effective approach progress: Topics by Science.gov

Sample records for effective approach progress

Presenters in Focus: Updating Your Toolkit for Monitoring Progress of Younger Struggling Readers--Q&A with Nathan Clemens

ERIC Educational Resources Information Center

Clemens, Nathan

2017-01-01

Using a data-driven approach to effectively monitor progress remains an important staple for school psychologists. However, progress monitoring approaches vary significantly based on the age and development of the student, requiring a nuanced and unique approach, particularly for young emerging readers. In this Presenters in Focus Q&A,…
A Curricular-Sampling Approach to Progress Monitoring: Mathematics Concepts and Applications

ERIC Educational Resources Information Center

Fuchs, Lynn S.; Fuchs, Douglas; Zumeta, Rebecca O.

2008-01-01

Progress monitoring is an important component of effective instructional practice. Curriculum-based measurement (CBM) is a form of progress monitoring that has been the focus of rigorous research. Two approaches for formulating CBM systems exist. The first is to assess performance regularly on a task that serves as a global indicator of competence…
Unloading joints to treat osteoarthritis, including joint distraction.

PubMed

Lafeber, Floris P J G; Intema, Femke; Van Roermund, Peter M; Marijnissen, Anne C A

2006-09-01

Patients are increasingly becoming interested in nonpharmacologic approaches to manage their osteoarthritis. This review examines the recent literature on the potential beneficial effects of unloading joints in the treatment of osteoarthritis, with a focus on joint distraction. Mechanical factors are involved in the development and progression of osteoarthritis. If "loading" is a major cause in development and progression of osteoarthritis, then "unloading" may be able to prevent progression. There is evidence that unloading may be effective in reducing pain and slowing down structural damage. This review describes unloading by footwear and bracing (nonsurgical), unloading by osteotomy (surgical), and has a focus on unloading by joint distraction. Excellent reviews in all these three fields have been published over the past few years. Recent studies argue for the usefulness of a biomechanical approach to improve function and possibly reduce disease progression in osteoarthritis. To improve patient function and possibly reduce disease progression, a biomechanical approach should be considered in treating patients with osteoarthritis. Further research (appropriate high-quality clinical trials) and analysis (clinical as well as preclinical and fundamental) are still necessary, however, to understand, validate, and refine the different approaches of unloading to treat osteoarthritis.
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.
Department of Clinical Investigation Annual Research Progress Report, Fiscal Year 1984. Volume 1,

DTIC Science & Technology

1984-10-01

on a low dosage of medication . Technical Approach: None. Progress: The placebo has not been received from the company. Since the drug company...determine the effect of high dose Ar-C intensification therapy on the -. incidence of CNS relapse. - Technical Approach: All patients with a new...Enrolled to Date: 7 Date of Periodic Review Results Objective(s): To determine the incidence of
Equity in health care financing in Palestine: the value-added of the disaggregate approach.

PubMed

Abu-Zaineh, Mohammad; Mataria, Awad; Luchini, Stéphane; Moatti, Jean-Paul

2008-06-01

This paper analyzes the redistributive effect and progressivity associated with the current health care financing schemes in the Occupied Palestinian Territory, using data from the first Palestinian Household Health Expenditure Survey conducted in 2004. The paper goes beyond the commonly used "aggregate summary index approach" to apply a more detailed "disaggregate approach". Such an approach is borrowed from the general economic literature on taxation, and examines redistributive and vertical effects over specific parts of the income distribution, using the dominance criterion. In addition, the paper employs a bootstrap method to test for the statistical significance of the inequality measures. While both the aggregate and disaggregate approaches confirm the pro-rich and regressive character of out-of-pocket payments, the aggregate approach does not ascertain the potential progressive feature of any of the available insurance schemes. The disaggregate approach, however, significantly reveals a progressive aspect, for over half of the population, of the government health insurance scheme, and demonstrates that the regressivity of the out-of-pocket payments is most pronounced among the worst-off classes of the population. Recommendations are advanced to improve the performance of the government insurance schemes to enhance its capacity in limiting inequalities in health care financing in the Occupied Palestinian Territory.
Effective progression of nuclear magnetic resonance-detected fragment hits.

PubMed

Eaton, Hugh L; Wyss, Daniel F

2011-01-01

Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade as an alternate lead generation tool to HTS approaches. Several compounds have now progressed into the clinic which originated from a fragment-based approach, demonstrating the utility of this emerging field. While fragment hit identification has become much more routine and may involve different screening approaches, the efficient progression of fragment hits into quality lead series may still present a major bottleneck for the broadly successful application of FBDD. In our laboratory, we have extensive experience in fragment-based NMR screening (SbN) and the subsequent iterative progression of fragment hits using structure-assisted chemistry. To maximize impact, we have applied this approach strategically to early- and high-priority targets, and those struggling for leads. Its application has yielded a clinical candidate for BACE1 and lead series in about one third of the SbN/FBDD projects. In this chapter, we will give an overview of our strategy and focus our discussion on NMR-based FBDD approaches. Copyright © 2011 Elsevier Inc. All rights reserved.
Estimation of Survival Probabilities for Use in Cost-effectiveness Analyses: A Comparison of a Multi-state Modeling Survival Analysis Approach with Partitioned Survival and Markov Decision-Analytic Modeling

PubMed Central

Williams, Claire; Lewsey, James D.; Mackay, Daniel F.; Briggs, Andrew H.

2016-01-01

Modeling of clinical-effectiveness in a cost-effectiveness analysis typically involves some form of partitioned survival or Markov decision-analytic modeling. The health states progression-free, progression and death and the transitions between them are frequently of interest. With partitioned survival, progression is not modeled directly as a state; instead, time in that state is derived from the difference in area between the overall survival and the progression-free survival curves. With Markov decision-analytic modeling, a priori assumptions are often made with regard to the transitions rather than using the individual patient data directly to model them. This article compares a multi-state modeling survival regression approach to these two common methods. As a case study, we use a trial comparing rituximab in combination with fludarabine and cyclophosphamide v. fludarabine and cyclophosphamide alone for the first-line treatment of chronic lymphocytic leukemia. We calculated mean Life Years and QALYs that involved extrapolation of survival outcomes in the trial. We adapted an existing multi-state modeling approach to incorporate parametric distributions for transition hazards, to allow extrapolation. The comparison showed that, due to the different assumptions used in the different approaches, a discrepancy in results was evident. The partitioned survival and Markov decision-analytic modeling deemed the treatment cost-effective with ICERs of just over £16,000 and £13,000, respectively. However, the results with the multi-state modeling were less conclusive, with an ICER of just over £29,000. This work has illustrated that it is imperative to check whether assumptions are realistic, as different model choices can influence clinical and cost-effectiveness results. PMID:27698003
Estimation of Survival Probabilities for Use in Cost-effectiveness Analyses: A Comparison of a Multi-state Modeling Survival Analysis Approach with Partitioned Survival and Markov Decision-Analytic Modeling.

PubMed

Williams, Claire; Lewsey, James D; Mackay, Daniel F; Briggs, Andrew H

2017-05-01

Modeling of clinical-effectiveness in a cost-effectiveness analysis typically involves some form of partitioned survival or Markov decision-analytic modeling. The health states progression-free, progression and death and the transitions between them are frequently of interest. With partitioned survival, progression is not modeled directly as a state; instead, time in that state is derived from the difference in area between the overall survival and the progression-free survival curves. With Markov decision-analytic modeling, a priori assumptions are often made with regard to the transitions rather than using the individual patient data directly to model them. This article compares a multi-state modeling survival regression approach to these two common methods. As a case study, we use a trial comparing rituximab in combination with fludarabine and cyclophosphamide v. fludarabine and cyclophosphamide alone for the first-line treatment of chronic lymphocytic leukemia. We calculated mean Life Years and QALYs that involved extrapolation of survival outcomes in the trial. We adapted an existing multi-state modeling approach to incorporate parametric distributions for transition hazards, to allow extrapolation. The comparison showed that, due to the different assumptions used in the different approaches, a discrepancy in results was evident. The partitioned survival and Markov decision-analytic modeling deemed the treatment cost-effective with ICERs of just over £16,000 and £13,000, respectively. However, the results with the multi-state modeling were less conclusive, with an ICER of just over £29,000. This work has illustrated that it is imperative to check whether assumptions are realistic, as different model choices can influence clinical and cost-effectiveness results.
Progress Report on SAM Reduced-Order Model Development for Thermal Stratification and Mixing during Reactor Transients

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

Hu, R.

This report documents the initial progress on the reduced-order flow model developments in SAM for thermal stratification and mixing modeling. Two different modeling approaches are pursued. The first one is based on one-dimensional fluid equations with additional terms accounting for the thermal mixing from both flow circulations and turbulent mixing. The second approach is based on three-dimensional coarse-grid CFD approach, in which the full three-dimensional fluid conservation equations are modeled with closure models to account for the effects of turbulence.
Progressive delamination in polymer matrix composite laminates: A new approach

NASA Technical Reports Server (NTRS)

Chamis, C. C.; Murthy, P. L. N.; Minnetyan, L.

1992-01-01

A new approach independent of stress intensity factors and fracture toughness parameters has been developed and is described for the computational simulation of progressive delamination in polymer matrix composite laminates. The damage stages are quantified based on physics via composite mechanics while the degradation of the laminate behavior is quantified via the finite element method. The approach accounts for all types of composite behavior, laminate configuration, load conditions, and delamination processes starting from damage initiation, to unstable propagation, and to laminate fracture. Results of laminate fracture in composite beams, panels, plates, and shells are presented to demonstrate the effectiveness and versatility of this new approach.
Micromechanics Based Failure Analysis of Heterogeneous Materials

NASA Astrophysics Data System (ADS)

Sertse, Hamsasew M.

