors for ASD that define specific mechanisms and pathways underlying the associated behavioural deficits. In this Review, we discuss how some of the latest advances in the genetics of ASD have facilitated parsing of the phenotypic heterogeneity of this disorder. We argue that only through such advances will we begin to define endophenotypes that can benefit from targeted, hypothesis-driven treatments. We review the latest technologies used to identify and characterize the genetics underlying ASD and then consider three themes—single-gene disorders, the gender bias in ASD, and the genetics of neurological comorbidities—that highlight ways in which we can use genetics to define the many phenotypes within the autism spectrum. We also present current clinical guidelines for genetic testing in ASD and their implications for prognosis and treatment. PMID:24468882

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

PubMed

Wilkinson, Trevor C I

2016-06-15

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

The Applications of Model-Based Geostatistics in Helminth Epidemiology and Control

PubMed Central

Magalhães, Ricardo J. Soares; Clements, Archie C.A.; Patil, Anand P.; Gething, Peter W.; Brooker, Simon

2011-01-01

Funding agencies are dedicating substantial resources to tackle helminth infections. Reliable maps of the distribution of helminth infection can assist these efforts by targeting control resources to areas of greatest need. The ability to define the distribution of infection at regional, national and subnational levels has been enhanced greatly by the increased availability of good quality survey data and the use of model-based geostatistics (MBG), enabling spatial prediction in unsampled locations. A major advantage of MBG risk mapping approaches is that they provide a flexible statistical platform for handling and representing different sources of uncertainty, providing plausible and robust information on the spatial distribution of infections to inform the design and implementation of control programmes. Focussing on schistosomiasis and soil-transmitted helminthiasis, with additional examples for lymphatic filariasis and onchocerciasis, we review the progress made to date with the application of MBG tools in large-scale, real-world control programmes and propose a general framework for their application to inform integrative spatial planning of helminth disease control programmes. PMID:21295680

Regulation of T-cell receptor signalling by membrane microdomains

PubMed Central

Razzaq, Tahir M; Ozegbe, Patricia; Jury, Elizabeth C; Sembi, Phupinder; Blackwell, Nathan M; Kabouridis, Panagiotis S

2004-01-01

There is now considerable evidence suggesting that the plasma membrane of mammalian cells is compartmentalized by functional lipid raft microdomains. These structures are assemblies of specialized lipids and proteins and have been implicated in diverse biological functions. Analysis of their protein content using proteomics and other methods revealed enrichment of signalling proteins, suggesting a role for these domains in intracellular signalling. In T lymphocytes, structure/function experiments and complementary pharmacological studies have shown that raft microdomains control the localization and function of proteins which are components of signalling pathways regulated by the T-cell antigen receptor (TCR). Based on these studies, a model for TCR phosphorylation in lipid rafts is presented. However, despite substantial progress in the field, critical questions remain. For example, it is unclear if membrane rafts represent a homogeneous population and if their structure is modified upon TCR stimulation. In the future, proteomics and the parallel development of complementary analytical methods will undoubtedly contribute in further delineating the role of lipid rafts in signal transduction mechanisms. PMID:15554919

Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases

PubMed Central

Skeate, Joseph G.; Woodham, Andrew W.; Einstein, Mark H.; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

ABSTRACT Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed. PMID:26835746

Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia.

PubMed

Rogalski, E; Cobia, D; Harrison, T M; Wieneke, C; Weintraub, S; Mesulam, M-M

2011-05-24

To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials. Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S). There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere. The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects.

Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia

PubMed Central

Cobia, D.; Harrison, T.M.; Wieneke, C.; Weintraub, S.; Mesulam, M.-M.

2011-01-01

Objectives: To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials. Methods: Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S). Results: There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere. Conclusions: The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects. PMID:21606451

Interobserver agreement on Poser's and the new McDonald's diagnostic criteria for multiple sclerosis.

PubMed

Zipoli, V; Portaccio, E; Siracusa, G; Pracucci, G; Sorbi, S; Amato, M P

2003-10-01

We assessed the interobserver agreement on the diagnosis of multiple sclerosis (MS) in a study sample consisting of 41 MS (15 relapsing remitting, two secondary progressive, five primary progressive and 19 presenting their first clinical attack) and three non-MS cases. Clinical and paraclinical information was recorded in standardized forms. Four neurologists were asked to make a diagnosis using Poser's and McDonald's criteria and to assess MRI scans according to the McDonald's guidelines. In terms of the kappa statistic (kappa), we found a moderate agreement on the overall diagnosis using both Poser's and McDonald's criteria (kappa, respectively 0.57 and 0.52). As for distinct diagnostic categories, we observed a moderate to substantial agreement for the three McDonald categories (range of kappa values 0.49-0.64) and a fair to substantial agreement for the nine Poser categories (range of kappa values 0.37-0.67). Taking into account clinical information, the agreement on dissemination over time was substantially higher (kappa = 0.69) than that found on dissemination over space (kappa = 0.46). In contrast, for MRI assessment, the agreement for spatial dissemination was substantial (kappa = 0.74) compared with the fair agreement (kappa = 0.25) yielded by dissemination over time. The new McDonald's criteria yield a good overall diagnostic reliability, and compare favourably with Poser's classification in terms of agreement on distinct diagnostic categories.

Progress toward understanding the contribution of alkali generation in dental biofilms to inhibition of dental caries

PubMed Central

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

Imaging Cellular Architecture with X-rays

PubMed Central

Larabell, Carolyn A.; Nugent, Keith A.

2012-01-01

X-ray imaging of biological samples is progressing rapidly. In this paper we review the progress to date in high resolution imaging of cellular architecture. In particular we survey the progress in soft X-ray tomography and argue that the field is coming of age and that important biological insights are starting to emerge. We then review the new ideas based on coherent diffraction. These methods are at a much earlier stage of development but, as they eliminate the need for X-ray optics, have the capacity to provide substantially better spatial resolution than zone plate based methods. PMID:20869868

A perspective on renewable bioenergy from photosynthetic algae as feedstock for biofuels and bioproducts

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

Laurens, Lieve M. L.; Chen-Glasser, Melodie; McMillan, James D.

There has been substantial technical progress in developing algae-based bioenergy in recent years and a large part of industry and academic research and deployment projects have pivoted away from a pure biofuels strategy. This letter summarizes the findings of a recently completed, comprehensive report, that represents a collaborative effort of at least 20 co-authors, where we analyzed the prospects for using microalgae and macroalgae as feedstocks for biofuels and bioenergy production. The scope of this report includes a discussion of international activities advancing bioenergy and non-energy bioproducts from algae, progress on the use of macroalgae (both cast and cultivated seaweeds)more » for biogas applications, distinct biochemical and thermochemical conversion pathways, multi-product biorefining opportunities, as well as a thorough review of process economics and sustainability considerations. It is envisioned that a higher value algal biomass-based bioproducts industry will provide the additional revenue needed to reduce the net cost of producing algae-based biofuels. As such, a biorefinery approach that generates multiple high-value products from algae will be essential to fully valorize algal biomass and enable economically viable coproduction of bioenergy. Furthermore, to accelerate the implementation of algae-based production, minimizing energy, water, nutrients and land use footprints of integrated algae-based operations needs to be a primary objective of larger scale demonstrations and future research and development.« less

A greedy, graph-based algorithm for the alignment of multiple homologous gene lists.

PubMed

Fostier, Jan; Proost, Sebastian; Dhoedt, Bart; Saeys, Yvan; Demeester, Piet; Van de Peer, Yves; Vandepoele, Klaas

2011-03-15

Many comparative genomics studies rely on the correct identification of homologous genomic regions using accurate alignment tools. In such case, the alphabet of the input sequences consists of complete genes, rather than nucleotides or amino acids. As optimal multiple sequence alignment is computationally impractical, a progressive alignment strategy is often employed. However, such an approach is susceptible to the propagation of alignment errors in early pairwise alignment steps, especially when dealing with strongly diverged genomic regions. In this article, we present a novel accurate and efficient greedy, graph-based algorithm for the alignment of multiple homologous genomic segments, represented as ordered gene lists. Based on provable properties of the graph structure, several heuristics are developed to resolve local alignment conflicts that occur due to gene duplication and/or rearrangement events on the different genomic segments. The performance of the algorithm is assessed by comparing the alignment results of homologous genomic segments in Arabidopsis thaliana to those obtained by using both a progressive alignment method and an earlier graph-based implementation. Especially for datasets that contain strongly diverged segments, the proposed method achieves a substantially higher alignment accuracy, and proves to be sufficiently fast for large datasets including a few dozens of eukaryotic genomes. http://bioinformatics.psb.ugent.be/software. The algorithm is implemented as a part of the i-ADHoRe 3.0 package.

Non-invasive Diagnosis of Fibrosis in Non-alcoholic Fatty Liver Disease

PubMed Central

Arora, Anil; Sharma, Praveen

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed as well as in developing countries. Its prevalence continues to rise currently affecting approximately 20-30% of adults and 10% of children in the United States. Non-alcoholic fatty liver disease represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign non-progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several non-invasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. There has been a substantial development of non-invasive risk scores, biomarker panels, and radiological modalities to identify at risk patients with NAFLD without recourse to liver biopsy on a routine basis. Examples include combination of serum markers like NAFLD fibrosis score (NFS), BARD score, fibrometer, FIB4, and non-invasive tools like fibroscan which assess fibrosis in patients with NAFLD. Other markers of fibrosis that have been evaluated include high-sensitivity C-reactive protein, plasma pentraxin 3, interleukin-6, and cytokeratin-18. This review focuses on the methods currently available in daily clinical practice in hepatology and touches briefly on the potential future markers under investigation. PMID:25755423

A perspective on renewable bioenergy from photosynthetic algae as feedstock for biofuels and bioproducts

DOE PAGES

Laurens, Lieve M. L.; Chen-Glasser, Melodie; McMillan, James D.

2017-04-15

There has been substantial technical progress in developing algae-based bioenergy in recent years and a large part of industry and academic research and deployment projects have pivoted away from a pure biofuels strategy. This letter summarizes the findings of a recently completed, comprehensive report, that represents a collaborative effort of at least 20 co-authors, where we analyzed the prospects for using microalgae and macroalgae as feedstocks for biofuels and bioenergy production. The scope of this report includes a discussion of international activities advancing bioenergy and non-energy bioproducts from algae, progress on the use of macroalgae (both cast and cultivated seaweeds)more » for biogas applications, distinct biochemical and thermochemical conversion pathways, multi-product biorefining opportunities, as well as a thorough review of process economics and sustainability considerations. It is envisioned that a higher value algal biomass-based bioproducts industry will provide the additional revenue needed to reduce the net cost of producing algae-based biofuels. As such, a biorefinery approach that generates multiple high-value products from algae will be essential to fully valorize algal biomass and enable economically viable coproduction of bioenergy. Furthermore, to accelerate the implementation of algae-based production, minimizing energy, water, nutrients and land use footprints of integrated algae-based operations needs to be a primary objective of larger scale demonstrations and future research and development.« less

Role of nonresolving inflammation in hepatocellular carcinoma development and progression.

PubMed

Yu, Le-Xing; Ling, Yan; Wang, Hong-Yang

2018-01-01

Hepatocellular carcinoma (HCC) has become a leading cause of cancer-related death, making the elucidation of its underlying mechanisms an urgent priority. Inflammation is an adaptive response to infection and tissue injury under strict regulations. When the host regulatory machine runs out of control, nonresolving inflammation occurs. Nonresolving inflammation is a recognized hallmark of cancer that substantially contributes to the development and progression of HCC. The HCC-associated inflammation can be initiated and propagated by extrinsic pathways through activation of pattern-recognition receptors (PRRs) by pathogen-associated molecule patterns (PAMPs) derived from gut microflora or damage-associated molecule patterns (DAMPs) released from dying liver cells. The inflammation can also be orchestrated by the tumor itself through secreting factors that recruit inflammatory cells to the tumor favoring the buildup of a microenvironment. Accumulating datas from human and mouse models showed that inflammation promotes HCC development by promoting proliferative and survival signaling, inducing angiogenesis, evading immune surveillance, supporting cancer stem cells, activating invasion and metastasis as well as inducing genomic instability. Targeting inflammation may represent a promising avenue for the HCC treatment. Some inhibitors targeting inflammatory pathways have been developed and under different stages of clinical trials, and one (sorafenib) have been approved by FDA. However, as most of the data were obtained from animal models, and there is a big difference between human HCC and mouse HCC models, it is challenging on successful translation from bench to bedside.

Are the lowest-cost healthful food plans culturally and socially acceptable?

PubMed Central

Maillot, Matthieu; Darmon, Nicole; Drewnowski, Adam

2014-01-01

Objective Nutritious yet inexpensive foods do exist. However, many such foods are rejected by the low-income consumer. Is it because their use violates unspoken social norms? The present study was designed to assess the variety and cost of the lowest-cost market basket of foods that simultaneously met required dietary standards and progressively stricter consumption constraints. Design A mathematical optimisation model was used to develop the lowest-cost food plans to meet three levels of nutritional requirements and seven levels of consumption constraints. Subjects: The nationally representative INCA (National Individual Survey of Food Consumption) dietary survey study of 1332 adults provided population estimates of food consumption patterns in France. Food plan costs were based on retail food prices. Results The lowest-cost food plans that provided 9204 kJ/d (2200 kcal/d) for men and 7531 kJ/d (1800 kcal/d) for women and met specified dietary standards could be obtained for ,1?50 h/d. The progressive imposition of consumption constraints designed to create more mainstream French diets sharply increased food plan costs, without improving nutritional value. Conclusions Minimising diet costs, while meeting nutrition standards only, led to food plans that provided little variety and deviated substantially from social norms. Aligning the food plan with mainstream consumption led to higher costs. Food plans designed for low-income groups need to be socially acceptable as well as affordable and nutritious. PMID:20105388

Progression of Inflammatory Bowel Disease to Cancer: Is the Patient Better Off without Lymphatic Vessels or Nodes (or Angiopoietin 2)?

DTIC Science & Technology

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

Early Rockets

NASA Image and Video Library

1940-03-21

Goddard rocket in launching tower at Roswell, New Mexico, March 21, 1940. Fuel was injected by pumps from the fueling platform at left. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets, which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

Early Rockets

NASA Image and Video Library

2004-04-15

Goddard rocket with four rocket motors. This rocket attained an altitude of 200 feet in a flight, November 1936, at Roswell, New Mexico. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

42 CFR 423.265 - Submission of bids and related information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... calendar year. (2) Substantial differences between bids. Potential Part D sponsors' bid submissions must reflect differences in benefit packages or plan costs that CMS determines to represent substantial...) General. Not later than the first Monday in June, each potential Part D sponsor must submit bids and...

42 CFR 423.265 - Submission of bids and related information.

Code of Federal Regulations, 2011 CFR

2011-10-01

... calendar year. (2) Substantial differences between bids. Potential Part D sponsors' bid submissions must reflect differences in benefit packages or plan costs that CMS determines to represent substantial...) General. Not later than the first Monday in June, each potential Part D sponsor must submit bids and...

Open Questions on the Global Contraction of Mercury

NASA Astrophysics Data System (ADS)

Klimczak, C.; Byrne, P. K.

2018-05-01

Substantial progress has been made on determining the amount, timing, and rate of global contraction on Mercury. But many open questions remain to be answered about the process itself, associated landforms, and interactions with other processes.

Recent Progress in Development of SWOT River Discharge Algorithms

NASA Astrophysics Data System (ADS)

Pavelsky, Tamlin M.; Andreadis, Konstantinos; Biancamaria, Sylvian; Durand, Michael; Moller, Dewlyn; Rodriguez, Enersto; Smith, Laurence C.

2013-09-01

The Surface Water and Ocean Topography (SWOT) Mission is a satellite mission under joint development by NASA and CNES. The mission will use interferometric synthetic aperture radar technology to continuously map, for the first time, water surface elevations and water surface extents in rivers, lakes, and oceans at high spatial resolutions. Among the primary goals of SWOT is the accurate retrieval of river discharge directly from SWOT measurements. Although it is central to the SWOT mission, discharge retrieval represents a substantial challenge due to uncertainties in SWOT measurements and because traditional discharge algorithms are not optimized for SWOT-like measurements. However, recent work suggests that SWOT may also have unique strengths that can be exploited to yield accurate estimates of discharge. A NASA-sponsored workshop convened June 18-20, 2012 at the University of North Carolina focused on progress and challenges in developing SWOT-specific discharge algorithms. Workshop participants agreed that the only viable approach to discharge estimation will be based on a slope-area scaling method such as Manning's equation, but modified slightly to reflect the fact that SWOT will estimate reach-averaged rather than cross- sectional discharge. While SWOT will provide direct measurements of some key parameters such as width and slope, others such as baseflow depth and channel roughness must be estimated. Fortunately, recent progress has suggested several algorithms that may allow the simultaneous estimation of these quantities from SWOT observations by using multitemporal observations over several adjacent reaches. However, these algorithms will require validation, which will require the collection of new field measurements, airborne imagery from AirSWOT (a SWOT analogue), and compilation of global datasets of channel roughness, river width, and other relevant variables.

Enhanced Heme Function and Mitochondrial Respiration Promote the Progression of Lung Cancer Cells

PubMed Central

Alam, Md Maksudul; Shah, Ajit; Cao, Thai M.; Sullivan, Laura A.; Brekken, Rolf; Zhang, Li

2013-01-01

Lung cancer is the leading cause of cancer-related mortality, and about 85% of the cases are non-small-cell lung cancer (NSCLC). Importantly, recent advance in cancer research suggests that altering cancer cell bioenergetics can provide an effective way to target such advanced cancer cells that have acquired mutations in multiple cellular regulators. This study aims to identify bioenergetic alterations in lung cancer cells by directly measuring and comparing key metabolic activities in a pair of cell lines representing normal and NSCLC cells developed from the same patient. We found that the rates of oxygen consumption and heme biosynthesis were intensified in NSCLC cells. Additionally, the NSCLC cells exhibited substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins HRG1 and HCP1 that are involved in heme uptake, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. Several types of human tumor xenografts also displayed increased levels of such proteins. Furthermore, we found that lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. In contrast, lowering heme degradation does not have an effect on lung cancer cells. These results show that increased heme flux and function are a key feature of NSCLC cells. Further, increased generation and supply of heme and oxygen-utilizing hemoproteins in cancer cells will lead to intensified oxygen consumption and cellular energy production by mitochondrial respiration, which would fuel cancer cell proliferation and progression. The results show that inhibiting heme and respiratory function can effectively arrest the progression of lung cancer cells. Hence, understanding heme function can positively impact on research in lung cancer biology and therapeutics. PMID:23704904

Natural Language Processing (NLP), Machine Learning (ML), and Semantics in Polar Science

NASA Astrophysics Data System (ADS)

Duerr, R.; Ramdeen, S.

2017-12-01

One of the interesting features of Polar Science is that it historically has been extremely interdisciplinary, encompassing all of the physical and social sciences. Given the ubiquity of specialized terminology in each field, enabling researchers to find, understand, and use all of the heterogeneous data needed for polar research continues to be a bottleneck. Within the informatics community, semantics has broadly accepted as a solution to these problems, yet progress in developing reusable semantic resources has been slow. The NSF-funded ClearEarth project has been adapting the methods and tools from other communities such as Biomedicine to the Earth sciences with the goal of enhancing progress and the rate at which the needed semantic resources can be created. One of the outcomes of the project has been a better understanding of the differences in the way linguists and physical scientists understand disciplinary text. One example of these differences is the tendency for each discipline and often disciplinary subfields to expend effort in creating discipline specific glossaries where individual terms often are comprised of more than one word (e.g., first-year sea ice). Often each term in a glossary is imbued with substantial contextual or physical meaning - meanings which are rarely explicitly called out within disciplinary texts; meaning which are therefore not immediately accessible to those outside that discipline or subfield; meanings which can often be represented semantically. Here we show how recognition of these difference and the use of glossaries can be used to speed up the annotation processes endemic to NLP, enable inter-community recognition and possible reconciliation of terminology differences. A number of processes and tools will be described, as will progress towards semi-automated generation of ontology structures.

Mild cognitive impairment, amnestic type: an epidemiologic study.

PubMed

Ganguli, Mary; Dodge, Hiroko H; Shen, Changyu; DeKosky, Steven T

2004-07-13

To estimate the prevalence and examine the course of mild cognitive impairment (MCI), amnestic type, using current criteria, within a representative community sample. Retroactive application of MCI criteria to data collected during a prospective epidemiologic study was performed. The subjects were drawn from voter registration lists, composing a cohort of 1,248 individuals with mean age of 74.6 (5.3) years, who were nondemented at entry and who were assessed biennially over 10 years of follow-up. The Petersen amnestic MCI criteria were operationalized as 1) impaired memory: Word List Delayed Recall score of <1 SD below mean; 2) normal mental status: Mini-Mental State Examination score of 25+; 3) normal daily functioning: no instrumental impairments; 4) memory complaint: subjective response to standardized question; 5) not demented: Clinical Dementia Rating Scale score of <1. At the five assessments, amnestic MCI criteria were met by 2.9 to 4.0% of the cohort. Of 40 persons with MCI at the first assessment, 11 (27%) developed dementia over the next 10 years. Over each 2-year interval, MCI persons showed increased risk of dementing (odds ratio = 3.9, 95% CI = 2.1 to 7.2); 11.1 to 16.7% progressed to Alzheimer disease and 0 to 5.0% progressed to other dementias. Over the same intervals, 11.1 to 21.2% of those with MCI remained MCI; of 33.3 to 55.6% who no longer had MCI, half had reverted to normal. In this community-based sample, 3 to 4% of nondemented persons met MCI operational criteria; despite increased risk of progressing to dementia, a substantial proportion also remained stable or reverted to normal during follow-up. Amnestic MCI as currently defined is a high-risk but unstable and heterogeneous group.

Societal and Family Lifetime Cost of Dementia: Implications for Policy.

PubMed

Jutkowitz, Eric; Kane, Robert L; Gaugler, Joseph E; MacLehose, Richard F; Dowd, Bryan; Kuntz, Karen M

2017-10-01

To estimate the cost of dementia and the extra cost of caring for someone with dementia over the cost of caring for someone without dementia. We developed an evidence-based mathematical model to simulate disease progression for newly diagnosed individuals with dementia. Data-driven trajectories of cognition, function, and behavioral and psychological symptoms were used to model disease progression and predict costs. Using modeling, we evaluated lifetime and annual costs of individuals with dementia, compared costs of those with and without clinical features of dementia, and evaluated the effect of reducing functional decline or behavioral and psychological symptoms by 10% for 12 months (implemented when Mini-Mental State Examination score ≤21). Mathematical model. Representative simulated U.S. incident dementia cases. Value of informal care, out-of-pocket expenditures, Medicaid expenditures, and Medicare expenditures. From time of diagnosis (mean age 83), discounted total lifetime cost of care for a person with dementia was $321,780 (2015 dollars). Families incurred 70% of the total cost burden ($225,140), Medicaid accounted for 14% ($44,090), and Medicare accounted for 16% ($52,540). Costs for a person with dementia over a lifetime were $184,500 greater (86% incurred by families) than for someone without dementia. Total annual cost peaked at $89,000, and net cost peaked at $72,400. Reducing functional decline or behavioral and psychological symptoms by 10% resulted in $3,880 and $680 lower lifetime costs than natural disease progression. Dementia substantially increases lifetime costs of care. Long-lasting, effective interventions are needed to support families because they incur the most dementia cost. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Administration of Progress Payments at Defense Contract Management District-West

DTIC Science & Technology

1993-08-05

the progress payment is calculated from the contractor’s incurred cost, the actual amount payable is always limited by the fair value of the...progress payments exceed the fair value of undelivered work. In addition to assessing the validity of the EAC relative to the progress payment request...were overpaid because Air Force Plant Representative Offices incorrectly calculated progress payment reductions for fair value of remaining work

Dr. Robert H. Goddard and His Rocket

NASA Technical Reports Server (NTRS)

2004-01-01

Goddard rocket with four rocket motors. This rocket attained an altitude of 200 feet in a flight, November 1936, at Roswell, New Mexico. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

Dr. Robert H. Goddard and His Rocket

NASA Technical Reports Server (NTRS)

1940-01-01

Goddard rocket in launching tower at Roswell, New Mexico, March 21, 1940. Fuel was injected by pumps from the fueling platform at left. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets, which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

Strengthening of accountability systems to create healthy food environments and reduce global obesity.

PubMed

Swinburn, Boyd; Kraak, Vivica; Rutter, Harry; Vandevijvere, Stefanie; Lobstein, Tim; Sacks, Gary; Gomes, Fabio; Marsh, Tim; Magnusson, Roger

2015-06-20

To achieve WHO's target to halt the rise in obesity and diabetes, dramatic actions are needed to improve the healthiness of food environments. Substantial debate surrounds who is responsible for delivering effective actions and what, specifically, these actions should entail. Arguments are often reduced to a debate between individual and collective responsibilities, and between hard regulatory or fiscal interventions and soft voluntary, education-based approaches. Genuine progress lies beyond the impasse of these entrenched dichotomies. We argue for a strengthening of accountability systems across all actors to substantially improve performance on obesity reduction. In view of the industry opposition and government reluctance to regulate for healthier food environments, quasiregulatory approaches might achieve progress. A four step accountability framework (take the account, share the account, hold to account, and respond to the account) is proposed. The framework identifies multiple levers for change, including quasiregulatory and other approaches that involve government-specified and government-monitored progress of private sector performance, government procurement mechanisms, improved transparency, monitoring of actions, and management of conflicts of interest. Strengthened accountability systems would support government leadership and stewardship, constrain the influence of private sector actors with major conflicts of interest on public policy development, and reinforce the engagement of civil society in creating demand for healthy food environments and in monitoring progress towards obesity action objectives. Copyright © 2015 Elsevier Ltd. All rights reserved.

Astaxanthin Inhibits JAK/STAT-3 Signaling to Abrogate Cell Proliferation, Invasion and Angiogenesis in a Hamster Model of Oral Cancer

PubMed Central

Kowshik, J.; Baba, Abdul Basit; Giri, Hemant; Deepak Reddy, G.; Dixit, Madhulika; Nagini, Siddavaram

2014-01-01

Identifying agents that inhibit STAT-3, a cytosolic transcription factor involved in the activation of various genes implicated in tumour progression is a promising strategy for cancer chemoprevention. In the present study, we investigated the effect of dietary astaxanthin on JAK-2/STAT-3 signaling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model by examining the mRNA and protein expression of JAK/STAT-3 and its target genes. Quantitative RT-PCR, immunoblotting and immunohistochemical analyses revealed that astaxanthin supplementation inhibits key events in JAK/STAT signaling especially STAT-3 phosphorylation and subsequent nuclear translocation of STAT-3. Furthermore, astaxanthin downregulated the expression of STAT-3 target genes involved in cell proliferation, invasion and angiogenesis, and reduced microvascular density, thereby preventing tumour progression. Molecular docking analysis confirmed inhibitory effects of astaxanthin on STAT signaling and angiogenesis. Cell culture experiments with the endothelial cell line ECV304 substantiated the role of astaxanthin in suppressing angiogenesis. Taken together, our data provide substantial evidence that dietary astaxanthin prevents the development and progression of HBP carcinomas through the inhibition of JAK-2/STAT-3 signaling and its downstream events. Thus, astaxanthin that functions as a potent inhibitor of tumour development and progression by targeting JAK/STAT signaling may be an ideal candidate for cancer chemoprevention. PMID:25296162

Child Maltreatment among Children with Intellectual Disability in the Canadian Incidence Study

ERIC Educational Resources Information Center

Dion, Jacinthe; Paquette, Geneviève; Tremblay, Karine-N.; Collin-Vézina, Delphine; Chabot, Martin

2018-01-01

This study aims to compare, among a representative sample of substantiated child maltreatment cases, the characteristics of those with intellectual disability (ID) from those without ID. Using the 2008 Canadian Incidence Study of Reported Child Abuse and Neglect, 5,797 cases of substantiated maltreatment that involved children aged between 0 and…

Evolution of the global use of unsafe medical injections, 2000-2010.

PubMed

Pépin, Jacques; Abou Chakra, Claire Nour; Pépin, Eric; Nault, Vincent

2013-01-01

Since 1999, substantial efforts have been made by the international community to reduce the risks associated with unsafe injections, through ministries of health, international donors, the World Health Organization and the Safe Injection Global Network. The present study attempted to measure the progress, or lack thereof, made over the 2000-2010 decade in reducing unsafe injections in ten regions of the world corresponding to developing and transitional economies. Data about the number of injections per person per year and the proportion of re-use of syringes and needles were obtained for 2010, mainly from population surveys, and compared with previous estimates for 2000 which had used various sources of information including injection safety assessments, population surveys and published studies on injection practices. From 2000 to 2010, in developing countries and transitional economies, the average number of injections per person per year decreased from 3.40 to 2.88, while the proportion of re-use of injection devices dropped from 39.8% to 5.5%. Combining both factors the number of unsafe injections per person per year decreased from 1.35 to 0.16. Even if substantial progress has been made, the Eastern Mediterranean region remains problematic, with 0.57 unsafe injections per person per year. In sub-Saharan Africa and Latin America, people now receive on average only 0.04-0.05 unsafe injections per year. Substantial progress has been made in reducing the number of unsafe injections in developing countries and transitional economies, essentially through a reduction in the re-use of injection devices. In some regions, elimination of unsafe injections might become a reasonable goal.

Sequential Progressions in a Theory of Mind Scale: Longitudinal Perspectives

PubMed Central

Wellman, Henry M.; Fuxi, Fang; Peterson, Candida C.

2011-01-01

Consecutive re-testings of 92 U.S. preschoolers (n = 30), Chinese preschoolers (n = 31), and deaf children (n = 31) examined whether the sequences of development apparent in cross-sectional results with a theory-of-mind scale also appeared in longitudinal assessment. Longitudinal data confirmed that theory-of-mind progressions apparent in cross-sectional scaling data also characterized longitudinal sequences of understanding for individual children. The match between cross-sectional and longitudinal sequences appeared for children who exhibit different progressions across cultures (U.S. vs. China) and for children with substantial delays (deaf children of hearing parents). Moreover, greater scale distances reflected larger longitudinal age differences. PMID:21428982

Lightweight and Statistical Techniques for Petascale Debugging: Correctness on Petascale Systems (CoPS) Preliminry Report

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

de Supinski, B R; Miller, B P; Liblit, B

2011-09-13

Petascale platforms with O(10{sup 5}) and O(10{sup 6}) processing cores are driving advancements in a wide range of scientific disciplines. These large systems create unprecedented application development challenges. Scalable correctness tools are critical to shorten the time-to-solution on these systems. Currently, many DOE application developers use primitive manual debugging based on printf or traditional debuggers such as TotalView or DDT. This paradigm breaks down beyond a few thousand cores, yet bugs often arise above that scale. Programmers must reproduce problems in smaller runs to analyze them with traditional tools, or else perform repeated runs at scale using only primitive techniques.more » Even when traditional tools run at scale, the approach wastes substantial effort and computation cycles. Continued scientific progress demands new paradigms for debugging large-scale applications. The Correctness on Petascale Systems (CoPS) project is developing a revolutionary debugging scheme that will reduce the debugging problem to a scale that human developers can comprehend. The scheme can provide precise diagnoses of the root causes of failure, including suggestions of the location and the type of errors down to the level of code regions or even a single execution point. Our fundamentally new strategy combines and expands three relatively new complementary debugging approaches. The Stack Trace Analysis Tool (STAT), a 2011 R&D 100 Award Winner, identifies behavior equivalence classes in MPI jobs and highlights behavior when elements of the class demonstrate divergent behavior, often the first indicator of an error. The Cooperative Bug Isolation (CBI) project has developed statistical techniques for isolating programming errors in widely deployed code that we will adapt to large-scale parallel applications. Finally, we are developing a new approach to parallelizing expensive correctness analyses, such as analysis of memory usage in the Memgrind tool. In the first two years of the project, we have successfully extended STAT to determine the relative progress of different MPI processes. We have shown that the STAT, which is now included in the debugging tools distributed by Cray with their large-scale systems, substantially reduces the scale at which traditional debugging techniques are applied. We have extended CBI to large-scale systems and developed new compiler based analyses that reduce its instrumentation overhead. Our results demonstrate that CBI can identify the source of errors in large-scale applications. Finally, we have developed MPIecho, a new technique that will reduce the time required to perform key correctness analyses, such as the detection of writes to unallocated memory. Overall, our research results are the foundations for new debugging paradigms that will improve application scientist productivity by reducing the time to determine which package or module contains the root cause of a problem that arises at all scales of our high end systems. While we have made substantial progress in the first two years of CoPS research, significant work remains. While STAT provides scalable debugging assistance for incorrect application runs, we could apply its techniques to assertions in order to observe deviations from expected behavior. Further, we must continue to refine STAT's techniques to represent behavioral equivalence classes efficiently as we expect systems with millions of threads in the next year. We are exploring new CBI techniques that can assess the likelihood that execution deviations from past behavior are the source of erroneous execution. Finally, we must develop usable correctness analyses that apply the MPIecho parallelization strategy in order to locate coding errors. We expect to make substantial progress on these directions in the next year but anticipate that significant work will remain to provide usable, scalable debugging paradigms.« less

Report: Fiscal Year 2006 Federal Information Security Management Act Report Status of EPA’s Computer Security Program

EPA Pesticide Factsheets

Report #2006-S-00008, September 25, 2006. Although the Agency has made substantial progress to improve its security program, the OIG identified weaknesses in the Agency’s incident reporting practices.

FY2014 National Clean Diesel Funding Assistance (Diesel Emissions Reduction Act) Programmatic Terms and Conditions

EPA Pesticide Factsheets

EPA will provide substantial involvement in the form of technical assistance, development ofoutputs, and oversight. EPA and the recipient in program content, review of project progress, and quantification and reporting of results.

Projecting the release of carbon from permafrost soils using a perturbed physics ensemble

NASA Astrophysics Data System (ADS)

MacDougall, A. H.; Knutti, R.

2015-12-01

The soils of the Northern Hemisphere permafrost region are estimated to contain 1100 to 1500 Pg of carbon (Pg C). A substantial fraction of this carbon has been frozen and therefore protected from microbial decay for millennia. As anthropogenic climate warming progresses much of this permafrost is expected to thaw. Here we conduct perturbed physics experiments on a climate model of intermediate complexity, with an improved permafrost carbon module, to estimate with formal uncertainty bounds the release of carbon from permafrost soils by year 2100 and 2300. We estimate that by 2100 the permafrost region may release between 56 (13 to 118) Pg C under Representative Concentration Pathway (RCP) 2.6 and 102 (27 to 199) Pg C under RCP 8.5, with substantially more to be released under each scenario by year 2300. A subset of 25 model variants were projected 8000 years into the future under continued RCP 4.5 and 8.5 forcing. Under the high forcing scenario the permafrost carbon pool decays away over several thousand years. Under the moderate scenario forcing a remnant near-surface permafrost region persists in the high Arctic which develops a large permafrost carbon pool, leading to global recovery of the pool beginning in mid third millennium of the common era (CE). Overall our simulations suggest that the permafrost carbon cycle feedback to climate change will make a significant but not cataclysmic contribution to climate change over the next centuries and millennia.

Projecting the release of carbon from permafrost soils using a perturbed physics ensemble modelling approach

NASA Astrophysics Data System (ADS)

MacDougall, Andrew; Knutti, Reto

2016-04-01

The soils of the northern hemisphere permafrost region are estimated to contain 1100 to 1500 Pg of carbon. A substantial fraction of this carbon has been frozen and therefore protected from microbial decay for millennia. As anthropogenic climate warming progresses permafrost soils are expected to thaw. Here we conduct perturbed physics experiments on a climate model of intermediate complexity, with an improved permafrost carbon module, to estimate with formal uncertainty bounds the release of carbon from permafrost soils by year 2100 and 2300. We estimate that by year 2100 the permafrost region may release between 56 (13 to 118)Pg C under Representative Concentration Pathway (RCP) 2.6 and 102 (27 to 199) Pg C under RCP 8.5, with substantially more to be released under each scenario by 2300. A subset of 25 model variants is projected 8000 years into the future under continued RCP 4.5 and 8.5 forcing. Under the high forcing scenario the permafrost carbon pool decays away over several thousand years. Under the moderate forcing scenario a remnant near-surface permafrost region persists in the High-Arctic, which develops a large permafrost carbon pool, leading to a global recovery of the pool beginning in mid third millennium of the common era. Overall our simulations suggest that the permafrost carbon cycle feedback to climate change will make a significant but not cataclysmic contribution to climate change over the next centuries and millennia.

Progression of initially mild hepatic fibrosis in patients with chronic hepatitis C infection.

PubMed

Williams, M J; Lang-Lenton, M

2011-01-01

A significant number of patients with chronic hepatitis C infection have minimal fibrosis at presentation. Although the short-term outlook for such patients is good, there are limited data available on long-term progression. We assessed the risk of fibrosis progression in 282 patients with chronic hepatitis C with Ishak stage 0 or 1 fibrosis on initial liver biopsy. Progression of fibrosis stage occurred in 118 patients (42%) over a median interval of 52.5 months. Thirteen (5%) progressed to severe (Ishak stage 4 or more) fibrosis. Progression was significantly associated with both age at initial biopsy [odds ratio (OR) for progression of 1.31 per 10 year increase in age] and median alanine transaminase (ALT) levels during follow-up (OR of 1.06 per 10 IU/L increase). There was no significant association with gender, histological inflammatory grade, hepatic steatosis or body mass index. We conclude that hepatitis C with initially mild fibrosis does progress in a substantial proportion of patients and should not be viewed as a benign disease. Early antiviral therapy should be considered in older patients and those with high ALT levels.