In recent decades, heterogeneous materials are extensively used in various industries such as aerospace, defense, automotive and others due to their desirable specific properties and excellent capability of accumulating damage. Despite their wide use, there are numerous challenges associated with the application of these materials. One of the main challenges is lack of accurate tools to predict the initiation, progression and final failure of these materials under various thermomechanical loading conditions. Although failure is usually treated at the macro and meso-scale level, the initiation and growth of failure is a complex phenomena across multiple scales. The objective of this work is to enable the mechanics of structure genome (MSG) and its companion code SwiftComp to analyze the initial failure (also called static failure), progressive failure, and fatigue failure of heterogeneous materials using micromechanics approach. The initial failure is evaluated at each numerical integration point using pointwise and nonlocal approach for each constituent of the heterogeneous materials. The effects of imperfect interfaces among constituents of heterogeneous materials are also investigated using a linear traction-displacement model. Moreover, the progressive and fatigue damage analyses are conducted using continuum damage mechanics (CDM) approach. The various failure criteria are also applied at a material point to analyze progressive damage in each constituent. The constitutive equation of a damaged material is formulated based on a consistent irreversible thermodynamics approach. The overall tangent modulus of uncoupled elastoplastic damage for negligible back stress effect is derived. The initiation of plasticity and damage in each constituent is evaluated at each numerical integration point using a nonlocal approach. The accumulated plastic strain and anisotropic damage evolution variables are iteratively solved using an incremental algorithm. The damage analyses are performed for both brittle failure/high cycle fatigue (HCF) for negligible plastic strain and ductile failure/low cycle fatigue (LCF) for large plastic strain. The proposed approach is incorporated in SwiftComp and used to predict the initial failure envelope, stress-strain curve for various loading conditions, and fatigue life of heterogeneous materials. The combined effects of strain hardening and progressive fatigue damage on the effective properties of heterogeneous materials are also studied. The capability of the current approach is validated using several representative examples of heterogeneous materials including binary composites, continuous fiber-reinforced composites, particle-reinforced composites, discontinuous fiber-reinforced composites, and woven composites. The predictions of MSG are also compared with the predictions obtained using various micromechanics approaches such as Generalized Methods of Cells (GMC), Mori-Tanaka (MT), and Double Inclusions (DI) and Representative Volume Element (RVE) Analysis (called as 3-dimensional finite element analysis (3D FEA) in this document). This study demonstrates that a micromechanics based failure analysis has a great potential to rigorously and more accurately analyze initiation and progression of damage in heterogeneous materials. However, this approach requires material properties specific to damage analysis, which are needed to be independently calibrated for each constituent.
View-Based Searching Systems--Progress Towards Effective Disintermediation.

ERIC Educational Resources Information Center

Pollitt, A. Steven; Smith, Martin P.; Treglown, Mark; Braekevelt, Patrick

This paper presents the background and then reports progress made in the development of two view-based searching systems--HIBROWSE for EMBASE, searching Europe's most important biomedical bibliographic database, and HIBROWSE for EPOQUE, improving access to the European Parliament's Online Query System. The HIBROWSE approach to searching promises…
The Effectiveness of the Progression of Widex Zen Tinnitus Therapy: A Pilot Study.

PubMed

Tyler, Richard S; Deshpande, Aniruddha K; Lau, Chi C; Kuk, Francis

2017-09-18

The aim of this study was to measure the progression of benefits to individuals with tinnitus from providing informational counseling, hearing aids, a brief tinnitus activities treatment and Zen therapy. Several magnitude estimation scales and tinnitus handicap scales were administered for the duration of the study to 20 participants. Results indicated that all participants benefited from this sequential approach of providing different components of this tinnitus treatment. Large benefits were observed following the tinnitus activities treatment and the Zen treatments. We conclude that the progressive approach of treatment demonstrated here should be of benefit to most individuals with tinnitus and that the Widex Zen sound therapy is a worthwhile treatment for many tinnitus sufferers.
"I'm still me - I'm still here!" Understanding the person's sense of self in the provision of self-management support for people with progressive neurological long-term conditions.

PubMed

Kulnik, Stefan Tino; Hollinshead, Lucinda; Jones, Fiona

2018-01-11

There is increasing interest in tailoring self-management support, but little detail is available on the relevance and impact of such approaches for people with progressive neurological conditions. The aim of this study was to draw on individuals' experiences to inform the practice of self-management support for these groups. Community rehabilitation service users were purposively recruited and took part in in-depth qualitative interviews. Interviews were audio-recorded and transcribed. Data analysis was iterative and interpretative, taking a phenomenological approach. Strategies to enhance rigor were auditability, peer review, and researcher reflexivity. The sample consisted of 10 adults (age 20-79 years) who were living with a range of progressive neurological conditions. Individuals demonstrated resourcefulness in developing practice-based self-management strategies. Beyond practical strategies, interviewees' experiences were signified by reflecting on and upholding a sense of identity and a desire for purpose against the background of losses and gains over time. Linking with this overarching theme of "Sense of self" were aspects of "My body and mind", "Time", "Space", "Relationships", and "What I do". Self-management approaches for individuals with progressive neurological conditions will benefit from incorporating ways of recognizing, articulating, and supporting the person's sense of identity and purpose. Implications for rehabilitation Self-management approaches for people with progressive neurological conditions need to take account of individuals' wishes to contribute, connect with others, and be valued as a person. Person-centred self-management support can be realized through a broader approach than solely managing disease progression. The experiences and words of people with progressive neurological conditions can be used to inform meaningful evaluation of self-management support to drive service delivery by measuring what really matters. Rehabilitation practitioners need to adapt their conceptualisations of goal setting to account for how people with progressive neurological conditions themselves interpret "progress" and "improvement". Person-centred conversation that values who the person is can be an effective starting point for self-management interventions in people with progressive neurological conditions.
A Year of Unprecedented Progress in Down Syndrome Basic Research

ERIC Educational Resources Information Center

Reeves, Roger H.; Garner, Craig C.

2007-01-01

The years 2006 and 2007 saw the publication of three new and different approaches to prevention or amelioration of Down syndrome effects on the brain and cognition. We describe the animal model systems that were critical to this progress, review these independent breakthrough studies, and discuss the implications for therapeutic approaches…
Target identification of small molecules based on chemical biology approaches.

PubMed

Futamura, Yushi; Muroi, Makoto; Osada, Hiroyuki

2013-05-01

Recently, a phenotypic approach-screens that assess the effects of compounds on cells, tissues, or whole organisms-has been reconsidered and reintroduced as a complementary strategy of a target-based approach for drug discovery. Although the finding of novel bioactive compounds from large chemical libraries has become routine, the identification of their molecular targets is still a time-consuming and difficult process, making this step rate-limiting in drug development. In the last decade, we and other researchers have amassed a large amount of phenotypic data through progress in omics research and advances in instrumentation. Accordingly, the profiling methodologies using these datasets expertly have emerged to identify and validate specific molecular targets of drug candidates, attaining some progress in current drug discovery (e.g., eribulin). In the case of a compound that shows an unprecedented phenotype likely by inhibiting a first-in-class target, however, such phenotypic profiling is invalid. Under the circumstances, a photo-crosslinking affinity approach should be beneficial. In this review, we describe and summarize recent progress in both affinity-based (direct) and phenotypic profiling (indirect) approaches for chemical biology target identification.
Progression of motor and nonmotor features of Parkinson's disease and their response to treatment

PubMed Central

Vu, Thuy C.; Nutt, John G.; Holford, Nicholas H. G.

2012-01-01

AIMS (i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments. METHODS Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D). Analysis was performed using a nonlinear mixed effects approach with an asymptotic model for natural disease progression. Treatment effects (i.e. symptomatic and disease modifying) were evaluated by describing changes in the natural history model parameters. RESULTS Tremor progressed more slowly (half-time of 3.9 years) than all other motor features (half-time 2–3 years). The MMSE progression was negligible, while HAM-D progressed with a half-time of 5 years. Levodopa had marked symptomatic effects on all features, but low potency for effect on PIGD (ED50 of 1237 mg day−1 compared with 7–24 mg day−1 for other motor and nonmotor features). Other anti-parkinsonian treatments had much smaller symptomatic effects. All treatments had disease-modifying effects on the cardinal features of PD. Baseline PD subtypes only explained small differences in disease progression. CONCLUSIONS This analysis indicates that tremor progresses more slowly than other cardinal features and that PIGD is less treatment responsive in early PD patients. There was no evidence of baseline PD subtypes as a clinically useful predictor of disease progression rate. Anti-parkinsonian treatments have symptomatic and disease-modifying effects on all major features of PD. PMID:22283961
Curcumin: a potential candidate in prevention of cancer via modulation of molecular pathways.

PubMed

Rahmani, Arshad H; Al Zohairy, Mohammad A; Aly, Salah M; Khan, Masood A

2014-01-01

Cancer is the most dreadful disease worldwide in terms of morbidity and mortality. The exact cause of cancer development and progression is not fully known. But it is thought that cancer occurs due to the structural and functional changes in the genes. The current approach to cancer treatment based on allopathic is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a safe and effective mode of treatment is needed to control the cancer development and progression. Some medicinal plants provide a safe, effective and affordable remedy to control the progression of malignant cells. The importance of medicinal plants and their constituents has been documented in Ayurveda, Unani medicine, and various religious books. Curcumin, a vital constituent of the spice turmeric, is an alternative approach in the prevention of cancer. Earlier studies have shown the effect of curcumin as an antioxidant, antibacterial, antitumor and it also has a noteworthy role in the control of different diseases. In this review, we summarize the understanding of chemopreventive effects of curcumin in the prevention of cancer via the regulation of various cell signaling and genetic pathways.
Curcumin: A Potential Candidate in Prevention of Cancer via Modulation of Molecular Pathways

PubMed Central

Rahmani, Arshad H.; Al Zohairy, Mohammad A.; Aly, Salah M.; Khan, Masood A.

2014-01-01

Cancer is the most dreadful disease worldwide in terms of morbidity and mortality. The exact cause of cancer development and progression is not fully known. But it is thought that cancer occurs due to the structural and functional changes in the genes. The current approach to cancer treatment based on allopathic is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a safe and effective mode of treatment is needed to control the cancer development and progression. Some medicinal plants provide a safe, effective and affordable remedy to control the progression of malignant cells. The importance of medicinal plants and their constituents has been documented in Ayurveda, Unani medicine, and various religious books. Curcumin, a vital constituent of the spice turmeric, is an alternative approach in the prevention of cancer. Earlier studies have shown the effect of curcumin as an antioxidant, antibacterial, antitumor and it also has a noteworthy role in the control of different diseases. In this review, we summarize the understanding of chemopreventive effects of curcumin in the prevention of cancer via the regulation of various cell signaling and genetic pathways. PMID:25295272

Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention.

PubMed

Cathcart, Mary-Clare; Lysaght, Joanne; Pidgeon, Graham P

2011-12-01

Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways leads to the generation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Eicosanoid expression levels vary during tumor development and progression of a range of malignancies, including colorectal cancer. The actions of these autocoids are also directly influenced by diet, as demonstrated by recent evidence for omega-3 fatty acids in colorectal cancer (CRC) prevention and/or treatment. Eicosanoids regulate CRC development and progression, while inhibition of these pathways has generally been shown to inhibit tumor growth/progression. A progressive sequence of colorectal cancer development has been identified, ranging from normal colon, to colitis, dysplasia, and carcinoma. While both COX and LOX inhibition are both promising candidates for colorectal cancer prevention and/or treatment, there is an urgent need to understand the mechanisms through which these signalling pathways mediate their effects on tumorigenesis. This will allow identification of safer, more effective strategies for colorectal cancer prevention and/or treatment. In particular, binding to/signalling through prostanoid receptors have recently been the subject of considerable interest in this area. In this review, we discuss the role of the eicosanoid signalling pathways in the development and progression of colorectal cancer. We discuss the effects of the eicosanoids on tumor cell proliferation, their roles in cell death induction, effects on angiogenesis, migration, invasion and their regulation of the immune response. Signal transduction pathways involved in these processes are also discussed. Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of colorectal cancer are outlined.
An Update on the Progress of the Extended One-Generation Reproductive Protocol

EPA Science Inventory

Consistent with a more science-based approach assessing potential adverse effects of pesticides, the ILSI-HESI Agricultural Chemical Safety Assessment (ACSA) Technical Committee, proposed a new tiered toxicity testing strategy. This approach utilizes fewer animals and provides an...
The Effect of Delamination on Damage Path and Failure Load Prediction for Notched Composite Laminates

NASA Technical Reports Server (NTRS)

Satyanarayana, Arunkumar; Bogert, Philip B.; Chunchu, Prasad B.

2007-01-01

The influence of delamination on the progressing damage path and initial failure load in composite laminates is investigated. Results are presented from a numerical and an experimental study of center-notched tensile-loaded coupons. The numerical study includes two approaches. The first approach considers only intralaminar (fiber breakage and matrix cracking) damage modes in calculating the progression of the damage path. In the second approach, the model is extended to consider the effect of interlaminar (delamination) damage modes in addition to the intralaminar damage modes. The intralaminar damage is modeled using progressive damage analysis (PDA) methodology implemented with the VUMAT subroutine in the ABAQUS finite element code. The interlaminar damage mode has been simulated using cohesive elements in ABAQUS. In the experimental study, 2-3 specimens each of two different stacking sequences of center-notched laminates are tensile loaded. The numerical results from the two different modeling approaches are compared with each other and the experimentally observed results for both laminate types. The comparisons reveal that the second modeling approach, where the delamination damage mode is included together with the intralaminar damage modes, better simulates the experimentally observed damage modes and damage paths, which were characterized by splitting failures perpendicular to the notch tips in one or more layers. Additionally, the inclusion of the delamination mode resulted in a better prediction of the loads at which the failure took place, which were higher than those predicted by the first modeling approach which did not include delaminations.
Student Perceptions of the Progress Test in Two Settings and the Implications for Test Deployment

ERIC Educational Resources Information Center

Wade, Louise; Harrison, Chris; Hollands, James; Mattick, Karen; Ricketts, Chris; Wass, Val

2012-01-01

Background: The Progress Test (PT) was developed to assess student learning within integrated curricula. Whilst it is effective in promoting and rewarding deep approaches to learning in some settings, we hypothesised that implementation of the curriculum (design and assessment) may impact on students' preparation for the PT and their learning.…
Teacher Progress Monitoring of Instructional and Behavioral Management Practices: An Evidence-Based Approach to Improving Classroom Practices

ERIC Educational Resources Information Center

Reddy, Linda A.; Dudek, Christopher M.

2014-01-01

In the era of teacher evaluation and effectiveness, assessment tools that identify and monitor educators' instruction and behavioral management practices are in high demand. The Classroom Strategies Scale (CSS) Observer Form is a multidimensional teacher progress monitoring tool designed to assess teachers' usage of instructional and behavioral…
Scientific and Technological Progress, Political Beliefs and Environmental Sustainability

ERIC Educational Resources Information Center

Makrakis, Vassilios

2012-01-01

With the development of science and technology, a basically optimistic ideology of progress has emerged. This deterministic attitude has been challenged in recent decades as a result of harmful side-effects generated by the way technology and science have been approached and used. The study presented here is a part of a larger international and…
Chlamydia vaccine candidates and tools for chlamydial antigen discovery.

PubMed

Rockey, Daniel D; Wang, Jie; Lei, Lei; Zhong, Guangming

2009-10-01

The failure of the inactivated Chlamydia-based vaccine trials in the 1960s has led researchers studying Chlamydia to take cautious and rational approaches to develop safe and effective chlamydial vaccines. Subsequent research efforts focused on three areas. The first is the analysis of the immunobiology of chlamydial infection in animal models, with supporting clinical studies, to identify the immune correlates of both protective immunity and pathological responses. Second, recent radical improvements in genomics, proteomics and associated technologies have assisted in the implementation of creative approaches to search for suitable vaccine candidates. Third, progress in the analysis of host response and adjuvanticity regulating both innate and adaptive immunity at the mucosal site of infection has led to progress in the design of optimal delivery and adjuvant systems for enhancing protective immunity. Considerable progress has been made in the first two areas but research efforts to better define the factors that regulate immunity at mucosal sites of infection and to develop strategies to boost protective immunity via immunomodulation, effective delivery systems and potent adjuvants, have remained elusive. In this article, we will summarize progress in these areas with a focus on chlamydial vaccine antigen discovery, and discuss future directions towards the development of a safe and effective chlamydial vaccine.
Achievement goals and emotions: The mediational roles of perceived progress, control, and value.

PubMed

Hall, Nathan C; Sampasivam, Lavanya; Muis, Krista R; Ranellucci, John

2016-06-01

The link between achievement goals and achievement emotions is well established; however, research exploring potential mediators of this relationship is lacking. The control-value theory of achievement emotions (Pekrun, 2006, Educational Psychology Review, 18, 315) posits that perceptions of control and value mediate the relationship between achievement goals and achievement emotions, whereas the bidirectional theory of affect (Linnenbrink & Pintrich, 2002, Educational Psychologist, 37, 69) proposes that perceived progress mediates this relationship. The present study empirically evaluated three hypothesized mediators of the effects of achievement goals on learning-related emotions as proposed in the control-value theory and the bidirectional theory of affect. Undergraduate students (N = 273) from humanities, social science, and STEM disciplines participated. Participants completed web-based questionnaires evaluating academic achievement goals, perceptions of control, perceived task value, and achievement emotions. Results provided empirical support primarily for perceived progress as a mediator of mastery-approach goal effects on positive emotions (enjoyment, hope), showing indirect effects of mastery- and performance-approach goals on outcome-related emotions (hope, anxiety) via perceived control. Indirect effects of mastery- and performance-approach goals were further observed on anxiety via perceived value, with higher value levels predicting greater anxiety. Study findings partially support Linnenbrink and Pintrich's (2002, Educational Psychologist, 37, 69) bidirectional theory of affect while underscoring the potential for indirect effects of goals on emotions through perceived control as proposed by Pekrun (2006, Educational Psychology Review, 18, 315). © 2016 The British Psychological Society.
Recent progress in half-Heusler thermoelectric materials

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

Huang, Lihong; Zhang, Qinyong; Yuan, Bo

2016-04-15

Highlights: • Summarize the recent progress and advances in HH thermoelectric materials. • Preparing nanocomposites could reduce thermal conductivity. • Introducing enhance phonon scattering could further reduce the thermal conductivity. • Forming ternary systems to reducing the cost effectively. • The new class of HHs presents another opportunity to further optimize the HH system. - Abstract: Half-Heusler (HH) thermoelectric (TE) materials have been attracting extensive research interest over the last two decades, owing to their thermal stability, mechanical strength, and moderate ZT. This material system are potential candidates for medium to high temperature applications, which is close to the temperaturemore » range of most industrial waste heat sources. In this mini-review article, we briefly summarize the recent progress and advances in HH thermoelectric materials. Some effectively available approaches, such as HH nanocomposites to reduce thermal conductivity, using larger atomic mass and size differences to enhance phonon scattering to further reduce the thermal conductivity, forming ternary systems following the cost effective approach. In addition, new thermoelectric HH members are also discussed in this article, which points out that many new HH compounds may be possible for TE applications.« less
Labor Dystocia: A Common Approach to Diagnosis.

PubMed

Neal, Jeremy L; Lowe, Nancy K; Schorn, Mavis N; Holley, Sharon L; Ryan, Sharon L; Buxton, Margaret; Wilson-Liverman, Angela M

2015-01-01

Contemporary labor and birth population norms should be the basis for evaluating labor progression and determining slow progress that may benefit from intervention. The aim of this article is to present guidelines for a common, evidence-based approach for determination of active labor onset and diagnosis of labor dystocia based on a synthesis of existing professional guidelines and relevant contemporary publications. A 3-point approach for diagnosing active labor onset and classifying labor dystocia-related labor aberrations into well-defined, mutually exclusive categories that can be used clinically and validated by researchers is proposed. The approach comprises identification of 1) an objective point that strictly defines active labor onset (point of active labor determination); 2) an objective point that identifies when labor progress becomes atypical, beyond which interventions aimed at correcting labor dystocia may be justified (point of protraction diagnosis); and 3) an objective point that identifies when interventions aimed at correcting labor dystocia, if used, can first be determined to be unsuccessful, beyond which assisted vaginal or cesarean birth may be justified (earliest point of arrest diagnosis). Widespread adoption of a common approach for diagnosing labor dystocia will facilitate consistent evaluation of labor progress, improve communications between clinicians and laboring women, indicate when intervention aimed at speeding labor progress or facilitating birth may be appropriate, and allow for more efficient translation of safe and effective management strategies into clinical practice. Correct application of the diagnosis of labor dystocia may lead to a decrease in the rate of cesarean birth, decreased health care costs, and improved health of childbearing women and neonates. © 2015 by the American College of Nurse-Midwives.
Mind body therapies in rehabilitation of patients with rheumatic diseases.