Hypothesis: spring-loaded boomerang mechanism of influenza hemagglutinin-mediated membrane fusion.

PubMed

Tamm, Lukas K

2003-07-11

Substantial progress has been made in recent years to augment the current understanding of structures and interactions that promote viral membrane fusion. This progress is reviewed with a particular emphasis on recently determined structures of viral fusion domains and their interactions with lipid membranes. The results from the different structural and thermodynamic experimental approaches are synthesized into a new proposed mechanism, termed the "spring-loaded boomerang" mechanism of membrane fusion, which is presented here as a hypothesis.

Real time gamma-ray signature identifier

DOEpatents

Rowland, Mark [Alamo, CA; Gosnell, Tom B [Moraga, CA; Ham, Cheryl [Livermore, CA; Perkins, Dwight [Livermore, CA; Wong, James [Dublin, CA

2012-05-15

A real time gamma-ray signature/source identification method and system using principal components analysis (PCA) for transforming and substantially reducing one or more comprehensive spectral libraries of nuclear materials types and configurations into a corresponding concise representation/signature(s) representing and indexing each individual predetermined spectrum in principal component (PC) space, wherein an unknown gamma-ray signature may be compared against the representative signature to find a match or at least characterize the unknown signature from among all the entries in the library with a single regression or simple projection into the PC space, so as to substantially reduce processing time and computing resources and enable real-time characterization and/or identification.

Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database

PubMed Central

Nestor, Sean M.; Rupsingh, Raul; Borrie, Michael; Smith, Matthew; Accomazzi, Vittorio; Wells, Jennie L.; Fogarty, Jennifer

2008-01-01

Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T1-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n = 152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an ε4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P = 0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular enlargement than stable MCI subjects (P = 0.0270). Ventricular enlargement was different between Apolipoprotein E genotypes within the AD group (P = 0.010). The number of subjects required to demonstrate a 20% change in ventricular enlargement was substantially lower than that required to demonstrate a 20% change in cognitive scores. Ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studies. PMID:18669512

FY2014 National Clean Diesel Funding Assistance (Diesel Emissions Reduction Act) Programmatic Terms and Conditions

EPA Pesticide Factsheets

Substantial federal involvement will take the form of monitoring the project by EPA, participation and collaboration between EPA and the recipient in program content, review of project progress, and quantification and reporting ofresults.

The case for the relativistic hot big bang cosmology

NASA Technical Reports Server (NTRS)

Peebles, P. J. E.; Schramm, D. N.; Kron, R. G.; Turner, E. L.

1991-01-01

What has become the standard model in cosmology is described, and some highlights are presented of the now substantial range of evidence that most cosmologists believe convincingly establishes this model, the relativistic hot big bang cosmology. It is shown that this model has yielded a set of interpretations and successful predictions that substantially outnumber the elements used in devising the theory, with no well-established empirical contradictions. Brief speculations are made on how the open puzzles and work in progress might affect future developments in this field.

What progress have we made with tinnitus? The Tonndorf Lecture 2005.

PubMed

Baguley, David M

2006-12-01

The field of tinnitus research is vibrant and active. Prospects for progress are high, but would be optimized by the growth of inter-disciplinary collaborations. Tinnitus remains a source of urgent scientific investigation, and truly effective treatments continue to be elusive. The Tonndorf Lecture of the International Tinnitus Seminars represents an opportunity to reflect upon progress to date regarding tinnitus, and the actions needed to further that progress in future. Progress regarding tinnitus mechanisms is reviewed, with particular regard to the conceptual distinction between ignition sites for tinnitus, and the physiological mechanisms that then promote the tinnitus through the central auditory pathway. The current status of both the Jastreboff neurophysiological model and the psychological model of tinnitus is reviewed. Some concerns regarding each model are raised, and the need for models that integrate the insights of both perspectives is identified as urgent. There are clear indications of progress in tinnitus, specifically regarding mechanisms, models and treatments. For knowledge to progress further, however, there is a pressing need for an inter-disciplinary approach to tinnitus, more involvement in teaching at a postgraduate level, and the development of experimental models of tinnitus that are both congruent with, and represent the complexity of, human experience of tinnitus.

Porcine models of muscular dystrophy

USDA-ARS?s Scientific Manuscript database

Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein, dystrophin. This disease is modeled by a variety of animal models including several fish models, mice, rats, and dogs. While these models have contributed substantially t...

Strategies to improve water productivity in a water-stressed future

USDA-ARS?s Scientific Manuscript database

In the fiscal years 2011 through 2014, ARS scientists and engineers made substantial progress in addressing research problems related to improving water productivity and creating new knowledge, products and outcomes to improve American agricultural production, efficiency of resource use, safety and ...

34 CFR 380.20 - What requirements must a grantee meet before it provides for the transition of an individual in...

Code of Federal Regulations, 2011 CFR

2011-07-01

... EMPLOYMENT SERVICES TO INDIVIDUALS WITH THE MOST SEVERE DISABILITIES AND TECHNICAL ASSISTANCE PROJECTS What... individual's program of services, and only if the individual has made substantial progress toward meeting his...

A systematic review of US rangeland social science

USDA-ARS?s Scientific Manuscript database

Rangeland science aims to create knowledge to sustain rangeland social-ecological systems over the long term. Range science has made substantial progress on understanding ecological dynamics of rangeland systems and the management practices that sustain them, and these findings have been systematica...

77 FR 26604 - Progressive Rail, Incorporated-Lease and Operation Exemption-Rail Line of Union Pacific Railroad...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-04

... contains an interchange commitment with substantial economic rewards for PGR if it interchanges with UP. One has to wonder why such an economic incentive is necessary if there is little chance that PGR would...

(Photosynthesis in intact plants)

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

Not Available

Progress in the two years since the last renewal application has been excellent. We have made substantial contributions on both main fronts of the projects, and are particularly happy with the progress of our research on intact plants. The approach of basing our field work on a sound foundation of laboratory studies has enabled is to use methods which provide unambiguous assays of well characterized reactions. We have also made excellent progress in several laboratory studies which will have direct applications in future field work, and have introduced to the laboratory a range of molecular genetics techniques which will allowmore » us to explore new options in the attempt to understand function at the level of molecular structure.« less

Development of clinical recommendations for progressive return to activity after military mild traumatic brain injury: guidance for rehabilitation providers.

PubMed

McCulloch, Karen L; Goldman, Sarah; Lowe, Lynn; Radomski, Mary Vining; Reynolds, John; Shapiro, Rita; West, Therese A

2015-01-01

Previously published mild traumatic brain injury (mTBI) management guidelines provide very general recommendations to return individuals with mTBI to activity. This lack of specific guidance creates variation in military rehabilitation. The Office of the Army Surgeon General in collaboration with the Defense and Veterans Brain Injury Center, a component center of the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, convened an expert working group to review the existing literature and propose clinical recommendations that standardize rehabilitation activity progression following mTBI. A Progressive Activity Working Group consisted of 11 Department of Defense representatives across all service branches, 7 Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury representatives, and 8 academic/research/civilian experts with experience assessing and treating individuals with mTBI for return to activity. An expert working group meeting included the Progressive Activity Working Group and 15 additional subject matter experts. In February 2012, the Progressive Activity Working Group was established to determine the need and purpose of the rehabilitation recommendations. Following literature review, a table was created on the basis of the progression from the Zurich consensus statement on concussion in sport. Issues were identified for discussion with a meeting of the larger expert group during a July 2012 conference. Following development of rehabilitation guidance, the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury coordinated a similar process for military primary care providers. End products for rehabilitation and primary care providers include specific recommendations for return to activity after concussion. A 6-stage progression specifies activities in physical, cognitive, and balance/vestibular domains and allows for resumption of activity for those with low-level or preinjury symptom complaints. The clinical recommendations for progressive return to activity represent an important effort to standardize activity progression across functional domains and offer providers duty-specific activities to incorporate into intervention. Recommendations were released in January 2014.

Myeloid-derived suppressor cells in multiple myeloma: pre-clinical research and translational opportunities.

PubMed

Botta, Cirino; Gullà, Annamaria; Correale, Pierpaolo; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

2014-01-01

Immunosuppressive cells have been reported to play an important role in tumor-progression mainly because of their capability to promote immune-escape, angiogenesis, and metastasis. Among them, myeloid-derived suppressor cells (MDSCs) have been recently identified as immature myeloid cells, induced by tumor-associated inflammation, able to impair both innate and adaptive immunity. While murine MDSCs are usually identified by the expression of CD11b and Gr1, human MDSCs represent a more heterogeneous population characterized by the expression of CD33 and CD11b, low or no HLA-DR, and variable CD14 and CD15. In particular, the last two may alternatively identify monocyte-like or granulocyte-like MDSC subsets with different immunosuppressive properties. Recently, a substantial increase of MDSCs has been found in peripheral blood and bone marrow (BM) of multiple myeloma (MM) patients with a role in disease progression and/or drug resistance. Pre-clinical models recapitulating the complexity of the MM-related BM microenvironment (BMM) are major tools for the study of the interactions between MM cells and cells of the BMM (including MDSCs) and for the development of new agents targeting MM-associated immune-suppressive cells. This review will focus on current strategies for human MDSCs generation and investigation of their immunosuppressive function in vitro and in vivo, taking into account the relevant relationship occurring within the MM-BMM. We will then provide trends in MDSC-associated research and suggest potential application for the treatment of MM.

The Gaseous Disks of Young Stellar Objects

NASA Technical Reports Server (NTRS)

Glassgold, A. E.

2006-01-01

Disks represent a crucial stage in the formation of stars and planets. They are novel astrophysical systems with attributes intermediate between the interstellar medium and stars. Their physical properties are inhomogeneous and are affected by hard stellar radiation and by dynamical evolution. Observing disk structure is difficult because of the small sizes, ranging from as little as 0.05 AU at the inner edge to 100-1000 AU at large radial distances. Nonetheless, substantial progress has been made by observing the radiation emitted by the dust from near infrared to mm wavelengths, i.e., the spectral energy distribution of an unresolved disk. Many fewer results are available for the gas, which is the main mass component of disks over much of their lifetime. The inner disk gas of young stellar objects (henceforth YSOs) have been studied using the near infrared rovibrational transitions of CO and a few other molecules, while the outer regions have been explored with the mm and sub-mm lines of CO and other species. Further progress can be expected in understanding the physical properties of disks from observations with sub-mm arrays like SMA, CARMA and ALMA, with mid infrared measurements using Spitzer, and near infrared spectroscopy with large ground-based telescopes. Intense efforts are also being made to model the observations using complex thermal-chemical models. After a brief review of the existing observations and modeling results, some of the weaknesses of the models will be discussed, including the absence of good laboratory and theoretical calculations for essential microscopic processes.

Progress in vaccination towards hepatitis B control and elimination in the Region of the Americas.

PubMed

Ropero Álvarez, Alba Maria; Pérez-Vilar, Silvia; Pacis-Tirso, Carmelita; Contreras, Marcela; El Omeiri, Nathalie; Ruiz-Matus, Cuauhtémoc; Velandia-González, Martha

2017-04-17

Over recent decades, the Region of the Americas has made significant progress towards hepatitis B elimination. We summarize the countries/territories' efforts in introducing and implementing hepatitis B (HB) vaccination and in evaluating its impact on HB virus seroprevalence. We collected information about HB vaccination schedules, coverage estimates, and year of vaccine introduction from countries/territories reporting to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF Joint Reporting Form on Immunization. We obtained additional information regarding countries/territories vaccination recommendations and strategies through communications with Expanded Program on Immunization (EPI) managers and national immunization survey reports. We identified vaccine impact studies conducted and published in the Americas. As of October 2016, all 51 countries/territories have included infant HB vaccination in their official immunization schedule. Twenty countries, whose populations represent over 90% of the Region's births, have included nationwide newborn HB vaccination. We estimated at 89% and 75%, the regional three-dose series and the birth dose HB vaccination coverage, respectively, for 2015. The impact evaluations of infant HB immunization programs in the Region have shown substantial reductions in HB surface antigen (HBsAg) seroprevalence. The achievements of vaccination programs in the Americas suggest that the elimination of perinatal and early childhood HB transmission could be feasible in the short-term. Moreover, the data gathered indicate that the Region may have already achieved the 2020 WHO goal for HB control.

AKT-mediated stabilization of histone methyltransferase WHSC1 promotes prostate cancer metastasis

PubMed Central

Li, Ni; Xue, Wei; Yuan, Huairui; Dong, Baijun; Ding, Yufeng; Liu, Yongfeng; Jiang, Min; Kan, Shan; Sun, Tongyu; Ren, Jiale; Pan, Qiang; Li, Xiang; Zhang, Peiyuan; Wang, Yan; Wang, Xiaoming; Li, Qintong

2017-01-01

Loss of phosphatase and tensin homolog (PTEN) and activation of the PI3K/AKT signaling pathway are hallmarks of prostate cancer (PCa). However, these alterations alone are insufficient for cells to acquire metastatic traits. Here, we have shown that the histone dimethyl transferase WHSC1 critically drives indolent PTEN-null tumors to become metastatic PCa. In a PTEN-null murine PCa model, WHSC1 overexpression in prostate epithelium cooperated with Pten deletion to produce a metastasis-prone tumor. Conversely, genetic ablation of Whsc1 prevented tumor progression in PTEN-null mice. Molecular characterization revealed that increased AKT activity due to PTEN loss directly phosphorylates WHSC1 at S172, preventing WHSC1 degradation by CRL4Cdt2 E3 ligase. Increased WHSC1 expression transcriptionally upregulates expression of RICTOR, a pivotal component of mTOR complex 2 (mTORC2), to further enhance AKT activity. Therefore, the AKT/WHSC1/mTORC2 signaling cascade represents a vicious feedback loop that elicits unrestrained AKT signaling. Furthermore, we determined that WHSC1 positively regulates Rac1 transcription to increase tumor cell motility. The biological importance of a WHSC1-mediated signaling cascade is substantiated by patient sample analysis in which WHSC1 signaling is tightly correlated with disease progression and recurrence. Taken together, our findings highlight a pivotal link between an epigenetic regulator, WHSC1, and key intracellular signaling molecules, AKT, RICTOR, and Rac1, to drive PCa metastasis. PMID:28319045

Evolution of the Global Use of Unsafe Medical Injections, 2000–2010

PubMed Central

Pépin, Jacques; Abou Chakra, Claire Nour; Pépin, Eric; Nault, Vincent

2013-01-01

Objective Since 1999, substantial efforts have been made by the international community to reduce the risks associated with unsafe injections, through ministries of health, international donors, the World Health Organization and the Safe Injection Global Network. The present study attempted to measure the progress, or lack thereof, made over the 2000–2010 decade in reducing unsafe injections in ten regions of the world corresponding to developing and transitional economies. Methods Data about the number of injections per person per year and the proportion of re-use of syringes and needles were obtained for 2010, mainly from population surveys, and compared with previous estimates for 2000 which had used various sources of information including injection safety assessments, population surveys and published studies on injection practices. Results From 2000 to 2010, in developing countries and transitional economies, the average number of injections per person per year decreased from 3.40 to 2.88, while the proportion of re-use of injection devices dropped from 39.8% to 5.5%. Combining both factors the number of unsafe injections per person per year decreased from 1.35 to 0.16. Even if substantial progress has been made, the Eastern Mediterranean region remains problematic, with 0.57 unsafe injections per person per year. In sub-Saharan Africa and Latin America, people now receive on average only 0.04–0.05 unsafe injections per year. Conclusion Substantial progress has been made in reducing the number of unsafe injections in developing countries and transitional economies, essentially through a reduction in the re-use of injection devices. In some regions, elimination of unsafe injections might become a reasonable goal. PMID:24324650

The Serrano Problem: An Analysis of Equalization of Public School Support in California.

ERIC Educational Resources Information Center

Lindman, Erick L.

The Serrano case controversy raises the fundamental question: Do differences in school district per pupil expenditures represent cost differences incurred in providing essentially equivalent programs, or do they represent substantial differences in educational offerings? Although the answer is debatable, the California legislature increased…

29 CFR 453.21 - Interests held in agents, brokers, and surety companies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... any surety company in which any labor organization or any officer, agent, shop steward, or other..., in which any labor organization or any officer, agent, shop steward, or other representative of a... a substantial number of officers, agents, shop stewards, or other representatives of a labor...

29 CFR 453.21 - Interests held in agents, brokers, and surety companies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... any surety company in which any labor organization or any officer, agent, shop steward, or other..., in which any labor organization or any officer, agent, shop steward, or other representative of a... a substantial number of officers, agents, shop stewards, or other representatives of a labor...

29 CFR 453.21 - Interests held in agents, brokers, and surety companies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... any surety company in which any labor organization or any officer, agent, shop steward, or other..., in which any labor organization or any officer, agent, shop steward, or other representative of a... a substantial number of officers, agents, shop stewards, or other representatives of a labor...

Professional Human Service Occupation Biases Represented in General Psychology Textbooks

ERIC Educational Resources Information Center

Firmin, Michael W.; Johnson, Erica J.; Wikler, Jeremiah

2009-01-01

We examined the coverage given by General Psychology textbooks, representing 8 major commercial publishers, regarding the professions of psychology, counseling, marriage & family therapy, and social workers. Of the 24 textbooks assessed, we found substantial bias favoring the coverage of psychology. While 25% of the texts mentioned social workers,…

Cohort Study on Predictors of Need for Nursing Care in Alzheimer's Disease: An Analysis of Healthcare Data.

PubMed

Brüggenjürgen, Bernd; Andersohn, Frank; Burkowitz, Jörg; Ezzat, Nadja; Gaudig, Maren; Willich, Stefan N

2016-10-18

The individual and societal burden of Alzheimer's disease (AD) is substantial. Identifying relevant factors deteriorating AD and inducing need for nursing care would be of high relevance for healthcare planning. The main objective of this study was the identification of predictors of first assignment of a level of long-term care in AD, used as an approximation for disease progression. In a retrospective cohort study using data from a large German statutory health and long-term care insurance (SHI) company, co-morbidities and drug exposure were evaluated with respect to their predictive value for disease progression (first day the amount of daily nursing care exceeded 1.5 hours). Time to disease progression was modeled using COX-proportional hazard regression with stepwise selection of predictor variables. The risk of nursing care need increased substantially with increasing age. Number of hospitalizations and number of different drugs used were significant indicators for progression, whereas outpatient visits were associated with a reduced need for care. Gender did not indicate significant influence on progression. Malignant neoplasms of ill-defined, secondary, and unspecified sites, malnutrition, renal failure, and injuries increased the risk of need for nursing care most significantly. Among prescribed drugs, significant increased risks were associated with drugs used in diabetes, preparations for treatment of wounds and ulcers, antiseptics and disinfectants, and analgesics. Physical comorbidities are relevant contributors to an increase in need for nursing care. Some medical predicting conditions may be linked to cognition, while others may be directly linked to demand for care. AD patients with these comorbidities should be monitored with special attention, as they may be under an increased risk of care dependency.

Economic analysis of new space transportation systems: Executive summary

NASA Technical Reports Server (NTRS)

1971-01-01

An economic analysis of alternative space transportation systems is presented. Results indicate that the expendable systems represent modest investments, but the recurring costs of operation would remain high. The space shuttle and tug system requires a substantial investment, but would substantially reduce the recurring costs of operation. Economic benefits and costs of the different systems are also analyzed. Findings are summarized.

Plant diversity and invasives in blue oak savannas of the southern Sierra Nevada

Treesearch

Jon E. Keeley

2002-01-01

Blue oak savannas were found to be substantially more diverse at all scales from localized point diversity to the community scale, than higher elevation shrubland and coniferous forests in the southern Sierra Nevada. Also, alien plants were more diverse and represented a substantial fraction of the understory flora in these blue oak savannas, comprising three-fourths...

Burial of downed deadwood is strongly affected by log attributes, forest ground vegetation, edaphic conditions, and climate zones

Treesearch

Jogeir N. Stokland; Christopher W. Woodall; Jonas Fridman; Göran Ståhl

2016-01-01

Deadwood can represent a substantial portion of forest ecosystem carbon stocks and is often reported following good practice guidance associated with national greenhouse gas inventories. In high-latitude forest ecosystems, a substantial proportion of downed deadwood is overgrown by ground vegetation and buried in the humus layer. Such burial obfuscates the important...

US metric study mission to the United Kingdom and the Federal Republic of Germany: Report of the NASA representative (Executive Summary)

NASA Technical Reports Server (NTRS)

Vlannes, P. N.

1976-01-01

The trip report is given of the NASA representative of the U.S. metric study mission to the United Kingdom and the Federal Republic of Germany. The mission was organized and conducted under the aegis of the American National Metric Council to learn at first hand the progress of metrication in the United Kingdom and the progress of metrication in the aerospace industry in both the United Kingdom and the Federal Republic of Germany. Representatives of the mission included a cross section of government, industry, labor, and other segments of the private sector. After general and special meetings in the United Kingdom, U.S. members with aerospace related interests met with aerospace representatives in the Federal Republic of Germany.

NASA's Space Launch System: A Transformative Capability for Deep Space Missions

NASA Technical Reports Server (NTRS)

Creech, Stephen D.

2017-01-01

Already making substantial progress toward its first launches, NASA’s Space Launch System (SLS) exploration-class launch vehicle presents game-changing new opportunities in spaceflight, enabling human exploration of deep space, as well as a variety of missions and mission profiles that are currently impossible. Today, the initial configuration of SLS, able to deliver more than 70 metric tons of payload to low Earth orbit (LEO), is well into final production and testing ahead of its planned first flight, which will send NASA’s new Orion crew vehicle around the moon and will deploy 13 CubeSats, representing multiple disciplines, into deep space. At the same time, production work is already underway toward the more-capable Block 1B configuration, planned to debut on the second flight of SLS, and capable of lofting 105 tons to LEO or of co-manifesting large exploration systems with Orion on launches to the lunar vicinity. Progress being made on the vehicle for that second flight includes initial welding of its core stage and testing of one of its engines, as well as development of new elements such as the powerful Exploration Upper Stage and the Universal Stage Adapter “payload bay.” Ultimately, SLS will evolve to a configuration capable of delivering more than 130 tons to LEO to support humans missions to Mars. In order to enable human deep-space exploration, SLS provides unrivaled mass, volume, and departure energy for payloads, offering numerous benefits for a variety of other missions. For robotic science probes to the outer solar system, for example, SLS can cut transit times to less than half that of currently available vehicles or substantially increased spacecraft mass. In the field of astrophysics, SLS’ high payload volume, in the form of payload fairings with a diameter of up to 10 meters, creates the opportunity for launch of large-aperture telescopes providing an unprecedented look at our universe. This presentation will give an overview of SLS’ capabilities and its current status, and discuss the vehicle’s potential for human exploration of deep space and other game-changing utilization opportunities.

Magnetic blocking in a linear iron(I) complex.

PubMed

Zadrozny, Joseph M; Xiao, Dianne J; Atanasov, Mihail; Long, Gary J; Grandjean, Fernande; Neese, Frank; Long, Jeffrey R

2013-07-01

Single-molecule magnets that contain one spin centre may represent the smallest possible unit for spin-based computational devices. Such applications, however, require the realization of molecules with a substantial energy barrier for spin inversion, achieved through a large axial magnetic anisotropy. Recently, significant progress has been made in this regard by using lanthanide centres such as terbium(III) and dysprosium(III), whose anisotropy can lead to extremely high relaxation barriers. We contend that similar effects should be achievable with transition metals by maintaining a low coordination number to restrict the magnitude of the d-orbital ligand-field splitting energy (which tends to hinder the development of large anisotropies). Herein we report the first two-coordinate complex of iron(I), [Fe(C(SiMe3)3)2](-), for which alternating current magnetic susceptibility measurements reveal slow magnetic relaxation below 29 K in a zero applied direct-current field. This S =  complex exhibits an effective spin-reversal barrier of Ueff = 226(4) cm(-1), the largest yet observed for a single-molecule magnet based on a transition metal, and displays magnetic blocking below 4.5 K.

Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model.

PubMed

Keeney, Michael; Chung, Michael T; Zielins, Elizabeth R; Paik, Kevin J; McArdle, Adrian; Morrison, Shane D; Ransom, Ryan C; Barbhaiya, Namrata; Atashroo, David; Jacobson, Gunilla; Zare, Richard N; Longaker, Michael T; Wan, Derrick C; Yang, Fan

2016-08-01

Scaffold-mediated gene delivery holds great promise for tissue regeneration. However, previous attempts to induce bone regeneration using scaffold-mediated non-viral gene delivery rarely resulted in satisfactory healing. We report a novel platform with sustained release of minicircle DNA (MC) from PLGA scaffolds to accelerate bone repair. MC was encapsulated inside PLGA scaffolds using supercritical CO2 , which showed prolonged release of MC. Skull-derived osteoblasts transfected with BMP-2 MC in vitro result in higher osteocalcin gene expression and mineralized bone formation. When implanted in a critical-size mouse calvarial defect, scaffolds containing luciferase MC lead to robust in situ protein production up to at least 60 days. Scaffold-mediated BMP-2 MC delivery leads to substantially accelerated bone repair as early as two weeks, which continues to progress over 12 weeks. This platform represents an efficient, long-term nonviral gene delivery system, and may be applicable for enhancing repair of a broad range of tissues types. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2099-2107, 2016. © 2016 Wiley Periodicals, Inc.

The potential oral health impact of cost barriers to dental care: findings from a Canadian population-based study

PubMed Central

2014-01-01

Background Prior to the 2007/09 Canadian Health Measures Survey, there was no nationally representative clinical data on the oral health of Canadians experiencing cost barriers to dental care. The aim of this study was to determine the oral health status and dental treatment needs of Canadians reporting cost barriers to dental care. Methods A secondary data analysis of the 2007/09 Canadian Health Measures Survey was undertaken using a sample of 5,586 Canadians aged 6 to 79. Chi square tests were conducted to test the association between reporting cost barriers to care and oral health outcomes. Logistic regressions were conducted to identify predictors of reporting cost barriers. Results Individuals who reported cost barriers to dental care had poorer oral health and more treatment needs compared to their counterparts. Conclusions Avoiding dental care and/or foregoing recommended treatment because of cost may contribute to poor oral health. This study substantiates the potential likelihood of progressive dental problems caused by an inability to treat existing conditions due to financial barriers. PMID:24962622

Health Informatics via Machine Learning for the Clinical Management of Patients.

PubMed

Clifton, D A; Niehaus, K E; Charlton, P; Colopy, G W

2015-08-13

To review how health informatics systems based on machine learning methods have impacted the clinical management of patients, by affecting clinical practice. We reviewed literature from 2010-2015 from databases such as Pubmed, IEEE xplore, and INSPEC, in which methods based on machine learning are likely to be reported. We bring together a broad body of literature, aiming to identify those leading examples of health informatics that have advanced the methodology of machine learning. While individual methods may have further examples that might be added, we have chosen some of the most representative, informative exemplars in each case. Our survey highlights that, while much research is taking place in this high-profile field, examples of those that affect the clinical management of patients are seldom found. We show that substantial progress is being made in terms of methodology, often by data scientists working in close collaboration with clinical groups. Health informatics systems based on machine learning are in their infancy and the translation of such systems into clinical management has yet to be performed at scale.

Effect of Solute Segregation on Fracture Toughness in a Ni-Cr Steel

NASA Astrophysics Data System (ADS)

Kameda, Jun

1981-12-01

A study has been made of the influence of intergranular solute segregation on fracture toughness K1c in a series of Ni-Cr steels individually doped with Sb, Sn, and P. By means of toughness measurements in steels having two different intergranular Sb distributions, of measurements of acoustic emissions and of scanning electron micrographs of a load-interrupted and post-test-fatigued specimen, the values of K1c, computed from the “pop-in” load of the load vs clip gauge displacement curves, are found to represent the formation of many patches of contiguous intergranular microcracks ahead of the precrack. The present experiments demonstrate that in the early stage of solute segregation, K1c decreases more substantially than does the strength of grain boundaries σ* (measured in the notched bar tests), although the embrittlement effects of metalloid elements are the same order for both K1c and σ*. A proposed model for the stress-gradient-control of brittle fracture supports the finding that the measurements of K1c give a distorted view of the progress of intergranular embrittlement.

Lateral photovoltaic effect in flexible free-standing reduced graphene oxide film for self-powered position-sensitive detection

PubMed Central

Moon, In Kyu; Ki, Bugeun; Yoon, Seonno; Oh, Jungwoo

2016-01-01

Lightweight, simple and flexible self-powered photodetectors are urgently required for the development and application of advanced optical systems for the future of wearable electronic technology. Here, using a low-temperature reduction process, we report a chemical approach for producing freestanding monolithic reduced graphene oxide papers with different gradients of the carbon/oxygen concentration ratio. We also demonstrate a novel type of freestanding monolithic reduced graphene oxide self-powered photodetector based on a symmetrical metal–semiconductor–metal structure. Upon illumination by a 633-nm continuous wave laser, the lateral photovoltage is observed to vary linfearly with the laser position between two electrodes on the reduced graphene oxide surface. This result may suggest that the lateral photovoltaic effect in the reduced graphene oxide film originates from the built-in electric field by the combination of both the photothermal electric effect and the gradient of the oxygen-to-carbon composition. These results represent substantial progress toward novel, chemically synthesized graphene-based photosensors and suggest one-step integration of graphene-based optoelectronics in the future. PMID:27634110

Gliomagenesis and neural stem cells: Key role of hypoxia and concept of tumor "neo-niche".

PubMed

Diabira, Sylma; Morandi, Xavier

2008-01-01

Gliomas represent the most common primary brain tumors and the most devastating pathology of the central nervous system. Despite progress in conventional treatments, the prognosis remains dismal. Recent studies have suggested that a glioma brain tumor may arise from a "cancer stem cell". To understand this theory we summarize studies of the concepts of neural stem cell, and its specialized microenvironment, namely the niche which can regulate balanced self-renewal, differentiation and stem cell quiescence. We summarize the molecular mechanism known or postulated to be involved in the disregulation of normal stem cells features allowing them to undergo neoplasic transformation. We seek data pointing out the key role of hypoxia in normal homeostasis of stem cells and in the initiation, development and aggressiveness of gliomas. We develop the concept of tumor special microenvironment and we propose the new concept of neo-niche, surrounding the glioma, in which hypoxia could be a key factor to recruit and deregulate different stem cells for gliogenesis process. Substantial advances in treatment would come from obtaining better knowledge of molecular impairs of this disease.

The applications of model-based geostatistics in helminth epidemiology and control.

PubMed

Magalhães, Ricardo J Soares; Clements, Archie C A; Patil, Anand P; Gething, Peter W; Brooker, Simon

2011-01-01

Funding agencies are dedicating substantial resources to tackle helminth infections. Reliable maps of the distribution of helminth infection can assist these efforts by targeting control resources to areas of greatest need. The ability to define the distribution of infection at regional, national and subnational levels has been enhanced greatly by the increased availability of good quality survey data and the use of model-based geostatistics (MBG), enabling spatial prediction in unsampled locations. A major advantage of MBG risk mapping approaches is that they provide a flexible statistical platform for handling and representing different sources of uncertainty, providing plausible and robust information on the spatial distribution of infections to inform the design and implementation of control programmes. Focussing on schistosomiasis and soil-transmitted helminthiasis, with additional examples for lymphatic filariasis and onchocerciasis, we review the progress made to date with the application of MBG tools in large-scale, real-world control programmes and propose a general framework for their application to inform integrative spatial planning of helminth disease control programmes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structural evolution and growth mechanisms of RF-magnetron sputter-deposited hydroxyapatite thin films on the basis of unified principles

NASA Astrophysics Data System (ADS)

Ivanova, Anna A.; Surmeneva, Maria A.; Surmenev, Roman A.; Depla, Diederik

2017-12-01

The structural features of RF-magnetron sputter-deposited hydroxyapatite (HA) coatings are investigated in order to reveal the effect of the working gas composition and the sample position of the substrate relative to the target erosion zone. The film properties were observed to change as a result of bombardment with energetic ions. XRD analysis of the coated substrates indicates that with the increase of the ion-to-atom ratio, the fiber texture changes from a mixed (11 2 bar 2) + (0002) over (0002) orientation, finally reaching a (30 3 bar 0) out-of-plane orientation at high ion-to-atom ratios. TEM reveals that the microstructure of the HA coating consists of columnar grains and differs with the coating texture. The contribution of Ji/Ja to the development of microstructure and texture of the HA coating is schematically represented and discussed. The obtained results may contribute substantially to the progress of research into the development of HA coatings with tailored properties, and these coatings may be applied on the surfaces of metal implants used in bone surgery.

Telework for persons with disabilities in the E.U. and the U.S.A: what can we learn from each other?

PubMed

Schopp, Laura H

2004-01-01

Persons with disabilities represent a growing population in both the European Union (EU) and the United States (USA). The ability to work is a key component in achieving independence and full inclusion in society, and employability is increasingly seen as an important outcome variable for studies in health and disability. However, persons with disabilities face considerable challenges in returning to work due to barriers related to transportation, job changes after disability, lack of support services in the workplace, and related barriers. Telework, or work from a distance, may help to mitigate these obstacles, while expanding the range of work options available for persons with disabilities. The EU has made substantial policy progress to support telework, but persons with disabilities have had only limited long-term success in telework initiatives due to lack of work support services. The USA has generally strong support services but lacks telework policy infrastructure. The EU and the USA can benefit from collaborative work to enhance their complementary strengths.

A meta-analysis of education effects on chronic disease: the causal dynamics of the Population Education Transition Curve.

PubMed

Smith, William C; Anderson, Emily; Salinas, Daniel; Horvatek, Renata; Baker, David P

2015-02-01

As the Epidemiological Transition progresses worldwide, chronic diseases account for the majority of deaths in developed countries and a rising proportion in developing countries indicating a new global pattern of mortality and health challenges into the future. Attainment of formal education is widely reported to have a negative gradient with risk factors and onset of chronic disease, yet there has not been a formal assessment of this research. A random-effects meta-analysis finds that across 414 published effects more education significantly reduces the likelihood of chronic disease, except for neoplastic diseases with substantial genetic causes. Some studies, however, report null effects and other research on infectious disease report positive education gradients. Instead of assuming these contradictory results are spurious, it is suggested that they are part of a predictable systemic interaction between multiple mediating effects of education and the Epidemiological Transition stage of the population; and thus represent one case of the Population Education Transition Curve modeling changes in the association between education and health as dependent on population context. Copyright © 2014 Elsevier Ltd. All rights reserved.

Household and school-level influences on smoking behavior among Korean adolescents: a multilevel analysis.

PubMed

Heo, Jongho; Oh, Juhwan; Subramanian, S V; Kawachi, Ichiro

2014-01-01

Trends in adolescent smoking rates in South Korea have not shown substantial progress due to a lack of effective anti-smoking interventions and policies in school settings. We examined individual- and school-level determinants of adolescent smoking behavior (ever smoking, current smoking, and daily smoking) using the nationally representative fifth Korean Youth Risk Behavior Web-based Survey conducted in 2009. We found that students in coeducation schools or vocational high schools had greater risks of smoking for each type of smoking behavior than those in single-sex schools or general high schools, respectively even after controlling for individual-level factors. Higher family affluence and higher weekly allowances were associated with greater risks of ever smoking, current smoking and daily smoking even after controlling for parental education and other confounders. Whilst caution is required in interpreting results given the cross-sectional nature of the study, our findings suggest that in addition to raising the price of cigarettes, youth anti-smoking interventions in South Korea may benefit from focusing on coeducation schools and vocational high schools.

WTEC panel report on research submersibles and undersea technologies

NASA Technical Reports Server (NTRS)

Seymore, Richard J.; Blidberg, D. Richard; Brancart, Claude P.; Gentry, Larry L.; Kalvaitis, Algis N.; Lee, Michael J.; Mooney, Brad; Walsh, Don

1994-01-01

This report covers research submersibles and related subsea technologies in Finland, France, Russia, Ukraine and the United Kingdom. Manned, teleoperated, and autonomous submersibles were of interest. The panel found that, in contrast to the United States, Europe is making substantial progress in cooperative and coordinated research in subsea technology, including the development of standards. France is a leader in autonomous vehicle technology. Because much less was known a priori about the technologies in Russia and Ukraine, there were more new findings in those countries than in those Western European nations visited. However, Russia and Ukraine have a sizeable (and currently underutilized) infrastructure in this field, including a highly educated and experienced manpower pool, impressive (in some cases unique) facilities for physical testing, extensive fleets of seagoing research vessels capable of long voyages, and state-of-the-art facilities for conducting oceanographic investigations. The panel visited newly-formed commercial companies associated with long-standing submersible R&D and production centers in Russia and Ukraine. So far, these new efforts are undercapitalized, and as such represent opportunities at very low cost for Western nations, as detailed in the site reports.

KUS121, an ATP regulator, mitigates chorioretinal pathologies in animal models of age-related macular degeneration.

PubMed

Muraoka, Yuki; Iida, Yuto; Ikeda, Hanako O; Iwai, Sachiko; Hata, Masayuki; Iwata, Takeshi; Nakayama, Mao; Shimozawa, Nobuhiro; Katakai, Yuko; Kakizuka, Akira; Yoshimura, Nagahisa; Tsujikawa, Akitaka

2018-05-01

Age-related macular degeneration (AMD) is a leading cause of blindness among elderly people. The appearance of drusen is a clinical manifestation and a harbinger of both exudative and atrophic AMD. Recently, antibody-based medicines have been used to treat the exudative type. However, they do not restore good vision in patients. Moreover, no effective treatment is available for atrophic AMD. We have created small chemicals (Kyoto University Substances; KUSs) that act as ATP regulators inside cells. In the present study, we examined the in vivo efficacy of KUS121 in C-C chemokine receptor type 2-deficient mice, a mouse model of AMD. Systemic administration of KUS121 prevented or reduced drusen-like lesions and endoplasmic reticulum stress, and then substantially mitigated chorioretinal pathologies with significant preservation of visual function. Additionally, we confirmed that long-term oral administration of KUS121 caused no systemic complications in drusen-affected monkeys. ATP regulation by KUSs may represent a novel strategy in the treatment of drusen and prevention of disease progression in AMD.