PubMed

Del Rosso, Angela; Maddali-Bongi, Susanna

2016-02-01

Mind body therapies (MBT) share a global approach involving both mental and physical dimensions, and focus on relationship between brain, mind, body and behavior and their effects on health and disease. MBT include concentration based therapies and movement based therapies, comprising traditional Oriental practices and somatic techniques. The greatest part of rheumatic diseases have a chronic course, leading to progressive damages at musculoskeletal system and causing physical problems, psychological and social concerns. Thus, rheumatic patients need to be treated with a multidisciplinary approach integrating pharmacological therapies and rehabilitation techniques, that not should only aim to reduce the progression of damages at musculoskeletal system. Thus, MBT, using an overall approach, could be useful in taking care of the overall health of the patients with chronic rheumatic diseases. This review will deal with different MBT and with their effects in the most common chronic rheumatic diseases (Rheumatoid Arthritis, Ankylosing Spondylitis, Fibromyalgia Syndrome). Copyright © 2015. Published by Elsevier Ltd.
Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in diabetes patients with Cardiovascular History (APPROACH): study design and baseline characteristics.

PubMed

Ratner, Robert E; Cannon, Christopher P; Gerstein, Hertzel C; Nesto, Richard W; Serruys, Patrick W; Van Es, Gerrit-Anne; Kolatkar, Nikheel S; Kravitz, Barbara G; Zalewski, Andrew; Fitzgerald, Peter J

2008-12-01

Rosiglitazone, a thiazolidinedione, has effects on insulin sensitivity and cardiovascular risk factors that may favorably impact the progression of coronary atherosclerosis. APPROACH is a double-blind randomized clinical trial comparing the effects of the insulin sensitizer rosiglitazone with the insulin secretagogue glipizide on the progression of coronary atherosclerosis. Patients with type 2 diabetes and coronary artery disease undergoing clinically indicated coronary angiography or percutaneous coronary intervention are randomized to receive rosiglitazone or glipizide for 18 months using a titration algorithm designed to provide comparable glycemic control between treatment groups. The primary end point is change in percent atheroma volume from baseline to study completion in a nonintervened coronary artery, as measured by intravascular ultrasound. Cardiovascular events are adjudicated by an end point committee. A total of 672 patients were randomized. The mean age was 61 years, hemoglobin A(1c) (HbA(1c)) 7.2%, body mass index 29.5 kg/m(2), and median duration of diabetes 4.8 years. At baseline, approximately half of the participants were receiving oral antidiabetic monotherapy (53.9%) with 27.5% receiving dual combination therapy and 17.9% treated with diet and exercise alone. Approximately two thirds of the participants (68%) had dyslipidemia, 79.9% hypertension, and 24% prior myocardial infarction. APPROACH has fully enrolled a high-risk patient population and will compare the glucose-independent effects of rosiglitazone and glipizide on the progression of coronary atherosclerosis, as well as provide additional data on the cardiovascular safety of rosiglitazone in patients with type 2 diabetes and coronary artery disease.
Progressing quality control in environmental impact assessment beyond legislative compliance: An evaluation of the IEMA EIA Quality Mark certification scheme

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

Bond, Alan, E-mail: alan.bond@uea.ac.uk; Research Unit for Environmental Sciences and Management, North-West University; Fischer, Thomas B, E-mail: fischer@liverpool.ac.uk

The effectiveness of Environmental Impact Assessment (EIA) systems is contingent on a number of control mechanisms: procedural; judicial; evaluative; public and government agency; professional; and development aid agency. If we assume that procedural and judicial controls are guaranteed in developed EIA systems, then progressing effectiveness towards an acceptable level depends on improving the performance of other control mechanisms over time. These other control mechanisms are either absent, or are typically centrally controlled, requiring public finances; this we argue is an unpopular model in times of greater Government austerity. Here we evaluate a market-based mechanism for improving the performance of evaluativemore » and professional control mechanisms, the UK Institute of Environmental Management and Assessments' EIA Quality Mark. We do this by defining dimensions of effectiveness for the purposes of our evaluation, and by identifying international examples of the approaches taken to delivering the other control measures to validate the approach taken in the EIA Quality Mark. We then evaluate the EIA Quality Mark, when used in combination with legal procedures and an active judiciary, against the effectiveness dimensions and use time-series analysis of registrant data to examine its ability to progress practice. We conclude that the EIA Quality Mark has merit as a model for a market-based mechanism, and may prove a more financially palatable approach for delivering effective EIA in mature systems in countries that lack centralised agency oversight. It may, therefore, be of particular interest to some Member States of the European Union for ensuring forthcoming certification requirements stemming from recent amendments to the EIA Directive. - Highlights: • Quality control mechanisms in EIA are identified. • Effectiveness of EIA is conceptualised for evaluation purposes. • The UK IEMA EIA Quality Mark is introduced as a market-based mechanism. • The EIA Quality Mark is found to progress quality in many, but not all, areas.« less
Exploring Wellness Interventions in Progressive Multiple Sclerosis: an Evidence-Based Review.

PubMed

Venasse, Myriam; Edwards, Thomas; Pilutti, Lara A

2018-04-10

There has been recent interest in the role of lifestyle and wellness-based approaches in the treatment and management of multiple sclerosis (MS). These approaches may be particularly relevant for patients with progressive MS, considering limited therapeutic options currently available. The purpose of this review is to examine the role of wellness-based interventions including exercise training, emotional well-being therapies, and dietary modification in patients with progressive MS. We conducted a literature search on the efficacy of wellness-based interventions in patients with progressive MS published between 1985 and July 2017. The level of evidence for each trial was evaluated using the American Academy of Neurology criteria. Overall, 21 articles reporting on 16 wellness-based interventions were identified: ten trials involved exercise training, three involved emotional wellness therapies, two involved dietary modification, and one was a combined wellness intervention. There is level C evidence (possibly effective; one class II study) for the efficacy of aerobic exercise training on cardiorespiratory fitness in patients with progressive MS. There is level B evidence (probably effective; one class I study) for the efficacy of mindfulness training on psychological distress, depression, anxiety, pain, and quality of life in patients with progressive MS. There is inadequate evidence (level U) for efficacy of dietary modification (one class III study and one class IV study) and combined wellness interventions involving exercise training, meditation, and dietary modification (one class IV study). High-quality research is needed to provide evidence-based recommendations for wellness behaviors and lifestyle change in patients with progressive MS.
Setting a research agenda for progressive multiple sclerosis: the International Collaborative on Progressive MS.

PubMed

Fox, Robert J; Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim

2012-11-01

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS.
Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS

PubMed Central

Thompson, Alan; Baker, David; Baneke, Peer; Brown, Doug; Browne, Paul; Chandraratna, Dhia; Ciccarelli, Olga; Coetzee, Timothy; Comi, Giancarlo; Feinstein, Anthony; Kapoor, Raj; Lee, Karen; Salvetti, Marco; Sharrock, Kersten; Toosy, Ahmed; Zaratin, Paola; Zuidwijk, Kim

2012-01-01

Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS. PMID:22917690
Progressive fracture of polymer matrix composite structures: A new approach

NASA Technical Reports Server (NTRS)

Chamis, C. C.; Murthy, P. L. N.; Minnetyan, L.

1992-01-01

A new approach independent of stress intensity factors and fracture toughness parameters has been developed and is described for the computational simulation of progressive fracture of polymer matrix composite structures. The damage stages are quantified based on physics via composite mechanics while the degradation of the structural behavior is quantified via the finite element method. The approach account for all types of composite behavior, structures, load conditions, and fracture processes starting from damage initiation, to unstable propagation and to global structural collapse. Results of structural fracture in composite beams, panels, plates, and shells are presented to demonstrate the effectiveness and versatility of this new approach. Parameters and guidelines are identified which can be used as criteria for structural fracture, inspection intervals, and retirement for cause. Generalization to structures made of monolithic metallic materials are outlined and lessons learned in undertaking the development of new approaches, in general, are summarized.
Treatment of hypertension and metabolic syndrome: lowering blood pressure is not enough for organ protection, new approach-arterial destiffening.

PubMed

Zimlichman, Reuven

2014-10-01

Cardiovascular risk factors (CVRFs) have been shown to induce end organ damage. Until now, the main approach to reduce CVRF-induced end organ damage was by normalization of CVRFs; this approach was found effective to reduce damage and cardiovascular (CV) events. However, a residual risk always remained even when CVRFs were optimally balanced. An additional risk factor which has an immense effect on the progression of end organ damage is aging. Aging is accompanied by gradual stiffening of the arteries which finally leads to CV events. Until recently, the process of arterial aging was considered as unmodifiable, but this has changed. Arterial stiffening caused by the aging process is similar to the changes seen as a result of CVRF-induced arterial damage. Actually, the presence of CVRFs causes faster arterial stiffening, and the extent of damage is proportional to the severity of the CVRF, the length of its existence, the patient's genetic factors, etc. Conventional treatments of osteoporosis and of hormonal decline at menopause are potential additional approaches to positively affect progression of arterial stiffening. The new approach to further decrease progression of arteriosclerosis, thus preventing events, is the prevention of age-associated arterial structural changes. This approach should further decrease age-associated arterial stiffening. A totally new promising approach is to study the possibility of affecting collagen, elastin, and other components of connective tissue that participate in the process of arterial stiffening. Reduction of pulse pressure by intervention in arterial stiffening process by novel methods as breaking collagen cross-links or preventing their formation is an example of future directions in treatment. This field is of enormous potential that might be revolutionary in inducing further significant reduction of cardiovascular events.
The Predictive Validity of Measures of Teacher Candidate Programs and Performance: Toward an Evidence-Based Approach to Teacher Preparation

ERIC Educational Resources Information Center

Henry, Gary T.; Campbell, Shanyce L.; Thompson, Charles L.; Patriarca, Linda A.; Luterbach, Kenneth J.; Lys, Diana B.; Covington, Vivian Martin

2013-01-01

Calls for evidence-based reform of teacher preparation programs (TPPs) suggest the question: Do the current indicators of progress and performance used by TPPs predict effectiveness of their graduates when they become teachers? In this study, the indicators of progress and performance used by one program are examined for their ability to predict…
Systematic process synthesis and design methods for cost effective waste minimization

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

Biegler, L.T.; Grossman, I.E.; Westerberg, A.W.