Ab Initio structure prediction for Escherichia coli: towards genome-wide protein structure modeling and fold assignment

PubMed Central

Xu, Dong; Zhang, Yang

2013-01-01

Genome-wide protein structure prediction and structure-based function annotation have been a long-term goal in molecular biology but not yet become possible due to difficulties in modeling distant-homology targets. We developed a hybrid pipeline combining ab initio folding and template-based modeling for genome-wide structure prediction applied to the Escherichia coli genome. The pipeline was tested on 43 known sequences, where QUARK-based ab initio folding simulation generated models with TM-score 17% higher than that by traditional comparative modeling methods. For 495 unknown hard sequences, 72 are predicted to have a correct fold (TM-score > 0.5) and 321 have a substantial portion of structure correctly modeled (TM-score > 0.35). 317 sequences can be reliably assigned to a SCOP fold family based on structural analogy to existing proteins in PDB. The presented results, as a case study of E. coli, represent promising progress towards genome-wide structure modeling and fold family assignment using state-of-the-art ab initio folding algorithms. PMID:23719418

WTEC panel report on research submersibles and undersea technologies

NASA Astrophysics Data System (ADS)

Seymore, Richard J.; Blidberg, D. Richard; Brancart, Claude P.; Gentry, Larry L.; Kalvaitis, Algis N.; Lee, Michael J.; Mooney, Brad; Walsh, Don

1994-06-01

This report covers research submersibles and related subsea technologies in Finland, France, Russia, Ukraine and the United Kingdom. Manned, teleoperated, and autonomous submersibles were of interest. The panel found that, in contrast to the United States, Europe is making substantial progress in cooperative and coordinated research in subsea technology, including the development of standards. France is a leader in autonomous vehicle technology. Because much less was known a priori about the technologies in Russia and Ukraine, there were more new findings in those countries than in those Western European nations visited. However, Russia and Ukraine have a sizeable (and currently underutilized) infrastructure in this field, including a highly educated and experienced manpower pool, impressive (in some cases unique) facilities for physical testing, extensive fleets of seagoing research vessels capable of long voyages, and state-of-the-art facilities for conducting oceanographic investigations. The panel visited newly-formed commercial companies associated with long-standing submersible R&D and production centers in Russia and Ukraine. So far, these new efforts are undercapitalized, and as such represent opportunities at very low cost for Western nations, as detailed in the site reports.

Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy

PubMed Central

Imamura, Aya; Ogawa, Miho; Yasukawa, Masato; Yamazaki, Hiromichi; Morita, Ritsuko; Ikeda, Etsuko; Nakao, Kazuhisa; Takano-Yamamoto, Teruko; Kasugai, Shohei; Saito, Masahiro; Tsuji, Takashi

2011-01-01

Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy. PMID:21765896

Space Weather Needs of an Evolving Customer Base (Invited)

NASA Astrophysics Data System (ADS)

Rutledge, B.; Viereck, R. A.; Onsager, T. G.

2013-12-01

Great progress has been made in raising the global awareness of space weather and the associated impacts on Earth and our technological systems. However, significant gaps still exist in providing comprehensive and easily understood space weather information, products, and services to the diverse and growing customer base. As technologies, such as Global Navigation Satellite Systems (GNSS), have become more ingrained in applications and fields of work that previously did not rely on systems sensitive to space weather, the customer base has grown substantially. Furthermore, the causes and effects of space weather can be difficult to interpret without a detailed understanding of the scientific underpinnings. In response to this change, space weather service providers must address this evolution by both improving services and by representing space weather information and impacts in ways that are meaningful to each facet of this diverse customer base. The NOAA Space Weather Prediction Center (SWPC) must work with users, spanning precision agriculture, emergency management, power grid operators and beyond, to both identify unmet space weather service requirements and to ensure information and decision support services are provided in meaningful and more easily understood forms.

A plane wave source with minimal harmonic distortion for investigating nonlinear acoustic properties

PubMed Central

Lloyd, Christopher W.; Wallace, Kirk D.; Holland, Mark R.; Miller, James G.

2008-01-01

The objective of this investigation is to introduce and validate a practical ultrasound source to be used in the investigation of the nonlinear material properties of liquids and soft tissues studied in vitro. Methods based on the progressive distortion of finite amplitude ultrasonic waves in the low megahertz frequency-range are most easily implemented under the assumption of plane wave propagation. However, achieving an approximately planar ultrasonic field over substantial propagation distances can be challenging. Furthermore, undesired harmonic distortion of the ultrasonic field prior to insonification of the specified region of interest represents another serious limitation. This paper introduces an approach based on the use of the ultrasonic field emanating from a stainless-steel delay line. Both simulation and direct experimental measurement demonstrate that such a field exhibits relatively planar wavefronts to a good approximation (such that a 3 mm diameter receiver would be exposed to no more than 3 dB of loss across its face) and is free from the significant harmonic distortion that would occur in a conventional water path. PMID:17614467

Transcranial Electrical Stimulation

PubMed Central

Fertonani, Anna; Miniussi, Carlo

2016-01-01

In recent years, there has been remarkable progress in the understanding and practical use of transcranial electrical stimulation (tES) techniques. Nevertheless, to date, this experimental effort has not been accompanied by substantial reflections on the models and mechanisms that could explain the stimulation effects. Given these premises, the aim of this article is to provide an updated picture of what we know about the theoretical models of tES that have been proposed to date, contextualized in a more specific and unitary framework. We demonstrate that these models can explain the tES behavioral effects as distributed along a continuum from stimulation dependent to network activity dependent. In this framework, we also propose that stochastic resonance is a useful mechanism to explain the general online neuromodulation effects of tES. Moreover, we highlight the aspects that should be considered in future research. We emphasize that tES is not an “easy-to-use” technique; however, it may represent a very fruitful approach if applied within rigorous protocols, with deep knowledge of both the behavioral and cognitive aspects and the more recent advances in the application of stimulation. PMID:26873962

A generic framework for individual-based modelling and physical-biological interaction

PubMed Central

2018-01-01

The increased availability of high-resolution ocean data globally has enabled more detailed analyses of physical-biological interactions and their consequences to the ecosystem. We present IBMlib, which is a versatile, portable and computationally effective framework for conducting Lagrangian simulations in the marine environment. The purpose of the framework is to handle complex individual-level biological models of organisms, combined with realistic 3D oceanographic model of physics and biogeochemistry describing the environment of the organisms without assumptions about spatial or temporal scales. The open-source framework features a minimal robust interface to facilitate the coupling between individual-level biological models and oceanographic models, and we provide application examples including forward/backward simulations, habitat connectivity calculations, assessing ocean conditions, comparison of physical circulation models, model ensemble runs and recently posterior Eulerian simulations using the IBMlib framework. We present the code design ideas behind the longevity of the code, our implementation experiences, as well as code performance benchmarking. The framework may contribute substantially to progresses in representing, understanding, predicting and eventually managing marine ecosystems. PMID:29351280

CANCER RISK ASSESSMENT AND PREVENTION: WHERE DO WE STAND?

EPA Science Inventory

This paper reviews selected aspects of progress and setbacks in cancer risk assessment and prevention during the four decades since the founding in 1947 of the Institute of Environmental Medicine at the New York University Medical Center. he period has heen marked by substantial ...

The history and future of dietary guidance in America

USDA-ARS?s Scientific Manuscript database

Evidence-based dietary guidance in the US has progressed substantially since its inception over 100 years ago. This review describes the historical development and significance of dietary guidance in the US, including the Dietary Guidelines for Americans, and emphasizes the foundations upon which th...

An Innovative Approach to Integrated Training for Smallholder Dairying

ERIC Educational Resources Information Center

Chagunda, Mizeck Gift Gibson; Munthali, David Pusi; Gondwe, Timothy N.; Wood, Bethan; Roberts, David J.

2014-01-01

Purpose: This paper assesses an integrated approach in smallholder dairy training through a partnership between Malawi and Scotland. Design/ methodology/ approach: Acute staff shortages and inadequate expertise hamper progress in Malawi's smallholder dairy production despite its potential to substantially contribute to sustainable household…

The impact of tobacco control research on policy: 20 years of progress.

PubMed

Warner, Kenneth E; Tam, Jamie

2012-03-01

To assess progress in tobacco control policy research and the relevance of research to policy making. Over 100 experts were surveyed about their opinions on the body of research existing in 1992 and 2011 concerning 11 areas of tobacco control policy, the state of policy implementation in both years, the extent to which research has affected policy adoption and how experience with policy has influenced research. Case studies of how research and policy implementation have interacted were developed. The body of research was not judged 'substantial' in any of the policy areas in 1992. In 2011, 6 of the 11 areas were evaluated as substantial. None ranked as substantial regarding policy implementation in 1992, but by 2011 half were so ranked for developed countries; in low-income and middle-income countries policy implementation moved from very low to moderate. Respondents judged the role of research in actual policy making as 'substantial' regarding clean indoor air, taxation and cessation treatment policy. Case studies illustrate how research can directly affect policy (taxation), how policy and research can have iterative effects (clean indoor air), and how research and policy interact in the case of novel policies (graphic cigarette pack warnings). The role of research in the formulation of the Framework Convention on Tobacco Control is also examined. Policy research goals established in 1992 have been largely realised. For select tobacco control policies, research has made truly important contributions to saving lives. Evidence-based policy adoption will continue to be essential to minimising the toll of tobacco, especially in the world's poorer countries.

Graphical Man/Machine Communications

DTIC Science & Technology

Progress is reported concerning the use of computer controlled graphical displays in the areas of radiaton diffusion and hydrodynamics, general...ventricular dynamics. Progress is continuing on the use of computer graphics in architecture. Some progress in halftone graphics is reported with no basic...developments presented. Colored halftone perspective pictures are being used to represent multivariable situations. Nonlinear waveform processing is

2016 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

Satyapal, Sunita

In the past year, the DOE Hydrogen Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

Robert H. Goddard and His Liquid-Gasoline Rocket

NASA Technical Reports Server (NTRS)

1926-01-01

Dr. Goddard's 1926 rocket configuration. Dr. Goddard's liquid oxygen-gasoline rocket was fired on March 16, 1926, at Auburn, Massachusetts. It flew for only 2.5 seconds, climbed 41 feet, and landed 184 feet away in a cabbage patch. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets, which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

2010 Annual Progress Report: DOE Hydrogen Program

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

Not Available

In the past year, the DOE Hydrogen Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

2015 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

Popovich, Neil

In the past year, the DOE Hydrogen Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

Early Rockets

NASA Image and Video Library

1926-03-16

Dr. Goddard's 1926 rocket configuration. Dr. Goddard's liquid oxygen-gasoline rocket was fired on March 16, 1926, at Auburn, Massachusetts. It flew for only 2.5 seconds, climbed 41 feet, and landed 184 feet away in a cabbage patch. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets, which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

Early Rockets

NASA Image and Video Library

1926-03-16

Dr. Robert H. Goddard and liquid oxygen-gasoline rocket in the frame from which it was fired on March 16, 1926, at Auburn, Mass. It flew for only 2.5 seconds, climbed 41 feet, and landed 184 feet away in a cabbage patch. From 1930 to 1941, Dr. Goddard made substantial progress in the development of progressively larger rockets, which attained altitudes of 2400 meters, and refined his equipment for guidance and control, his techniques of welding, and his insulation, pumps, and other associated equipment. In many respects, Dr. Goddard laid the essential foundations of practical rocket technology

2012 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

Not Available

In the past year, the DOE Hydrogen Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

A degradation debt? Large-scale shifts in community composition and loss of biomass in a tropical forest fragment after 40 years of isolation.

PubMed

Zahawi, Rakan A; Oviedo-Brenes, Federico; Peterson, Chris J

2017-01-01

Habitat loss and fragmentation are among the biggest threats to tropical biodiversity and associated ecosystem services. We examined forest dynamics in a mid-elevation 365-ha fragment in southern Costa Rica. The fragment was isolated in the mid-1970s and belongs to the Las Cruces Biological Station. A 2.25-ha permanent plot was established in the center of the old-growth forest (>400 m to nearest edge boundary) and all plants >5 cm DBH were censused, mapped, and identified to species in two surveys taken ~5-6 years apart (>3,000 stems/survey). Although the reserve maintains high species richness (>200 spp.), with many rare species represented by only one individual, we document a strong shift in composition with a two-fold increase in the number of soft-wooded pioneer individuals. The dominant late-successional understory tree species, Chrysochlamys glauca (Clusiaceae), and most species in the Lauraceae, declined dramatically. Turnover was high: 22.9% of stems in the first survey were lost, and 27.8% of stems in the second survey represented new recruits. Mean tree diameter decreased significantly and there was a 10% decrease in overall biomass. Such alteration has been documented previously but only in smaller fragments or within ~100 m of an edge boundary. Further penetration into this fragment was perhaps driven by a progressive invasion of disturbance-adapted species into the fragment's core over time; the loss of once-dominant late successional species could be a contributing factor. The pattern found is of particular concern given that such fragments represent a substantial portion of today's remaining tropical habitat; further studies in similar-sized fragments that have been isolated for similar prolonged periods are called for.

The Role of Gene Therapy in the Treatment of Retinal Diseases: A Review.

PubMed

Campa, C; Gallenga, C E; Bolletta, E; Perri, P

2017-01-01

Gene therapy represents the therapeutic delivery of nucleic acid polymers into patient cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ. It is not surprising therefore that several clinical trials are now ongoing in this field. The purpose of this review was to provide an update on gene therapy for retinal diseases, discussing differences in treatment strategies, vector designs and surgical techniques. Research was performed on PubMed, ClinicalTrials.gov, and Home Genetic Reference. We additionally utilized the internet database for genetics of retinal diseases, the portal for rare diseases and orphan drugs and the NCBI database Online Mendelian Inheritance in Man. No restriction was applied on the language of publications. We present the available results of current active clinical trials for inherited retinal disease such as Leber's congenital amaurosis type 2, choroideremia, Stargardt disease, achromatopsia and juvenile X-linked retinoschisis. We also illustrate a new approach of this therapy for the treatment of much more common ocular diseases such as age-related macular degeneration and diabetic retinopathy. Gene therapy represents an emerging and promising therapeutic approach for the treatment not only of rare inherited retinal diseases but also much more common retinal pathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A degradation debt? Large-scale shifts in community composition and loss of biomass in a tropical forest fragment after 40 years of isolation

PubMed Central

2017-01-01

Habitat loss and fragmentation are among the biggest threats to tropical biodiversity and associated ecosystem services. We examined forest dynamics in a mid-elevation 365-ha fragment in southern Costa Rica. The fragment was isolated in the mid-1970s and belongs to the Las Cruces Biological Station. A 2.25-ha permanent plot was established in the center of the old-growth forest (>400 m to nearest edge boundary) and all plants >5 cm DBH were censused, mapped, and identified to species in two surveys taken ~5–6 years apart (>3,000 stems/survey). Although the reserve maintains high species richness (>200 spp.), with many rare species represented by only one individual, we document a strong shift in composition with a two-fold increase in the number of soft-wooded pioneer individuals. The dominant late-successional understory tree species, Chrysochlamys glauca (Clusiaceae), and most species in the Lauraceae, declined dramatically. Turnover was high: 22.9% of stems in the first survey were lost, and 27.8% of stems in the second survey represented new recruits. Mean tree diameter decreased significantly and there was a 10% decrease in overall biomass. Such alteration has been documented previously but only in smaller fragments or within ~100 m of an edge boundary. Further penetration into this fragment was perhaps driven by a progressive invasion of disturbance-adapted species into the fragment’s core over time; the loss of once-dominant late successional species could be a contributing factor. The pattern found is of particular concern given that such fragments represent a substantial portion of today’s remaining tropical habitat; further studies in similar-sized fragments that have been isolated for similar prolonged periods are called for. PMID:28832611

A case-study in the clinical epidemiology of psoriatic arthritis: multistate models and causal arguments

PubMed Central

O'Keeffe, Aidan G; Tom, Brian D M; Farewell, Vernon T

2011-01-01

In psoriatic arthritis, permanent joint damage characterizes disease progression and represents a major debilitating aspect of the disease. Understanding the process of joint damage will assist in the treatment and disease management of patients. Multistate models provide a means to examine patterns of disease, such as symmetric joint damage. Additionally, the link between damage and the dynamic course of disease activity (represented by joint swelling and stress pain) at both the individual joint level and otherwise can be represented within a correlated multistate model framework. Correlation is reflected through the use of random effects for progressive models and robust variance estimation for non-progressive models. Such analyses, undertaken with data from a large psoriatic arthritis cohort, are discussed and the extent to which they permit causal reasoning is considered. For this, emphasis is given to the use of the Bradford Hill criteria for causation in observational studies and the concept of local (in)dependence to capture the dynamic nature of the relationships. PMID:22163372

The Future of Adaptive Learning: Does the Crowd Hold the Key?

ERIC Educational Resources Information Center

Heffernan, Neil T.; Ostrow, Korinn S.; Kelly, Kim; Selent, Douglas; Van Inwegen, Eric G.; Xiong, Xiaolu; Williams, Joseph Jay

2016-01-01

Due to substantial scientific and practical progress, learning technologies can effectively adapt to the characteristics and needs of students. This article considers how learning technologies can adapt over time by crowdsourcing contributions from teachers and students--explanations, feedback, and other pedagogical interactions. Considering the…

76 FR 68617 - National Diabetes Month, 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-04

... have made substantial progress in combating diabetes, the number of Americans burdened by this disease... and children alike. It is essential that all Americans take steps to assess and reduce their risk of... Americans joining a new health plan can receive recommended preventive services, like diabetes screenings...

37 CFR 11.306 - Trial publicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... statement that the practitioner knows or reasonably should know will be disseminated by means of public communication and will have a substantial likelihood of materially prejudicing an adjudicative proceeding in the...) Information contained in a public record; (3) That an investigation of a matter is in progress; (4) The...

37 CFR 11.306 - Trial publicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... statement that the practitioner knows or reasonably should know will be disseminated by means of public communication and will have a substantial likelihood of materially prejudicing an adjudicative proceeding in the...) Information contained in a public record; (3) That an investigation of a matter is in progress; (4) The...

24 CFR 597.403 - Revocation of designation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND... area; (2) Has failed to make progress in achieving the benchmarks set forth in the strategic plan; or (3) Has not complied substantially with the strategic plan. (b) Letter of warning. Before revoking...

The Nation's Report Card: Mathematics 2011. National Assessment of Educational Progress at Grades 4 and 8. NCES 2012-458

ERIC Educational Resources Information Center

National Center for Education Statistics, 2011

2011-01-01

This report presents results of the 2011 National Assessment of Educational Progress (NAEP) in mathematics at grades 4 and 8. Nationally representative samples of 209,000 fourth-graders and 175,200 eighth-graders participated in the 2011 National Assessment of Educational Progress (NAEP) in mathematics. At each grade, students responded to…

Microenvironmental Regulation of Mammary Carcinogenesis

DTIC Science & Technology

2008-06-01

cells. These models share many of the hallmarks of multistage human breast cancer development including histological disease progression and immune cell... developed by Muller and colleagues20, represents a reasonable recapitulation of late-stage human breast cancer as determined by histological progression ...Annual Progress Report d. Develop a profile of proteolytic activities in normal and neoplastic mammary tissues from mouse models of mammary

Projecting the release of carbon from permafrost soils using a perturbed parameter ensemble modelling approach

NASA Astrophysics Data System (ADS)

MacDougall, Andrew H.; Knutti, Reto

2016-04-01

The soils of the northern hemispheric permafrost region are estimated to contain 1100 to 1500 Pg of carbon. A substantial fraction of this carbon has been frozen and therefore protected from microbial decay for millennia. As anthropogenic climate warming progresses much of this permafrost is expected to thaw. Here we conduct perturbed model experiments on a climate model of intermediate complexity, with an improved permafrost carbon module, to estimate with formal uncertainty bounds the release of carbon from permafrost soils by the year 2100 and 2300 CE. We estimate that by year 2100 the permafrost region may release between 56 (13 to 118) Pg C under Representative Concentration Pathway (RCP) 2.6 and 102 (27 to 199) Pg C under RCP 8.5, with substantially more to be released under each scenario by the year 2300. Our analysis suggests that the two parameters that contribute most to the uncertainty in the release of carbon from permafrost soils are the size of the non-passive fraction of the permafrost carbon pool and the equilibrium climate sensitivity. A subset of 25 model variants are integrated 8000 years into the future under continued RCP forcing. Under the moderate RCP 4.5 forcing a remnant near-surface permafrost region persists in the high Arctic, eventually developing a new permafrost carbon pool. Overall our simulations suggest that the permafrost carbon cycle feedback to climate change will make a significant contribution to climate change over the next centuries and millennia, releasing a quantity of carbon 3 to 54 % of the cumulative anthropogenic total.

Neural and behavioral mechanisms of proactive and reactive inhibition

PubMed Central

Meyer, Heidi C.

2016-01-01

Response inhibition is an important component of adaptive behavior. Substantial prior research has focused on reactive inhibition, which refers to the cessation of a motor response that is already in progress. More recently, a growing number of studies have begun to examine mechanisms underlying proactive inhibition, whereby preparatory processes result in a response being withheld before it is initiated. It has become apparent that proactive inhibition is an essential component of the overall ability to regulate behavior and has implications for the success of reactive inhibition. Moreover, successful inhibition relies on learning the meaning of specific environmental cues that signal when a behavioral response should be withheld. Proactive inhibitory control is mediated by stopping goals, which reflect the desired outcome of inhibition and include information about how and when inhibition should be implemented. However, little is known about the circuits and cellular processes that encode and represent features in the environment that indicate the necessity for proactive inhibition or how these representations are implemented in response inhibition. In this article, we will review the brain circuits and systems involved in implementing inhibitory control through both reactive and proactive mechanisms. We also comment on possible cellular mechanisms that may contribute to inhibitory control processes, noting that substantial further research is necessary in this regard. Furthermore, we will outline a number of ways in which the temporal dynamics underlying the generation of the proactive inhibitory signal may be particularly important for parsing out the neurobiological correlates that contribute to the learning processes underlying various aspects of inhibitory control. PMID:27634142

Beneficial and detrimental role of adenosine signaling in diseases and therapy

PubMed Central

Liu, Hong

2015-01-01

Adenosine is a major signaling nucleoside that orchestrates cellular and tissue adaptation under energy depletion and ischemic/hypoxic conditions by activation of four G protein-coupled receptors (GPCR). The regulation and generation of extracellular adenosine in response to stress are critical in tissue protection. Both mouse and human studies reported that extracellular adenosine signaling plays a beneficial role during acute states. However, prolonged excess extracellular adenosine is detrimental and contributes to the development and progression of various chronic diseases. In recent years, substantial progress has been made to understand the role of adenosine signaling in different conditions and to clarify its significance during the course of disease progression in various organs. These efforts have and will identify potential therapeutic possibilities for protection of tissue injury at acute stage by upregulation of adenosine signaling or attenuation of chronic disease progression by downregulation of adenosine signaling. This review is to summarize current progress and the importance of adenosine signaling in different disease stages and its potential therapeutic effects. PMID:26316513

Pakistan and the Millennium Development Goals for Maternal and Child Health: progress and the way forward.

PubMed

Rizvi, Arjumand; Bhatti, Zaid; Das, Jai K; Bhutta, Zulfiqar A

2015-01-01

The world has made substantial progress in reducing maternal and child mortality, but many countries are projected to fall short of achieving their Millennium Development Goals (MDGs) 4 and 5 targets. The major objective of this paper is to examine progress in Pakistan in reducing maternal and child mortality and malnutrition over the last two decades. Data from recent national and international surveys suggest that Pakistan lags behind on all of its MDGs related to maternal and child health and, for some indicators especially related to nutrition, the situation has worsened from the baseline of 1990. Progress in addressing key social determinants such as poverty, female education and empowerment has also been slow and unregulated population growth has further compromised progress. There is a need to integrate the various different sectors and programmes to achieve the desired results effectively and efficiently as many of the determinants and influencing factors are outside the health sector.

Case management considerations of progressive dementia in a home setting.

PubMed

Pierce, Mary Ellen

2010-01-01

Nursing theory, research, and best practice guidelines contribute substantially to the field of dementia care. Interventional plans are challenged most by those dementias considered progressive and deteriorative in nature, requiring ongoing reassessment and modification of care practices as the clinical course changes. The purpose of this article is to provide guidelines for case managers in the development of effective, individualized care plans for clients with progressive dementia residing in a home setting. The application of these guidelines is illustrated through the presentation of an actual case. The practice setting is a private home in the Pacific Northwest. Geriatric case management is provided by an RN case manager. Progressive dementia presents challenges to home care. Professional case management using comprehensive, holistic assessment, collaborative approaches, and best practice fundamentals serve to create an effective, individualized plan of care. The increasing geriatric population presents great opportunities for case managers in strategic management for creating successful home care models in clients with progressive dementia. Use of nursing diagnoses, dementia research, and collaborative approaches with families and other medical providers creates a viable alternative for clients with progressive dementia.

RECENT PROGRESS IN GLYCOCHEMISTRY AND GREEN CHEMISTRY. (R826123)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Experimental and Theoretical Studies of Atmosphereic Inorganic Chlorine Chemistry

NASA Technical Reports Server (NTRS)

Sander, Stanley P.; Friedl, Randall R.

1993-01-01

Over the last five years substantial progress has been made in defining the realm of new chlorine chemistry in the polar stratosphere. Application of existing experimental techniques to potentially important chlorine-containing compounds has yielded quantitative kinetic and spectroscopic data as well as qualitative mechanistic insights into the relevant reactions.

78 FR 61811 - National Domestic Violence Awareness Month, 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-04

... Proclamation Since the passage of the Violence Against Women Act (VAWA) nearly 20 years ago, our Nation's... National Domestic Violence Awareness Month, we stand with domestic abuse survivors, celebrate our Nation's.... Although we have made substantial progress in reducing domestic violence, one in four women and one in...

How Reliable is the Temperature Forecast?

ERIC Educational Resources Information Center

Christmann, Edwin P.

2005-01-01

Project 2061 suggests "technology provides the eyes and ears of science--and some of the muscle too. The electronic computer, for example, has led to substantial progress in the study of weather systems...." Obviously, now that teachers have access to a kaleidoscope of technological advancements, middle school science teachers can engage students…

Progress and successes of the Specialty Crop Research Initiative on acrylamide reduction in processed potato products

USDA-ARS?s Scientific Manuscript database

Acrylamide, a suspected human carcinogen, is a Maillard reaction product that forms when carbohydrate-rich foods are cooked at high temperatures. Processed potato products, including French fries and potato chips, make a substantial contribution to total dietary acrylamide. Health safety concerns ra...

What is Job Satisfaction?

ERIC Educational Resources Information Center

Locke. Edwin A.

Despite considerable interest in the study of job satisfaction and dissatisfaction, our understanding of these phenomena has not increased substantially in the past 30 years. It is argued that a major reason for this lack of progress is the implicit conception of casuality accepted by most psychologists. It is called the policy of "correlation…

Ten Years after "A Nation at Risk."

ERIC Educational Resources Information Center

Asayesh, Gelareh

1993-01-01

In April 1983, the National Commission on Excellence in Education issued a 32-page report ("A Nation at Risk") calling for drastic educational reforms. A decade later, four top education reformers--John Goodlad, Henry Levin, Phillip Schlechty, and Ted Sizer--assess this document and its legacy. Most see substantial progress despite the…

Report: EPA Needs to Direct More Attention, Efforts, and Funding to Enhance Its Speciation Monitoring Program for Measuring Fine Particulate Matter

EPA Pesticide Factsheets

Report #2005-P-00004, February 7, 2005. EPA has made substantial progress in establishing a speciation monitoring network, but still faces a number of challenges in ensuring that the controls are implemented at the right sources.

Attachment in Middle Childhood: Progress and Prospects

ERIC Educational Resources Information Center

Bosmans, Guy; Kerns, Kathryn A.

2015-01-01

Contrary to the substantial amount of research on infant, preschool, adolescent, and adult attachment, middle childhood has long been neglected by the international attachment research community. In the past two decades, however, there has been a steep increase in research focusing on middle childhood attachment. This article provides an overview…

Genome editing: progress and challenges for medical applications.

PubMed

Carroll, Dana

2016-11-15

The development of the CRISPR-Cas platform for genome editing has greatly simplified the process of making targeted genetic modifications. Applications of genome editing are expected to have a substantial impact on human therapies through the development of better animal models, new target discovery, and direct therapeutic intervention.

12 CFR 213.4 - Content of disclosures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... mathematical progression of how the scheduled periodic payment is derived, in a format substantially similar to... the end of the lease term; and the amount or a description of the method for determining the amount of... specify the amount or method for determining any charge for excess mileage. (i) Purchase option. A...

Social Programs That Work.

ERIC Educational Resources Information Center

Crane, Jonathan, Ed.

In recent years, social programs for the poor have lost the support of the American public. This book describes some of the very best programs and documents their benefits, demonstrating that we can, in fact, make substantial progress in the fight against educational failure, family dissolution, violent crime, substance abuse, unemployment, and…

NIMH's TADS: More than Just a Tad of Progress?

ERIC Educational Resources Information Center

Jensen, Peter S.

2005-01-01

The Treatment for Adolescents With Depression Study (TADS) derives substantial public health significance from its head-to-head comparisons of carefully administered medication versus a carefully crafted cognitive-behavioral therapy in youth with major depression, the first major clinical trial of its kind. Although the study has a number of…

Why Do Teachers Leave? CenterView

ERIC Educational Resources Information Center

Center for the Future of Teaching and Learning, 2007

2007-01-01

While California has made substantial progress in easing its teacher shortage and reducing the concentration of the least prepared teachers in the lowest achieving schools, the effort to strengthen schools for all students is hampered by the large number of teachers who leave the profession prematurely. Policymakers at the state and local levels…

Monitoring clinical progression with mitochondrial disease biomarkers

PubMed Central

Steele, Hannah E; Horvath, Rita; Lyon, Jon J; Chinnery, Patrick F

2017-01-01

Abstract Mitochondrial disorders are genetically determined metabolic diseases due to a biochemical deficiency of the respiratory chain. Given that multi-system involvement and disease progression are common features of mitochondrial disorders they carry substantial morbidity and mortality. Despite this, no disease-modifying treatments exist with clear clinical benefits, and the current best management of mitochondrial disease is supportive. Several therapeutic strategies for mitochondrial disorders are now at a mature preclinical stage. Some are making the transition into early-phase patient trials, but the lack of validated biomarkers of disease progression presents a challenge when developing new therapies for patients. This update discusses current biomarkers of mitochondrial disease progression including metabolomics, circulating serum markers, exercise physiology, and both structural and functional imaging. We discuss the advantages and disadvantages of each approach, and consider emerging techniques with a potential role in trials of new therapies. PMID:28969370

Qualitative methods in health services and management research: pockets of excellence and progress, but still a long way to go.

PubMed

Devers, Kelly J

2011-02-01

The 10-year systematic review of published health services and management research by Weiner et al. (2011) chronicles the contributions of qualitative methods, highlights areas of substantial progress, and identifies areas in need of more progress. This article (Devers, 2011) discusses possible reasons for lack of progress in some areas--related to the under-supply of well-trained qualitative researchers and more tangible demand for their research--and mechanisms for future improvement. To ensure a robust health services research toolbox, the field must take additional steps to provide stronger education and training in qualitative methods and more funding and publication opportunities. Given the rapidly changing health care system post the passage of national health reform and the chalresearch issues associated with it, the health services research and management field will not meet its future challenges with quantitative methods alone or with a half-empty toolbox.

Progress and challenges in maternal health in western China: a Countdown to 2015 national case study.

PubMed

Gao, Yanqiu; Zhou, Hong; Singh, Neha S; Powell-Jackson, Timothy; Nash, Stephen; Yang, Min; Guo, Sufang; Fang, Hai; Alvarez, Melisa Martinez; Liu, Xiaoyun; Pan, Jay; Wang, Yan; Ronsmans, Carine

2017-05-01

China is one of the few Countdown countries to have achieved Millennium Development Goal 5 (75% reduction in maternal mortality ratio between 1990 and 2015). We aimed to examine the health systems and contextual factors that might have contributed to the substantial decline in maternal mortality between 1997 and 2014. We chose to focus on western China because poverty, ethnic diversity, and geographical access represent particular challenges to ensuring universal access to maternal care in the region. In this systematic assessment, we used data from national census reports, National Statistical Yearbooks, the National Maternal and Child Health Routine Reporting System, the China National Health Accounts report, and National Health Statistical Yearbooks to describe changes in policies, health financing, health workforce, health infrastructure, coverage of maternal care, and maternal mortality by region between 1997 and 2014. We used a multivariate linear regression model to examine which contextual and health systems factors contributed to the regional variation in maternal mortality ratio in the same period. Using data from a cross-sectional survey in 2011, we also examined equity in access to maternity care in 42 poor counties in western China. Maternal mortality declined by 8·9% per year between 1997 and 2014 (geometric mean ratio for each year 0·91, 95% CI 0·91-0·92). After adjusting for GDP per capita, length of highways, female illiteracy, the number of licensed doctors per 1000 population, and the proportion of ethnic minorities, the maternal mortality ratio was 118% higher in the western region (2·18, 1·44-3·28) and 41% higher in the central region (1·41, 0·99-2·01) than in the eastern region. In the rural western region, the proportion of births in health facilities rose from 41·9% in 1997 to 98·4% in 2014. Underpinning such progress was the Government's strong commitment to long-term strategies to ensure access to delivery care in health facilities-eg, professionalisation of maternity care in large hospitals, effective referral systems for women medically or socially at high risk, and financial subsidies for antenatal and delivery care. However, in the poor western counties, substantial disparity by education level of the mother existed in access to health facility births (44% of illiterate women vs 100% of those with college or higher education), antenatal care (17% vs 69%) had at least four visits), and caesarean section (8% vs 44%). Despite remarkable progress in maternal survival in China, substantial disparities remain, especially for the poor, less educated, and ethnic minority groups in remote areas in western China. Whether China's highly medicalised model of maternity care will be an answer for these populations is uncertain. A strategy modelled after China's immunisation programme, whereby care is provided close to the women's homes, might need to be explored, with township hospitals taking a more prominent role. Government of Canada, UNICEF, and the Bill & Melinda Gates Foundation. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Mathematical Models of Breast and Ovarian Cancers

PubMed Central

Botesteanu, Dana-Adriana; Lipkowitz, Stanley; Lee, Jung-Min; Levy, Doron

2016-01-01

Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed. Such integrated frameworks could offer innovative contributions to the clinical women's cancers community, since answers to clinical questions cannot always be reached with contemporary clinical and experimental tools. Here, we recapitulate clinically known data regarding the progression and treatment of the breast and ovarian cancers. We compare and contrast the two malignancies whenever possible, in order to emphasize areas where substantial contributions could be made by clinically inspired and validated mathematical modeling. We show how current paradigms in the mathematical oncology community focusing on the two malignancies do not make comprehensive use of, nor substantially reflect existing clinical data, and we highlight the modeling areas in most critical need of clinical data integration. We emphasize that the primary goal of any mathematical study of women's cancers should be to address clinically relevant questions. PMID:27259061

Comparison of left anterior descending coronary artery hemodynamics before and after angioplasty.

PubMed

Ramaswamy, S D; Vigmostad, S C; Wahle, A; Lai, Y G; Olszewski, M E; Braddy, K C; Brennan, T M H; Rossen, J D; Sonka, M; Chandran, K B

2006-02-01

Coronary artery disease (CAD) is characterized by the progression of atherosclerosis, a complex pathological process involving the initiation, deposition, development, and breakdown of the plaque. The blood flow mechanics in arteries play a critical role in the targeted locations and progression of atherosclerotic plaque. In coronary arteries with motion during the cardiac contraction and relaxation, the hemodynamic flow field is substantially different from the other arterial sites with predilection of atherosclerosis. In this study, our efforts focused on the effects of arterial motion and local geometry on the hemodynamics of a left anterior descending (LAD) coronary artery before and after clinical intervention to treat the disease. Three-dimensional (3D) arterial segments were reconstructed at 10 phases of the cardiac cycle for both pre- and postintervention based on the fusion of intravascular ultrasound (IVUS) and biplane angiographic images. An arbitrary Lagrangian-Eulerian formulation was used for the computational fluid dynamic analysis. The measured arterial translation was observed to be larger during systole after intervention and more out-of-plane motion was observed before intervention, indicating substantial alterations in the cardiac contraction after angioplasty. The time averaged axial wall shear stress ranged from -0.2 to 9.5 Pa before intervention compared to -0.02 to 3.53 Pa after intervention. Substantial oscillatory shear stress was present in the preintervention flow dynamics compared to that in the postintervention case.

A Twin Study of ADHD Symptoms in Early Adolescence: Hyperactivity-Impulsivity and Inattentiveness Show Substantial Genetic Overlap but Also Genetic Specificity

ERIC Educational Resources Information Center

Greven, Corina U.; Rijsdijk, Fruhling V.; Plomin, Robert

2011-01-01

A previous paper in this journal revealed substantial genetic overlap between the ADHD dimensions of hyperactivity-impulsivity and inattentiveness in a sample of 8-year old twins drawn from a UK-representative population sample. Four years later, when the twins were 12 years old, more than 5,500 pairs drawn from the same sample were rated again on…

Stimulus-Response-Outcome Coding in the Pigeon Nidopallium Caudolaterale

PubMed Central

Starosta, Sarah; Güntürkün, Onur; Stüttgen, Maik C.

2013-01-01

A prerequisite for adaptive goal-directed behavior is that animals constantly evaluate action outcomes and relate them to both their antecedent behavior and to stimuli predictive of reward or non-reward. Here, we investigate whether single neurons in the avian nidopallium caudolaterale (NCL), a multimodal associative forebrain structure and a presumed analogue of mammalian prefrontal cortex, represent information useful for goal-directed behavior. We subjected pigeons to a go-nogo task, in which responding to one visual stimulus (S+) was partially reinforced, responding to another stimulus (S–) was punished, and responding to test stimuli from the same physical dimension (spatial frequency) was inconsequential. The birds responded most intensely to S+, and their response rates decreased monotonically as stimuli became progressively dissimilar to S+; thereby, response rates provided a behavioral index of reward expectancy. We found that many NCL neurons' responses were modulated in the stimulus discrimination phase, the outcome phase, or both. A substantial fraction of neurons increased firing for cues predicting non-reward or decreased firing for cues predicting reward. Interestingly, the same neurons also responded when reward was expected but not delivered, and could thus provide a negative reward prediction error or, alternatively, signal negative value. In addition, many cells showed motor-related response modulation. In summary, NCL neurons represent information about the reward value of specific stimuli, instrumental actions as well as action outcomes, and therefore provide signals useful for adaptive behavior in dynamically changing environments. PMID:23437383

Cutting medical transcription costs.

PubMed

Forsman, John A

2003-07-01

Home-based, production-based medical transcription represents a substantial cost-saving opportunity. Fewer employees are required. Office space is not needed. Outsourcing costs are eliminated. Turnaround time is reduced.

Taking Targets to Task Revisited: How Indicators of Progress on Access to Education can Mislead. CREATE Pathways to Access. Research Monograph No. 54

ERIC Educational Resources Information Center

Lewin, Keith M.

2011-01-01

"Education for All" (EFA) identifies goals and targets and translates these into indicators which are used to evaluate progress and influence flows of external financing. The search for evidence based policy depends on measures of performance that can link cause and effect and that represent real gains in progress towards desired…

Elaboration of the Environmental Stress Hypothesis–Results from a Population-Based 6-Year Follow-Up

PubMed Central

Wagner, Matthias; Jekauc, Darko; Worth, Annette; Woll, Alexander

2016-01-01

The aim of this paper was to contribute to the elaboration of the Environmental Stress Hypothesis framework by testing eight hypotheses addressing the direct impact of gross motor coordination problems in elementary-school on selected physical, behavioral and psychosocial outcomes in adolescence. Results are based on a longitudinal sample of 940 participants who were (i) recruited as part of a population-based representative survey on health, physical fitness and physical activity in childhood and adolescence, (ii) assessed twice within 6 years, between the ages of 6 and 10 years old as well as between the ages of 12 and 16 years old (Response Rate: 55.9%) and (iii) classified as having gross motor coordination problems (N = 115) or having no gross motor coordination problems (N = 825) at baseline. Motor tests from the Körperkoordinationstest, measures of weight and height, a validated physical activity questionnaire as well as the Strength and Difficulties Questionnaire were conducted. Data were analyzed by use of binary logistic regressions. Results indicated that elementary-school children with gross motor coordination problems show a higher risk of persistent gross motor coordination problems (OR = 7.99, p < 0.001), avoiding organized physical activities (OR = 1.53, p < 0.05), an elevated body mass (OR = 1.78, p < 0.05), bonding with sedentary peers (OR = 1.84, p < 0.01) as well as emotional (OR = 1.73, p < 0.05) and conduct (OR = 1.79, p < 0.05) problems in adolescence in comparison to elementary-school children without gross motor coordination problems. However, elementary-school children with gross motor coordination problems did not show a significantly higher risk of peer problems (OR = 1.35, p = 0.164) or diminished prosocial behavior (OR = 1.90, p = 0.168) in adolescence, respectively in comparison to elementary-school children without gross motor coordination problems. This study is the first to provide population-based longitudinal data ranging from childhood to adolescence in the context of the Environmental Stress Hypothesis which can be considered a substantial methodological progress. In summary, gross motor coordination problems represent a serious issue for a healthy transition from childhood to adolescence which substantiates respective early movement interventions. PMID:28018254

Correlated alterations in prostate basal cell layer and basement membrane

PubMed Central

Liu, Aijun; Wei, Lixin; Gardner, William A.; Deng, Chu-Xia; Man, Yan-Gao

2009-01-01

Our recent studies revealed that focal basal cell layer disruption (FBCLD) induced auto-immunoreactions represented a contributing factor for human prostate tumor progression and invasion. As the basement membrane surrounds and attaches to the basal cell layer, our current study assessed whether FBCLD would impact the physical integrity of the associated basement membrane. Paraffin sections from 25-human prostate tumors were subjected to double immunohistochemistry to simultaneously elucidate the basal cell layer and the basement membrane with corresponding biomarkers. The physical integrity of the basement membrane overlying FBCLD was examined to determine the extent of correlated alterations. Of a total of 89 FBCLD encountered, 76 (85 %) showed correlated alterations in the overlying basement membrane, which included distinct focal disruptions or fragmentations. In the remaining 13 (15%) FBCLD, the overlying basement membrane showed significant attenuation or reduction of the immunostaining intensity. The basement membrane in all or nearly all ducts or acini with p63 positive basal cells was substantially thicker and more uniform than that in ducts or acini without p63 positive basal cells, and also, a vast majority of the focal disruptions occurred near basal cells that lack p63 expression. These findings suggest that focal disruptions in the basal cell layer and alterations in the basement membrane are correlated events and that the physical and functional status of the basal cells could significantly impact the physical integrity of the overlying basement membrane. As the degradation of both the basal cell layer and the basement membrane is a pre-requisite for prostate tumor invasion or progression, ducts or acini with focally disrupted basal cell layer and basement membrane are likely at greater risk to develop invasive lesions. Thus, further elucidation of the specific molecules and mechanism associated with these events may lead to the development of a more effective alternative for repeat biopsy to monitor tumor progression and invasion. PMID:19343113

Facilitating Progress towards the Sustainable Development Goals through Open Scientific Data and Indicators

NASA Astrophysics Data System (ADS)

Chen, R. S.; Levy, M. A.; de Sherbinin, A. M.; Fischer, A.

2015-12-01

The Sustainable Development Goals (SDGs) represent an unprecedented international commitment to a shared future encompassing sustainable management of the planet and significant improvement in the human condition around the world. The scientific community has both an ethical responsibility and substantial self-interest—as residents of this planet—to help the world community to better understand the complex, interlinked behavior of human and environmental systems and to elucidate pathways to achieve long-term sustainability. Critical to making progress towards the SDGs is the open availability of timely, reliable, usable, and well integrated data and indicators relevant to all SDGs and associated targets. Such data and indicators will not only be valuable in monitoring and evaluation of progress, but also in developing policies and making decisions on environmental and societal issues affecting sustainability from local to global scales. The open availability of such data and indicators can help motivate performance, promote accountability, and facilitate cooperation. A range of scientific, technical, organizational, political, and resource challenges need to be addressed in developing a coherent SDG monitoring and indicator framework. For example, assembling and integrating diverse data on consistent spatial and temporal scales across the relevant natural, social, health, and engineering sciences pose both scientific and technical difficulties, and may require new ways to interlink and organize existing cyberinfrastructure, reconcile different data policy regimes, and fund integration efforts. New information technologies promise more timely and efficient ways of collecting many types of data, but may also raise privacy, control, and equity issues. Scientific review processes to ensure data quality need to be coordinated with the types of quality control and review employed by national statistical agencies for trusted economic and social statistics. Although large investments are already being made in some observing systems such as satellite-based remote sensing, additional resources are needed to fill key gaps, make data useful for decision making, and build capacity in developing countries. Broad engagement by the scientific community is urgently needed.

An assessment of progress towards universal health coverage in Brazil, Russia, India, China, and South Africa (BRICS).

PubMed

Marten, Robert; McIntyre, Diane; Travassos, Claudia; Shishkin, Sergey; Longde, Wang; Reddy, Srinath; Vega, Jeanette

2014-12-13

Brazil, Russia, India, China, and South Africa (BRICS) represent almost half the world's population, and all five national governments recently committed to work nationally, regionally, and globally to ensure that universal health coverage (UHC) is achieved. This analysis reviews national efforts to achieve UHC. With a broad range of health indicators, life expectancy (ranging from 53 years to 73 years), and mortality rate in children younger than 5 years (ranging from 10·3 to 44·6 deaths per 1000 livebirths), a review of progress in each of the BRICS countries shows that each has some way to go before achieving UHC. The BRICS countries show substantial, and often similar, challenges in moving towards UHC. On the basis of a review of each country, the most pressing problems are: raising insufficient public spending; stewarding mixed private and public health systems; ensuring equity; meeting the demands for more human resources; managing changing demographics and disease burdens; and addressing the social determinants of health. Increases in public funding can be used to show how BRICS health ministries could accelerate progress to achieve UHC. Although all the BRICS countries have devoted increased resources to health, the biggest increase has been in China, which was probably facilitated by China's rapid economic growth. However, the BRICS country with the second highest economic growth, India, has had the least improvement in public funding for health. Future research to understand such different levels of prioritisation of the health sector in these countries could be useful. Similarly, the role of strategic purchasing in working with powerful private sectors, the effect of federal structures, and the implications of investment in primary health care as a foundation for UHC could be explored. These issues could serve as the basis on which BRICS countries focus their efforts to share ideas and strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spine lesion analysis in 3D CT data - Reporting on research progress

NASA Astrophysics Data System (ADS)

Jan, Jiri; Chmelik, Jiri; Jakubicek, Roman; Ourednicek, Petr; Amadori, Elena; Gavelli, Giampaolo

2018-04-01

The contribution describes progress in the long-term project concerning automatic diagnosis of spine bone lesions. There are two difficult problems: segmenting reliably possibly severely deformed vertebrae in the spine and then detect, segment and classify the lesions that are often hardly visible thus making even the medical expert decisions highly uncertain, with a large inter-expert variety. New approaches are described enabling to solve both problems with a success rate acceptable for clinical testing, at the same time speeding up the process substantially compared to the previous stage. The results are compared with previously published achievements.

2011 Annual Progress Report: DOE Hydrogen and Fuel Cells Program (Book)

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

Not Available

In the past year, the DOE Hydrogen and Fuel Cells Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

NASA's Space Launch System: Progress Toward the Proving Ground

NASA Technical Reports Server (NTRS)

Jackman, Angie; Johnson, Les

2017-01-01

With significant and substantial progress being accomplished toward readying the Space Launch System (SLS) rocket for its first test flight, work is already also underway on preparations for the second flight - using an upgraded version of the vehicle - and beyond. SLS is the most powerful human-rated launch vehicle the United States has ever undertaken, and together with the Orion spacecraft will support human exploration missions into the proving ground of cislunar space and ultimately to Mars. This paper will provide a description of the SLS vehicle, and an overview of the vehicle's capabilities and utilization potential.

FY 2014 Annual Progress Report - Advanced Combustion Engine Research and Development (Book)

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

Not Available

In the past year, the DOE Hydrogen Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

Radiation physics, biophysics and radiation biology. Progress report for October 1, 1979-September 30, 1980. [Lead abstract

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

Rossi, H.H.; Hall, E.J.

1980-07-01

Separate abstracts were prepared for 31 of the 32 papers presented in this progress report. The other paper is represented by an abstract only and deals with field shaping and recalibration of x-ray facilities.

Copy number variability in Parkinson's disease: assembling the puzzle through a systems biology approach.

PubMed

La Cognata, Valentina; Morello, Giovanna; D'Agata, Velia; Cavallaro, Sebastiano

2017-01-01

Parkinson's disease (PD), the second most common progressive neurodegenerative disorder of aging, was long believed to be a non-genetic sporadic origin syndrome. The proof that several genetic loci are responsible for rare Mendelian forms has represented a revolutionary breakthrough, enabling to reveal molecular mechanisms underlying this debilitating still incurable condition. While single nucleotide polymorphisms (SNPs) and small indels constitute the most commonly investigated DNA variations accounting for only a limited number of PD cases, larger genomic molecular rearrangements have emerged as significant PD-causing mutations, including submicroscopic Copy Number Variations (CNVs). CNVs constitute a prevalent source of genomic variations and substantially participate in each individual's genomic makeup and phenotypic outcome. However, the majority of genetic studies have focused their attention on single candidate-gene mutations or on common variants reaching a significant statistical level of acceptance. This gene-centric approach is insufficient to uncover the genetic background of polygenic multifactorial disorders like PD, and potentially masks rare individual CNVs that all together might contribute to disease development or progression. In this review, we will discuss literature and bioinformatic data describing the involvement of CNVs on PD pathobiology. We will analyze the most frequent copy number changes in familiar PD genes and provide a "systems biology" overview of rare individual rearrangements that could functionally act on commonly deregulated molecular pathways. Assessing the global genome-wide burden of CNVs in PD patients may reveal new disease-related molecular mechanisms, and open the window to a new possible genetic scenario in the unsolved PD puzzle.

Benchmarking progress in the implementation of the Fourth Joint Societies' Task Force Guidelines on the Prevention of Cardiovascular Disease in Clinical Practice.

PubMed

Morgan, Karen; Burke, Helen; McGee, Hannah

2013-02-01

The Fourth Joint Societies' Task Force (4th JTF) Guidelines on Cardiovascular Disease Prevention in Clinical Practice are agreed, evidence-based standards of care across European countries and professions. In advance of the publication of the 5th JTF Guidelines in 2012, this work assesses the extent to which the 4th JTF guidelines have been implemented. Qualitative study of guideline implementation in 13 European countries, focusing on the themes of guideline implementation structures, processes, and outcomes. Key personnel in 13 selected countries completed interviews or comparable questionnaires: they were national coordinators for CVD prevention (n = 14) and representatives of the national cardiac society (n = 9), heart foundations (n = 11), health ministry (n = 8), and service providers (n = 3). Interview and service-related data from each country were compiled to provide a detailed overview. Ten of the 13 countries used European Society of Cardiology (ESC) guidelines on prevention at a national level, where three broad approaches to implementation were identified. In all 10 countries, multidisciplinary alliances oversaw implementation, but ongoing promotion of the guidelines was not evident, with just two of the 10 countries conducting evaluation of implementation. Barriers to implementation included weak health authority support, the unwieldy nature of the guidelines, guideline fatigue, and the lesser role of prevention in national healthcare systems. Substantial progress had been made in implementing the guidelines, but countries struggled with the task. Some rebalancing of the ESC focus may be warranted so that part of the effort dedicated to improving guidelines might be redirected at translating them into practice.

Selective progressive response of soil microbial community to wild oat roots.

PubMed

DeAngelis, Kristen M; Brodie, Eoin L; DeSantis, Todd Z; Andersen, Gary L; Lindow, Steven E; Firestone, Mary K

2009-02-01

Roots moving through soil induce physical and chemical changes that differentiate rhizosphere from bulk soil, and the effects of these changes on soil microorganisms have long been a topic of interest. The use of a high-density 16S rRNA microarray (PhyloChip) for bacterial and archaeal community analysis has allowed definition of the populations that respond to the root within the complex grassland soil community; this research accompanies compositional changes reported earlier, including increases in chitinase- and protease-specific activity, cell numbers and quorum sensing signal. PhyloChip results showed a significant change compared with bulk soil in relative abundance for 7% of the total rhizosphere microbial community (147 of 1917 taxa); the 7% response value was confirmed by16S rRNA terminal restriction fragment length polymorphism analysis. This PhyloChip-defined dynamic subset was comprised of taxa in 17 of the 44 phyla detected in all soil samples. Expected rhizosphere-competent phyla, such as Proteobacteria and Firmicutes, were well represented, as were less-well-documented rhizosphere colonizers including Actinobacteria, Verrucomicrobia and Nitrospira. Richness of Bacteroidetes and Actinobacteria decreased in soil near the root tip compared with bulk soil, but then increased in older root zones. Quantitative PCR revealed rhizosphere abundance of beta-Proteobacteria and Actinobacteria at about 10(8) copies of 16S rRNA genes per g soil, with Nitrospira having about 10(5) copies per g soil. This report demonstrates that changes in a relatively small subset of the soil microbial community are sufficient to produce substantial changes in functions observed earlier in progressively more mature rhizosphere zones.

Neuropsychological function and cerebral glucose utilization in isolated memory impairment and Alzheimer's disease.

PubMed

Berent, S; Giordani, B; Foster, N; Minoshima, S; Lajiness-O'Neill, R; Koeppe, R; Kuhl, D E

1999-01-01

We hypothesized that 20 patients with isolated memory impairment (IMI) would demonstrate [18F]-2-fluoro-2-deoxy-D-glucose utilization and a progression of neuropsychological symptoms consistent with Alzheimer's disease (AD). IMI subjects performed similarly to AD in recall and verbal fluency, but comparable to normal subjects in other areas of cognitive functioning. A positron emission tomography (PET) diagnostic index based on parietal Z-scores categorized IMI patients into normal and abnormal metabolic patterns. Ten of the original 20 IMI patients (50%) reflected PET AD abnormalities. Clinical information was available for IMI patients at three-year follow-up. Ten (50%) had converted to AD, three were found to have pseudodementia and the seven remained IMI. Of the 10 IMI patients with an originally normal PET index, three (30%) were diagnosed with AD at three years. Of the 10 with an abnormal index originally, seven (70%) converted to AD. The finding that memory deficit in IMI was as pronounced as that in AD patients is consistent with the notion that memory is an initial symptom of AD. A substantial number of the IMI patients reflected regional hypometabolism similar to AD, suggesting that IMI is likely an early stage in progressive dementia. A large percentage of IMI patients converted clinically to AD within three years of initial study, though we observed impaired memory functioning well before a clinical diagnosis of AD could be made. In addition to potential clinical utility, IMI and PET represent an opportunity to study dementia in relation to brain chemistry at a time when brain pathology is in the process of development.

The Release 6 reference sequence of the Drosophila melanogaster genome

DOE PAGES

Hoskins, Roger A.; Carlson, Joseph W.; Wan, Kenneth H.; ...

2015-01-14

Drosophila melanogaster plays an important role in molecular, genetic, and genomic studies of heredity, development, metabolism, behavior, and human disease. The initial reference genome sequence reported more than a decade ago had a profound impact on progress in Drosophila research, and improving the accuracy and completeness of this sequence continues to be important to further progress. We previously described improvement of the 117-Mb sequence in the euchromatic portion of the genome and 21 Mb in the heterochromatic portion, using a whole-genome shotgun assembly, BAC physical mapping, and clone-based finishing. Here, we report an improved reference sequence of the single-copy andmore » middle-repetitive regions of the genome, produced using cytogenetic mapping to mitotic and polytene chromosomes, clone-based finishing and BAC fingerprint verification, ordering of scaffolds by alignment to cDNA sequences, incorporation of other map and sequence data, and validation by whole-genome optical restriction mapping. These data substantially improve the accuracy and completeness of the reference sequence and the order and orientation of sequence scaffolds into chromosome arm assemblies. Representation of the Y chromosome and other heterochromatic regions is particularly improved. The new 143.9-Mb reference sequence, designated Release 6, effectively exhausts clone-based technologies for mapping and sequencing. Highly repeat-rich regions, including large satellite blocks and functional elements such as the ribosomal RNA genes and the centromeres, are largely inaccessible to current sequencing and assembly methods and remain poorly represented. In conclusion, further significant improvements will require sequencing technologies that do not depend on molecular cloning and that produce very long reads.« less

The Release 6 reference sequence of the Drosophila melanogaster genome

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

Hoskins, Roger A.; Carlson, Joseph W.; Wan, Kenneth H.

Drosophila melanogaster plays an important role in molecular, genetic, and genomic studies of heredity, development, metabolism, behavior, and human disease. The initial reference genome sequence reported more than a decade ago had a profound impact on progress in Drosophila research, and improving the accuracy and completeness of this sequence continues to be important to further progress. We previously described improvement of the 117-Mb sequence in the euchromatic portion of the genome and 21 Mb in the heterochromatic portion, using a whole-genome shotgun assembly, BAC physical mapping, and clone-based finishing. Here, we report an improved reference sequence of the single-copy andmore » middle-repetitive regions of the genome, produced using cytogenetic mapping to mitotic and polytene chromosomes, clone-based finishing and BAC fingerprint verification, ordering of scaffolds by alignment to cDNA sequences, incorporation of other map and sequence data, and validation by whole-genome optical restriction mapping. These data substantially improve the accuracy and completeness of the reference sequence and the order and orientation of sequence scaffolds into chromosome arm assemblies. Representation of the Y chromosome and other heterochromatic regions is particularly improved. The new 143.9-Mb reference sequence, designated Release 6, effectively exhausts clone-based technologies for mapping and sequencing. Highly repeat-rich regions, including large satellite blocks and functional elements such as the ribosomal RNA genes and the centromeres, are largely inaccessible to current sequencing and assembly methods and remain poorly represented. In conclusion, further significant improvements will require sequencing technologies that do not depend on molecular cloning and that produce very long reads.« less

A Cell surface β-Hydroxylase is a biomarker and therapeutic target for hepatocellular carcinoma

PubMed Central

Aihara, Arihiro; Huang, Chiung-Kuei; Olsen, Mark J.; Lin, Qiushi; Chung, Waihong; Tang, Qi; Dong, Xiaoqun; Wands, Jack R.

2014-01-01

Hepatocellular carcinoma (HCC) has a poor prognosis due to widespread intrahepatic and extrahepatic metastases. There is an urgent need to understand signaling cascades that promote disease progression. Aspartyl-(Asparaginyl)-β-hydroxylase (ASPH) is a cell surface enzyme that generates enhanced cell motility, migration, invasion and metastatic spread in HCC. We hypothesize that inhibition of its enzymatic activity could have antitumor effects. Small molecule inhibitors (SMIs) were developed based on the crystal structure of the ASPH catalytic site followed by computer assisted drug design. Candidate compounds were tested for inhibition of β-hydroxylase activity and selected for their capability to modulate cell proliferation, migration, invasion and colony formation in vitro and to inhibit HCC tumor growth in vivo using orthotopic and subcutaneous murine models. The biologic effects of SMIs on the Notch signaling cascade were evaluated. The SMI inhibitor MO-I-1100 was selected since it reduced ASPH enzymatic activity by 80% and suppressed HCC cell migration, invasion and anchorage independent growth. Furthermore, substantial inhibition of HCC tumor growth and progression was observed in both animal models. The mechanism(s) for this antitumor effect was associated with reduced activation of Notch signaling both in vitro and in vivo. Conclusions These studies suggest that the enzymatic activity of ASPH was important for hepatic oncogenesis. Reduced β-hydroxylase activity generated by the SMI MO-I-1100 led to antitumor effects through inhibiting Notch signaling cascade in HCC. ASPH promotes the generation of an HCC malignant phenotype and represents an attractive molecular target for therapy of this fatal disease. PMID:24954865

Progress towards universal health coverage in BRICS: translating economic growth into better health.

PubMed

Rao, Krishna D; Petrosyan, Varduhi; Araujo, Edson Correia; McIntyre, Diane

2014-06-01

Brazil, the Russian Federation, India, China and South Africa--the countries known as BRICS--represent some of the world's fastest growing large economies and nearly 40% of the world's population. Over the last two decades, BRICS have undertaken health-system reforms to make progress towards universal health coverage. This paper discusses three key aspects of these reforms: the role of government in financing health; the underlying motivation behind the reforms; and the value of the lessons learnt for non-BRICS countries. Although national governments have played a prominent role in the reforms, private financing constitutes a major share of health spending in BRICS. There is a reliance on direct expenditures in China and India and a substantial presence of private insurance in Brazil and South Africa. The Brazilian health reforms resulted from a political movement that made health a constitutional right, whereas those in China, India, the Russian Federation and South Africa were an attempt to improve the performance of the public system and reduce inequities in access. The move towards universal health coverage has been slow. In China and India, the reforms have not adequately addressed the issue of out-of-pocket payments. Negotiations between national and subnational entities have often been challenging but Brazil has been able to achieve good coordination between federal and state entities via a constitutional delineation of responsibility. In the Russian Federation, poor coordination has led to the fragmented pooling and inefficient use of resources. In mixed health systems it is essential to harness both public and private sector resources.

Progress towards universal health coverage in BRICS: translating economic growth into better health

PubMed Central

Petrosyan, Varduhi; Araujo, Edson Correia; McIntyre, Diane

2014-01-01

Abstract Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – represent some of the world’s fastest growing large economies and nearly 40% of the world’s population. Over the last two decades, BRICS have undertaken health-system reforms to make progress towards universal health coverage. This paper discusses three key aspects of these reforms: the role of government in financing health; the underlying motivation behind the reforms; and the value of the lessons learnt for non-BRICS countries. Although national governments have played a prominent role in the reforms, private financing constitutes a major share of health spending in BRICS. There is a reliance on direct expenditures in China and India and a substantial presence of private insurance in Brazil and South Africa. The Brazilian health reforms resulted from a political movement that made health a constitutional right, whereas those in China, India, the Russian Federation and South Africa were an attempt to improve the performance of the public system and reduce inequities in access. The move towards universal health coverage has been slow. In China and India, the reforms have not adequately addressed the issue of out-of-pocket payments. Negotiations between national and subnational entities have often been challenging but Brazil has been able to achieve good coordination between federal and state entities via a constitutional delineation of responsibility. In the Russian Federation, poor coordination has led to the fragmented pooling and inefficient use of resources. In mixed health systems it is essential to harness both public and private sector resources. PMID:24940017

Biological indicators of illness risk in offspring of bipolar parents: targeting the hypothalamic-pituitary-adrenal axis and immune system.

PubMed

Duffy, Anne; Lewitzka, Ute; Doucette, Sarah; Andreazza, Ana; Grof, Paul

2012-05-01

The study aims to provide a selective review of the literature pertaining to the hypothalamic-pituitary-adrenal (HPA) axis and immune abnormalities as informative biological indicators of vulnerability in bipolar disorder (BD). We summarize key findings relating to HPA axis and immunological abnormalities in bipolar patients and their high-risk offspring. Findings derive from a review of selected original papers published in the literature, and supplemented by papers identified through bibliography review. Neurobiological findings are discussed in the context of emergent BD in those at genetic risk and synthesized into a neurodevelopmental model of illness onset and progression. BD is associated with a number of genetic and possibly epigenetic abnormalities associated with neurotransmitter, hormonal and immunologically mediated neurobiological pathways. Data from clinical and high-risk studies implicate HPA axis and immune system abnormalities, which may represent inherited vulnerabilities important for the transition to illness onset. Post-mortem and clinical studies implicate intracellular signal transduction processes and disturbance in energy metabolism associated with established BD. Specifically, long-standing maladaptive alterations such as changes in neuronal systems may be mediated through changes in intracellular signalling pathways, oxidative stress, cellular energy metabolism and apoptosis associated with substantial burden of illness. Prospective longitudinal studies of endophenotypes and biomarkers such as HPA axis and immune abnormalities in high-risk offspring will be helpful to understand genetically mediated biological pathways associated with illness onset and progression. A clinical staging model describing emergent illness in those at genetic risk should facilitate this line of investigation. © 2011 Blackwell Publishing Asia Pty Ltd.

Potential of Progressive Construction Systems in Slovakia

NASA Astrophysics Data System (ADS)

Kozlovska, Maria; Spisakova, Marcela; Mackova, Daniela

2017-10-01

Construction industry is a sector with rapid development. Progressive technologies of construction and new construction materials also called modern methods of construction (MMC) are developed constantly. MMC represent the adoption of construction industrialisation and the use of prefabrication of components in building construction. One of these modern methods is also system Varianthaus, which is based on, insulated concrete forms principle and provides complete production plant for wall, ceiling and roof elements for a high thermal insulation house construction. Another progressive construction system is EcoB, which represents an insulated precast concrete panel based on combination of two layers, insulation and concrete, produced in a factory as a whole. Both modern methods of construction are not yet known and wide-spread in the Slovak construction market. The aim of this paper is focused on demonstration of MMC using potential in Slovakia. MMC potential is proved based on comparison of the selected parameters of construction process - construction costs and construction time. The subject of this study is family house modelled in three material variants - masonry construction (as a representative of traditional methods of construction), Varianthaus and EcoB (as the representatives of modern methods of construction). The results of this study provide the useful information in decision-making process for potential investors of construction.

Welfare Reform: Progress in Meeting Work-Focused TANF Goals. Testimony before the Subcommittee on Human Resources, Committee on Ways and Means, House of Representatives.

ERIC Educational Resources Information Center

Fagnoni, Cynthia M.

The General Accounting Office (GAO) examined progress in meeting work-focused goals of the Temporary Assistance for Needy Families (TANF) program. The following issues were considered: (1) states' progress in implementing TANF; (2) the status of families who have left welfare; (3) the characteristics of adults currently receiving TANF; (4) states'…

Dual renin-angiotensin-aldosterone system blockade for diabetic kidney disease.

PubMed

Pichler, Raimund H; de Boer, Ian H

2010-08-01

Blockade of the renin-angiotensin-aldosterone system (RAAS) prevents the development and progression of diabetic kidney disease (DKD). It is controversial whether the simultaneous use of two RAAS inhibitors (ie, dual RAAS blockade) further improves renal outcomes. This review examines the scientific rationale and current clinical evidence addressing the use of dual RAAS blockade to prevent and treat DKD. It is concluded that dual RAAS blockade should not be routinely applied to patients with low or moderate risk of progressive kidney disease (normoalbuminuria or microalbuminuria with preserved glomerular filtration rate). For patients with high risk of progressive kidney disease (substantial albuminuria or impaired glomerular filtration rate), clinicians should carefully weigh the potential risks and benefits of dual RAAS blockade on an individual basis until ongoing clinical trials provide further insight.

Obesity and heart failure as a mediator of the cerebrorenal interaction.

PubMed

Jindal, Ankur; Whaley-Connell, Adam; Sowers, James R

2013-01-01

The obesity epidemic is contributing substantially to the burden of cardiovascular disease including heart disease and congestive heart failure, in the United States and the rest of the world. Overnutrition as a driver of obesity, promotes alterations in fatty acid, lipid, and glucose metabolism that influence myocardial function and progression of heart failure from diastolic to systolic failure. The association of progressive heart failure and progressive chronic kidney disease is well documented and often referred to as the cardiorenal syndrome, as well as a prognosticator for cerebrovascular disease (e.g. stroke). Whether the relationship between obesity, heart disease/failure and risk for chronic kidney disease and stroke is direct or a confluence of risk factors is poorly understood. Copyright © 2013 S. Karger AG, Basel.

A fishmeal-free diet for post-smolt Atlantic salmon in RAS

USDA-ARS?s Scientific Manuscript database

Rising costs and static supply of ocean-harvested fishmeal have spurred decades of research to identify sustainable feed ingredients for salmon diets. There has been substantial progress. The amount of fishmeal and fish oil used in commercial diets has declined and there is now a long list of altern...

Soil Respiration at Dominant Patch Types within a Managed Northern Wisconsin Landscape

Treesearch

Eug& #233; nie Euskirchen; Jiquan Chen; Eric J. Gustafson; Siyan Ma; Siyan Ma

2003-01-01

Soil respiration (SR), a substantial component of the forest carbon budget, has been studied extensively at the ecosystem, regional, continental, and global scales, but little progress has been made toward understanding SR over managed forest landscapes. Soil respiration is often influenced by soil temperature (Ts), soil moisture (Ms...

Soil respiration at dominant patch types within a managed northern Wisconsin landscape

Treesearch

Eugenie S. Euskirchen; Jiquan Chen; Eric J. Gustafson; Siyan Ma

2003-01-01

Soil respiration (SR), a substantial component of the forest carbon budget, has been studied extensively at the ecosystem, regional, continental, and global scales, but little progress has been made toward understanding SR over managed forest landscapes. Soil respiration is often influenced by soil temperature (Ts), soil moisture (Ms...

Sailing the Stormy Seas: The Illness Experience of Persons with Parkinson's Disease

ERIC Educational Resources Information Center

Stanley-Hermanns, Melinda; Engebretson, Joan

2010-01-01

Parkinson's disease is a chronic, progressive disorder with no known cause or promising cure. While substantial information is known about the pathophysiology, little is known about the illness experience of living with the disease. A qualitative study using an ethnographic approach was conducted to provide a rich understanding of the illness…

Assessing Risk and Opportunity in Conflict Studies: A Human Rights Analysis

ERIC Educational Resources Information Center

Poe, Steven C.; Rost, Nicolas; Carey, Sabine C.

2006-01-01

Over the past two decades, substantial progress has been made toward a theoretical understanding of why physical integrity abuses are committed. Unfortunately, these theoretical developments have been devoid of much practical application. In this article, the authors explore the feasibility of risk assessment in the study of these human rights.…

[Integral assessment of learning subjects difficulties].

PubMed

Grebniak, N P; Shchudro, S A

2010-01-01

The integral criterion for subject difficulties in senior classes is substantiated in terms of progress in studies, variation coefficient, and subjective and expert appraisals of the difficulty of subjects. The compiled regression models adequately determine the difficulty of academic subjects. According to the root-mean-square deviation, all subjects were found to have 3 degrees of difficulty.

ORNL Annual Sustainability Report

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

Lapsa, Melissa Voss; Nichols, Teresa A.

2014-02-01

As described in this report, we have made substantial progress across the 25 roadmaps of the Sustainable Campus Initiative. The report also outlines our plans to continue integrating sustainable practices into the planning, execution, and evaluation of all ORNL activities. We appreciate your interest in our journey to sustainability, and we welcome your comments, questions, and suggestions.

Higher Education Research Community in Taiwan: An Emerging Field

ERIC Educational Resources Information Center

Chan, Sheng-Ju; Chan, Ying

2015-01-01

This paper aims to explore the evolution and characteristics of the higher education research community in Taiwan. In echoing the development of the East Asian region, Taiwan has made substantial progress during the past two decades. The massification of higher education itself has played a major role in promoting the academic differentiation or…

Current and innovative pain management techniques in total knee arthroplasty.

PubMed

Dalury, David F; Lieberman, Jay R; Macdonald, Steven J

2012-01-01

Pain management is a major concern for patients contemplating total knee replacement surgery and is one of the leading causes of dissatisfaction after knee replacement. Substantial progress has been made over the past several years in improving pain control after total knee replacement using multimodal pain control, preemptive analgesia, and periarticular injections.

Failure of pheromone traps in detecting incipient populations of boll weevils (Coleoptera: Curculionidae): Investigation of two potential contributing factors

USDA-ARS?s Scientific Manuscript database

Progress towards complete eradication of the boll weevil has been delayed in some areas of Texas due to the inconsistent performance of pheromone traps in detecting incipient weevil populations. In 2008 substantial infestations of boll weevils, Anthonomus grandis Boheman, were detected in several c...

Measurement Issues in State Achievement Comparisons. Research Report. ETS RR-10-19

ERIC Educational Resources Information Center

Zwick, Rebecca

2010-01-01

Political perspectives on the advisability of state achievement comparisons have changed substantially over the last half-century. As Selden (2004) noted regarding the National Assessment of Educational Progress (NAEP), "[w]hen it began in the 1960s, NAEP specifically was designed "not" to provide comparisons among states. This was…

A Comparison of Speech Sound Intervention Delivered by Telepractice and Side-by-Side Service Delivery Models

ERIC Educational Resources Information Center

Grogan-Johnson, Sue; Schmidt, Anna Marie; Schenker, Jason; Alvares, Robin; Rowan, Lynne E.; Taylor, Jacquelyn

2013-01-01

Telepractice has the potential to provide greater access to speech-language intervention services for children with communication impairments. Substantiation of this delivery model is necessary for telepractice to become an accepted alternative delivery model. This study investigated the progress made by school-age children with speech sound…

34 CFR 75.253 - Continuation of a multi-year project after the first budget period.

Code of Federal Regulations, 2010 CFR

2010-07-01

... sufficient funds under the program; (2) The recipient has either— (i) Made substantial progress toward meeting the objectives in its approved application; or (ii) Obtained the Secretary's approval of changes... those objectives in succeeding budget periods; (3) The recipient has submitted all reports as required...

Knowledge Mobilisation in the Polish Education System

ERIC Educational Resources Information Center

Fazlagic, Jan; Erkol, Arif

2015-01-01

Poland has made substantial progress in improving the quality of its education system in recent years. This paper aims to describe the situation of the Polish education system from a knowledge management perspective and, to some extent, through innovation policies in education. The many challenges, this paper argues, can be tackled only through…

Leadership for Learning: Lessons from 40 Years of Empirical Research

ERIC Educational Resources Information Center

Hallinger, Philip

2011-01-01

Purpose: This paper aims to present a research-based model of leadership for learning. It argues that the field has made substantial progress over the past 40 years in identifying ways in which leadership contributes to learning and school improvement. Four specific dimensions of leading for learning are presented: values and beliefs, leadership…

Cold Rolled Steel and Knowledge: What Can Higher Education Learn about Productivity?