We present progress on our work to develop synthesis methods to aid in the design of cost effective approaches to waste minimization. Work continues to combine the approaches of Douglas and coworkers and of Grossmann and coworkers on a hierarchical approach where bounding information allows it to fit within a mixed integer programming approach. We continue work on the synthesis of reactors and of flexible separation processes. In the first instance, we strive for methods we can use to reduce the production of potential pollutants, while in the second we look for ways to recover and recycle solvents.

Recent Progress in Using Advanced Characterization and Modeling Approaches to Study Radiation Effects in Oxide Ceramics

DOE PAGES

Bai, Xian-Ming

2014-10-23

I serve as a Guest Editor for the Nuclear Materials Committee of the TMS Structural Materials Division, and coordinated the topic ‘‘Radiation Effects in Oxide Ceramics and Novel LWR Fuels" for JOM in the December 2014 issue. I selected five articles related this topic. These articles talk about some recent progress of using advanced experimental and modeling tools to study radiation effects in oxide ceramics at atomistic scale and mesoscale. In this guest editor commentary article, I summarize the novel aspects of these papers and also provide some suggestions for future research directions.
Improving Classroom Dynamics to Support Students' Learning and Social Inclusion: A Collaborative Approach

ERIC Educational Resources Information Center

Doveston, Mary; Keenaghan, Marian

2006-01-01

In this article, Mary Doveston and Marian Keenaghan discuss their work with teachers and students in developing more effective and satisfying interpersonal relationships in the classroom. Their approach focuses on increasing the capacity of a classroom community to address and measure its progress in the social and emotional competencies which…
The Effectiveness of Using a Multiple Gating Approach to Discriminate among ADHD Subtypes

ERIC Educational Resources Information Center

Simonsen, Brandi M.; Bullis, Michael D.

2007-01-01

This study explored the ability of Systematically Progressive Assessment (SPA), a multiple gating approach for assessing students with attention-deficit/hyperactivity disorder (ADHD), to discriminate between subtypes of ADHD. A total of 48 students with ADHD (ages 6-11) were evaluated with three "gates" of assessment. Logistic regression analysis…
How to do (or not to do) … a health financing incidence analysis

PubMed Central

Asante, Augustine D; Limwattananon, Supon; Wiseman, Virginia

2018-01-01

Abstract Financing incidence analysis (FIA) assesses how the burden of health financing is distributed in relation to household ability to pay (ATP). In a progressive financing system, poorer households contribute a smaller proportion of their ATP to finance health services compared to richer households. A system is regressive when the poor contribute proportionately more. Equitable health financing is often associated with progressivity. To conduct a comprehensive FIA, detailed household survey data containing reliable information on both a cardinal measure of household ATP and variables for extracting contributions to health services via taxes, health insurance and out-of-pocket (OOP) payments are required. Further, data on health financing mix are needed to assess overall FIA. Two major approaches to conducting FIA described in this article include the structural progressivity approach that assesses how the share of ATP (e.g. income) spent on health services varies by quantiles, and the effective progressivity approach that uses indices of progressivity such as the Kakwani index. This article provides some detailed practical steps for analysts to conduct FIA. This includes the data requirements, data sources, how to extract or estimate health payments from survey data and the methods for assessing FIA. It also discusses data deficiencies that are common in many low- and middle-income countries (LMICs). The results of FIA are useful in designing policies to achieve an equitable health system. PMID:29346547
How to do (or not to do) … a health financing incidence analysis.

PubMed

Ataguba, John E; Asante, Augustine D; Limwattananon, Supon; Wiseman, Virginia

2018-04-01

Financing incidence analysis (FIA) assesses how the burden of health financing is distributed in relation to household ability to pay (ATP). In a progressive financing system, poorer households contribute a smaller proportion of their ATP to finance health services compared to richer households. A system is regressive when the poor contribute proportionately more. Equitable health financing is often associated with progressivity. To conduct a comprehensive FIA, detailed household survey data containing reliable information on both a cardinal measure of household ATP and variables for extracting contributions to health services via taxes, health insurance and out-of-pocket (OOP) payments are required. Further, data on health financing mix are needed to assess overall FIA. Two major approaches to conducting FIA described in this article include the structural progressivity approach that assesses how the share of ATP (e.g. income) spent on health services varies by quantiles, and the effective progressivity approach that uses indices of progressivity such as the Kakwani index. This article provides some detailed practical steps for analysts to conduct FIA. This includes the data requirements, data sources, how to extract or estimate health payments from survey data and the methods for assessing FIA. It also discusses data deficiencies that are common in many low- and middle-income countries (LMICs). The results of FIA are useful in designing policies to achieve an equitable health system.
Wii Fit balance training or progressive balance training in patients with chronic stroke: a randomised controlled trial.

PubMed

Yatar, Gozde Iyigun; Yildirim, Sibel Aksu

2015-04-01

[Purpose] The aim of this study was to compare the effects of Wii Fit balance training (WBT) and progressive balance training (PBT) approaches on balance functions, balance confidence, and activities of daily living in chronic stroke patients. [Subjects] A total of 30 patients were randomized into the WBT (n=15) and PBT (n=15) groups. [Methods] All of the subjects received exercise training based on a neurodevelopemental approach in addition to either Wii Fit or progressive balance training for total of 1 hour a day, 3 days per week for 4 weeks. Primary measurements were static balance function measured with a Wii Balance Board and dynamic balance function assessed with the Berg Balance Scale, Timed Up and Go test, Dynamic Gait Index, and Functional Reach Test. Secondary measures were balance confidence assessed with the Activities-specific Balance Confidence scale and activities of daily living evaluated with the Frenchay Activity Index. [Results] There was not remarkable difference between the two treatments in dynamic balance functions, balance confidence, and activities of daily living. [Conclusion] Although both of the approaches were found to be effective in improving the balance functions, balance confidence, and activities of daily living, neither of them were more preferable than the other for the treatment of balance in patients with chronic stroke.
Evaluating progressive-rendering algorithms in appearance design tasks.

PubMed

Jiawei Ou; Karlik, Ondrej; Křivánek, Jaroslav; Pellacini, Fabio

2013-01-01

Progressive rendering is becoming a popular alternative to precomputational approaches to appearance design. However, progressive algorithms create images exhibiting visual artifacts at early stages. A user study investigated these artifacts' effects on user performance in appearance design tasks. Novice and expert subjects performed lighting and material editing tasks with four algorithms: random path tracing, quasirandom path tracing, progressive photon mapping, and virtual-point-light rendering. Both the novices and experts strongly preferred path tracing to progressive photon mapping and virtual-point-light rendering. None of the participants preferred random path tracing to quasirandom path tracing or vice versa; the same situation held between progressive photon mapping and virtual-point-light rendering. The user workflow didn’t differ significantly with the four algorithms. The Web Extras include a video showing how four progressive-rendering algorithms converged (at http://youtu.be/ck-Gevl1e9s), the source code used, and other supplementary materials.
Model-based economic evaluation in Alzheimer's disease: a review of the methods available to model Alzheimer's disease progression.

PubMed

Green, Colin; Shearer, James; Ritchie, Craig W; Zajicek, John P

2011-01-01

To consider the methods available to model Alzheimer's disease (AD) progression over time to inform on the structure and development of model-based evaluations, and the future direction of modelling methods in AD. A systematic search of the health care literature was undertaken to identify methods to model disease progression in AD. Modelling methods are presented in a descriptive review. The literature search identified 42 studies presenting methods or applications of methods to model AD progression over time. The review identified 10 general modelling frameworks available to empirically model the progression of AD as part of a model-based evaluation. Seven of these general models are statistical models predicting progression of AD using a measure of cognitive function. The main concerns with models are on model structure, around the limited characterization of disease progression, and on the use of a limited number of health states to capture events related to disease progression over time. None of the available models have been able to present a comprehensive model of the natural history of AD. Although helpful, there are serious limitations in the methods available to model progression of AD over time. Advances are needed to better model the progression of AD and the effects of the disease on peoples' lives. Recent evidence supports the need for a multivariable approach to the modelling of AD progression, and indicates that a latent variable analytic approach to characterising AD progression is a promising avenue for advances in the statistical development of modelling methods. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
FY08 DRMRP Clinical Trial: Strengthening Pathways to PTSD Recovery Using Systems-Level Intervention

DTIC Science & Technology

2016-05-01

consent forms and store them centrally at RTI for the required six year time period rather than storing the hard copies at their respective posts was...care. In progress. Lavelle T, et al. The cost-effectiveness of a collaborative care approach to treating depression and post -traumatic stress...effectiveness of a collaborative care approach to treating depression and post -traumatic stress disorder in military personnel. AcademyHealth
Pulmonary manifestations of rheumatologic diseases.

PubMed

Cidon, Michal; Bansal, Manvi; Hartl, Dominik

2017-06-01

The present review intends to provide an overview of the diversity and complexity of pulmonary manifestations of rheumatologic diseases and gaps in knowledge to effectively manage them. Diffuse lung disease in children with rheumatologic diseases represents a heterogeneous group of autoimmune disorders. Despite their significant morbidity and mortality, we have limited understanding about their pathogenesis. Here, we provide an overview of the pathophysiology and current management approach of these disorders, highlighting tools which assist with diagnosis, risk stratification and therapy. In this context, we address the need to develop a standardized approach to diagnose at-risk patients with rheumatologic disease and to predict their progression and the need to develop robust studies which evaluate the factors and interventions that influence pulmonary disease outcome. Diffuse lung disease in children with rheumatologic diseases represents a heterogeneous group of severe autoimmune disorders. By adopting a collaborative research approach among multicenters to help diagnose, risk stratify, and understand disease progression, effective management decisions can be optimized to improve clinical outcome.
The Interplay between inflammation and fibrosis in kidney transplantation.

PubMed

Torres, Irina B; Moreso, Francesc; Sarró, Eduard; Meseguer, Anna; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.
The Interplay between Inflammation and Fibrosis in Kidney Transplantation

PubMed Central

Torres, Irina B.; Moreso, Francesc; Sarró, Eduard; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis. PMID:24991565
Therapy for Duchenne muscular dystrophy: renewed optimism from genetic approaches.

PubMed

Fairclough, Rebecca J; Wood, Matthew J; Davies, Kay E

2013-06-01

Duchenne muscular dystrophy (DMD) is a devastating progressive disease for which there is currently no effective treatment except palliative therapy. There are several promising genetic approaches, including viral delivery of the missing dystrophin gene, read-through of translation stop codons, exon skipping to restore the reading frame and increased expression of the compensatory utrophin gene. The lessons learned from these approaches will be applicable to many other disorders.
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…
Alzheimer,s Disease Risk and Progression: The Role of Nutritional Supplements and their Effect on Drug Therapy Outcome

PubMed Central

Giulietti, A.; Vignini, A.; Nanetti, L.; Mazzanti, L.; Primio, R. Di; Salvolini, E.

2016-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly population. Despite significant advancements in understanding the genetic and molecular basis of AD, the pathology still lacks treatments that can slow down or reverse the progression of cognitive deterioration. Recently, the relationship between nutrient deficiency and dementia onset has been highlighted. AD is in fact a multifactorial pathology, so that a multi-target approach using combinations of micronutrients and drugs could have beneficial effects on cognitive function in neurodegenerative brain disorders leading to synaptic degeneration. Primarily, this review examines the most recent literature regarding the effects of nutrition on the risk/progression of the disease, focusing attention mostly on antioxidants agents, polyunsaturated fatty acids and metals. Secondly, it aims to figure out if nutritional supplements might have beneficial effects on drug therapy outcome. Even if nutritional supplements showed contrasting evidence of a likely effect of decreasing the risk of AD onset that could be studied more deeply in other clinical trials, no convincing data are present about their usefulness in combination with drug therapies and their effectiveness in slowing down the disease progression. PMID:26415975
A Learning Progressions Approach to Early Algebra Research and Practice

ERIC Educational Resources Information Center

Fonger, Nicole L.; Stephens, Ana; Blanton, Maria; Knuth, Eric

2015-01-01

We detail a learning progressions approach to early algebra research and how existing work around learning progressions and trajectories in mathematics and science education has informed our development of a four-component theoretical framework consisting of: a curricular progression of learning goals across big algebraic ideas; an instructional…
Overview of gene therapy clinical progress including cancer treatment with gene-modified T cells

PubMed Central

Brenner, Malcolm K.; Okur, Fatma V.

2010-01-01

It is now twenty years since the first legal gene transfer studies were approved, and there has been considerable disappointment in the slow rate of progress that followed the initial studies. Gradually, however, as the limitations of available vectors are acknowledged and overcome, and with advances in our understanding of the molecular and cell biology of genetic diseases and of cancer, unequivocal successes are now being reported. In this paper we describe the remaining major roadblocks to successful gene therapy and outline approaches to overcome them. We also illustrate how genetically modified immune system cells are already being used for the effective treatment of hematological and other malignancies, and how these approaches are being modified so that they can be effective in treating a broader range of malignancies. PMID:20008253
Tumor infiltrating lymphocytes in ovarian cancer

PubMed Central

Santoiemma, Phillip P; Powell, Daniel J

2015-01-01

The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment. PMID:25894333
Global Effects of DDX3 Inhibition on Cell Cycle Regulation Identified by a Combined Phosphoproteomics and Single Cell Tracking Approach.

PubMed

Heerma van Voss, Marise R; Kammers, Kai; Vesuna, Farhad; Brilliant, Justin; Bergman, Yehudit; Tantravedi, Saritha; Wu, Xinyan; Cole, Robert N; Holland, Andrew; van Diest, Paul J; Raman, Venu

2018-06-01

DDX3 is an RNA helicase with oncogenic properties. The small molecule inhibitor RK-33 is designed to fit into the ATP binding cleft of DDX3 and hereby block its activity. RK-33 has shown potent activity in preclinical cancer models. However, the mechanism behind the antineoplastic activity of RK-33 remains largely unknown. In this study we used a dual phosphoproteomic and single cell tracking approach to evaluate the effect of RK-33 on cancer cells. MDA-MB-435 cells were treated for 24 hours with RK-33 or vehicle control. Changes in phosphopeptide abundance were analyzed with quantitative mass spectrometry using isobaric mass tags (Tandem Mass Tags). At the proteome level we mainly observed changes in mitochondrial translation, cell division pathways and proteins related to cell cycle progression. Analysis of the phosphoproteome indicated decreased CDK1 activity after RK-33 treatment. To further evaluate the effect of DDX3 inhibition on cell cycle progression over time, we performed timelapse microscopy of Fluorescent Ubiquitin Cell Cycle Indicators labeled cells after RK-33 or siDDX3 exposure. Single cell tracking indicated that DDX3 inhibition resulted in a global delay in cell cycle progression in interphase and mitosis. In addition, we observed an increase in endoreduplication. Overall, we conclude that DDX3 inhibition affects cells in all phases and causes a global cell cycle progression delay. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Spasmodic dysphonia: onset, course, socioemotional effects, and treatment response.

PubMed

Tanner, Kristine; Roy, Nelson; Merrill, Ray M; Sauder, Cara; Houtz, Daniel R; Smith, Marshall E

2011-07-01

This investigation explored the onset, progression, socioemotional effects, and treatment outcomes of spasmodic dysphonia (SD). A cross-sectional epidemiological approach was used to examine questionnaire responses from 150 individuals with SD. Symptoms of SD (mean age at onset, 46 years) began gradually in 76% of cases and were progressive (ie, failed to plateau) in 34% of cases. Botulinum toxin A (Botox) helped to attenuate voice symptoms in 91% of cases; however, the scores on the Voice-Related Quality of Life questionnaire (V-RQOL) were not associated with this effect. The V-RQOL scores improved with time since symptom onset, independent of age and treatment. The patients with only SD experienced onset, course, and progression of symptoms similar to those of the patients with SD and coexisting vocal tremor. The symptoms of SD begin gradually and worsen over time. New evidence indicates that SD symptoms may continue to progress without plateau in at least a subset of patients. Individuals with SD and coexisting vocal tremor experience symptom trajectories similar to those of patients with SD only. Although Botox may attenuate voice symptoms, these effects do not appear to be strongly related to the V-RQOL scores. These results provide new and valuable insights regarding the onset, course, progression, and treatment of SD.

What to do? The effects of discrepancies, incentives, and time on dynamic goal prioritization.

PubMed

Schmidt, Aaron M; DeShon, Richard P

2007-07-01

This study examined factors that influence the dynamic pursuit of multiple goals over time. As hypothesized, goal-performance discrepancies were significantly related to subsequent time allocation. Greater distance from a given goal resulted in greater time subsequently allocated to that goal. In addition, the incentives offered for goal attainment determined the relative influence of discrepancies for each goal. When the incentives for each goal were equivalent, progress toward each goal exhibited equal influence, with greater time allocated to whichever goal was furthest from completion at the time. However, with an incentive available for only 1 of the 2 goals, time allocation was largely determined by progress toward the rewarded goal. Likewise, when incentives for each task differed in their approach-avoidance framing, progress toward the avoidance-framed goal was a stronger predictor of subsequent allocation than was progress toward the approach-framed goal. Finally, the influence of goal-performance discrepancies differed as a function of the time remaining for goal pursuit. The implications for future work on dynamic goal prioritization and the provision of performance incentives are discussed.
Interdisciplinary and participatory approaches: the key to effective groundwater management

NASA Astrophysics Data System (ADS)

Barthel, Roland; Foster, Stephen; Villholth, Karen G.

2017-11-01

The challenges of a changing world, which are progressively threatening sustainable use of groundwater resources, can only be rationally and effectively addressed through close collaboration between experts and practitioners from different disciplines. Furthermore, science and management need to build on stakeholder opinions and processes in order to generate useful knowledge and positive outcomes in terms of sustainable and equitable groundwater management. This essay provides a discussion of the status of and vision for participatory and inter-disciplinary approaches to groundwater evaluation and management as well as a conceptual framework and relevant research questions that will facilitate such approaches.
Item Response Theory as an Efficient Tool to Describe a Heterogeneous Clinical Rating Scale in De Novo Idiopathic Parkinson's Disease Patients.

PubMed

Buatois, Simon; Retout, Sylvie; Frey, Nicolas; Ueckert, Sebastian

2017-10-01

This manuscript aims to precisely describe the natural disease progression of Parkinson's disease (PD) patients and evaluate approaches to increase the drug effect detection power. An item response theory (IRT) longitudinal model was built to describe the natural disease progression of 423 de novo PD patients followed during 48 months while taking into account the heterogeneous nature of the MDS-UPDRS. Clinical trial simulations were then used to compare drug effect detection power from IRT and sum of item scores based analysis under different analysis endpoints and drug effects. The IRT longitudinal model accurately describes the evolution of patients with and without PD medications while estimating different progression rates for the subscales. When comparing analysis methods, the IRT-based one consistently provided the highest power. IRT is a powerful tool which enables to capture the heterogeneous nature of the MDS-UPDRS.
Wii Fit balance training or progressive balance training in patients with chronic stroke: a randomised controlled trial

PubMed Central

Yatar, Gozde Iyigun; Yildirim, Sibel Aksu

2015-01-01

[Purpose] The aim of this study was to compare the effects of Wii Fit balance training (WBT) and progressive balance training (PBT) approaches on balance functions, balance confidence, and activities of daily living in chronic stroke patients. [Subjects] A total of 30 patients were randomized into the WBT (n=15) and PBT (n=15) groups. [Methods] All of the subjects received exercise training based on a neurodevelopemental approach in addition to either Wii Fit or progressive balance training for total of 1 hour a day, 3 days per week for 4 weeks. Primary measurements were static balance function measured with a Wii Balance Board and dynamic balance function assessed with the Berg Balance Scale, Timed Up and Go test, Dynamic Gait Index, and Functional Reach Test. Secondary measures were balance confidence assessed with the Activities-specific Balance Confidence scale and activities of daily living evaluated with the Frenchay Activity Index. [Results] There was not remarkable difference between the two treatments in dynamic balance functions, balance confidence, and activities of daily living. [Conclusion] Although both of the approaches were found to be effective in improving the balance functions, balance confidence, and activities of daily living, neither of them were more preferable than the other for the treatment of balance in patients with chronic stroke. PMID:25995576
Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.