ERIC Educational Resources Information Center

Thille, Candace; Smith, Joel

2011-01-01

Higher education is simply not making substantial progress in addressing its most significant challenges: educating an increasingly diverse body of students while containing the cost that is putting postsecondary education beyond the reach of a growing percentage of the world's population. Tweaking long-standing strategies to achieve incremental…

Threshold Concepts in Higher Education: A Synthesis of the Literature Relating to Measurement of Threshold Crossing

ERIC Educational Resources Information Center

Nicola-Richmond, Kelli; Pépin, Geneviève; Larkin, Helen; Taylor, Charlotte

2018-01-01

In relation to teaching and learning approaches that improve student learning outcomes, threshold concepts have generated substantial interest in higher education. They have been described as "portals" that lead to a transformed way of understanding or thinking, enabling learners to progress, and have been enthusiastically adopted to…

Responsible decision-making for plant research and breeding innovations in the European Union.

PubMed

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.

Five-Segment Solid Rocket Motor Development Status

NASA Technical Reports Server (NTRS)

Priskos, Alex S.

2012-01-01

In support of the National Aeronautics and Space Administration (NASA), Marshall Space Flight Center (MSFC) is developing a new, more powerful solid rocket motor for space launch applications. To minimize technical risks and development costs, NASA chose to use the Space Shuttle s solid rocket boosters as a starting point in the design and development. The new, five segment motor provides a greater total impulse with improved, more environmentally friendly materials. To meet the mass and trajectory requirements, the motor incorporates substantial design and system upgrades, including new propellant grain geometry with an additional segment, new internal insulation system, and a state-of-the art avionics system. Significant progress has been made in the design, development and testing of the propulsion, and avionics systems. To date, three development motors (one each in 2009, 2010, and 2011) have been successfully static tested by NASA and ATK s Launch Systems Group in Promontory, UT. These development motor tests have validated much of the engineering with substantial data collected, analyzed, and utilized to improve the design. This paper provides an overview of the development progress on the first stage propulsion system.

Prevalence and Predictors of Grandparent Childcare in Ireland: Findings from a Nationally Representative Sample of Infants and Their Families

ERIC Educational Resources Information Center

McNally, Sinead; Share, Michelle; Murray, Aisling

2014-01-01

Anecdotal evidence suggests that grandparents provide a substantial amount of childcare support to parents of infants in Ireland yet there has been little attention to the provision of grandparent childcare at policy level. Using nationally representative data on childcare provision in the Republic of Ireland, this study examined the prevalence of…

Progressive taxation, income inequality, and happiness.

PubMed

Oishi, Shigehiro; Kushlev, Kostadin; Schimmack, Ulrich

2018-01-01

Income inequality has become one of the more widely debated social issues today. The current article explores the role of progressive taxation in income inequality and happiness. Using historical data in the United States from 1962 to 2014, we found that income inequality was substantially smaller in years when the income tax was more progressive (i.e., a higher tax rate for higher income brackets), even when controlling for variables like stock market performance and unemployment rate. Time lag analyses further showed that higher progressive taxation predicted increasingly lower income inequality up to 5 years later. Data from the General Social Survey (1972-2014; N = 59,599) with U.S. residents (hereafter referred to as "Americans") showed that during years with higher progressive taxation rates, less wealthy Americans-those in the lowest 40% of the income distribution-tended to be happier, whereas the richest 20% were not significantly less happy. Mediational analyses confirmed that the association of progressive taxation with the happiness of less wealthy Americans can be explained by lower income inequality in years with higher progressive taxation. A separate sample of Americans polled online (N = 373) correctly predicted the positive association between progressive taxation and the happiness of poorer Americans but incorrectly expected a strong negative association between progressive taxation and the happiness of richer Americans. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

En route air traffic controllers' use of flight progress strips : a graph-theoretic analysis.

DOT National Transportation Integrated Search

1992-11-01

In the United States, flight data are represented on a paper Flight Progress Strip (FPS). The role of the FPS has recently attracted attention because of plans to automate this aspect of air traffic control. The communication activities and FPS activ...

Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease

PubMed Central

Beltran, William A.; Cideciyan, Artur V.; Iwabe, Simone; Swider, Malgorzata; Kosyk, Mychajlo S.; McDaid, Kendra; Martynyuk, Inna; Ying, Gui-Shuang; Shaffer, James; Deng, Wen-Tao; Boye, Sanford L.; Lewin, Alfred S.; Hauswirth, William W.; Jacobson, Samuel G.; Aguirre, Gustavo D.

2015-01-01

Inherited retinal degenerations cause progressive loss of photoreceptor neurons with eventual blindness. Corrective or neuroprotective gene therapies under development could be delivered at a predegeneration stage to prevent the onset of disease, as well as at intermediate-degeneration stages to slow the rate of progression. Most preclinical gene therapy successes to date have been as predegeneration interventions. In many animal models, as well as in human studies, to date, retinal gene therapy administered well after the onset of degeneration was not able to modify the rate of progression even when successfully reversing dysfunction. We evaluated consequences of gene therapy delivered at intermediate stages of disease in a canine model of X-linked retinitis pigmentosa (XLRP) caused by a mutation in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene. Spatiotemporal natural history of disease was defined and therapeutic dose selected based on predegeneration results. Then interventions were timed at earlier and later phases of intermediate-stage disease, and photoreceptor degeneration monitored with noninvasive imaging, electrophysiological function, and visual behavior for more than 2 y. All parameters showed substantial and significant arrest of the progressive time course of disease with treatment, which resulted in long-term improved retinal function and visual behavior compared with control eyes. Histology confirmed that the human RPGR transgene was stably expressed in photoreceptors and associated with improved structural preservation of rods, cones, and ON bipolar cells together with correction of opsin mislocalization. These findings in a clinically relevant large animal model demonstrate the long-term efficacy of RPGR gene augmentation and substantially broaden the therapeutic window for intervention in patients with RPGR-XLRP. PMID:26460017

Strategic plan for geriatrics and extended care in the veterans health administration: background, plan, and progress to date.

PubMed

Shay, Kenneth; Hyduke, Barbara; Burris, James F

2013-04-01

The leaders of Geriatrics and Extended Care (GEC) in the Veterans Health Administration (VHA) undertook a strategic planning process that led to approval in 2009 of a multidisciplinary, evidence-guided strategic plan. This article reviews the four goals contained in that plan and describes VHA's progress in addressing them. The goals included transforming the healthcare system to a veteran-centric approach, achieving universal access to a panel of services, ensuring that the Veterans Affair's (VA) healthcare workforce was adequately prepared to manage the needs of the growing elderly veteran population, and integrating continuous improvement into all care enhancements. There has been substantial progress in addressing all four goals. All VHA health care has undergone an extensive transformation to patient-centered care, has enriched the services it can offer caregivers of dependent veterans, and has instituted models to better integrate VA and non-VA cares and services. A range of successful models of geriatric care described in the professional literature has been adapted to VA environments to gauge suitability for broader implementation. An executive-level task force developed a three-pronged approach for enhancing the VA's geriatric workforce. The VHA's performance measurement approaches increasingly include incentives to enhance the quality of management of vulnerable elderly adults in primary care. The GEC strategic plan was intended to serve as a road map for keeping VHA aligned with an ambitious but important long-term vision for GEC services. Although no discrete set of resources was appropriated for fulfillment of the plan's recommendations, this initial report reflects substantial progress in addressing most of its goals. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

[Survey on the measures of asepsis taken by general practitioners].

PubMed

Chambonet, Jean-Yves; Cluis, Patrice

2004-01-31

CURRENT STATE OF THE QUESTION: Many legislative and administrative texts rule asepsis and prophylaxis in health care centres. The deontological code provides the guidelines for medical corps. To identify the measures set-up to prevent the transmission of infections in general practitioners' consulting rooms and to compare them with the data in the literature. A postal survey using a questionnaire was sent to a representative sample of 119 general practitioners in the Loire-Atlantique area in France. The response rate was of 69%. The majority of physicians declared that had a wash basin in the consulting room, 43% declared that they did not systematically wash their hands between 2 patients in their consulting rooms and 78% during home visits, 23% used an ordinary soap, 49% a hydro-alcoholic solution, and 62% wiped their hands with a cotton towel. Blood interventions were performed with gloves by more than 80% of the participants, complete decontamination procedures of the material were performed by 6%, but more than 80% used single use material. Although 45% believed they had changed their habits, 23% remained wary of any eventual recommendations and 43% made no comments. This survey method collects declarative data and remains limited with regard to information. In-depth analysis of the daily activity of the participants would be useful for an approach of performance criteria, in view of the fact that some consultations do not include any, or even partial, clinical examination. The investments required for the purchase of the material compatible with the specifications applicable to health care centres may appear excessive for their current activity. The generalisation of the use of single use material represents a great progress in the field of prevention. Comparison with similar earlier studies shows the good progress made and the improvement in quality. Nevertheless, studies using a strict methodology are necessary to establish guidelines to be applied in general medical practice. The drawing-up of Referentials requires great rigour and the participation of the practitioners in their development and organisation would lead to substantial benefits.

Can we predict failure in couple therapy early enough to enhance outcome?

PubMed

Pepping, Christopher A; Halford, W Kim; Doss, Brian D

2015-02-01

Feedback to therapists based on systematic monitoring of individual therapy progress reliably enhances therapy outcome. An implicit assumption of therapy progress feedback is that clients unlikely to benefit from therapy can be detected early enough in the course of therapy for corrective action to be taken. To explore the possibility of using feedback of therapy progress to enhance couple therapy outcome, the current study tested whether weekly therapy progress could detect off-track clients early in couple therapy. In an effectiveness trial of couple therapy, 136 couples were monitored weekly on relationship satisfaction and an expert derived algorithm was used to attempt to predict eventual therapy outcome. As expected, the algorithm detected a significant proportion of couples who did not benefit from couple therapy at Session 3, but prediction was substantially improved at Session 4 so that eventual outcome was accurately predicted for 70% of couples, with little improvement of prediction thereafter. More sophisticated algorithms might enhance prediction accuracy, and a trial of the effects of therapy progress feedback on couple therapy outcome is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

NAFTA Guidance Document for Conducting Terrestrial Field Dissipation Studies

EPA Pesticide Factsheets

Harmonized guidance for TFD studies that demonstrate transformation, transport and fate of pesticides under representative actual use conditions. Field studies substantiate physicochemical, mobility and biotransformation data from laboratory studies.

Ion acceleration in a plasma focus

NASA Technical Reports Server (NTRS)

Gary, S. P.

1974-01-01

The electric and magnetic fields associated with anomalous diffusion to the axis of a linear plasma discharge are used to compute representative ion trajectories. Substantial axial acceleration of the ions is demonstrated.

20 CFR 411.180 - What is timely progress toward self-supporting employment?

Code of Federal Regulations, 2011 CFR

2011-04-01

... representing a trial work service month), and complete 66.7 percent of the requisite credit hours in an... hours that are considered to represent an academic year of full-time study in the program by the end of... credit hours that are considered to represent an academic year of full-time study in the program by the...

Accounting for water quality in monitoring access to safe drinking-water as part of the Millennium Development Goals: lessons from five countries.

PubMed

Bain, Rob E S; Gundry, Stephen W; Wright, Jim A; Yang, Hong; Pedley, Steve; Bartram, Jamie K

2012-03-01

To determine how data on water source quality affect assessments of progress towards the 2015 Millennium Development Goal (MDG) target on access to safe drinking-water. Data from five countries on whether drinking-water sources complied with World Health Organization water quality guidelines on contamination with thermotolerant coliform bacteria, arsenic, fluoride and nitrates in 2004 and 2005 were obtained from the Rapid Assessment of Drinking-Water Quality project. These data were used to adjust estimates of the proportion of the population with access to safe drinking-water at the MDG baseline in 1990 and in 2008 made by the Joint Monitoring Programme for Water Supply and Sanitation, which classified all improved sources as safe. Taking account of data on water source quality resulted in substantially lower estimates of the percentage of the population with access to safe drinking-water in 2008 in four of the five study countries: the absolute reduction was 11% in Ethiopia, 16% in Nicaragua, 15% in Nigeria and 7% in Tajikistan. There was only a slight reduction in Jordan. Microbial contamination was more common than chemical contamination. The criterion used by the MDG indicator to determine whether a water source is safe can lead to substantial overestimates of the population with access to safe drinking-water and, consequently, also overestimates the progress made towards the 2015 MDG target. Monitoring drinking-water supplies by recording both access to water sources and their safety would be a substantial improvement.

Modifications of the mouse bone marrow microenvironment favor angiogenesis and correlate with disease progression from asymptomatic to symptomatic multiple myeloma

PubMed Central

Calcinotto, Arianna; Ponzoni, Maurilio; Ria, Roberto; Grioni, Matteo; Cattaneo, Elena; Villa, Isabella; Sabrina Bertilaccio, Maria Teresa; Chesi, Marta; Rubinacci, Alessandro; Tonon, Giovanni; Bergsagel, P Leif; Vacca, Angelo; Bellone, Matteo

2015-01-01

While multiple myeloma (MM) is almost invariably preceded by asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering MM (SMM), the alterations of the bone marrow (BM) microenvironment that establish progression to symptomatic disease are circumstantial. Here we show that in Vk*MYC mice harboring oncogene-driven plasma cell proliferative disorder, disease appearance associated with substantial modifications of the BM microenvironment, including a progressive accumulation of both CD8+ and CD4+ T cells with a dominant T helper type 1 (Th1) response. Progression from asymptomatic to symptomatic MM was characterized by further BM accrual of T cells with reduced Th1 and persistently increased Th2 cytokine production, which associated with accumulation of CD206+Tie2+ macrophages, and increased pro-angiogenic cytokines and microvessel density (MVD). Notably, MVD was also increased at diagnosis in the BM of MGUS and SMM patients that subsequently progressed to MM when compared with MGUS and SMM that remained quiescent. These findings suggest a multistep pathogenic process in MM, in which the immune system may contribute to angiogenesis and disease progression. They also suggest initiating a large multicenter study to investigate MVD in asymptomatic patients as prognostic factor for the progression and outcome of this disease. PMID:26155424

Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

PubMed

Wilczynski, Bartek; Furlong, Eileen E M

2010-04-15

Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Using systems of care to reduce incarceration of youth with serious mental illness.

PubMed

Erickson, Chris D

2012-06-01

Youth with serious mental illness come into contact with juvenile justice more than 3 times as often as other youth, obliging communities to expend substantial resources on adjudicating and incarcerating many who, with proper treatment, could remain in the community for a fraction of the cost. Incarceration is relatively ineffective at remediating behaviors associated with untreated serious mental illness and may worsen some youths' symptoms and long-term prognoses. Systems of care represent a useful model for creating systems change to reduce incarceration of these youth. This paper identifies the systemic factors that contribute to the inappropriate incarceration of youth with serious mental illness, including those who have committed non-violent offenses or were detained due to lack of available treatment. It describes the progress of on-going efforts to address this problem including wraparound and diversion programs and others utilizing elements of systems of care. The utility of systems of care principles for increasing access to community-based mental health care for youth with serious mental illness is illustrated and a number of recommendations for developing collaborations with juvenile justice to further reduce the inappropriate incarceration of these youth are offered.

"Falling leaves": a survey of the history of apoptosis.

PubMed

Formigli, L; Conti, A; Lippi, D

2004-04-01

Cell death has long been defined using morphological criteria. A first important concept, "necrosis", was early identified by Areteo from Cappadocia and by Galen. The term apoptosis was introduced by Kerr in 1972 to indicate a particular form of death in which cells commit suicide by chopping themselves into membrane-bounded apoptotic bodies. Apoptosis is distinguished from necrosis, or accidental cell death, which is characterized by nuclear autolysis and cell disintegration. The aim of this study was an evaluation of the concepts of apoptosis and necrosis, starting from the first definition of cell death by Rudolph Virchow in 1859. In recent years substantial progress has been made in the understanding of apoptotic and necrotic cell death. In particular, cell death researchers have evolved a paradigm change, from one in which apoptosis and necrosis were considered distinct forms of cell demise, to one in which the 2 cell deaths share common features, as an integral part of a same cell death process. Since pure apoptosis and necrosis are only extremes in a continuum spectrum of aponecrotic response, a mixture of features associated with both apoptosis and necrosis represents the more typical tissue and cell response to damaging stimuli.

Enabling the sharing of neuroimaging data through well-defined intermediate levels of visibility.

PubMed

Smith, Kenneth; Jajodia, Sushil; Swarup, Vipin; Hoyt, Jeffrey; Hamilton, Gail; Faatz, Donald; Cornett, Todd

2004-08-01

The sharing of neuroimagery data offers great benefits to science, however, data owners sharing their data face substantial custodial responsibilities, such as ensuring data sets are correctly interpreted in their new shared context, protecting the identity and privacy of human research participants, and safeguarding the understood order of use. Given choices of sharing widely or not at all, the result will often be no sharing, due to the inability of data owners to control their exposure to the risks associated with data sharing. In this context, data sharing is enabled by providing data owners with well-defined intermediate levels of data visibility, progressing incrementally toward public visibility. In this paper, we define a novel and general data sharing model, Structured Sharing Communities (SSC), meeting this requirement. Arbitrary visibility levels representing collaborative agreements, consortium memberships, research organizations, and other affiliations are structured into a policy space through explicit paths of permissible information flow. Operations enable users and applications to manage the visibility of data and enforce access permissions and restrictions. We show how a policy space can be implemented in realistic neuroinformatic architectures with acceptable assurance of correctness, and briefly describe an open source implementation effort.

New ground-based lidar enables volcanic CO2 flux measurements.

PubMed

Aiuppa, Alessandro; Fiorani, Luca; Santoro, Simone; Parracino, Stefano; Nuvoli, Marcello; Chiodini, Giovanni; Minopoli, Carmine; Tamburello, Giancarlo

2015-09-01

There have been substantial advances in the ability to monitor the activity of hazardous volcanoes in recent decades. However, obtaining early warning of eruptions remains challenging, because the patterns and consequences of volcanic unrests are both complex and nonlinear. Measuring volcanic gases has long been a key aspect of volcano monitoring since these mobile fluids should reach the surface long before the magma. There has been considerable progress in methods for remote and in-situ gas sensing, but measuring the flux of volcanic CO2-the most reliable gas precursor to an eruption-has remained a challenge. Here we report on the first direct quantitative measurements of the volcanic CO2 flux using a newly designed differential absorption lidar (DIAL), which were performed at the restless Campi Flegrei volcano. We show that DIAL makes it possible to remotely obtain volcanic CO2 flux time series with a high temporal resolution (tens of minutes) and accuracy (<30%). The ability of this lidar to remotely sense volcanic CO2 represents a major step forward in volcano monitoring, and will contribute improved volcanic CO2 flux inventories. Our results also demonstrate the unusually strong degassing behavior of Campi Flegrei fumaroles in the current ongoing state of unrest.

Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group.

PubMed

Laubach, J; Garderet, L; Mahindra, A; Gahrton, G; Caers, J; Sezer, O; Voorhees, P; Leleu, X; Johnsen, H E; Streetly, M; Jurczyszyn, A; Ludwig, H; Mellqvist, U-H; Chng, W-J; Pilarski, L; Einsele, H; Hou, J; Turesson, I; Zamagni, E; Chim, C S; Mazumder, A; Westin, J; Lu, J; Reiman, T; Kristinsson, S; Joshua, D; Roussel, M; O'Gorman, P; Terpos, E; McCarthy, P; Dimopoulos, M; Moreau, P; Orlowski, R Z; Miguel, J S; Anderson, K C; Palumbo, A; Kumar, S; Rajkumar, V; Durie, B; Richardson, P G

2016-05-01

The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.

Exo-Skeletal Engine: Novel Engine Concept

NASA Technical Reports Server (NTRS)

Chamis, Cristos C.; Blankson, Isaiah M.

2004-01-01

The exo-skeletal engine concept represents a new radical engine technology with the potential to substantially revolutionize engine design. It is an all-composite drum-rotor engine in which conventionally heavy shafts and discs are eliminated and are replaced by rotating casings that support the blades in spanwise compression. Thus the rotating blades are in compression rather than tension. The resulting open channel at the engine centerline has immense potential for jet noise reduction and can also accommodate an inner combined-cycle thruster such as a ramjet. The exo-skeletal engine is described in some detail with respect to geometry, components, and potential benefits. Initial evaluations and results for drum rotors, bearings, and weights are summarized. Component configuration, assembly plan, and potential fabrication processes are also identified. A finite element model of the assembled engine and its major components is described. Preliminary results obtained thus far show at least a 30-percent reduction of engine weight and about a 10-dB noise reduction, compared with a baseline conventional high-bypass-ratio engine. Potential benefits in all aspects of this engine technology are identified and tabulated. Quantitative assessments of potential benefits are in progress.

A Rapid Turnaround Cryogenic Detector Characterization System

NASA Technical Reports Server (NTRS)

Benford, Dominic j.; Dipirro, Michael J.; Forgione, Joshua B.; Jackson, Clifton E.; Jackson, Michael L.; Kogut, Al; Moseley, S. Harvey; Shirron, Peter J.

2004-01-01

Upcoming major NASA missions such as the Einstein Inflation Probe and the Single Aperture Far-Infrared Observatory require arrays of detectors with thousands of elements, operating at temperatures near l00 mK and sensitive to wavelengths from approx. 100 microns to approx. 3 mm. Such detectors represent a substantial enabling technology for these missions, and must be demonstrated soon in order for them to proceed. In order to make rapid progress on detector development, the cryogenic testing cycle must be made convenient and quick. We have developed a cryogenic detector characterization system capable of testing superconducting detector arrays in formats up to 8 x 32, read out by SQUID multiplexers. The system relies on the cooling of a two-stage adiabatic demagnetization refrigerator immersed in a liquid helium bath. This approach permits a detector to be cooled from 300K to 50 mK in about 4 hours, so that a test cycle begun in the morning will be over by the end of the day. Tine system is modular, with two identical immersible units, so that while one unit is cooling, the second can be reconfigured for the next battery of tests. We describe the design, construction, and performance of this cryogenic detector testing facility.

Preparation and Characterization of Anode-Supported YSZ Thin Film Electrolyte by Co-Tape Casting and Co-Sintering Process

NASA Astrophysics Data System (ADS)

Liu, Q. L.; Fu, C. J.; Chan, S. H.; Pasciak, G.

2011-06-01

In this study, a co-tape casting and co-sintering process has been developed to prepare yttria-stabilized zirconia (YSZ) electrolyte films supported on Ni-YSZ anode substrates in order to substantially reduce the fabrication cost of solid oxide fuel cells (SOFC). Through proper control of the process, the anode/electrolyte bilayer structures with a size of 7.8cm × 7.8cm were achieved with good flatness. Scanning electron microscopy (SEM) observation indicated that the YSZ electrolyte film was about 16 μm in thickness, highly dense, crack free and well-bonded to the anode support. The electrochemical properties of the prepared anode-supported electrolyte film was evaluated in a button cell mode incorporating a (LaSr)MnO3-YSZ composite cathode. With humidified hydrogen as the fuel and stationary air as the oxidant, the cell demonstrated an open-circuit voltage of 1.081 V and a maximum power density of 1.01 W/cm2 at 800°C. The obtained results represent the important progress in the development of anode-supported intermediate temperature SOFC with reduced fabrication cost.

[Ultrasonography of the prostate gland : From B‑image through multiparametric ultrasound to targeted biopsy].

PubMed

Steinkohl, F; Luger, A; Bektic, J; Aigner, F

2017-08-01

Prostate cancer is the most frequent cancer in men. The diagnosis is normally achieved by a systematic prostate biopsy; however, this is a randomized approach by which a substantial number of significant carcinomas go undetected. For this reason, in recent years imaging techniques have been continuously developed, which enable visualization and therefore targeted biopsies. The use of systematic biopsies is a standard procedure for the detection of prostate cancer. The quality of biopsies can be increased if the prostate is examined for the presence of suspected cancerous alterations during the biopsy. This can be carried out using multiparametric transrectral ultrasound. Multiparametric ultrasound within the framework of a targeted biopsy increases the detection rate of significant prostate carcinomas with a simultaneous decrease in detection of insignificant carcinomas; however, the diagnostic reliability and the evidence level of multiparametric transrectal ultrasound are not yet sufficiently high to be able to replace a systematic biopsy. In the hands of a well-trained examiner multiparametric transrectal ultrasound represents a good method for detection of prostate carcinomas. With the progression in technical developments of ultrasound technology, the detection rate will presumably be further increased.

Evidence of subduction and crust-mantle mixing from a single diamond

NASA Astrophysics Data System (ADS)

Schulze, Daniel J.; Harte, Ben; Valley, John W.; Channer, Dominic M. DeR.

2004-09-01

Cathodoluminescence (CL) imaging of polished sections of a diamond from the Guaniamo region of Venezuela suggests a history of the diamond involving two periods of growth separated by a period of resorption and possibly brittle deformation. In situ electron probe analysis of multiple eclogitic garnet inclusions reveals a correlation between garnet composition and location in the stone. An early-formed garnet in the diamond core has higher Ca/(Ca+Mg) and lower Mg/(Mg+Fe) values than later garnets associated with the second period of diamond growth. This variation conforms to an extensive trend of variation in the suite of eclogitic garnets extracted from Venezuelan diamonds. The diamond is zoned in carbon isotope composition (in situ secondary ion mass spectrometry, SIMS, data). The core compositions ( δ13C PDB), corresponding to the first stage of growth, average -17.7‰. The second period of growth is apparently in two sub-sets of CL zones with mean values of -13.0‰ and -7.9‰. Nitrogen contents of diamond are low (30-300 atomic ppm) and do not correlate with carbon isotope composition. Oxygen isotope ratios of the garnet inclusions are elevated substantially above those expected for "common mantle"; δ18O VSMOW of early garnet is approximately +10.5‰ and two late garnets average +8.8‰. The evolutionary trend of magnesium enrichment in garnet is unlikely to represent igneous fractionation. The stable isotope data are consistent with diamond formation in subducted meta-basic rocks that had interacted with sea water at low temperatures at or near the sea floor and contained a substantial biogenic carbon component. During or following subduction, diamonds continued to form in an evolving system that was progressively modified by interaction with mantle material.

NASA'S Space Launch System Mission Capabilities for Exploration

NASA Technical Reports Server (NTRS)

Creech, Stephen D.; Crumbly, Christopher M.; Robinson, Kimberly F.

2015-01-01

Designed to enable human space exploration missions, including eventual landings on Mars, NASA’s Space Launch System (SLS) represents a unique launch capability with a wide range of utilization opportunities, from delivering habitation systems into the lunar vicinity to high-energy transits through the outer solar system. Developed with the goals of safety, affordability and sustainability in mind, SLS is a foundational capability for NASA’s future plans for exploration, along with the Orion crew vehicle and upgraded ground systems at the agency’s Kennedy Space Center. Substantial progress has been made toward the first launch of the initial configuration of SLS, which will be able to deliver more than 70 metric tons of payload into low Earth orbit (LEO), greater mass-to-orbit capability than any contemporary launch vehicle. The vehicle will then be evolved into more powerful configurations, culminating with the capability to deliver more than 130 metric tons to LEO, greater even than the Saturn V rocket that enabled human landings on the moon. SLS will also be able to carry larger payload fairings than any contemporary launch vehicle, and will offer opportunities for co-manifested and secondary payloads. Because of its substantial mass-lift capability, SLS will also offer unrivaled departure energy, enabling mission profiles currently not possible. Early collaboration with science teams planning future decadal-class missions have contributed to a greater understanding of the vehicle’s potential range of utilization. This presentation will discuss the potential opportunities this vehicle poses for the planetary sciences community, relating the vehicle’s evolution to practical implications for mission capture. As this paper will explain, SLS will be a global launch infrastructure asset, employing sustainable solutions and technological innovations to deliver capabilities for space exploration to power human and robotic systems beyond our Moon and in to deep space.

NASA's Space Launch System Mission Capabilities for Exploration

NASA Technical Reports Server (NTRS)

Creech, Stephen D.; Crumbly, Christopher M.; Robinson, Kimberly F.

2015-01-01

Designed to enable human space exploration missions, including eventual landings on Mars, NASA's Space Launch System (SLS) represents a unique launch capability with a wide range of utilization opportunities, from delivering habitation systems into the lunar vicinity to high-energy transits through the outer solar system. Developed with the goals of safety, affordability and sustainability in mind, SLS is a foundational capability for NASA's future plans for exploration, along with the Orion crew vehicle and upgraded ground systems at the agency's Kennedy Space Center. Substantial progress has been made toward the first launch of the initial configuration of SLS, which will be able to deliver more than 70 metric tons of payload into low Earth orbit (LEO), greater mass-to-orbit capability than any contemporary launch vehicle. The vehicle will then be evolved into more powerful configurations, culminating with the capability to deliver more than 130 metric tons to LEO, greater even than the Saturn V rocket that enabled human landings on the moon. SLS will also be able to carry larger payload fairings than any contemporary launch vehicle, and will offer opportunities for co-manifested and secondary payloads. Because of its substantial mass-lift capability, SLS will also offer unrivaled departure energy, enabling mission profiles currently not possible. Early collaboration with science teams planning future decadal-class missions have contributed to a greater understanding of the vehicle's potential range of utilization. This presentation will discuss the potential opportunities this vehicle poses for the planetary sciences community, relating the vehicle's evolution to practical implications for mission capture. As this paper will explain, SLS will be a global launch infrastructure asset, employing sustainable solutions and technological innovations to deliver capabilities for space exploration to power human and robotic systems beyond our Moon and in to deep space.

The Landsat 7 mission: terrestrial research and applications for the 21st century

USGS Publications Warehouse

Goward, Samuel N.; Masek, Jeffrey G.; Williams, Darrel L.; Irons, James R.; Thompson, R.J.

2001-01-01

The Landsat Earth observation approach introduced in 1972 created a new way of monitoring land cover and land use globally. The Landsat 7 mission, successfully launched on April 15, 1999, continues those observations and demonstrates significant progress in precise numerical radiometry, spectral differentiation, and seasonally repetitive monitoring. Substantial improvements in calibration procedures, both prior to launch and during normal operations, have also been made to ensure long-term stability in the acquired spectral radiometry. Landsat 7 data acquisitions are being driven by a long-term data acquisition plan that was designed to ensure that substantially cloud-free, seasonal coverage would be recorded and archived in the US for all land areas of the globe. NASA competitively selected a Landsat Science Team, consisting of representatives from US universities and government agencies, to exploit the Landsat 7 record for global change research. This team is addressing the technical and analytical means to process and analyze the core of this observation record, and for the first time in the history of the Landsat mission, the technical and operational aspects of the mission are being driven by the goals of the US science community. The expected outcome of these efforts is a rapid improvement in understanding the Earth system, as well as conceptual knowledge that will underpin significant advancements in the application of this technology for commercial, operational, educational, and research purposes. Pathways to achieve effective Landsat continuity in the early decades of the 21st century are also being given careful attention, and there is no question that the lessons learned from the Landsat 7 mission will strongly influence these next-generation sensor systems.

Chinas Future SSBN Command and Control Structure

DTIC Science & Technology

2016-11-01

ndupress.ndu.edu SF No. 299 1 China’s ongoing modernization program is transforming the country’s nuclear arsenal from one consisting of a few...also be mediated by bureaucratic poli- tics, including the time-honored tradition of interservice rivalry. The emergent SSBN fleet may represent a prime...represent a reliable source of resources. China has dedicated substantial resources to undertaking a nuclear modernization program designed to ensure

Investing in Equal Opportunity: What Would It Take to Build the Balance Wheel?

ERIC Educational Resources Information Center

Rice, Jennifer King

2015-01-01

More than 150 years ago Horace Mann persuasively reasoned that education is the "balance wheel" of the social structure. He argued that education should be free and universal. While much progress has been made in establishing a universal education system since Mann spoke those words, substantial disparities in educational resources,…

Empirically Guided Coordination of Multiple Evidence-Based Treatments: An Illustration of Relevance Mapping in Children's Mental Health Services

ERIC Educational Resources Information Center

Chorpita, Bruce F.; Bernstein, Adam; Daleiden, Eric L.

2011-01-01

Objective: Despite substantial progress in the development and identification of psychosocial evidence-based treatments (EBTs) in mental health, there is minimal empirical guidance for selecting an optimal "set" of EBTs maximally applicable and generalizable to a chosen service sample. Relevance mapping is a proposed methodology that…

NASA-GIT predoctoral design training program. [systems and mechanical engineering

NASA Technical Reports Server (NTRS)

1974-01-01

The training program is discussed briefly, and the quantity and quality of academic achievement of those students who were supported by the traineeships are summarized. Dissertations which were completed or on which substantial progress was made are listed, along with a short description of the activities and status of each of the former trainees.

Southern forest resource conditions and management practices from 1950-2000: Benefits of research

Treesearch

Jacek P. Siry

2004-01-01

Over the past five decades, research progress and implementation have been the leading factors supporting the rapid development of southern forestry. The South has become the leading timber-supplying region in the United States, taking advantage of a large accumulation of growing stock and a substantial investment in intensive, research-based management treatments....

A comparison of two rodent repellents in broadcast seeding Douglas-fir.

Treesearch

Edward J. Dimock

1957-01-01

Broadcast seeding of cutover lands is a promising, yet still problematical, means of tree regeneration. Substantial progress has been made since 1950, particularly with the introduction of new rodenticides and repellents suitable for direct application to the seed. One of these is tetramine (tetramethylene disulpho tetramine), a highly lethal repellent that has shown...

Comparison of matrix effects on phytate analysis in Mehlich-3 and Alkaline-EDTA extracts by ICP, NMR, Chromatography and (HRAM) Mass Spectrometry.

USDA-ARS?s Scientific Manuscript database

Phosphorus (P) is a leading cause of water quality degradation in impaired fresh water systems. Although substantial progress has been made in understanding the fate and transport of P from nonpoint agricultural sources based on measures of total P and orthophosphate-P, a comprehensive understanding...

First-Year Seminar Intervention: Enhancing First-Year Mathematics Performance at the University of Johannesburg

ERIC Educational Resources Information Center

Jacobs, Melanie; Pretorius, Estherna

2016-01-01

South Africa has opened up access to higher education over the past 20 years. The massive increase in enrolments (with almost 70% first-generation students) substantially affects progress and graduation rates in Science programmes in higher education. First-year students in Science realise that university mathematics requires knowledge and skills…

The U.S. Partnership for Education for Sustainable Development: Progress and Challenges Ahead

ERIC Educational Resources Information Center

Rowe, Debra; Gentile, Susan Jane; Clevey, Lilah

2015-01-01

There has been substantial growth in Education for Sustainability (EfS) in the United States over the past 10 years. Efforts within higher education have created thousands of new programs, majors, minors, specializations, certificates, and across-the-curricula integrations of sustainability learning with an emphasis on real-world problem-solving…

Engineering in Scotland's Colleges: A Report by HM Inspectors for the Scottish Funding Council

ERIC Educational Resources Information Center

Her Majesty's Inspectorate of Education, 2007

2007-01-01

Engineering has played an important role in Scotland's industrial history. Over the years, the skills requirements of industry have changed as the technology has progressed and the industrial base of the country has developed. Over the past decade, there have been substantial changes in the employment opportunities for people with engineering…

Racial-Ethnic Differences at the Intersection of Math Course-Taking and Achievement

ERIC Educational Resources Information Center

Riegle-Crumb, Catherine; Grodsky, Eric

2010-01-01

Despite increases in the representation of African American and Hispanic youth in advanced math courses in high school over the past two decades, recent national reports indicate that substantial inequality in achievement remains. These inequalities can temper one's optimism about the degree to which the United States has made real progress toward…

Making Progress Toward Graduation: Evidence from the Talent Development High School Model

ERIC Educational Resources Information Center

Kemple, James J.; Herlihy, Corinne M.; Smith, Thomas J.

2005-01-01

In low-performing public high schools in U.S. cities, high proportions of students drop out, students who stay in school typically do not succeed academically, and efforts to make substantial reforms often meet with little success. The Talent Development High School model is a comprehensive school reform initiative that has been developed to…

Challenge and Change in Appalachia: The Story of Hindman Settlement School.

ERIC Educational Resources Information Center

Stoddart, Jess

Founded in 1902 by Katherine Pettit and May Stone, the Hindman Settlement School in Knott County, Kentucky, grew out of the Progressive movement. During the golden age of the school, 1915-32, the reputation of its academic program, health work, and other settlement activities brought substantial renown and influence to the school and its founders.…

Effect of an Arabic Program of Direct Instruction for Phonological Awareness on Phonological Awareness Abilities

ERIC Educational Resources Information Center

Elhoweris, Hala; Alsheikh, Negmeldin; Al Mekhlafi, Abdurrahman; Alhosani, Najwa; Alzyoudi, Mohammad

2017-01-01

Reading in Arabic is a vital skill for academic success and progress in the United Arab Emirates (UAE) elementary schools and beyond. However, there is substantial evidence to suggest that a significant number of UAE children in lower elementary grades experience difficulties in reading school-related materials. Research in reading has clearly…

Factors That Affect South African Reading Literacy Achievement: Evidence from prePIRLS 2011

ERIC Educational Resources Information Center

van Staden, Surette; Bosker, Roel

2014-01-01

This study aims to identify factors that predict reading literacy achievement among Grade 4 learners in South Africa by utilising aspects of Carroll's model of school learning. The study draws on the preProgress in International Reading Literacy Study (prePIRLS) 2011 data, which places South African Grade 4 learners' results substantially below…

Fragmented Foundations: Education and Chronic Crisis in the Occupied Palestinian Territory

ERIC Educational Resources Information Center

Nicolai, Susan

2007-01-01

This study explores the setting up and development of the first Palestinian-led education system, from 1994 to 2005. Given the context of chronic crisis, and the immensity of the endeavour, the Palestinians have made substantial progress in a relatively short time. However, the Palestinian education story does not end here. The author looks at…

A Longitudinal Examination of Students' Health Behaviours during Their First Year at University

ERIC Educational Resources Information Center

Gibson, Ann-Marie; Shaw, Johanna; Hewitt, Allan; Easton, Chris; Robertson, Sarah; Gibson, Neil

2018-01-01

During the transition from school to higher education, young adults experience a substantial amount of change where they progress from the highly controlled setting of school to the autonomous and self-motivated environment of university. Time spent at university is considered a critical period during which young adults establish a clear sense of…

49 CFR 213.337 - Defective rails.

Code of Federal Regulations, 2010 CFR

2010-10-01

... crystalline center or nucleus inside the head from which it spreads outward as a smooth, bright, or dark... a smooth, bright, or dark surface progressing until substantially at a right angle to the length of... through it. A crack or rust streak may show under the head close to the web or pieces may be split off the...