PubMed

Goeree, Ron; Villeneuve, Julie; Goeree, Jeff; Penrod, John R; Orsini, Lucinda; Tahami Monfared, Amir Abbas

2016-06-01

Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost, outcomes, and incremental cost-utility.
Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments

PubMed Central

Tefera, Tesfaye W.; Borges, Karin

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily characterized by loss of motor neurons in brain and spinal cord. The death of motor neurons leads to denervation of muscle which in turn causes muscle weakness and paralysis, decreased respiratory function and eventually death. Growing evidence indicates disturbances in energy metabolism in patients with ALS and animal models of ALS, which are likely to contribute to disease progression. Particularly, defects in glucose metabolism and mitochondrial dysfunction limit the availability of ATP to CNS tissues and muscle. Several metabolic approaches improving mitochondrial function have been investigated in vitro and in vivo and showed varying effects in ALS. The effects of metabolic approaches in ALS models encompass delays in onset of motor symptoms, protection of motor neurons and extension of survival, which signifies an important role of metabolism in the pathogenesis of the disease. There is now an urgent need to test metabolic approaches in controlled clinical trials. In addition, more detailed studies to better characterize the abnormalities in energy metabolism in patients with ALS and ALS models are necessary to develop metabolically targeted effective therapies that can slow the progression of the disease and prolong life for patients with ALS. PMID:28119559
Impact resistance of fiber composites - Energy-absorbing mechanisms and environmental effects

NASA Technical Reports Server (NTRS)

Chamis, C. C.; Sinclair, J. H.

1985-01-01

Energy absorbing mechanisms were identified by several approaches. The energy absorbing mechanisms considered are those in unidirectional composite beams subjected to impact. The approaches used include: mechanic models, statistical models, transient finite element analysis, and simple beam theory. Predicted results are correlated with experimental data from Charpy impact tests. The environmental effects on impact resistance are evaluated. Working definitions for energy absorbing and energy releasing mechanisms are proposed and a dynamic fracture progression is outlined. Possible generalizations to angle-plied laminates are described.
Impact resistance of fiber composites: Energy absorbing mechanisms and environmental effects

NASA Technical Reports Server (NTRS)

Chamis, C. C.; Sinclair, J. H.

1983-01-01

Energy absorbing mechanisms were identified by several approaches. The energy absorbing mechanisms considered are those in unidirectional composite beams subjected to impact. The approaches used include: mechanic models, statistical models, transient finite element analysis, and simple beam theory. Predicted results are correlated with experimental data from Charpy impact tests. The environmental effects on impact resistance are evaluated. Working definitions for energy absorbing and energy releasing mechanisms are proposed and a dynamic fracture progression is outlined. Possible generalizations to angle-plied laminates are described.
Stopping tuberculosis: a biosocial model for sustainable development.

PubMed

Ortblad, Katrina F; Salomon, Joshua A; Bärnighausen, Till; Atun, Rifat

2015-12-05

Tuberculosis transmission and progression are largely driven by social factors such as poor living conditions and poor nutrition. Increased standards of living and social approaches helped to decrease the burden of tuberculosis before the introduction of chemotherapy in the 1940s. Since then, management of tuberculosis has been largely biomedical. More funding for tuberculosis since 2000, coinciding with the Millennium Development Goals, has yielded progress in tuberculosis mortality but smaller reductions in incidence, which continues to pose a risk to sustainable development, especially in poor and susceptible populations. These at-risk populations need accelerated progress to end tuberculosis as resolved by the World Health Assembly in 2015. Effectively addressing the worldwide tuberculosis burden will need not only enhancement of biomedical approaches but also rebuilding of the social approaches of the past. To combine a biosocial approach, underpinned by social, economic, and environmental actions, with new treatments, new diagnostics, and universal health coverage, will need multisectoral coordination and action involving the health and other governmental sectors, as well as participation of the civil society, and especially the poor and susceptible populations. A biosocial approach to stopping tuberculosis will not only target morbidity and mortality from disease but would also contribute substantially to poverty alleviation and sustainable development that promises to meet the needs of the present, especially the poor, and provide them and subsequent generations an opportunity for a better future. Copyright © 2015 Elsevier Ltd. All rights reserved.
Comparing self-guided learning and educator-guided learning formats for simulation-based clinical training.

PubMed

Brydges, Ryan; Carnahan, Heather; Rose, Don; Dubrowski, Adam

2010-08-01

In this paper, we tested the over-arching hypothesis that progressive self-guided learning offers equivalent learning benefit vs. proficiency-based training while limiting the need to set proficiency standards. We have shown that self-guided learning is enhanced when students learn on simulators that progressively increase in fidelity during practice. Proficiency-based training, a current gold-standard training approach, requires achievement of a criterion score before students advance to the next learning level. Baccalaureate nursing students (n = 15/group) practised intravenous catheterization using simulators that differed in fidelity (i.e. students' perceived realism). Data were collected in 2008. Proficiency-based students advanced from low- to mid- to high-fidelity after achieving a proficiency criterion at each level. Progressive students self-guided their progression from low- to mid- to high-fidelity. Yoked control students followed an experimenter-defined progressive practice schedule. Open-ended students moved freely between the simulators. One week after practice, blinded experts evaluated students' skill transfer on a standardized patient simulation. Group differences were examined using analyses of variance. Proficiency-based students scored highest on the high-fidelity post-test (effect size = 1.22). An interaction effect showed that the Progressive and Open-ended groups maintained their performance from post-test to transfer test, whereas the Proficiency-based and Yoked control groups experienced a significant decrease (P < 0.05). Surprisingly, most Open-ended students (73%) chose the progressive practice schedule. Progressive training and proficiency-based training resulted in equivalent transfer test performance, suggesting that progressive students effectively self-guided when to transition between simulators. Students' preference for the progressive practice schedule indicates that educators should consider this sequence for simulation-based training.
Assessment approaches in massive open online courses: Possibilities, challenges and future directions

NASA Astrophysics Data System (ADS)

Xiong, Yao; Suen, Hoi K.

2018-03-01

The development of massive open online courses (MOOCs) has launched an era of large-scale interactive participation in education. While massive open enrolment and the advances of learning technology are creating exciting potentials for lifelong learning in formal and informal ways, the implementation of efficient and effective assessment is still problematic. To ensure that genuine learning occurs, both assessments for learning (formative assessments), which evaluate students' current progress, and assessments of learning (summative assessments), which record students' cumulative progress, are needed. Providers' more recent shift towards the granting of certificates and digital badges for course accomplishments also indicates the need for proper, secure and accurate assessment results to ensure accountability. This article examines possible assessment approaches that fit open online education from formative and summative assessment perspectives. The authors discuss the importance of, and challenges to, implementing assessments of MOOC learners' progress for both purposes. Various formative and summative assessment approaches are then identified. The authors examine and analyse their respective advantages and disadvantages. They conclude that peer assessment is quite possibly the only universally applicable approach in massive open online education. They discuss the promises, practical and technical challenges, current developments in and recommendations for implementing peer assessment. They also suggest some possible future research directions.
Deriving Flood-Mediated Connectivity between River Channels and Floodplains: Data-Driven Approaches

NASA Astrophysics Data System (ADS)

Zhao, Tongtiegang; Shao, Quanxi; Zhang, Yongyong

2017-03-01

The flood-mediated connectivity between river channels and floodplains plays a fundamental role in flood hazard mapping and exerts profound ecological effects. The classic nearest neighbor search (NNS) fails to derive this connectivity because of spatial heterogeneity and continuity. We develop two novel data-driven connectivity-deriving approaches, namely, progressive nearest neighbor search (PNNS) and progressive iterative nearest neighbor search (PiNNS). These approaches are illustrated through a case study in Northern Australia. First, PNNS and PiNNS are employed to identify flood pathways on floodplains through forward tracking. That is, progressive search is performed to associate newly inundated cells in each time step to previously inundated cells. In particular, iterations in PiNNS ensure that the connectivity is continuous - the connection between any two cells along the pathway is built through intermediate inundated cells. Second, inundated floodplain cells are collectively connected to river channel cells through backward tracing. Certain river channel sections are identified to connect to a large number of inundated floodplain cells. That is, the floodwater from these sections causes widespread floodplain inundation. Our proposed approaches take advantage of spatial-temporal data. They can be applied to achieve connectivity from hydro-dynamic and remote sensing data and assist in river basin planning and management.
Enhancing Conceptual Change in Preschool Children's Representations of Light: A Sociocognitive Approach

NASA Astrophysics Data System (ADS)

Ravanis, Konstantinos; Christidou, Vasilia; Hatzinikita, Vassilia

2013-12-01

The aim of this study is to investigate the effect of a sociocognitive teaching strategy on young children's understanding of light. It explores their understanding of the concept of light as an entity that is transmitted independently of the light source and the final receiver. The study was conducted in three phases: pretest, teaching intervention, and post-tests. The sample consisted of 170 preschool children who were assigned to two groups. The children in the first group participated in activities which adopted a sociocognitive approach. In the context of this approach, a familiar metaphor was introduced in order to facilitate children to construct a "precursor model" about light. The children in the second group participated in activities with the same teaching objectives, but adopting an empiricist perspective. Statistical analysis using the Mann-Whitney U test indicated that the cognitive progress of the sociocognitive group was more significant than the progress of the empiricist group. This provides evidence for the effect of the sociocognitive strategy on enhancing children in constructing a "precursor model" for the concept of light.
Case Study of a Research Intervention: The University of Utah's Collaborative Approach.

ERIC Educational Resources Information Center

Driscoll, Amy

A report is presented on the progress of the Applying Research to Teacher Education (ARTE) Research Utilization in Elementary Teacher Education (RUETE) study. The purpose of the study is to develop preservice instruction incorporating current research findings on effective instruction and effective schools and to assess the impact of the…
Treatment to sustain a Th17-type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer.