49 CFR 213.337 - Defective rails.

Code of Federal Regulations, 2011 CFR

2011-10-01

... crystalline center or nucleus inside the head from which it spreads outward as a smooth, bright, or dark... a smooth, bright, or dark surface progressing until substantially at a right angle to the length of... through it. A crack or rust streak may show under the head close to the web or pieces may be split off the...

49 CFR 213.337 - Defective rails.

Code of Federal Regulations, 2013 CFR

2013-10-01

... crystalline center or nucleus inside the head from which it spreads outward as a smooth, bright, or dark... a smooth, bright, or dark surface progressing until substantially at a right angle to the length of... through it. A crack or rust streak may show under the head close to the web or pieces may be split off the...

49 CFR 213.337 - Defective rails.

Code of Federal Regulations, 2012 CFR

2012-10-01

... crystalline center or nucleus inside the head from which it spreads outward as a smooth, bright, or dark... a smooth, bright, or dark surface progressing until substantially at a right angle to the length of... through it. A crack or rust streak may show under the head close to the web or pieces may be split off the...

49 CFR 213.337 - Defective rails.

Code of Federal Regulations, 2014 CFR

2014-10-01

... crystalline center or nucleus inside the head from which it spreads outward as a smooth, bright, or dark... a smooth, bright, or dark surface progressing until substantially at a right angle to the length of... through it. A crack or rust streak may show under the head close to the web or pieces may be split off the...

Work-Related Health Limitations, Education, and the Risk of Marital Disruption

ERIC Educational Resources Information Center

Teachman, Jay

2010-01-01

Despite progress in identifying the covariates of divorce, there remain substantial gaps in the knowledge. One of these gaps is the relationship between health and risk of marital dissolution. I extend prior research by examining the linkages between work-related health limitations and divorce using 25 years of data (N = 7919) taken from the 1979…

The Effects of Relaxation Training with Cognitive or Nondirective Therapy and the Role of Relaxation-Induced Anxiety in the Treatment of Generalized Anxiety.

ERIC Educational Resources Information Center

Borkovec, T. D.; And Others

1987-01-01

Provided 30 volunteers with generalized anxiety disorder with training in progressive muscle relaxation. Clients were also given cognitive or nondirective therapy. All showed substantial reductions in anxiety measured by psychiatric assessor ratings, questionnaires, and daily self-monitoring. Relaxation plus cognitive therapy produced…

The Within-Job Motherhood Wage Penalty in Norway, 1979-1996

ERIC Educational Resources Information Center

Petersen, Trond; Penner, Andrew M.; Hogsnes, Geir

2010-01-01

The motherhood wage penalty is a substantial obstacle to progress in gender equality at work. Using matched employer-employee data from Norway (1979-1996, N = 236,857 individuals, N = 1,027,462 individual-years), a country with public policies that promote combining family and career, we investigate (a) whether the penalty arises from differential…

India at the crossroads of millennium development goals 4 and 5.

PubMed

Hazarika, Indrajit

2012-05-01

The current year marks the completion of two thirds of the period between the adoption of the millennium development goals (MDGs) and the target date of 2015. Although there has been some progress, it is incontestable that much more needs to be done. India contributes to 20% of births worldwide and has the highest proportion of children younger than 5 years. Global progress toward MDG 4 and 5 depends significantly on improvements in maternal and child health indicators in India. Although it has been reported that the country has made substantial progress, the pace has been slow and marred by vast regional variability. Certain states continue to have unacceptably high mortality and morbidity rates. This article provides a context to the current status of maternal and child health in India, highlights the achievements, and uses the available data effectively to emphasize the progress. The authors acknowledge the new initiatives and make recommendations for reinforcing the continuum of care.

Forward progress of scientific inquiry into the early father-child relationship: introduction to the special issue on very young children and their fathers.

PubMed

Bocknek, Erika L; Hossain, Ziarat; Roggman, Lori

2014-01-01

Research on fathering and the father-child relationship has made substantial progress in the most recent 15 years since the last special issue of the Infant Mental Health Journal on fathers and young children. This special issue on fathers and young children contains a series of papers exemplifying this progress, including advances in methodology-more direct assessment and more observational measures-in addition to the increasing dynamic complexity of the conceptual models used to study fathers, the diversity of fathers studied, and the growth of programs to support early father involvement. In assessing the current state of the field, special attention is given to contributions made by the papers contained in this special issue, and two critical areas for continued progress are addressed: (1) methodological and measurement development that specifically address fathers and fathering relationships and (2) cross-cultural and ecologically valid research examining the diversity of models of fathering. © 2014 Michigan Association for Infant Mental Health.

Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse.

PubMed

Kim, Jeesun; Zhao, Hongbo; Dan, Jiameng; Kim, Soojin; Hardikar, Swanand; Hollowell, Debra; Lin, Kevin; Lu, Yue; Takata, Yoko; Shen, Jianjun; Chen, Taiping

2016-04-01

Oocyte meiotic progression and maternal-to-zygote transition are accompanied by dynamic epigenetic changes. The functional significance of these changes and the key epigenetic regulators involved are largely unknown. Here we show that Setdb1, a lysine methyltransferase, controls the global level of histone H3 lysine 9 di-methyl (H3K9me2) mark in growing oocytes. Conditional deletion of Setdb1 in developing oocytes leads to meiotic arrest at the germinal vesicle and meiosis I stages, resulting in substantially fewer mature eggs. Embryos derived from these eggs exhibit severe defects in cell cycle progression, progressive delays in preimplantation development, and degeneration before reaching the blastocyst stage. Rescue experiments by expressing wild-type or inactive Setdb1 in Setdb1-deficient oocytes suggest that the catalytic activity of Setdb1 is essential for meiotic progression and early embryogenesis. Mechanistically, up-regulation of Cdc14b, a dual-specificity phosphatase that inhibits meiotic progression, greatly contributes to the meiotic arrest phenotype. Setdb1 deficiency also leads to derepression of transposons and increased DNA damage in oocytes, which likely also contribute to meiotic defects. Thus, Setdb1 is a maternal-effect gene that controls meiotic progression and is essential for early embryogenesis. Our results uncover an important link between the epigenetic machinery and the major signaling pathway governing meiotic progression.

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

Kahl, S.B.

Although significant progress toward the application of boronated LDL for site selective boron drug delivery has been made during the past year, the loss of our animal and cell culture testing site at WSU has seriously hampered progress on this project. Results are reported of one in vivo biodistribution study in B16BL6-bearing mice and a series of in vitro studies that demonstrate very substantial uptake of boronated LDL in certain cell lines. The influence of 17{alpha}-ethinyl estradiol (EE) on cellular uptake has also been probed. Most significantly LDL loaded with HC was demonstrated to be taken up with exceptional ariditymore » in several lines. Significant progress has also been made in the development of a rapid infrared analysis of boron in boronated LDL solution, which may be useful for clinical BNCT studies in Finland.« less

An evidence-based update on myopia and interventions to retard its progression

PubMed Central

Leo, Seo-Wei; Young, Terri L.

2011-01-01

Summary Myopia is the most common human eye disorder. With its increasing prevalence and earlier age-of-onset in recent birth cohorts, myopia now affects almost 33% of adult individuals in the United States, and epidemic proportions of 85% to 90% adult individuals in Asian cities. Unlike children in Western populations, where the prevalence of myopia is very low (less than 5%), Asian children have prevalences as high as 29% in 7-year-olds. In addition to the direct economic and social burdens of myopia, associated ocular complications may lead to substantial vision loss. This workshop summarizes the current literature regarding myopia epidemiology, genetics, animal model studies, risk factors, and clinical treatments. Published treatment strategies to retard the progression of myopia in children, such as pharmacologic agents, progressive addition lenses, neural adaptation programs are outlined. PMID:21596297

[Research progress and development trend of quantitative assessment techniques for urban thermal environment.

PubMed

Sun, Tie Gang; Xiao, Rong Bo; Cai, Yun Nan; Wang, Yao Wu; Wu, Chang Guang

2016-08-01

Quantitative assessment of urban thermal environment has become a focus for urban climate and environmental science since the concept of urban heat island has been proposed. With the continual development of space information and computer simulation technology, substantial progresses have been made on quantitative assessment techniques and methods of urban thermal environment. The quantitative assessment techniques have been developed to dynamics simulation and forecast of thermal environment at various scales based on statistical analysis of thermal environment on urban-scale using the historical data of weather stations. This study reviewed the development progress of ground meteorological observation, thermal infrared remote sensing and numerical simulation. Moreover, the potential advantages and disadvantages, applicability and the development trends of these techniques were also summarized, aiming to add fundamental knowledge of understanding the urban thermal environment assessment and optimization.

Flat-plate techniques for measuring reflectance of macro-algae (Ulva curvata)

USGS Publications Warehouse

Ramsey, Elijah W.; Rangoonwala, Amina; Thomsen, Mads Solgaard; Schwarzschild, Arthur

2012-01-01

We tested the consistency and accuracy of flat-plate spectral measurements (400–1000 nm) of the marine macrophyte Ulva curvata. With sequential addition of Ulva thallus layers, the reflectance progressively increased from 6% to 9% with six thalli in the visible (VIS) and from 5% to 19% with ten thalli in the near infrared (NIR). This progressive increase was simulated by a mathematical calculation based on an Ulva thallus diffuse reflectance weighted by a transmittance power series. Experimental and simulated reflectance differences that were particularly high in the NIR most likely resulted from residual water and layering structure unevenness in the experimental progression. High spectral overlap existed between fouled and non-fouled Ulva mats and the coexistent lagoon mud in the VIS, whereas in the NIR, spectral contrast was retained but substantially dampened by fouling.

The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases

PubMed Central

Boucharaba, Ahmed; Serre, Claire-Marie; Guglielmi, Julien; Bordet, Jean-Claude; Clézardin, Philippe; Peyruchaud, Olivier

2006-01-01

Platelet-derived lysophosphatidic acid (LPA) supports the progression of breast and ovarian cancer metastasis to bone. The mechanisms through which LPA promotes bone metastasis formation are, however, unknown. Here we report that silencing of the type 1 LPA receptor (LPA1) in cancer cells blocks the production of tumor-derived cytokines that are potent activators of osteoclast-mediated bone destruction and significantly reduces the progression of osteolytic bone metastases. Moreover, functional blockade of LPA action on its cognate receptor LPA1 using a pharmacological antagonist mimics the effects of silencing LPA1 in tumor cells in vitro and substantially reduces bone metastasis progression in animals. Overall, these results suggest that inhibition of platelet-derived LPA action on LPA1 expressed by tumor cells may be a promising therapeutic target for patients with bone metastases. PMID:16769891

Mechanisms underlying progressive polyuria in familial neurohypophysial diabetes insipidus.

PubMed

Arima, H; Oiso, Y

2010-07-01

Familial neurohypophysial diabetes insipidus (FNDI), an autosomal dominant disorder, is mostly caused by mutations in the gene of neurophysin II (NPII), the carrier protein of arginine vasopressin (AVP). The analyses of knock-in mice expressing a mutant NPII that causes FNDI in humans demonstrated that polyuria progressed substantially in the absence of loss of AVP neurones. Morphological analyses revealed that inclusion bodies were present in the AVP neurones in the supraoptic nucleus and that the size and numbers of inclusion bodies gradually increased in parallel with the increases in urine volume. Electron microscopic analyses showed that aggregates existed in the endoplasmic reticulum (ER) of AVP neurones. These data suggest that cell death is not the primary cause of polyuria in FNDI, and that the aggregate formation in the ER is likely to be related to the pathogenesis of the progressive polyuria.

Progress in Aluminum Electrolysis Control and Future Direction for Smart Aluminum Electrolysis Plant

NASA Astrophysics Data System (ADS)

Zhang, Hongliang; Li, Tianshuang; Li, Jie; Yang, Shuai; Zou, Zhong

2017-02-01

The industrial aluminum reduction cell is an electrochemistry reactor that operates under high temperatures and highly corrosive conditions. However, these conditions have restricted the measurement of key control parameters, making the control of aluminum reduction cells a difficult problem in the industry. Because aluminum electrolysis control systems have a significant economic influence, substantial research has been conducted on control algorithms, control systems and information systems for aluminum reduction cells. This article first summarizes the development of control systems and then focuses on the progress made since 2000, including alumina concentration control, temperature control and electrolyte molecular ratio control, fault diagnosis, cell condition prediction and control system expansion. Based on these studies, the concept of a smart aluminum electrolysis plant is proposed. The frame construction, key problems and current progress are introduced. Finally, several future directions are discussed.

[Prognosis and progression of cognitive impairment. Preventive measures].

PubMed

López Mongil, Rosa; López Trigo, José Antonio

2016-06-01

Because of the substantial increase in population ageing, age-related processes, such as dementia and Alzheimer disease (AD), are becoming highly prevalent. The course of this disease, including preprodromic phases, lasts at least 20 years. The presence of comorbidities, especially those of vascular origin, can trigger and aggravate disease progression. On the other hand, cognitive reserve, the absence or control of comorbid factors and healthy lifestyles can protect or modify -in the sense of slow down- disease progression. Knowledge of the phases of AD and their functional impact on affected individuals helps to identify the average prognosis and, in particular, to establish and predict care plans based on the individual's needs. Copyright © 2016 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

The COMET Initiative database: progress and activities update (2015).

PubMed

Gargon, E; Williamson, P R; Altman, D G; Blazeby, J M; Tunis, S; Clarke, M

2017-02-03

This letter describes the substantial activity on the Core Outcome Measure in Effectiveness Trials (COMET) website in 2015, updating our earlier progress reports for the period from the launch of the COMET website and database in August 2011 to December 2014. As in previous years, 2015 saw further increases in the annual number of visits to the website, the number of pages viewed and the number of searches undertaken. The sustained growth in use of the website and database suggests that COMET is continuing to gain interest and prominence, and that the resources are useful to people interested in the development of core outcome sets.

[Indicators of general, cerebral, and regional hemodynamics in myopic schoolchildren aged 13-15 years].

PubMed

Iastrebtseva, T A; Chuprov, A D; Plotnikova, Iu A

2002-01-01

110 schoolchildren aged 13-15 years were examined. 24 of them had pseudomyopia and 6 patients myopia of various forms. A control group consisted of 38 children. Central hemodynamics was estimated by average dynamic pressure, cerebral hemodynamics--by rheoencephalography, regional hemodynamics--by dopplerography of the internal carotid and suprapubic arteries. It was found that with myopia progression, the average dynamic pressure positively comes down with reduction of reographic waves amplitude in rheogram. The blood flow rate in internal carotid and suprapubic arteries has no substantial impact on myopia course. Predisposition to arterial hypotension is a risk factor for myopia development and progression.

Krikalev dismantles probe-and-cone docking mechanism (StM) in the Progress M-53 (18P)

NASA Image and Video Library

2005-06-19

ISS011-E-09204 (19 June 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, dismantles the probe-and-cone docking mechanism in the Progress 18 spacecraft. The Progress docked to the aft port of the Zvezda Service Module of the International Space Station (ISS) at 7:42 p.m. (CDT) as the Station flew approximately 225 statute miles, above a point near Beijing, China.

Reliability analysis of the AOSpine thoracolumbar spine injury classification system by a worldwide group of naïve spinal surgeons.

PubMed

Kepler, Christopher K; Vaccaro, Alexander R; Koerner, John D; Dvorak, Marcel F; Kandziora, Frank; Rajasekaran, Shanmuganathan; Aarabi, Bizhan; Vialle, Luiz R; Fehlings, Michael G; Schroeder, Gregory D; Reinhold, Maximilian; Schnake, Klaus John; Bellabarba, Carlo; Cumhur Öner, F

2016-04-01

The aims of this study were (1) to demonstrate the AOSpine thoracolumbar spine injury classification system can be reliably applied by an international group of surgeons and (2) to delineate those injury types which are difficult for spine surgeons to classify reliably. A previously described classification system of thoracolumbar injuries which consists of a morphologic classification of the fracture, a grading system for the neurologic status and relevant patient-specific modifiers was applied to 25 cases by 100 spinal surgeons from across the world twice independently, in grading sessions 1 month apart. The results were analyzed for classification reliability using the Kappa coefficient (κ). The overall Kappa coefficient for all cases was 0.56, which represents moderate reliability. Kappa values describing interobserver agreement were 0.80 for type A injuries, 0.68 for type B injuries and 0.72 for type C injuries, all representing substantial reliability. The lowest level of agreement for specific subtypes was for fracture subtype A4 (Kappa = 0.19). Intraobserver analysis demonstrated overall average Kappa statistic for subtype grading of 0.68 also representing substantial reproducibility. In a worldwide sample of spinal surgeons without previous exposure to the recently described AOSpine Thoracolumbar Spine Injury Classification System, we demonstrated moderate interobserver and substantial intraobserver reliability. These results suggest that most spine surgeons can reliably apply this system to spine trauma patients as or more reliably than previously described systems.

Organizing Hazards, Engineering Disasters? Improving the Recognition of Political-Economic Factors in the Creation of Disasters

ERIC Educational Resources Information Center

Freudenburg, William R.; Gramling, Robert; Laska, Shirley; Erikson, Kai T.

2008-01-01

Disaster studies have made important progress in recognizing the unequally distributed consequences of disasters, but there has been less progress in analyzing social factors that help create "natural" disasters. Even well-known patterns of hazard-creation tend to be interpreted generically--as representing "economic development" or…

Perspectives on Progress: The School-to-Work National Customer Dialogues. Final Report.

ERIC Educational Resources Information Center

Public Forum Inst., Washington, DC.

"Perspectives on Progress: The School-to-Work (STW) National Customer Dialogues" was a series of six regional and two national discussions that were held between December 1999 and July 2000 to gather the views of more than 700 employers, educators, labor union representatives, students, parents, community-based organizations, and state…

Straight A's: Public Education Policy and Progress. Volume 7, Number 13

ERIC Educational Resources Information Center

Amos, Jason, Ed.

2007-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) "A Plan for Success": Alliance Joins Nine National Organizations Representing Communities of Color in Historic Campaign for…

Development of Career Progression Systems for Employees in the Foodservice Industry. Final Report.

ERIC Educational Resources Information Center

National Restaurant Association, Chicago, IL.

Firms representing four segments of the foodservice industry (institutional foodservice (9 jobs), commercial restaurants (19 jobs), hotel foodservice (100 jobs), and airline foodservice (10 jobs), participated in a career and training study to test the feasibility of designing and implementing career progression (c.p.) systems within these…

An Introduction to NAEP: National Assessment of Educational Progress. NCES 2010-468

ERIC Educational Resources Information Center

National Center for Education Statistics, 2010

2010-01-01

The National Assessment of Educational Progress (NAEP) is a continuing and nationally representative assessment of what this nation's students know and can do. NAEP has often been called the "gold standard" of assessments because it is developed using the best thinking of assessment and content specialists, education experts, and…

Getting the Most Out of Progress Files and Personal Development Planning

ERIC Educational Resources Information Center

Croot, David; Gedye, Sharon

2006-01-01

Progress Files have been set by the government as a specific element of all higher education provision in England and "should consist of two elements: a transcript recording student achievement which should follow a common format devised by institutions collectively through their representative bodies; and a means by which students can …

THE U.S. ENVIRONMENTAL PROTECTION AGENCY PARTICULATE MATTER HEALTH EFFECTS RESEARCH CENTERS PROGRAM: A MIDCOURSE REPORT OF STATUS, PROGRESS, AND PLANS. (R827351)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Examining a progressive model of self-stigma and its impact on people with serious mental illness.

PubMed

Corrigan, Patrick W; Rafacz, Jennifer; Rüsch, Nicolas

2011-10-30

The self-esteem of some people with serious psychiatric disorders may be hurt by internalizing stereotypes about mental illness. A progressive model of self-stigma yields four stages leading to diminished self-esteem and hope: being aware of associated stereotypes, agreeing with them, applying the stereotypes to one's self, and suffering lower self-esteem. We expect to find associations between proximal stages - awareness and agreement - to be greater than between more distal stages: awareness and harm. The model was tested on 85 people with schizophrenia or other serious mental illnesses who completed measures representing the four stages of self-stigma, another independently-developed instrument representing self-stigma, proxies of harm (lowered self-esteem and hopelessness), and depression. These measures were also repeated at 6-month follow-up. Results were mixed but some evidence supported the progressive nature of self-stigma. Most importantly, separate stages of the progressive model were significantly associated with lowered self-esteem and hope. Implications of the model for stigma change are discussed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Safety and efficacy of collagen crosslinking for the treatment of keratoconus.

PubMed

Kolli, Sai; Aslanides, Ioannis M

2010-11-01

Keratoconus is a condition that causes corneal ectasia and reduced vision in young adults. A proportion of these patients have progressive disease requiring corneal transplantation. A revolutionary new treatment that is purported to halt progression of keratoconus, known as collagen crosslinking (CXL), has recently been introduced into clinical practice. CXL involves the treatment of the cornea with riboflavin followed by photoactivation with UVA light leading to corneal strengthening. This article reviews the basic science, clinical protocols, safety aspects and clinical results of CXL. The reader will gain a comprehensive understanding of: i) the basic science of CXL; ii) the optimised protocols for clinical use of CXL; iii) the results of all the main clinical trials in the literature; iv) contraindications to treatment and v) full clinical safety profile of CXL. CXL represents a new treatment that uniquely allows the halt of progression of keratoconus, thus preventing visual loss and the need for surgical intervention. Available data suggest that this treatment has high efficacy and is very safe and may represent the future standard treatment for progressive keratoconus.

Design and application of electromechanical actuators for deep space missions

NASA Technical Reports Server (NTRS)

Haskew, Tim A.; Wander, John

1993-01-01

The annual report Design and Application of Electromechanical Actuators for Deep Space Missions is presented. The reporting period is 16 Aug. 1992 to 15 Aug. 1993. However, the primary focus will be work performed since submission of our semi-annual progress report in Feb. 1993. Substantial progress was made. We currently feel confident in providing guidelines for motor and control strategy selection in electromechanical actuators to be used in thrust vector control (TVC) applications. A small portion was presented in the semi-annual report. At this point, we have implemented highly detailed simulations of various motor/drive systems. The primary motor candidates were the brushless dc machine, permanent magnet synchronous machine, and the induction machine. The primary control implementations were pulse width modulation and hysteresis current control. Each of the two control strategies were applied to each of the three motor choices. With either pulse width modulation or hysteresis current control, the induction machine was always vector controlled. A standard test position command sequence for system performance evaluation is defined. Currently, we are gathering all of the necessary data for formal presentation of the results. Briefly stated for TVC application, we feel that the brushless dc machine operating under PWM current control is the best option. Substantial details on the topic, with supporting simulation results, will be provided later, in the form of a technical paper prepared for submission and also in the next progress report with more detail than allowed for paper publication.

Progressive transmission of road network

NASA Astrophysics Data System (ADS)

Ai, Bo; Ai, Tinghua; Tang, Xinming; Li, Zhen

2009-10-01

The progressive transmission of vector map data requires efficient multi-scale data model to process the data into hierarchical structure. This paper presents such a data structure of road network without redundancy of geometry for progressive transmission. For a given scale, the road network display has to settle two questions. One is which road objects to be represented and the other is what geometric details to be visualized for the selected roads. This paper combines the Töpfer law and the BLG-tree structure into a multi-scale representation matrix to answer simultaneously the above two questions. In the matrix, rows from top to bottom represent the roads in the sequence of descending classification of traffic and length, which can support the Töpfer law to retrieve the more important roads. In a row, columns record one road by a linear BLG-tree to provide good line graphics.

RNA-Targeted Therapeutics.

PubMed

Crooke, Stanley T; Witztum, Joseph L; Bennett, C Frank; Baker, Brenda F

2018-04-03

RNA-targeted therapies represent a platform for drug discovery involving chemically modified oligonucleotides, a wide range of cellular RNAs, and a novel target-binding motif, Watson-Crick base pairing. Numerous hurdles considered by many to be impassable have been overcome. Today, four RNA-targeted therapies are approved for commercial use for indications as diverse as Spinal Muscular Atrophy (SMA) and reduction of low-density lipoprotein cholesterol (LDL-C) and by routes of administration including subcutaneous, intravitreal, and intrathecal delivery. The technology is efficient and supports approaching "undruggable" targets. Three additional agents are progressing through registration, and more are in clinical development, representing several chemical and structural classes. Moreover, progress in understanding the molecular mechanisms by which these drugs work has led to steadily better clinical performance and a wide range of mechanisms that may be exploited for therapeutic purposes. Here we summarize the progress, future challenges, and opportunities for this drug discovery platform. Copyright © 2018 Elsevier Inc. All rights reserved.

Field defects in progression to gastrointestinal tract cancers

PubMed Central

Bernstein, Carol; Bernstein, Harris; Payne, Claire M.; Dvorak, Katerina; Garewal, Harinder

2009-01-01

A field of defective tissue may represent a pre-malignant stage in progression to many cancers. However, field defects are often overlooked in studies of cancer progression through assuming tissue at some distance from the cancer is normal. We indicate, however, the generality of field defects in gastrointestinal cancers, including cancers of the oropharynx, esophagus, stomach, bile duct, pancreas, small intestine and colon/rectum. Common features of these field defects are reduced apoptosis competence, aberrant proliferation and genomic instability. These features are often associated with high bile acid exposure and may explain the association of dietary-related factors with cancer progression. PMID:18164807

Category Captain Management: a new approach for healthcare suppliers to partner with their hospital customers.

PubMed

Trombetta, Bill

2007-01-01

Hospitals represent a substantial market for pharmaceutical and medical device companies. The typical approach by healthcare manufacturers and suppliers to hospitals is to send representatives or detailers to hospitals and meet with representatives of hospital formularies and purchasing officials. Classic channels systems, and specifically, Category Captain Management ("CCM") may provide more of a sustainable competitive advantage than traditional hospital detailing. The purpose of this article is to discuss how CCM might apply as an approach for healthcare suppliers to truly partner with their hospital customers.

Review of the magnetic fusion program by the 1986 ERAB Fusion Panel

NASA Astrophysics Data System (ADS)

Davidson, Ronald C.

1987-09-01

The 1986 ERAB Fusion Panel finds that fusion energy continues to be an attractive energy source with great potential for the future, and that the magnetic fusion program continues to make substantial technical progress. In addition, fusion research advances plasma physics, a sophisticated and useful branch of applied science, as well as technologies important to industry and defense. These factors fully justify the substantial expenditures by the Department of Energy in fusion research and development (R&D). The Panel endorses the overall program direction, strategy, and plans, and recognizes the importance and timeliness of proceeding with a burning plasma experiment, such as the proposed Compact Ignition Tokamak (CIT) experiment.

A plot twist: the continuing story of VCSELs at AOC

NASA Astrophysics Data System (ADS)

Guenter, James K.; Tatum, Jim A.; Hawthorne, Robert A., III; Johnson, Ralph H.; Mathes, David T.; Hawkins, Bobby M.

2005-03-01

During a year of substantial consolidation in the VCSEL industry, Honeywell sold their VCSEL Optical Products Division, which has now officially changed its name to Advanced Optical Components (AOC). Both manufacture and applied research continue, however. Some of the developments of the past year are discussed in this paper. They include advances in the understanding of VCSEL degradation physics, substantial improvements in long-wavelength VCSEL performance, and continuing progress in manufacturing technology. In addition, higher speed serial communications products, at 10 gigabits and particularly at 4 gigabits per second, have shown faster than predicted growth. We place these technologies and AOC's approach to them in a market perspective, along with other emerging applications.

Subjects harboring presenilin familial Alzheimer’s disease mutations exhibit diverse white matter biochemistry alterations

PubMed Central

Roher, Alex E; Maarouf, Chera L; Malek-Ahmadi, Michael; Wilson, Jeffrey; Kokjohn, Tyler A; Daugs, Ian D; Whiteside, Charisse M; Kalback, Walter M; Macias, MiMi P; Jacobson, Sandra A; Sabbagh, Marwan N; Ghetti, Bernardino; Beach, Thomas G

2013-01-01

Alzheimer’s disease (AD) dementia impacts all facets of higher order cognitive function and is characterized by the presence of distinctive pathological lesions in the gray matter (GM). The profound alterations in GM structure and function have fostered the view that AD impacts are primarily a consequence of GM damage. However, the white matter (WM) represents about 50% of the cerebrum and this area of the brain is substantially atrophied and profoundly abnormal in both sporadic AD (SAD) and familial AD (FAD). We examined the WM biochemistry by ELISA and Western blot analyses of key proteins in 10 FAD cases harboring mutations in the presenilin genes PSEN1 and PSEN2 as well as in 4 non-demented control (NDC) individuals and 4 subjects with SAD. The molecules examined were direct substrates of PSEN1 such as Notch-1 and amyloid precursor protein (APP). In addition, apolipoproteins, axonal transport molecules, cytoskeletal and structural proteins, neurotrophic factors and synaptic proteins were examined. PSEN-FAD subjects had, on average, higher amounts of WM amyloid-beta (Aβ) peptides compared to SAD, which may play a role in the devastating dysfunction of the brain. However, the PSEN-FAD mutations we examined did not produce uniform increases in the relative proportions of Aβ42 and exhibited substantial variability in total Aβ levels. These observations suggest that neurodegeneration and dementia do not depend solely on enhanced Aβ42 levels. Our data revealed additional complexities in PSEN-FAD individuals. Some direct substrates of γ-secretase, such as Notch, N-cadherin, Erb-B4 and APP, deviated substantially from the NDC group baseline for some, but not all, mutation types. Proteins that were not direct γ-secretase substrates, but play key structural and functional roles in the WM, likewise exhibited varied concentrations in the distinct PSEN mutation backgrounds. Detailing the diverse biochemical pathology spectrum of PSEN mutations may offer valuable insights into dementia progression and the design of effective therapeutic interventions for both SAD and FAD. PMID:24093083

Proton Radiotherapy for Childhood Ependymoma: Initial Clinical Outcomes and Dose Comparisons

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

MacDonald, Shannon M.; Safai, Sairos; Trofimov, Alexei

2008-07-15

Purpose: To report preliminary clinical outcomes for pediatric patients treated with proton beam radiation for intracranial ependymoma and compare the dose distributions of intensity-modulated radiation therapy with photons (IMRT), three-dimensional conformal proton radiation, and intensity-modulated proton radiation therapy (IMPT) for representative patients. Methods and Materials: All children with intracranial ependymoma confined to the supratentorial or infratentorial brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron between November 2000 and March 2006 were included in this study. Seventeen patients were treated with protons. Proton, IMRT, and IMPT plans were generated with similar clinical constraints for representative infratentorial andmore » supratentorial ependymoma cases. Tumor and normal tissue dose-volume histograms were calculated and compared. Results: At a median follow-up of 26 months from the start date of radiation therapy, local control, progression-free survival, and overall survival rates were 86%, 80%, and 89%, respectively. Subtotal resection was significantly associated with decreased local control (p = 0.016). Similar tumor volume coverage was achieved with IMPT, proton therapy, and IMRT. Substantial normal tissue sparing was seen with proton therapy compared with IMRT. Use of IMPT will allow for additional sparing of some critical structures. Conclusions: Preliminary disease control with proton therapy compares favorably with the literature. Dosimetric comparisons show the advantage of proton radiation compared with IMRT in the treatment of ependymoma. Further sparing of normal structures appears possible with IMPT. Superior dose distributions were accomplished with fewer beam angles with the use of protons and IMPT.« less

20 CFR 201.1 - Words and phrases.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., sleeping-car company, or carrier by railroad, subject to part I of the Interstate Commerce Act (24 Stat... authorized to and does represent that organization on all of a particular railroad or on a substantial...

20 CFR 201.1 - Words and phrases.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., sleeping-car company, or carrier by railroad, subject to part I of the Interstate Commerce Act (24 Stat... authorized to and does represent that organization on all of a particular railroad or on a substantial...

20 CFR 201.1 - Words and phrases.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., sleeping-car company, or carrier by railroad, subject to part I of the Interstate Commerce Act (24 Stat... authorized to and does represent that organization on all of a particular railroad or on a substantial...

20 CFR 201.1 - Words and phrases.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., sleeping-car company, or carrier by railroad, subject to part I of the Interstate Commerce Act (24 Stat... authorized to and does represent that organization on all of a particular railroad or on a substantial...

20 CFR 266.4 - Information considered in selecting a representative payee.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., including the type of relationship, e.g., family or legal guardianship; degree of relationship, if the... payee unless such appointment poses no substantial conflict of interest and unless the creditor is: (1...

Vinogradov practices docking procedures of the Progress 21 in the SM during Expedition 13

NASA Image and Video Library

2006-04-26

ISS013-E-10225 (26 April 2006) --- Cosmonaut Pavel V. Vinogradov, Expedition 13 commander representing Russia's Federal Space Agency, practices docking procedures with the TORU teleoperated control system in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 21 spacecraft. Vinogradov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system.

Magnitude Knowledge: The Common Core of Numerical Development

ERIC Educational Resources Information Center

Siegler, Robert S.

2016-01-01

The integrated theory of numerical development posits that a central theme of numerical development from infancy to adulthood is progressive broadening of the types and ranges of numbers whose magnitudes are accurately represented. The process includes four overlapping trends: (1) representing increasingly precisely the magnitudes of non-symbolic…

Magnitude Knowledge: The Common Core of Numerical Development

ERIC Educational Resources Information Center

Siegler, Robert S.

2016-01-01

The integrated theory of numerical development posits that a central theme of numerical development from infancy to adulthood is progressive broadening of the types and ranges of numbers whose magnitudes are accurately represented. The process includes four overlapping trends: 1) representing increasingly precisely the magnitudes of non-symbolic…

Educator Outcomes Associated with Implementation of Mississippi's K-3 Early Literacy Professional Development Initiative. REL 2017-270

ERIC Educational Resources Information Center

Folsom, Jessica Sidler; Smith, Kevin G.; Burk, Kymyona; Oakley, Nathan

2017-01-01

Substantial research points to the importance of developing strong early literacy skills. However, according to the National Assessment of Educational Progress, between 2007 and 2013, no more than 55 percent of Mississippi grade 4 students were reading at or above the proficiency level that demonstrates solid academic performance for the grade…

PROGRESS REPORT OF VOCATIONAL-TECHNICAL EDUCATION PROGRAM DEVELOPMENT FOR PERSONS WITH SPECIAL NEEDS BY STATES. DISCUSSION COPY.

ERIC Educational Resources Information Center

DEMOND, ALBERT L.; AND OTHERS

PROGRAMS DEVELOPED SINCE THE PASSAGE OF THE VOCATIONAL EDUCATION ACT OF 1963 ARE REPORTED FOR EACH STATE, GUAM, PUERTO RICO AND THE VIRGIN ISLANDS. EACH REPORT INCLUDES INTRODUCTORY INFORMATION AND THE OCCUPATIONAL AREAS IN WHICH TRAINING IS BEING OFFERED. A LARGE NUMBER OF SUCCESSFUL PROGRAMS ARE GETTING SUBSTANTIAL RESULTS IN REDUCING SCHOOL…

Progress in analysis of computed tomography (CT) images of hardwood logs for defect detection

Treesearch

Erol Sarigul; A. Lynn Abbott; Daniel L. Schmoldt

2003-01-01

This paper addresses the problem of automatically detecting internal defects in logs using computed tomography (CT) images. The overall purpose is to assist in breakdown optimization. Several studies have shown that the commercial value of resulting boards can be increased substantially if defect locations are known in advance, and if this information is used to make...

Learning to See by Learning to Draw: Probing the Perceptual Bases and Consequences of Highly Skilled Artistic Drawing

ERIC Educational Resources Information Center

Kozbelt, Aaron

2017-01-01

In this paper, I review the empirical evidence for advantages in visual perception and attention that may be associated with high levels of drawing skill. Particularly in the last few decades, some substantial progress on these issues has been made, although frequently with inconsistent or even contradictory results across studies, some…

Trends in Gender Differences in Academic Achievement from 1960 to 1994: An Analysis of Differences in Mean, Variance, and Extreme Scores.

ERIC Educational Resources Information Center

Nowell, Amy; Hedges, Larry V.

1998-01-01

Uses evidence from seven surveys of the U.S. 12th-grade population and the National Assessment of Educational Progress to show that gender differences in mean and variance in academic achievement are small from 1960 to 1994 but that differences in extreme scores are often substantial. (SLD)

25 CFR 1000.244 - May the Secretary suspend construction activities under an AFA?

Code of Federal Regulations, 2010 CFR

2010-04-01

... construction activities under an AFA? (a) The Secretary may require a Tribe/Consortium to suspend certain work under a construction portion of an AFA for up to 30 days only if: (1) Site conditions adversely affect health and safety; or (2) Work in progress or completed fails to substantially carry out the terms of the...

Kindergarten Black-White Test Score Gaps: Replicating and Updating Previous Findings with New National Data

ERIC Educational Resources Information Center

Quinn, David

2014-01-01

A substantial body of evidence has shown large academic test score gaps between black and white students in early childhood. These gaps remain, and probably grow, as students progress through school. Many researchers have sought to explain these persistent test score gaps, and particularly, to understand the role of students' socio-economic status…

Predicting armed conflict: Time to adjust our expectations?

PubMed

Cederman, Lars-Erik; Weidmann, Nils B

2017-02-03

This Essay provides an introduction to the general challenges of predicting political violence, particularly compared with predicting other types of events (such as earthquakes). What is possible? What is less realistic? We aim to debunk myths about predicting violence, as well as to illustrate the substantial progress in this field. Copyright © 2017, American Association for the Advancement of Science.

Solar and Space Physics Science Enabled by Pico and Nano Satellites

NASA Astrophysics Data System (ADS)

Swenson, C.; Fish, C. S.

2012-12-01

The most significant advances in solar and space physics, or Heliophysics, over the next decade are most likely to derive from new observational techniques. The connection between advances in scientific understanding and technology has historically been demonstrated across many disciplines and time. Progress on some of the most compelling scientific problems will most likely occur through multipoint observations within the space environment to understand the coupling between disparate regions: Heliosphere, magnetosphere, ionosphere, thermosphere and mesosphere. Multipoint measurements are also needed to develop understanding of the various scalars or vector field signatures (i.e gradients, divergence) that arise from coupling processes that occur across temporal and spatial scales or within localized regions. The resources that are available over the next decades for all areas of Heliophysics research have limits and it is therefore important that the community be innovative in developing new observational techniques to advance science. One of the most promising new observational techniques becoming available are miniaturized sensors and satellite systems called pico- or nano-satellites and CubeSats. These are enabled by the enormous investment of the commercial, medical, and defense industries in producing highly capable, portable and low-power battery-operated consumer electronics, in-situ composition probes, and novel reconnaissance sensors. The advancements represented by these technologies have direct application in developing pico- or nano-satellites and CubeSats system for Heliophysics research. In this talk we overview the current environment and technologies surrounding these novel small satellites and discuss the types and capabilities of the miniature sensors that are being developed. We discuss how pico- or nano-satellites and CubeSats can be used to address highest priority science identified in the Decadal Survey and the innovations and advancements that are required to make substantial progress.

Expression of the TPα and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer: clinical significance and diagnostic potential.

PubMed

Mulvaney, Eamon P; Shilling, Christine; Eivers, Sarah B; Perry, Antoinette S; Bjartell, Anders; Kay, Elaine W; Watson, R William; Kinsella, B Therese

2016-11-08

The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

Purging of the neuroblastoma stem cell compartment and tumor regression on exposure to hypoxia or cytotoxic treatment.

PubMed

Marzi, Ilaria; D'Amico, Massimo; Biagiotti, Tiziana; Giunti, Serena; Carbone, Maria Vittoria; Fredducci, David; Wanke, Enzo; Olivotto, Massimo

2007-03-15

We worked out an experimental protocol able to purge the stem cell compartment of the SH-SY5Y neuroblastoma clone. This protocol was based on the prolonged treatment of the wild-type cell population with either hypoxia or the antiblastic etoposide. Cell fate was monitored by immunocytochemical and electrophysiologic (patch-clamp) techniques. Both treatments produced the progressive disappearance of neuronal type (N) cells (which constitute the bulk of the tumor), leaving space for a special category of epithelial-like substrate-adherent cells (S(0)). The latter represent a minimal cell component of the untreated population and are endowed with immunocytochemical markers (p75, c-kit, and CD133) and the electrophysiologic "nude" profile, typical of the neural crest stem cells. S(0) cells displayed a highly clonogenic potency and a substantial plasticity, generating both the N component and an alternative subpopulation terminally committed to the fibromuscular lineage. Unlike the N component, this lineage was highly insensitive to the apoptotic activity of hypoxia and etoposide and developed only when the neuronal option was abolished. Under these conditions, the fibromuscular progeny of S(0) expanded and progressed up to the exhaustion of the staminal compartment and to the extinction of the tumor. When combined, hypoxia and etoposide cooperated in abolishing the N cell generation and promoting the conversion of the tumor described. This synergy might mirror a natural condition in the ischemic areas occurring in cancer. These results have relevant implications for the understanding of the documented tendency of neuroblastomas to regress from a malignant to a benign phenotype, either spontaneously or on antiblastic treatment.

Genomics and molecular breeding in lesser explored pulse crops: current trends and future opportunities.

PubMed

Bohra, Abhishek; Jha, Uday Chand; Kishor, P B Kavi; Pandey, Shailesh; Singh, Narendra P

2014-12-01

Pulses are multipurpose crops for providing income, employment and food security in the underprivileged regions, notably the FAO-defined low-income food-deficit countries. Owing to their intrinsic ability to endure environmental adversities and the least input/management requirements, these crops remain central to subsistence farming. Given their pivotal role in rain-fed agriculture, substantial research has been invested to boost the productivity of these pulse crops. To this end, genomic tools and technologies have appeared as the compelling supplement to the conventional breeding. However, the progress in minor pulse crops including dry beans (Vigna spp.), lupins, lablab, lathyrus and vetches has remained unsatisfactory, hence these crops are often labeled as low profile or lesser researched. Nevertheless, recent scientific and technological breakthroughs particularly the next generation sequencing (NGS) are radically transforming the scenario of genomics and molecular breeding in these minor crops. NGS techniques have allowed de novo assembly of whole genomes in these orphan crops. Moreover, the availability of a reference genome sequence would promote re-sequencing of diverse genotypes to unlock allelic diversity at a genome-wide scale. In parallel, NGS has offered high-resolution genetic maps or more precisely, a robust genetic framework to implement whole-genome strategies for crop improvement. As has already been demonstrated in lupin, sequencing-based genotyping of the representative sample provided access to a number of functionally-relevant markers that could be deployed straight away in crop breeding programs. This article attempts to outline the recent progress made in genomics of these lesser explored pulse crops, and examines the prospects of genomics assisted integrated breeding to enhance and stabilize crop yields. Copyright © 2014 Elsevier Inc. All rights reserved.

p53 predictive value for pT1-2 N0 disease at radical cystectomy.

PubMed

Shariat, Shahrokh F; Lotan, Yair; Karakiewicz, Pierre I; Ashfaq, Raheela; Isbarn, Hendrik; Fradet, Yves; Bastian, Patrick J; Nielsen, Matthew E; Capitanio, Umberto; Jeldres, Claudio; Montorsi, Francesco; Müller, Stefan C; Karam, Jose A; Heukamp, Lukas C; Netto, George; Lerner, Seth P; Sagalowsky, Arthur I; Cote, Richard J

2009-09-01

Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.

Comorbid Conditions in Idiopathic Pulmonary Fibrosis: Recognition and Management

PubMed Central

Oldham, Justin M.; Collard, Harold R.

2017-01-01

Idiopathic pulmonary fibrosis (IPF), a fibrosing interstitial pneumonia of unknown etiology, primarily affects older adults and leads to a progressive decline in lung function and quality of life. With a median survival of 3–5 years, IPF is the most common and deadly of the idiopathic interstitial pneumonias. Despite the poor survivorship, there exists substantial variation in disease progression, making accurate prognostication difficult. Lung transplantation remains the sole curative intervention in IPF, but two anti-fibrotic therapies were recently shown to slow pulmonary function decline and are now approved for the treatment of IPF in many countries around the world. While the approval of these therapies represents an important first step in combatting of this devastating disease, a comprehensive approach to diagnosing and treating patients with IPF remains critically important. Included in this comprehensive assessment is the recognition and appropriate management of comorbid conditions. Though IPF is characterized by single organ involvement, many comorbid conditions occur within other organ systems. Common cardiovascular processes include coronary artery disease and pulmonary hypertension (PH), while gastroesophageal reflux and hiatal hernia are the most commonly encountered gastrointestinal disorders. Hematologic abnormalities appear to place patients with IPF at increased risk of venous thromboembolism, while diabetes mellitus (DM) and hypothyroidism are prevalent metabolic disorders. Several pulmonary comorbidities have also been linked to IPF, and include emphysema, lung cancer, and obstructive sleep apnea. While the treatment of some comorbid conditions, such as CAD, DM, and hypothyroidism is recommended irrespective of IPF, the benefit of treating others, such as gastroesophageal reflux and PH, remains unclear. In this review, we highlight common comorbid conditions encountered in IPF, discuss disease-specific diagnostic modalities, and review the current state of treatment data for several key comorbidities. PMID:28824912

Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

PubMed Central

Kümler, Iben; Knoop, Ann S; Jessing, Christina A R; Ejlertsen, Bent; Nielsen, Dorte L

2016-01-01

Background Endocrine therapy constitutes a central modality in the treatment of oestrogen receptor (ER)-positive advanced breast cancer. Purpose To evaluate the evidence for endocrine treatment in postmenopausal patients with advanced breast cancer focusing on the aromatase inhibitors, letrozole, anastrozole, exemestane and fulvestrant. Methods A review was carried out using PubMed. Randomised phase II and III trials reporting on ≥100 patients were included. Results 35 trials met the inclusion criteria. If not used in the adjuvant setting, a non-steroid aromatase inhibitor was the optimal first-line option. In general, the efficacy of the different aromatase inhibitors and fulvestrant was similar in tamoxifen-refractory patients. A randomised phase II trial of palbociclib plus letrozole versus letrozole alone showed significantly increased progression-free survival (PFS) when compared with endocrine therapy alone in the first-line setting (20.2 vs 10.2 months). Furthermore, the addition of everolimus to exemestane in the Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) study resulted in an extension of median PFS by 4.5 months after recurrence/progression on a non-steroid aromatase inhibitor. However, overall survival was not significantly increased. Conclusion Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin-dependent kinase 4/6 (CDK4/6) inhibition might represent substantial advances for selected patients in some specific settings. However, there is an urgent need for prospective biomarker-driven trials to identify patients for whom these treatments are cost-effective. PMID:27843622

Fetal transesophageal echocardiography: clinical introduction as a monitoring tool during cardiac intervention in a human fetus.

PubMed

Kohl, T; Müller, A; Tchatcheva, K; Achenbach, S; Gembruch, U

2005-12-01

Because of insufficient imaging by maternal transabdominal fetal echocardiography (TAE) in a human fetus with aortic atresia, imperforate atrial septum and progressive cardiac failure, we assessed the feasibility of fetal transesophageal echocardiography (TEE) as a monitoring tool during fetal cardiac intervention at 24 + 6 weeks of gestation. Percutaneous fetoscopic intraesophageal deployment of the ultrasound catheter was achieved and did not result in any maternal or fetal complications. Fetal TEE permitted substantially clearer definition of fetal cardiac anatomy and intracardiac device manipulations than conventional maternal TAE. Despite the employment of various devices, no sufficiently large opening could be achieved within the atrial septum. Although the fetus tolerated the procedure remarkably well and satisfactory fetoplacental flow could be documented at the end of the procedure, the fetus died from progressive cardiac failure 3 days after the intervention. Fetoscopic TEE is feasible in the human fetus and permits substantially clearer definition of fetal cardiac anatomy and intracardiac manipulations than conventional maternal TAE. Based on the observation of spontaneous closure of multiple iatrogenic perforations of the atrial septum, specialized devices are required in order to improve the technical success rate of septoplasty methods and hence the survival odds of these high-risk patients.

Natural orifice translumenal endoscopic surgery: Progress in humans since white paper

PubMed Central

Santos, Byron F; Hungness, Eric S

2011-01-01

Since the first description of the concept of natural orifice translumenal endoscopic surgery (NOTES), a substantial number of clinical NOTES reports have appeared in the literature. This editorial reviews the available human data addressing research questions originally proposed by the white paper, including determining the optimal method of access for NOTES, developing safe methods of lumenal closure, suturing and anastomotic devices, advanced multitasking platforms, addressing the risk of infection, managing complications, addressing challenges with visualization, and training for NOTES procedures. An analysis of the literature reveals that so far transvaginal access and closure appear to be the most feasible techniques for NOTES, with a limited, but growing transgastric, transrectal, and transesophageal NOTES experience in humans. The theoretically increased risk of infection as a result of NOTES procedures has not been substantiated in transvaginal and transgastric procedures so far. Development of suturing and anastomotic devices and advanced platforms for NOTES has progressed slowly, with limited clinical data on their use so far. Data on the optimal management and incidence of intraoperative complications remain sparse, although possible factors contributing to complications are discussed. Finally, this editorial discusses the likely direction of future NOTES development and its possible role in clinical practice. PMID:21483624

Straight A's: Public Education Policy and Progress. Volume 10, Number 21

ERIC Educational Resources Information Center

Alliance for Excellent Education, 2010

2010-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) Divided We Stall?: Prospects for Education Reform Unclear After Republicans Take Control in the House of Representatives, Gain…

The Community College and International Education: A Report of Progress. Volume II.

ERIC Educational Resources Information Center

Fersh, Seymour, Ed.; Greene, William, Ed.

Designed to highlight the progress made by community colleges in the United States in the area of international education, this report presents a collection of materials representing various state and institutional initiatives and efforts. Part I contains articles by Hugh Adams and William Greene, and Maxwell King and Seymour Fersh that provide a…

Results from the Fourth Mathematics Assessment of the National Assessment of Educational Progress.

ERIC Educational Resources Information Center

Lindquist, Mary Montgomery, Ed.

The National Assessment of Educational Progress (NAEP) completed its fourth mathematics assessment during the 1985-86 school year and finished the analyses of the results in 1988. This monograph, prepared by an interpretive team of the National Council of Teachers of Mathematics, represents a comprehensive discussion of the results of the fourth…

The Effect of Daily Progress Reports on Parental Academic Support: Paper versus Electronic Communication

ERIC Educational Resources Information Center

Schneider, Jonathan D.

2016-01-01

In this age of data based decision making and accountability, parent involvement and data collection are paramount. This study represents a significant contribution to educational research by extending the understanding of home-school communication media with specific regard to daily progress reports. The purpose of this study was to compare…

STAGE-DEPENDENCE, SEASONAL CHANGES AND EFFECTS OF CADMIUM ON CELL CYCLE AND APOPTOTIC ACTIVITIES DURING THE SPERMATOGENIC PROGRESSION IN THE DOGFISH SHARK (SQUALUS ACANTHIAS). (R825434)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Science Framework for the 2009 National Assessment of Educational Progress

ERIC Educational Resources Information Center

National Assessment Governing Board, 2008

2008-01-01

This document sets forth recommendations for the design of a new science assessment. The assessment resulting from this framework will start a new NAEP science trend (i.e., measure of student progress in science) beginning in 2009. This framework represents a unique opportunity to build on previous NAEP science work as well as key developments in…

Current approaches to myopia control.

PubMed

Leo, Seo Wei

2017-05-01

Myopia is a global problem, being particularly prevalent in the urban areas of east and southeast Asia. In addition to the direct economic and social burdens, associated ocular complications may lead to substantial vision loss. With prevalence of myopia above 80% and high myopia over 20%, it is crucial to control myopia. The aim of this review to is provide an update on the interventions to slow the onset of myopia and retard its progression. The epidemic of myopia is characterized by increasingly early onset, combined with high myopia progression rates. There are two pathways for myopia control: firstly to slow the onset of myopia and secondly to reduce or prevent progression. Increased time outdoors can reduce the onset of myopia. Atropine 0.01% dose offers an appropriate risk-benefit ratio, with no clinically significant visual side effects balanced against a significant 50% reduction in myopia progression. Orthokeratology contact lenses can slow axial length elongation, but infective keratitis is a risk. Peripheral defocussing lenses may both have a role in slowing myopic progression in a subset of children and further help our understanding of the physiologic control of ocular growth. Myopia control can be achieved by slowing the onset of myopia, which now appears to be possible through increasing time outdoors and slowing the progression of myopia with interventions like atropine and orthokeratology.

Emergency Medicine

PubMed Central

Binder, Louis S.; Chappell, James A.

1991-01-01

The Scientific Board of the California Medical Association presents the following inventory of items of progress in emergency medicine. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in emergency medicine that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Emergency Medicine of the California Medical Association, and the summaries were prepared under its direction. PMID:1949777

Can a poverty-reducing and progressive tax and transfer system hurt the poor?

PubMed

Higgins, Sean; Lustig, Nora

2016-09-01

To analyze anti-poverty policies in tandem with the taxes used to pay for them, comparisons of poverty before and after taxes and transfers are often used. We show that these comparisons, as well as measures of horizontal equity and progressivity, can fail to capture an important aspect: that a substantial proportion of the poor are made poorer (or non-poor made poor) by the tax and transfer system. We illustrate with data from seventeen developing countries: in fifteen, the fiscal system is poverty-reducing and progressive, but in ten of these at least one-quarter of the poor pay more in taxes than they receive in transfers. We call this fiscal impoverishment, and axiomatically derive a measure of its extent. An analogous measure of fiscal gains of the poor is also derived, and we show that changes in the poverty gap can be decomposed into our axiomatic measures of fiscal impoverishment and gains.

Contributions of Peer Support to Health, Health Care, and Prevention: Papers from Peers for Progress.

PubMed

Fisher, Edwin B; Ayala, Guadalupe X; Ibarra, Leticia; Cherrington, Andrea L; Elder, John P; Tang, Tricia S; Heisler, Michele; Safford, Monika M; Simmons, David

2015-08-01

SUBSTANTIAL: evidence documents the benefits of peer support provided by community health workers, lay health advisors, promotores de salud, and others. The papers in this supplement, all supported by the Peers for Progress program of the American Academy of Family Physicians Foundation, contribute to the growing body of literature addressing the efficacy, effectiveness, feasibility, reach, sustainability, and adoption of peer support for diabetes self-management. They and additional papers supported by Peers for Progress contribute to understanding how peer support can be implemented in real world settings. Topics include examination of the peers who provide peer support, reaching the hardly reached, success factors in peer support interventions, proactive approaches, attention to emotions, peer support in behavioral health, dissemination models and their application in China, peer support in the patient-centered medical home, research challenges, and policy implications. © 2015 Annals of Family Medicine, Inc.

Innovations and Challenges in Reducing Maternal Mortality in Tamil Nadu, India

PubMed Central

Padmanaban, P.; Mavalankar, Dileep V.

2009-01-01

Although India has made slow progress in reducing maternal mortality, progress in Tamil Nadu has been rapid. This case study documents how Tamil Nadu has taken initiatives to improve maternal health services leading to reduction in maternal morality from 380 in 1993 to 90 in 2007. Various initiatives include establishment of maternal death registration and audit, establishment and certification of comprehensive emergency obstetric and newborn-care centres, 24-hour x 7-day delivery services through posting of three staff nurses at the primary health centre level, and attracting medical officers to rural areas through incentives in terms of reserved seats in postgraduate studies and others. This is supported by the better management capacity at the state and district levels through dedicated public-health officers. Despite substantial progress, there is some scope for further improvement of quality of infrastructure and services. The paper draws out lessons for other states and countries in the region. PMID:19489416

Data reduction procedures for traffic signal systems performance measures.

DOT National Transportation Integrated Search

2011-01-01

Traffic signal systems represent a substantial component of the highway transportation network in the United States. It is challenging for most agencies to find engineering resources to properly update signal policies and timing plans to accommodate ...

76 FR 63533 - Establishing an Emergency Board to Investigate Disputes Between Certain Railroads Represented by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-12

... by the National Mediation Board that in its judgment these disputes threaten substantially to... upon the Board's termination shall be maintained in the physical custody of the National Mediation...

Accounting for water quality in monitoring access to safe drinking-water as part of the Millennium Development Goals: lessons from five countries

PubMed Central

Bain, Rob ES; Wright, Jim A; Yang, Hong; Pedley, Steve; Bartram, Jamie K

2012-01-01

Abstract Objective To determine how data on water source quality affect assessments of progress towards the 2015 Millennium Development Goal (MDG) target on access to safe drinking-water. Methods Data from five countries on whether drinking-water sources complied with World Health Organization water quality guidelines on contamination with thermotolerant coliform bacteria, arsenic, fluoride and nitrates in 2004 and 2005 were obtained from the Rapid Assessment of Drinking-Water Quality project. These data were used to adjust estimates of the proportion of the population with access to safe drinking-water at the MDG baseline in 1990 and in 2008 made by the Joint Monitoring Programme for Water Supply and Sanitation, which classified all improved sources as safe. Findings Taking account of data on water source quality resulted in substantially lower estimates of the percentage of the population with access to safe drinking-water in 2008 in four of the five study countries: the absolute reduction was 11% in Ethiopia, 16% in Nicaragua, 15% in Nigeria and 7% in Tajikistan. There was only a slight reduction in Jordan. Microbial contamination was more common than chemical contamination. Conclusion The criterion used by the MDG indicator to determine whether a water source is safe can lead to substantial overestimates of the population with access to safe drinking-water and, consequently, also overestimates the progress made towards the 2015 MDG target. Monitoring drinking-water supplies by recording both access to water sources and their safety would be a substantial improvement. PMID:22461718

Pakistan and the Millennium Development Goals for Maternal and Child Health: progress and the way forward.

PubMed

Rizvi, Arjumand; Bhatti, Zaid; Das, Jai K; Bhutta, Zulfiqar A

2015-04-03

The world has made substantial progress in reducing maternal and child mortality, but many countries are projected to fall short of achieving their Millennium Development Goals (MDGs) 4 and 5 targets. The major objective of this paper is to examine progress in Pakistan in reducing maternal and child mortality and malnutrition over the last two decades. Data from recent national and international surveys suggest that Pakistan lags behind on all of its MDGs related to maternal and child health and, for some indicators especially related to nutrition, the situation has worsened from the baseline of 1990. Progress in addressing key social determinants such as poverty, female education and empowerment has also been slow and unregulated population growth has further compromised progress. There is a need to integrate the various different sectors and programmes to achieve the desired results effectively and efficiently as many of the determinants and influencing factors are outside the health sector. Pakistan has to accelerate improvement of access to maternal health services, particularly contraception, emergency obstetric care and skilled birth attendance; the need to improve maternal and child nutrition cannot be over-emphasised.

Antiretroviral treatment scale-up among persons living with HIV in Kenya: results from a nationally representative survey.

PubMed

Odhiambo, Jacob O; Kellogg, Timothy A; Kim, Andrea A; Ng'ang'a, Lucy; Mukui, Irene; Umuro, Mamo; Mohammed, Ibrahim; De Cock, Kevin M; Kimanga, Davies O; Schwarcz, Sandra

2014-05-01

In 2007, 29% of HIV-infected Kenyans in need of antiretroviral therapy (ART), based on an immunologic criterion of CD4 ≤350 cells per microliter, were receiving ART. Since then, substantial treatment scale-up has occurred in the country. We analyzed data from the second Kenya AIDS Indicator Survey (KAIS 2012) to assess progress of treatment scale-up in Kenya. KAIS 2012 was a nationally representative survey of persons aged 18 months to 64 years that collected information on HIV status, care, and treatment. ART eligibility was defined based on 2 standards: (1) 2011 Kenya eligibility criteria for ART initiation: CD4 ≤350 cells per microliter or co-infection with active tuberculosis and (2) 2013 World Health Organization (WHO) eligibility criteria for ART initiation: CD4 ≤500 cells per microliter, co-infection with active tuberculosis, currently pregnant or breastfeeding, and infected partners in serodiscordant relationships. Blood specimens were tested for HIV antibodies and HIV-positive specimens tested for CD4 cell counts. Among 13,720 adults and adolescents aged 15-64 years, 11,626 provided a blood sample, and 648 were HIV infected. Overall, 58.8% [95% confidence interval (CI): 52.0 to 65.5) were eligible for treatment using the 2011 Kenya eligibility criteria and 77.4% (95% CI: 72.4 to 82.4) using the 2013 WHO eligibility criteria. Coverage of ART was 60.5% (95% CI: 50.8 to 70.2) using the 2011 Kenya eligibility criteria and 45.9% (95% CI: 37.7 to 54.2) using the 2013 WHO eligibility criteria. ART coverage has increased from 29% in 2007 to 61% in 2012. If Kenya adopts the 2013 WHO guidelines for ART initiation, need for ART increases by an additional 19 percentage points and current coverage decreases by an additional 15 percentage points, representing an additional 214,000 persons who will need to be reached.

Slowly progressive aphasia associated with surface dyslexia.

PubMed

Chiacchio, L; Grossi, D; Stanzione, M; Trojano, L

1993-03-01

We report an Italian patient affected by slowly progressive aphasia (SPA) lasting since four years when he first came to our observation. During the successive four years, we documented a progressive language decline resembling transcortical sensory aphasia, associated with a reading disorder corresponding to surface dyslexia, a form extremely rare in patients with native transparent language. His performance at standard intelligence tasks remained in the normal range, without any variation. CT scan showed left temporal atrophy. We emphasize the heterogeneity of the syndrome of SPA and suggest that it can represent one of the pictures of focal cortical degenerative disease, with variable onset, progression, and evolution.

The important role of public-sector research in the United States.

PubMed

2013-02-01

Between 1970 and 2009, US public institutions participated in the research and development of 153 drugs, including 15 vaccines. Between 1990 and 2007, nearly 10% of all the new drugs and vaccines marketed in the US and about 20% of those representing a therapeutic advance originated in public institutions. The proportion of these drugs that represented a substantial therapeutic advance was over twice that of those produced exclusively by the private sector.

Cancer cachexia: understanding the molecular basis.

PubMed

Argilés, Josep M; Busquets, Sílvia; Stemmler, Britta; López-Soriano, Francisco J

2014-11-01

Cancer cachexia is a devastating, multifactorial and often irreversible syndrome that affects around 50-80% of cancer patients, depending on the tumour type, and that leads to substantial weight loss, primarily from loss of skeletal muscle and body fat. Since cachexia may account for up to 20% of cancer deaths, understanding the underlying molecular mechanisms is essential. The occurrence of cachexia in cancer patients is dependent on the patient response to tumour progression, including the activation of the inflammatory response and energetic inefficiency involving the mitochondria. Interestingly, crosstalk between different cell types ultimately seems to result in muscle wasting. Some of the recent progress in understanding the molecular mechanisms of cachexia may lead to new therapeutic approaches.

Recent advances in anti-neutrophil cytoplasmic antibody-associated vasculitis

PubMed Central

Lazarus, B.; John, G. T.; O’Callaghan, C.; Ranganathan, D.

2016-01-01

Anti-neutrophil cytoplasmic antibody-associated vasculitis is an uncommon inflammatory disease of small to medium-sized vessels that frequently presents with rapidly progressive glomerulonephritis and renal failure though it can affect any organ system. If untreated, the vast majority of patients will die within a year. Current treatments improve prognosis but affected patients remain at a substantially higher risk of death and adverse outcomes. We review the classification of the disease, our understanding of the pathogenesis and epidemiology, and propose future directions for research. We also evaluate the evidence supporting established treatment regimens and the progress of clinical trials for newer treatments to inform the design of future studies. PMID:27051131

Potential use of Plastic Waste as Construction Materials: Recent Progress and Future Prospect

NASA Astrophysics Data System (ADS)

Kamaruddin, M. A.; Abdullah, M. M. A.; Zawawi, M. H.; Zainol, M. R. R. A.

2017-11-01

Plastic associates products based have been considered as the world most consumer packaging solution. However, substantial quantities of plastic consumption have led to exponential increase of plastic derived waste. Recycling of plastic waste as valued added product such as concrete appears as one of promising solution for alternative use of plastic waste. This paper summarized recent progress on the development of concrete mixture which incorporates plastic wastes as partial aggregate replacement during concrete manufacturing. A collection of data from previous studies that have been researched which employed plastic waste in concrete mixtures were evaluated and conclusions are drawn based on the laboratory results of all the mentioned research papers studied.

Microfluidic technology for molecular diagnostics.

PubMed

Robinson, Tom; Dittrich, Petra S

2013-01-01

Molecular diagnostics have helped to improve the lives of millions of patients worldwide by allowing clinicians to diagnose patients earlier as well as providing better ongoing therapies. Point-of-care (POC) testing can bring these laboratory-based techniques to the patient in a home setting or to remote settings in the developing world. However, despite substantial progress in the field, there still remain many challenges. Progress in molecular diagnostics has benefitted greatly from microfluidic technology. This chapter aims to summarise the more recent advances in microfluidic-based molecular diagnostics. Sections include an introduction to microfluidic technology, the challenges of molecular diagnostics, how microfluidic advances are working to solve these issues, some alternative design approaches, and detection within these systems.

Persistent high-risk human papillomavirus (HPV) infections as surrogate endpoints of progressive cervical disease. Potential new endpoint for efficacy studies with new-generation (non-HPV 16/18) prophylactic HPV vaccines.

PubMed

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.

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression.

PubMed

Kiguoya, Marion W; Mann, Jaclyn K; Chopera, Denis; Gounder, Kamini; Lee, Guinevere Q; Hunt, Peter W; Martin, Jeffrey N; Ball, T Blake; Kimani, Joshua; Brumme, Zabrina L; Brockman, Mark A; Ndung'u, Thumbi

2017-07-01

There are marked differences in the spread and prevalence of HIV-1 subtypes worldwide, and differences in clinical progression have been reported. However, the biological reasons underlying these differences are unknown. Gag-protease is essential for HIV-1 replication, and Gag-protease-driven replication capacity has previously been correlated with disease progression. We show that Gag-protease replication capacity correlates significantly with that of whole isolates ( r = 0.51; P = 0.04), indicating that Gag-protease is a significant contributor to viral replication capacity. Furthermore, we investigated subtype-specific differences in Gag-protease-driven replication capacity using large well-characterized cohorts in Africa and the Americas. Patient-derived Gag-protease sequences were inserted into an HIV-1 NL4-3 backbone, and the replication capacities of the resulting recombinant viruses were measured in an HIV-1-inducible reporter T cell line by flow cytometry. Recombinant viruses expressing subtype C Gag-proteases exhibited substantially lower replication capacities than those expressing subtype B Gag-proteases ( P < 0.0001); this observation remained consistent when representative Gag-protease sequences were engineered into an HIV-1 subtype C backbone. We identified Gag residues 483 and 484, located within the Alix-binding motif involved in virus budding, as major contributors to subtype-specific replicative differences. In East African cohorts, we observed a hierarchy of Gag-protease-driven replication capacities, i.e., subtypes A/C < D < intersubtype recombinants ( P < 0.0029), which is consistent with reported intersubtype differences in disease progression. We thus hypothesize that the lower Gag-protease-driven replication capacity of subtypes A and C slows disease progression in individuals infected with these subtypes, which in turn leads to greater opportunity for transmission and thus increased prevalence of these subtypes. IMPORTANCE HIV-1 subtypes are unevenly distributed globally, and there are reported differences in their rates of disease progression and epidemic spread. The biological determinants underlying these differences have not been fully elucidated. Here, we show that HIV-1 Gag-protease-driven replication capacity correlates with the replication capacity of whole virus isolates. We further show that subtype B displays a significantly higher Gag-protease-mediated replication capacity than does subtype C, and we identify a major genetic determinant of these differences. Moreover, in two independent East African cohorts we demonstrate a reproducible hierarchy of Gag-protease-driven replicative capacity, whereby recombinants exhibit the greatest replication, followed by subtype D, followed by subtypes A and C. Our data identify Gag-protease as a major determinant of subtype differences in disease progression among HIV-1 subtypes; furthermore, we propose that the poorer viral replicative capacity of subtypes A and C may paradoxically contribute to their more efficient spread in sub-Saharan Africa. Copyright © 2017 American Society for Microbiology.

EOTAXIN REPRESENTS THE PRINCIPAL EOSINOPHIL CHEMOATTRACTANT IN A NOVEL MURINE ASTHMA MODEL INDUCED BY HOUSE DUST CONTAINING COCKROACH ALLERGENS. (R826710)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Nanotechnology for forest products. Part 1

Treesearch

Theodore Wegner; Phil Jones

2005-01-01

Nano-sized particles may be small, but for our industry they offer huge potential. Nanotechnology represents a major opportunity for the forest products industry to develop new products, substantially reduce processing costs, and open new markets in the coming decades.

Commuter choice managers and parking managers coordination

DOT National Transportation Integrated Search

2002-11-01

Shared use park and ride represents a unique approach for addressing parking problems, and can offer substantial savings in land and development costs. One of the fundamental factors that determines the success of this approach is the level of coordi...

Simulation of Flight-Type Engine Fan Noise in the NASA-Lewis 9X15 Anechoic Wind Tunnel

NASA Technical Reports Server (NTRS)

Heidmann, M. F.; Dietrich, D. A.

1976-01-01

Flight type noise as contrasted to the usual ground static test noise exhibits substantial reductions in the time unsteadiness of tone noise, and in the mean level of tones calculated to be nonpropagating or cut-off. A model fan designed with cuttoff of the fundamental tone was acoustically tested in the anechoic wind tunnel under both static and tunnel flow conditions. The properties that characterize flight type noise were progressively simulated with increasing tunnel flow. The distinctly lobed directivity pattern of propagating rotor/stator interaction modes was also observed. Excess noise attributed to the ingestion of the flow disturbances that prevail near most static test facilities is substantially reduced with tunnel flow.

Ability Grouping in English Secondary School: Effects on Attainment in English, Mathematics, and Science.

ERIC Educational Resources Information Center

Ireson, Judith; Hallam, Susan; Hack, Sarah; Clark, Helen; Plewis, Ian

2002-01-01

Studied the impact of ability grouping on attainment in a cohort of year-9 students in 45 mixed secondary schools in England representing a variety of grouping practices. In mathematics, students at higher levels by year 6 make more progress in sets, but those in lower levels make more progress in mixed ability classes. Discusses educational…

Evanston Women in the Progressive Era: Women Performed Social Work Representative of National Concerns.

ERIC Educational Resources Information Center

Fisher, Darlene Emmert

1986-01-01

Intended as an example of the kind of material that a student doing research on the Progressive Era might find at a local historical society or in the files of a hometown or city newspaper, this article details the philanthropic efforts of women living in the Chicago area in the early 1900s. (JDH)

A Learning Progression for Geometrical Measurement in One, Two, and Three Dimensions. Research Report. ETS RR-17-55

ERIC Educational Resources Information Center

Kim, Eun Mi; Haberstroh, Jeff; Peters, Stephanie; Howell, Heather; Olah, Leslie Nabors

2017-01-01

As part of the CBAL® learning and assessment initiative in mathematics, we developed a hypothesized learning progression (LP) for geometrical measurement in 1, 2, and 3 dimensions based on a synthesis of empirical literature in this field and through expert review. The geometrical measurement LP is intended to represent a developmental progression…

The Nation's Report Card: Science 2011. National Assessment of Educational Progress at Grade 8. NCES 2012-465

ERIC Educational Resources Information Center

National Center for Education Statistics, 2012

2012-01-01

This report presents results of the National Assessment of Educational Progress (NAEP) U.S. science assessment in 2011. A representative sample of 122,000 eighth-graders participated in the 2011 NAEP science assessment, which is designed to measure students' knowledge and abilities in the areas of physical science, life science, and Earth and…

Progress Report Phase I: Use, access, and fire/fuels management attitudes and preferences of user groups concerning the Valles Caldera National Preserve (VCNP) and adjacent areas

Treesearch

Kurt F. Anschuetz; Carol B. Raish

2010-01-01

This document represents a progress report of activities completed during Phase I of the study titled, Use, Access, and Fire/Fuels Management Attitudes and Preferences of User Groups Concerning the Valles Caldera National Preserve (VCNP) and Adjacent Areas, and the preliminary findings of this work.

Improved heavy-duty vehicle fuel efficiency in India, benefits, costs and environmental impacts

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

Gopal, Anand R.; Karali, Nihan; Sharpe, Ben

The main objectives of this analysis are to examine the benefits and costs of fuel-saving technologies for new heavy-duty vehicles (HDVs) in India over the next 10 years and, to explore how various scenarios for the deployment of vehicles with these technologies will impact petroleum consumption and carbon dioxide (CO 2) emissions over the next three decades. The study team developed simulation models for three representative HDV types—a 40-tonne tractor-trailer, 25-tonne rigid truck, and 16-tonne transit bus—based on top-selling vehicle models in the Indian market. The baseline technology profiles for all three vehicles were developed using India-specific engine data andmore » vehicle specification information from manufacturer literature and input from industry experts. For each of the three vehicles we developed a comprehensive set of seven efficiency technology packages drawing from five major areas: engine, transmission and driveline, tires, aerodynamics, and weight reduction. Our analysis finds that India has substantial opportunity to improve HDV fuel efficiency levels using cost-effective technologies. Results from our simulation modeling of three representative HDV types—a tractor-trailer, rigid truck, and transit bus—reveal that per-vehicle fuel consumption reductions between roughly 20% and 35% are possible with technologies that provide a return on the initial capital investment within 1 to 2 years. Though most of these technologies are currently unavailable in India, experiences in other more advanced markets such as the US and EU suggest that with sufficient incentives and robust regulatory design, significant progress can be made in developing and deploying efficiency technologies that can provide real-world fuel savings for new commercial vehicles in India over the next 10 years. Bringing HDVs in India up to world-class technology levels will yield substantial petroleum and GHG reductions. By 2030, the fuel and CO2 reductions of the scenarios range from 10% to 34%, and at the end of 2050, these reductions grow to 13% and 41%. If we constrain the analysis to select the most efficient technology package that provides the fleets with payback times of 3 years or less, there are annual fleet-wide savings of roughly 11 MTOE of diesel and 34 MMT of CO 2 in 2030, and this grows to 31 MTOE and 97 MMT by 2050.« less

Multi-Scale Hierarchical and Topological Design of Structures for Failure Resistance

DTIC Science & Technology

2013-10-04

materials, simulation, 3D printing , advanced manufacturing, design, fracture Markus J. Buehler Massachusetts Institute of Technology (MIT) 77...by Mineralized Natural Materials: Computation, 3D printing , and Testing, Advanced Functional Materials, (09 2013): 0. doi: 10.1002/adfm.201300215 10...have made substantial progress. Recent work focuses on the analysis of topological effects of composite design, 3D printing of bioinspired and

Analyzing Turkey's Data from TIMSS 2007 to Investigate Regional Disparities in Eighth Grade Science Achievement

ERIC Educational Resources Information Center

Erberber, Ebru

2009-01-01

Turkey is expected to be a full member of the European Union (EU) by 2013. In the course of its integration into the EU, Turkey has been simultaneously facing access, quality, and equity issues in education. Over the past decade, substantial progress has been made on increasing the access. However, improving the country's low level of education…

From Fancy to Reason: Scaling Deaf and Hearing Children's Understanding of Theory of Mind and Pretence

ERIC Educational Resources Information Center

Peterson, Candida C.; Wellman, Henry M.

2009-01-01

We examined deaf and hearing children's progression of steps in theory of mind (ToM) development including their understanding of social pretending. Ninety-three children (33 deaf; 60 hearing) aged 3-13 years were tested on a set of six closely matched ToM tasks. Results showed that deaf children were delayed substantially behind hearing children…

NAEP Validity Studies: Improving the Information Value of Performance Items in Large Scale Assessments. Working Paper No. 2003-08

ERIC Educational Resources Information Center

Pearson, P. David; Garavaglia, Diane R.

2003-01-01

The purpose of this essay is to explore both what is known and what needs to be learned about the information value of performance items "when they are used in large scale assessments." Within the context of the National Assessment of Educational Progress (NAEP), there is substantial motivation for answering these questions. Over the…

Karhunen-Loeve Analysis of SCIGN GPS Data

NASA Technical Reports Server (NTRS)

Rundle, John B.; Tiampo, Kristy; Gross, Susanna

2004-01-01

During the final year of this project, we made substantial progress on the proposed work. Specifically, we have continued the horizontal and vertical Karhunen-Loeve (KL) analysis of SCIGN data and implemented the study of a number of particular modes. In particular, we studied the spatial and temporal interactions of these modes in an effort to better understand and model the source of each signal.

Structural Integrity of Water Reactor Pressure Boundary Components.

DTIC Science & Technology

1979-12-31

fatigue crack growth is also on-going. Substantial progress in all three of the areas - fatigue data generation, fractography and micromechanism... Fractographie Examinations During the past year, there have been several fractographic studies and fractographically-related research efforts which have been...in the T-L orientation were characterized by a m icrostructural texture running parallel to the macroscopic crack propagation direction (Fig. 31). This

In vivo testing of chemicals that undergo substantial biotransformation: An opportunity to advance in vitro-in vivo metabolism extrapolation procedures for fish

EPA Science Inventory

This is one of several keynote presentations given at the beginning of a one-day workshop on in vivo testing with fish. The purpose of this talk is to describe recent progress on using in vitro data to predict metabolism impacts on chemical accumulation by fish. The focus of th...

Missing data in forest ecology and management: advances in quantitative methods [Preface

Treesearch

Tara Barrett; Matti Maltomo

2012-01-01

In recent years, substantial progress has been made for handling missing data issues for applications in forest ecology and management, particularly in the area of imputation techniques. A session on this topic was held at the XXlll IUFRO World Congress in Seoul, South Korea, on August 23-28, 2010, resulting in this special issue of six papers that address recent...

Status of silicon solar cell technology

NASA Technical Reports Server (NTRS)

Brandhorst, H. W., Jr.

1976-01-01

Major progress in solar cell technology leading to increased efficiency has occurred since 1970. Technical approaches leading to this increased output include surface texturing, improved antireflection coatings, reduced grid pattern area coverage, shallow junctions and back surface fields. The status of these developments and their incorporation into cell production is discussed. Future research and technology trends leading to further efficiency increases and substantial cost reductions are described.

Dental Caries Progression Among U.S. Marine Corps Personnel Following Operational Deployment

DTIC Science & Technology

2012-06-01

86 dental faculty members at 16 French universities, Tubert- Jeannin and colleagues37 found wide variation in restorative treatment thresholds...lesions, assessment of restorations, and treatment decisions, which ultimately led to variation in their 27     students’ treatment modalities...almost one-third of all teeth. This substantial variation among practitioners is most likely due to differences in individual practitioners’ criteria

The Relationship between Gross Motor Skills and School Readiness in Early Childhood: Making the Case in South Africa

ERIC Educational Resources Information Center

Sherry, Kate; Draper, Catherine E.

2013-01-01

Early childhood development (ECD) has gained substantial recognition in South Africa (SA) as a key issue to be addressed, but inequities and deficits remain evident, despite progressive policy and widespread effort by a range of role players in the non-governmental sector. ECD in SA requires far more attention if these are to be rectified, and…

Discovery of somatic mutations in the progression of chronic myeloid leukemia by whole-exome sequencing.

PubMed

Huang, Y; Zheng, J; Hu, J D; Wu, Y A; Zheng, X Y; Liu, T B; Chen, F L

2014-02-19

We performed whole-exome sequencing in samples representing accelerated phase (AP) and blastic crisis (BC) in a subject with chronic myeloid leukemia (CML). A total of 12.74 Gb clean data were generated, achieving a mean depth coverage of 64.45 and 69.53 for AP and BC samples, respectively, of the target region. A total of 148 somatic variants were detected, including 76 insertions and deletions (indels), 64 single-nucleotide variations (SNV), and 8 structural variations (SV). On the basis of annotation and functional prediction analysis, we identified 3 SNVs and 6 SVs that showed a potential association with CML progression. Among the genes that harbor the identified variants, GATA2 has previously been reported to play important roles in the progression from AP to BC in CML. Identification of these genes will allow us to gain a better understanding of the pathological mechanism of CML and represents a critical advance toward new molecular diagnostic tests for the development of potential therapies for CML.

In-situ fault detection apparatus and method for an encased energy storing device

DOEpatents

Hagen, Ronald A.; Comte, Christophe; Knudson, Orlin B.; Rosenthal, Brian; Rouillard, Jean

2000-01-01

An apparatus and method for detecting a breach in an electrically insulating surface of an electrically conductive power system enclosure within which a number of series connected energy storing devices are disposed. The energy storing devices disposed in the enclosure are connected to a series power connection. A detector is coupled to the series connection and detects a change of state in a test signal derived from the series connected energy storing devices. The detector detects a breach in the insulating layer of the enclosure by detecting a state change in the test signal from a nominal state to a non-nominal state. A voltage detector detects a state change of the test signals from a nominal state, represented by a voltage of a selected end energy storing device, to a non-nominal state, represented by a voltage that substantially exceeds the voltage of the selected opposing end energy storing device. Alternatively, the detector may comprise a signal generator that produces the test signal as a time-varying or modulated test signal and injects the test signal into the series connection. The detector detects the state change of the time-varying or modulated test signal from a nominal state, represented by a signal substantially equivalent to the test signal, to a non-nominal state, representative by an absence of the test signal.

Rosuvastatin Slows Progression of Subclinical Atherosclerosis in Patients with Treated HIV Infection

PubMed Central

Longenecker, Chris T.; Sattar, Abdus; Gilkeson, Robert; Mccomsey, Grace A.

2016-01-01

Objective To determine the effect of statins on the progression of subclinical atherosclerosis in a population of HIV-infected adults on antiretroviral therapy. Design Double-blind, randomized clinical trial Methods SATURN-HIV was a 96-week double-blind, randomized clinical trial of 10 mg daily rosuvastatin (n=72) versus placebo (n=75) in a population of HIV-infected subjects on stable antiretroviral therapy with LDL-cholesterol ≤130mg/dL (≤3.36mmol/L) and evidence of heightened T-cell activation (CD8+CD38+HLA-DR+ ≥19%) or increased inflammation (high sensitivity C-reactive protein ≥2mg/L (≥19mmol/L)). Change in common carotid artery IMT (CCA-IMT) was the primary outcome. Secondary outcomes were changes in LDL and coronary artery calcium (CAC). Results Median (Q1, Q3) age was 46 (40, 53) years; 78% were male and 68% African American; 49% were on a protease inhibitor. Mean (95% CI) change in LDL was −21 (−27 to −15) mg/dL [−0.54 (−0.70 to −0.39) mmol/L] in the rosuvastatin arm. In a multivariable linear mixed-effects model, assignment to statin was associated with 0.019mm (95% CI: 0.002–0.037mm) less progression of CCA-IMT over 96 weeks. We did not find substantial effect modification by level of inflammation or immune activation biomarkers, except for a borderline statistically significant interaction for soluble vascular cell adhesion molecule (p=0.065). There was no difference in CAC change (p=0.61). Conclusions Rosuvastatin effectively lowers LDL and appears to substantially slow progression of CCA-IMT in patients with treated HIV infection. Future study is needed to determine whether subjects with higher levels of inflammation or immune activation derive greater cardiovascular benefit from statin therapy. PMID:27203715

Nurses' participation in audit: a regional study.

PubMed

Cheater, F M; Keane, M

1998-03-01

To find out to what extent nurses were perceived to be participating in audit, to identify factors thought to impede their involvement, and to assess progress towards multidisciplinary audit. Qualitative. Focus groups and interviews. Chairs of audit groups and audit support staff in hospital, community and primary health care and audit leads in health authorities in the North West Region. In total 99 audit leads/support staff in the region participated representing 89% of the primary health care audit groups, 80% of acute hospitals, 73% of community health services, and 59% of purchasers. Many audit groups remain medically dominated despite recent changes to their structure and organisation. The quality of interprofessional relations, the leadership style of the audit chair, and nurses' level of seniority, audit knowledge, and experience influenced whether groups reflected a multidisciplinary, rather than a doctor centred approach. Nurses were perceived to be enthusiastic supporters of audit, although their active participation in the process was considered substantially less than for doctors in acute and community health services. Practice nurses were increasingly being seen as the local audit enthusiasts in primary health care. Reported obstacles to nurses' participation in audit included hierarchical nurse and doctor relationships, lack of commitment from senior doctors and managers, poor organisational links between departments of quality and audit, work load pressures and lack of protected time, availability of practical support, and lack of knowledge and skills. Progress towards multidisciplinary audit was highly variable. The undisciplinary approach to audit was still common, particularly in acute services. Multidisciplinary audit was more successfully established in areas already predisposed towards teamworking or where nurses had high involvement in decision making. Audit support staff were viewed as having a key role in helping teams to adopt a collaborative approach to audit. Although nurses were undertaking audit, and some were leading developments in their settings, a range of structural and organisational, interprofessional and intraprofessional factors was still impeding progress. If the ultimate goal of audit is to improve patient care, the obstacles that make it difficult for nurses to contribute actively to the process must be acknowledged and considered.

Clinical staging of Fibrodysplasia Ossificans Progressiva (FOP).

PubMed

Pignolo, Robert J; Kaplan, Frederick S

2018-04-01

Fibrodyplasia ossificans progressiva (FOP) is an ultra-rare genetic condition of heterotopic ossification (HO) that results in progressive loss of joint function, ultimately rendering movement impossible. Death is most commonly the result of thoracic insufficiency syndrome, or complications related to recurrent respiratory infections. There are no current treatments for FOP, but early and emerging clinical trials offer hope for this devastating disease. With the recent reporting of a comprehensive global natural history study, scales to assess joint dysfunction, and a more accurate prediction of joint survival, it is now possible to construct a conceptual framework for the clinical staging of FOP. Based on assessment of FOP features in seven areas, it is possible to assign five clinical stages. FOP features include flare-up activity, body regions affected, thoracic insufficiency, other complications, activities of daily living (ADLs), ambulatory status, and the cumulative joint involvement scale (CAJIS) score. Assessments of these features assign an individual with FOP to early/mild, moderate, severe, profound, or late-stage disease. These criteria seek to be flexible enough to be used by clinicians without reliance on advanced imaging or specialized testing, as well as by investigators involved in research or clinical trial studies who would have these tools available. These staging measures for FOP assess the influence of HO and accelerated joint dysfunction (due to congenital abnormalities) on the ability to perform common functional activities, and thus a delay or lack of progression from one stage to the next represents the ultimate test of efficacy for drug trials. This framework will serve both as a prediction tool for FOP progression as well as a critical opportunity to substantiate therapeutic interventions. The staging system proposed here will permit an accurate assessment of severity to appropriately develop or revise clinical plans of care, define operational research criteria, and identify the effectiveness of interventions. Ultimately, this clinical staging will aid the field in moving toward earlier intervention at a stage where disease-modifying therapies may be most efficacious. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimization of offsets and cycle length using high resolution signal event data.

DOT National Transportation Integrated Search

2011-01-01

Traffic signal systems represent a substantial component of the highway transportation network in the United States. It is challenging for most agencies to find engineering resources to properly update signal policies and timing plans to accommodate ...

Procurement procedures and specifications for performance measure capable traffic infrastructure data collection systems.

DOT National Transportation Integrated Search

2012-01-01

Traffic signal systems represent a substantial component of the highway transportation network in the United : States. It is challenging for most agencies to find engineering resources to properly update signal policies and : timing plans to accommod...

Influence of vane sweep on rotor-stator interaction noise

NASA Technical Reports Server (NTRS)

Envia, Edmane; Kerschen, Edward J.

1990-01-01

The influence of vane sweep in rotor-stator interaction noise is investigated. In an analytical approach, the interaction of a convected gust representing the rotor viscous wake, with a cascade of cascade of finite span swept airfoils, representing the stator, is analyzed. The analysis is based on the solution of the exact linearized equations of motion. High frequency convected gusts for which noise generation is concentrated near the leading edge of airfoils is considered. In a preliminary study, the problem of an isolated finite span swept airfoil interacting with a convected gust is analyzed. Results indicate that sweep can substantially reduce the farfield noise levels for a single airfoil. Using the single airfoil model, an approximate solution to the problem of noise radiation from a cascade of finite span swept airfoils interacting with a convected gust is derived. A parametric study of noise generated by gust cascade interaction is carried out to assess the effectiveness of vane sweep in reducing rotor-stator interaction noise. The results show that sweep is beneficial in reducing noise levels. Rotor wake twist or circumferential lean substantially influences the effectiveness of vane sweep. The orientation of vane sweep must be chosen to enhance the natural phase lag caused by wake lean, in which case rather small sweep angles substantially reduce the noise levels.

Influence of vane sweep on rotor-stator interaction noise

NASA Astrophysics Data System (ADS)

Envia, Edmane; Kerschen, Edward J.

1990-12-01

The influence of vane sweep in rotor-stator interaction noise is investigated. In an analytical approach, the interaction of a convected gust representing the rotor viscous wake, with a cascade of cascade of finite span swept airfoils, representing the stator, is analyzed. The analysis is based on the solution of the exact linearized equations of motion. High frequency convected gusts for which noise generation is concentrated near the leading edge of airfoils is considered. In a preliminary study, the problem of an isolated finite span swept airfoil interacting with a convected gust is analyzed. Results indicate that sweep can substantially reduce the farfield noise levels for a single airfoil. Using the single airfoil model, an approximate solution to the problem of noise radiation from a cascade of finite span swept airfoils interacting with a convected gust is derived. A parametric study of noise generated by gust cascade interaction is carried out to assess the effectiveness of vane sweep in reducing rotor-stator interaction noise. The results show that sweep is beneficial in reducing noise levels. Rotor wake twist or circumferential lean substantially influences the effectiveness of vane sweep. The orientation of vane sweep must be chosen to enhance the natural phase lag caused by wake lean, in which case rather small sweep angles substantially reduce the noise levels.

Actinic Keratosis and Non-Invasive Diagnostic Techniques: An Update

PubMed Central

Casari, Alice; Chester, Johanna; Pellacani, Giovanni

2018-01-01

Actinic keratosis represents the earliest manifestation of non-melanoma skin cancer. Because of their risk of progression to invasive squamous cell carcinoma, an earlier diagnosis and treatment are mandatory. Their diagnosis sometimes could represent a challenge even for expert dermatologists. Dermoscopy, confocal laser microscopy and optical coherence tomography could help clinicians in diagnosis. PMID:29316678

Dwindling Numbers of Female Computer Students: What Are We Missing?

ERIC Educational Resources Information Center

Saulsberry, Donna

2012-01-01

There is common agreement among researchers that women are under-represented in both 2-year and 4-year collegiate computer study programs. This leads to women being under-represented in the computer industry which may be limiting the progress of technology developments that will benefit mankind. It may also be depriving women of the opportunity to…

Association between Single Nucleotide Polymorphism of Vitamin D Receptor Gene FokI Polymorphism and Clinical Progress of Benign Prostatic Hyperplasia

PubMed Central

Ruan, Li; Zhu, Jian-guo; Pan, Cong; Hua, Xing; Yuan, Dong-bo; Li, Zheng-ming; Zhong, Wei-de

2015-01-01

Background. The aim of the study was to investigate the association between single nucleotide polymorphism (SNP) of vitamin D receptor (VDR) gene and clinical progress of benign prostatic hyperplasia (BPH) in Chinese men. Methods. The DNA was extracted from blood of 200 BPH patients with operation (progression group) and 200 patients without operation (control group), respectively. The genotypes of VDR gene FokI SNP represented by “F/f” were identified by PCR-restriction fragment length polymorphism. The odds ratio (OR) of having progression of BPH for having the genotype were calculated. Results. Our date indicated that the f alleles of the VDR gene FokI SNP associated with the progression of BPH (P = 0.009). Conclusion. For the first time, our study demonstrated that VDR gene FokI SNP may be associated with the risk of BPH progress. PMID:25685834

Synthesis of monolithic graphene – graphite integrated electronics

PubMed Central

Park, Jang-Ung; Nam, SungWoo; Lee, Mi-Sun; Lieber, Charles M.

2013-01-01

Encoding electronic functionality into nanoscale elements during chemical synthesis has been extensively explored over the past decade as the key to developing integrated nanosystems1 with functions defined by synthesis2-6. Graphene7-12 has been recently explored as a two-dimensional nanoscale material, and has demonstrated simple device functions based on conventional top-down fabrication13-20. However, the synthetic approach to encoding electronic functionality and thus enabling an entire integrated graphene electronics in a chemical synthesis had not previously been demonstrated. Here we report an unconventional approach for the synthesis of monolithically-integrated electronic devices based on graphene and graphite. Spatial patterning of heterogeneous catalyst metals permits the selective growth of graphene and graphite, with controlled number of graphene layers. Graphene transistor arrays with graphitic electrodes and interconnects were formed from synthesis. These functional, all-carbon structures were transferrable onto a variety of substrates. The integrated transistor arrays were used to demonstrate real-time, multiplexed chemical sensing, and more significantly, multiple carbon layers of the graphene-graphite device components were vertically assembled to form a three-dimensional flexible structure which served as a top-gate transistor array. These results represent a substantial progress towards encoding electronic functionality via chemical synthesis and suggest future promise for one-step integration of graphene-graphite based electronics. PMID:22101813

Synthesis of monolithic graphene-graphite integrated electronics.

PubMed

Park, Jang-Ung; Nam, SungWoo; Lee, Mi-Sun; Lieber, Charles M

2011-11-20

Encoding electronic functionality into nanoscale elements during chemical synthesis has been extensively explored over the past decade as the key to developing integrated nanosystems with functions defined by synthesis. Graphene has been recently explored as a two-dimensional nanoscale material, and has demonstrated simple device functions based on conventional top-down fabrication. However, the synthetic approach to encoding electronic functionality and thus enabling an entire integrated graphene electronics in a chemical synthesis had not previously been demonstrated. Here we report an unconventional approach for the synthesis of monolithically integrated electronic devices based on graphene and graphite. Spatial patterning of heterogeneous metal catalysts permits the selective growth of graphene and graphite, with a controlled number of graphene layers. Graphene transistor arrays with graphitic electrodes and interconnects were formed from the synthesis. These functional, all-carbon structures were transferable onto a variety of substrates. The integrated transistor arrays were used to demonstrate real-time, multiplexed chemical sensing and more significantly, multiple carbon layers of the graphene-graphite device components were vertically assembled to form a three-dimensional flexible structure which served as a top-gate transistor array. These results represent substantial progress towards encoding electronic functionality through chemical synthesis and suggest the future promise of one-step integration of graphene-graphite based electronics.

Small-molecule ligand docking into comparative models with Rosetta

PubMed Central

Combs, Steven A; DeLuca, Samuel L; DeLuca, Stephanie H; Lemmon, Gordon H; Nannemann, David P; Nguyen, Elizabeth D; Willis, Jordan R; Sheehan, Jonathan H; Meiler, Jens

2017-01-01

Structure-based drug design is frequently used to accelerate the development of small-molecule therapeutics. Although substantial progress has been made in X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, the availability of high-resolution structures is limited owing to the frequent inability to crystallize or obtain sufficient NMR restraints for large or flexible proteins. Computational methods can be used to both predict unknown protein structures and model ligand interactions when experimental data are unavailable. This paper describes a comprehensive and detailed protocol using the Rosetta modeling suite to dock small-molecule ligands into comparative models. In the protocol presented here, we review the comparative modeling process, including sequence alignment, threading and loop building. Next, we cover docking a small-molecule ligand into the protein comparative model. In addition, we discuss criteria that can improve ligand docking into comparative models. Finally, and importantly, we present a strategy for assessing model quality. The entire protocol is presented on a single example selected solely for didactic purposes. The results are therefore not representative and do not replace benchmarks published elsewhere. We also provide an additional tutorial so that the user can gain hands-on experience in using Rosetta. The protocol should take 5–7 h, with additional time allocated for computer generation of models. PMID:23744289

The critical role of volcano monitoring in risk reduction

USGS Publications Warehouse

Tilling, R.I.

2008-01-01

Data from volcano-monitoring studies constitute the only scientifically valid basis for short-term forecasts of a future eruption, or of possible changes during an ongoing eruption. Thus, in any effective hazards-mitigation program, a basic strategy in reducing volcano risk is the initiation or augmentation of volcano monitoring at historically active volcanoes and also at geologically young, but presently dormant, volcanoes with potential for reactivation. Beginning with the 1980s, substantial progress in volcano-monitoring techniques and networks - ground-based as well space-based - has been achieved. Although some geochemical monitoring techniques (e.g., remote measurement of volcanic gas emissions) are being increasingly applied and show considerable promise, seismic and geodetic methods to date remain the techniques of choice and are the most widely used. Availability of comprehensive volcano-monitoring data was a decisive factor in the successful scientific and governmental responses to the reawakening of Mount St. Helens (Washington, USA) in 1980 and, more recently, to the powerful explosive eruptions at Mount Pinatubo (Luzon, Philippines) in 1991. However, even with the ever-improving state-ofthe-art in volcano monitoring and predictive capability, the Mount St. Helens and Pinatubo case histories unfortunately still represent the exceptions, rather than the rule, in successfully forecasting the most likely outcome of volcano unrest.

Gap Junction Intercellular Communication: A Review of a Potential Platform to Modulate Craniofacial Tissue Engineering

PubMed Central

Rossello, Ricardo A.; Kohn, David H.

2009-01-01

Defects in craniofacial tissues, resulting from trauma, congenital abnormalities, oncologic resection or progressive deforming diseases, may result in aesthetic deformity, pain and reduced function. Restoring the structure, function and aesthetics of craniofacial tissues represents a substantial clinical problem in need of new solutions. More biologically-interactive biomaterials could potentially improve the treatment of craniofacial defects, and an understanding of developmental processes may help identify strategies and materials that can be used in tissue engineering. One such strategy that can potentially advance tissue engineering is cell–cell communication. Gap junction intercellular communication is the most direct way of achieving such signaling. Gap junction communication through connexin-mediated junctions, in particular connexin 43 (Cx43), plays a major role bone development. Given the important role of Cx43 in controlling development and differentiation, especially in bone cells, controlling the expression of Cx43 may provide control over cell-to-cell communication and may help overcome some of the challenges in craniofacial tissue engineering. Following a review of gap junctions in bone cells, the ability to enhance cell–cell communication and osteogenic differentiation via control of gap junctions is discussed, as is the potential utility of this approach in craniofacial tissue engineering. PMID:18481782

Thermal Integration of a Liquid Acquisition Device into a Cryogenic Feed System

NASA Technical Reports Server (NTRS)

Hastings, L. J.; Bolshinskiy, L. G.; Schunk, R. G.; Martin, A. K.; Eskridge, R. H.; Frenkel, A.; Grayson, G.; Pendleton, M. L.

2011-01-01

Primary objectives of this effort were to define the following: (1) Approaches for quantification of the accumulation of thermal energy within a capillary screen liquid acquisition device (LAD) for a lunar lander upper stage during periods of up to 210 days on the lunar surface, (2) techniques for mitigating heat entrapment, and (3) perform initial testing, data evaluation. The technical effort was divided into the following categories: (1) Detailed thermal modeling of the LAD/feed system interactions using both COMSOL computational fluid device and standard codes, (2) FLOW-3D modeling of bulk liquid to provide interfacing conditions for the LAD thermal modeling, (3) condensation conditioning of capillary screens to stabilize surface tension retention capability, and (4) subscale testing of an integrated LAD/feed system. Substantial progress was achieved in the following technical areas: (1) Thermal modeling and experimental approaches for evaluating integrated cryogen LAD/feed systems, at both the system and component levels, (2) reduced gravity pressure control analyses, (3) analytical modeling and testing for capillary screen conditioning using condensation and wicking, and (4) development of rapid turnaround testing techniques for evaluating LAD/feed system thermal and fluid integration. A comprehensive effort, participants included a diverse cross section of representatives from academia, contractors, and multiple Marshall Space Flight Center organizations.

The cascade of care for Australians living with chronic hepatitis B: measuring access to diagnosis, management and treatment.

PubMed

Allard, Nicole L; MacLachlan, Jennifer H; Cowie, Benjamin C

2015-06-01

To estimate the level of access to diagnosis, management and treatment for people living with chronic hepatitis B (CHB) in Australia, and to identify the gaps in clinical care for people living with CHB. Analysis of publicly available population level data including infectious disease notifications, Medicare and Pharmaceutical Benefits Scheme utilisation data, census-based estimates of CHB prevalence and burden, and mathematical modelling. In 2012, of the estimated 218,567 Australians living with CHB, 57% had been diagnosed, 17,367 people (8%) received recommended HBV DNA viral load testing (without treatment) and 10,987 (5%) received antiviral therapy. This analysis reveals substantial gaps in the cascade of care for CHB in Australia, most notably in diagnosis (with 43% undiagnosed) and in recommended yearly monitoring (87% not in care). The number receiving therapy represents only one-third of those estimated to require treatment to prevent progressive liver disease and liver cancer. These findings demonstrate that the majority of those affected are not receiving guideline-based care; highlight the need for improvements in opportunistic screening, engagement in care, and access to therapy; and provide a method to assess the impact of public health and clinical interventions in response to CHB over time. © 2015 Public Health Association of Australia.

Progress in development of an integrated dietary supplement ingredient database at the NIH Office of Dietary Supplements

PubMed Central

Dwyer, Johanna T.; Picciano, Mary Frances; Betz, Joseph M.; Fisher, Kenneth D.; Saldanha, Leila G.; Yetley, Elizabeth A.; Coates, Paul M.; Radimer, Kathy; Bindewald, Bernadette; Sharpless, Katherine E.; Holden, Joanne; Andrews, Karen; Zhao, Cuiwei; Harnly, James; Wolf, Wayne R.; Perry, Charles R.

2013-01-01

Several activities of the Office of Dietary Supplements (ODS) at the National Institutes of Health involve enhancement of dietary supplement databases. These include an initiative with US Department of Agriculture to develop an analytically substantiated dietary supplement ingredient database (DSID) and collaboration with the National Center for Health Statistics to enhance the dietary supplement label database in the National Health and Nutrition Examination Survey (NHANES). The many challenges that must be dealt with in developing an analytically supported DSID include categorizing product types in the database, identifying nutrients, and other components of public health interest in these products and prioritizing which will be entered in the database first. Additional tasks include developing methods and reference materials for quantifying the constituents, finding qualified laboratories to measure the constituents, developing appropriate sample handling procedures, and finally developing representative sampling plans. Developing the NHANES dietary supplement label database has other challenges such as collecting information on dietary supplement use from NHANES respondents, constant updating and refining of information obtained, developing default values that can be used if the respondent cannot supply the exact supplement or strength that was consumed, and developing a publicly available label database. Federal partners and the research community are assisting in making an analytically supported dietary supplement database a reality. PMID:25309034

Ultrahigh-Sensitivity Piezoresistive Pressure Sensors for Detection of Tiny Pressure.

PubMed

Li, Hongwei; Wu, Kunjie; Xu, Zeyang; Wang, Zhongwu; Meng, Yancheng; Li, Liqiang

2018-06-20

High-sensitivity pressure sensors are crucial for the ultrasensitive touch technology and E-skin, especially at the tiny-pressure range below 100 Pa. However, it is highly challenging to substantially promote sensitivity beyond the current level at several to 200 kPa -1 and to improve the detection limit lower than 0.1 Pa, which is significant for the development of pressure sensors toward ultrasensitive and highly precise detection. Here, we develop an efficient strategy to greatly improve the sensitivity near to 2000 kPa -1 using short-channel coplanar device structure and sharp microstructure, which is systematically proposed for the first time and rationalized by the mathematic calculation and analysis. Significantly, benefiting from the ultrahigh sensitivity, the detection limit is improved to be as small as 0.075 Pa. The sensitivity and detection limit are both superior to the current levels and far surpass the function of human skin. Furthermore, the sensor shows fast response time (50 μs), excellent reproducibility and stability, and low power consumption. Remarkably, the sensor shows excellent detection capacity in the tiny-pressure range, including light-emitting diode switching with a pressure of 7 Pa, ringtone (2-20 Pa) recognition, and ultrasensitive (0.1 Pa) electronic glove. This work represents a performance and strategic progress in the field of pressure sensing.

[Situational profile and intervention strategy in the Mesoamerican region in maternal, neonatal and reproductive health area].

PubMed

Hernández-Prado, Bernardo; Kestler, Edgar; Díaz, Juan; Walker, Dilys; Langer, Ana; Lewis, Sarah; De la Vara-Salazar, Elvia; Melo-Zurita, María del Carmen; Iriarte, Emma; Danel, Isabella; Donnay, France; Alemán, Denis; Serrano, Roselyn; Morales, Evelyn; Largaespada, Natalia; González, José Douglas Jarquín; Hernández, Ma Del Carmen; Mejía, Claudia E Quiroz; González, Geneva; Carrera, Yadira; Valverde, Clelia; Luna, Rufino; Valencia-Mendoza, Atanacio; Sosa-Rubí, Sandra G; Hernández-Prado, Bernardo; Kestler, Edgar; Díaz, Juan; Walker, Dilys; Langer, Ana; Lewis, Sarah; De la Vara-Salazar, Elvia; Melo-Zurita, María Del Carmen

2011-01-01

To present the main results of the regional situation diagnosis and intervention plan developed in 2010 as part of the planning activities of the Mesoamerican Health System by the Working Group on Maternal, Reproductive and Neonatal Health. A group of experts and representatives from countries in the region (Central America and nine southern Mexican states) conducted an exhaustive review of available data to construct a situational analysis and a review of effective practices for improving maternal, reproductive and neonatal health. Finally, the group proposed a regional action plan, defining regional goals and specific interventions. The situational diagnosis suggests that, although there has been progress in the last 10 years, maternal and neonatal mortality rates are still unnaceptably high in the region, with a substantial variability across countries. The group proposed as a regional goal the reduction of maternal and neonatal mortality in accordance with the Millenium Development Goals. The regional plan recommends specific maternal and neonatal health interventions emphasizing obstetric and neonatal emergency care, skilled birth attendance and family planning. The plan also includes a five year implementation strategy, along with training and evaluation strategies. The regional plan for maternal, neonatal and reproductive health has the potential to be successful, provided it is effectively implemented.

Exploring use of the ICF in health education.

PubMed

Bornbaum, Catherine C; Day, Adam M B; Izaryk, Kristen; Morrison, Stephanie J; Ravenek, Michael J; Sleeth, Lindsay E; Skarakis-Doyle, Elizabeth

2015-01-01

Currently, little is known regarding use of the International Classification of Functioning, Disability and Health (ICF) in health education applications. Therefore, this review sought to examine the scope of work that has been conducted regarding the application of the ICF in health education. A review of the current literature related to use of the ICF in health education programs was conducted. Twelve electronic databases were searched in accordance with a search protocol developed by a health sciences librarian. In total, 17,878 records were reviewed, and 18 articles met the criteria for inclusion in this review. Current evidence regarding use of the ICF in healthcare education revealed that program and participant properties can be essential facilitators or barriers to successful education programs. In addition, gaps in comprehensive outcome measurement were revealed as areas for future attention. Educational applications of the ICF are very much a work in progress as might be expected given the ICF's existence for only a little over a decade. To advance use of the ICF in education, it is important to incorporate the measurement of both knowledge acquisition and behavior change related to ICF-based programs. Ultimately, widespread implementation of the ICF represents not only a substantial opportunity but also poses a significant challenge.

Local spatio-temporal analysis in vision systems

NASA Astrophysics Data System (ADS)

Geisler, Wilson S.; Bovik, Alan; Cormack, Lawrence; Ghosh, Joydeep; Gildeen, David

1994-07-01

The aims of this project are the following: (1) develop a physiologically and psychophysically based model of low-level human visual processing (a key component of which are local frequency coding mechanisms); (2) develop image models and image-processing methods based upon local frequency coding; (3) develop algorithms for performing certain complex visual tasks based upon local frequency representations, (4) develop models of human performance in certain complex tasks based upon our understanding of low-level processing; and (5) develop a computational testbed for implementing, evaluating and visualizing the proposed models and algorithms, using a massively parallel computer. Progress has been substantial on all aims. The highlights include the following: (1) completion of a number of psychophysical and physiological experiments revealing new, systematic and exciting properties of the primate (human and monkey) visual system; (2) further development of image models that can accurately represent the local frequency structure in complex images; (3) near completion in the construction of the Texas Active Vision Testbed; (4) development and testing of several new computer vision algorithms dealing with shape-from-texture, shape-from-stereo, and depth-from-focus; (5) implementation and evaluation of several new models of human visual performance; and (6) evaluation, purchase and installation of a MasPar parallel computer.

Organogenic nodule development in hop (Humulus lupulus L.): Transcript and metabolic responses

PubMed Central

Fortes, Ana M; Santos, Filipa; Choi, Young H; Silva, Marta S; Figueiredo, Andreia; Sousa, Lisete; Pessoa, Fernando; Santos, Bartolomeu A; Sebastiana, Mónica; Palme, Klaus; Malhó, Rui; Verpoorte, Rob; Pais, Maria S

2008-01-01

Background Hop (Humulus lupulus L.) is an economically important plant forming organogenic nodules which can be used for genetic transformation and micropropagation. We are interested in the mechanisms underlying reprogramming of cells through stress and hormone treatments. Results An integrated molecular and metabolomic approach was used to investigate global gene expression and metabolic responses during development of hop's organogenic nodules. Transcript profiling using a 3,324-cDNA clone array revealed differential regulation of 133 unigenes, classified into 11 functional categories. Several pathways seem to be determinant in organogenic nodule formation, namely defense and stress response, sugar and lipid metabolism, synthesis of secondary metabolites and hormone signaling. Metabolic profiling using 1H NMR spectroscopy associated to two-dimensional techniques showed the importance of metabolites related to oxidative stress response, lipid and sugar metabolism and secondary metabolism in organogenic nodule formation. Conclusion The expression profile of genes pivotal for energy metabolism, together with metabolites profile, suggested that these morphogenic structures gain energy through a heterotrophic, transport-dependent and sugar-degrading anaerobic metabolism. Polyamines and auxins are likely to be involved in the regulation of expression of many genes related to organogenic nodule formation. These results represent substantial progress toward a better understanding of this complex developmental program and reveal novel information regarding morphogenesis in plants. PMID:18823540

Structure of a protective epitope of group B Streptococcus type III capsular polysaccharide.

PubMed

Carboni, Filippo; Adamo, Roberto; Fabbrini, Monica; De Ricco, Riccardo; Cattaneo, Vittorio; Brogioni, Barbara; Veggi, Daniele; Pinto, Vittoria; Passalacqua, Irene; Oldrini, Davide; Rappuoli, Rino; Malito, Enrico; Margarit, Immaculada Y Ros; Berti, Francesco

2017-05-09

Despite substantial progress in the prevention of group B Streptococcus (GBS) disease with the introduction of intrapartum antibiotic prophylaxis, this pathogen remains a leading cause of neonatal infection. Capsular polysaccharide conjugate vaccines have been tested in phase I/II clinical studies, showing promise for further development. Mapping of epitopes recognized by protective antibodies is crucial for understanding the mechanism of action of vaccines and for enabling antigen design. In this study, we report the structure of the epitope recognized by a monoclonal antibody with opsonophagocytic activity and representative of the protective response against type III GBS polysaccharide. The structure and the atomic-level interactions were determined by saturation transfer difference (STD)-NMR and X-ray crystallography using oligosaccharides obtained by synthetic and depolymerization procedures. The GBS PSIII epitope is made by six sugars. Four of them derive from two adjacent repeating units of the PSIII backbone and two of them from the branched galactose-sialic acid disaccharide contained in this sequence. The sialic acid residue establishes direct binding interactions with the functional antibody. The crystal structure provides insight into the molecular basis of antibody-carbohydrate interactions and confirms that the conformational epitope is not required for antigen recognition. Understanding the structural basis of immune recognition of capsular polysaccharide epitopes can aid in the design of novel glycoconjugate vaccines.