PubMed

Young, M Rita I; Levingston, Corinne A; Johnson, Sara D

2016-05-15

While immune suppression is a hallmark of head and neck squamous cell carcinoma (HSNCC), the immunological impact of premalignant oral lesions, which often precedes development of HNSCC, is unknown. The present study assessed the changes in splenic and draining lymph node CD4(+) cell populations and their production of select cytokines that occur in mice with carcinogen-induced premalignant oral lesions and the changes that occur as lesions progress to oral cancer. These studies found skewing toward Th1 and Th17-type phenotypes in the spleen and lymph nodes of mice with premalignant oral lesions and a shift to Treg as lesions progress to cancer. Since the role of Th17 cells in the progression from premalignant lesions to cancer is not clear, studies determined the immunological and clinical effect of treating mice bearing premalignant oral lesions with a TGF-β type 1 receptor inhibitor plus IL-23 as an approach to sustain the Th17 phenotype. These studies showed that the treatment approach not only sustained the Th17 phenotype, but also increased distal spleen cell and regional lymph node cell production of other stimulatory/inflammatory mediators and slowed premalignant lesion progression to cancer. © 2016 UICC.
Treatment to sustain a Th17-type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer

PubMed Central

Young, M. Rita I.; Levingston, Corinne A.; Johnson, Sara D.

2018-01-01

While immune suppression is a hallmark of head and neck squamous cell carcinoma (HSNCC), the immunological impact of premalignant oral lesions, which often precedes development of HNSCC, is unknown. The present study assessed the changes in splenic and draining lymph node CD4+cell populations and their production of select cytokines that occur in mice with carcinogen-induced premalignant oral lesions and the changes that occur as lesions progress to oral cancer. These studies found skewing toward Th1 and Th17-type phenotypes in the spleen and lymph nodes of mice with premalignant oral lesions and a shift to Treg as lesions progress to cancer. Since the role of Th17 cells in the progression from premalignant lesions to cancer is not clear, studies determined the immunological and clinical effect of treating mice bearing premalignant oral lesions with a TGF-β type 1 receptor inhibitor plus IL-23 as an approach to sustain the Th17 phenotype. These studies showed that the treatment approach not only sustained the Th17 phenotype, but also increased distal spleen cell and regional lymph node cell production of other stimulatory/inflammatory mediators and slowed premalignant lesion progression to cancer. PMID:26756968
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.
Pushing the Child Centred Approach in Myanmar: The Role of Cross National Policy Networks and the Effects in the Classroom

ERIC Educational Resources Information Center

Lall, Marie

2011-01-01

In Myanmar schools, rote learning is the norm. International aid and education organisations based in the country have been trying to promote the child centred approach (CCA) as a much more progressive form of teaching and learning. The CCA is being rolled out principally through monastic school networks aided by international and national…
Vincristine-induced peripheral neuropathy in pediatric cancer patients

PubMed Central

Mora, Erika; Smith, Ellen M Lavoie; Donohoe, Clare; Hertz, Daniel L

2016-01-01

Vincristine is a chemotherapeutic agent that is a component of many combination regimens for a variety of malignancies, including several common pediatric tumors. Vincristine treatment is limited by a progressive sensorimotor peripheral neuropathy. Vincristine-induced peripheral neuropathy (VIPN) is particularly challenging to detect and monitor in pediatric patients, in whom the side effect can diminish long term quality of life. This review summarizes the current state of knowledge regarding VIPN, focusing on its description, assessment, prediction, prevention, and treatment. Significant progress has been made in our knowledge about VIPN incidence and progression, and tools have been developed that enable clinicians to reliably measure VIPN in pediatric patients. Despite these successes, little progress has been made in identifying clinically useful predictors of VIPN or in developing effective approaches for VIPN prevention or treatment in either pediatric or adult patients. Further research is needed to predict, prevent, and treat VIPN to maximize therapeutic benefit and avoid unnecessary toxicity from vincristine treatment. PMID:27904761
Antisecretory Factor-mediated Inhibition of Cell Volume Dynamics Produces Anti-tumor Activity in Glioblastoma. | Office of Cancer Genomics

Cancer.gov

Interstitial fluid pressure (IFP) presents a barrier to drug uptake in solid tumors, including the aggressive primary brain tumor glioblastoma multiforme (GBM). It remains unclear how fluid dynamics impacts tumor progression and can be targeted therapeutically. To address this issue, a novel telemetry-based approach was developed to measure changes in IFP during progression of GBM xenografts. Antisecretory factor (AF) is an endogenous protein that displays anti-secretory effects in animals and patients.

Pathophysiology of Tumor Neovascularization

PubMed Central

Furuya, Mitsuko; Nishiyama, Mariko; Kasuya, Yoshitoshi; Kimura, Sadao; Ishikura, Hiroshi

2005-01-01

Neovascularization is essential to the process of development and differentiation of tissues in the vertebrate embryo, and is also involved in a wide variety of physiological and pathological conditions in adults, including wound repair, metabolic diseases, inflammation, cardiovascular disorders, and tumor progression. Thanks to cumulative studies on vasculature, new therapeutic approaches have been opened for us to some life-threatening diseases by controlling angiogenesis in the affected organs. In cancer therapy, for example, modulation of factors responsible for tumor angiogenesis may be beneficial in inhibiting of tumor progression. Several antiangiogenic approaches are currently under preclinical trial. However, the mechanisms of neovascularization in tumors are complicated and each tumor shows unique features in its vasculature, depending on tissue specificity, angiogenic micromilieu, grades and stages, host immunity, and so on. For better understanding and effective therapeutic approaches, it is important to clarify both the general mechanism of angiogenic events and the disease-specific mechanism of neovascularization. This review discusses the general features of angiogenesis under physiological and pathological conditions, mainly in tumor progression. In addition, recent topics such as contribution of the endothelial progenitor cells, tumor vasculogenic mimicry, markers for tumor-derived endothelial cells and pericytes, and angiogenic/angiostatic chemokines are summarized. PMID:17315600
Investigating the Effect of Damage Progression Model Choice on Prognostics Performance

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Roychoudhury, Indranil; Narasimhan, Sriram; Saha, Sankalita; Saha, Bhaskar; Goebel, Kai

2011-01-01

The success of model-based approaches to systems health management depends largely on the quality of the underlying models. In model-based prognostics, it is especially the quality of the damage progression models, i.e., the models describing how damage evolves as the system operates, that determines the accuracy and precision of remaining useful life predictions. Several common forms of these models are generally assumed in the literature, but are often not supported by physical evidence or physics-based analysis. In this paper, using a centrifugal pump as a case study, we develop different damage progression models. In simulation, we investigate how model changes influence prognostics performance. Results demonstrate that, in some cases, simple damage progression models are sufficient. But, in general, the results show a clear need for damage progression models that are accurate over long time horizons under varied loading conditions.
Molecular Pathogenesis of NASH

PubMed Central

Caligiuri, Alessandra; Gentilini, Alessandra; Marra, Fabio

2016-01-01

Nonalcoholic steatohepatitis (NASH) is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression. PMID:27657051
Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis.

PubMed

Carlesi, Cecilia; Pasquali, Livia; Piazza, Selina; Lo Gerfo, Annalisa; Caldarazzo Ienco, Elena; Alessi, Rosaria; Fornai, Francesco; Siciliano, Gabriele

2011-03-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disorder of unknown aetiology that involves the loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Significant progress in understanding the cellular mechanisms of motor neuron degeneration in ALS has not been matched with the development of therapeutic strategies to prevent disease progression, and riluzole remains the only available therapy, with only marginal effects on disease survival. More recently alterations of mRNA processing in genetically defined forms of ALS, as those related to TDP-43 and FUS-TLS gene mutations have provided important insights into the molecular networks implicated in the disease pathogenesis. Here we review some of the recent progress in promoting therapeutic strategies for neurodegeneration.
Plain packaging: a logical progression for tobacco control in one of the world's ‘darkest markets’

PubMed Central

Scollo, Michelle; Bayly, Megan; Wakefield, Melanie

2015-01-01

The Australian approach to tobacco control has been a comprehensive one, encompassing mass media campaigns, consumer information, taxation policy, access for smokers to smoking cessation advice and pharmaceutical treatments, protection from exposure to tobacco smoke and regulation of promotion. World-first legislation to standardise the packaging of tobacco was a logical next step to further reduce misleadingly reassuring promotion of a product known for the past 50 years to kill a high proportion of its long-term users. Similarly, refreshed, larger pack warnings which started appearing on packs at the end of 2012 were a logical progression of efforts to ensure that consumers are better informed about the health risks associated with smoking. Regardless of the immediate effects of legislation, further progress will continue to require a comprehensive approach to maintain momentum and ensure that government efforts on one front are not undermined by more vigorous efforts and greater investment by tobacco companies elsewhere. PMID:28407604
Optimizing management of actinic keratosis and photodamaged skin: utilizing a stepwise approach.

PubMed

Lee, Andrew D; Jorizzo, Joseph L

2009-09-01

The incidence of photodamaged skin and skin lesions of all degrees of severity, from actinic keratosis (AK) to skin cancers, has dramatically increased. Actinic keratoses are pathologic, reflecting damage of essential skin cell functions and potentially progressing to invasive squamous cell carcinoma (SCC). The rate of progression is uncertain but may be as high as 10%. Because it is impossible to predict which AKs will progress to SCC, all lesions should be treated. Options include topical therapies, cryotherapy, curettage, and photodynamic therapy. Unfortunately, many individuals do not seek treatment or avoid it because of irritation, discomfort, and concern for scarring. Combining field-directed therapy and cryotherapy has been more effective than cryotherapy alone. Incorporating patient education with treatment may optimize outcomes. We propose a comprehensive 5-step approach for managing AK lesions and photodamaged skin that includes periodic clinical skin examinations; treating AK lesions with a combination of field- and lesion-directed therapy; and patient education regarding sun-protective measures and regular skin self-examinations.
Hybrid antibiotics - clinical progress and novel designs.

PubMed

Parkes, Alastair L; Yule, Ian A

2016-07-01

There is a growing need for new antibacterial agents, but success in development of antibiotics in recent years has been limited. This has led researchers to investigate novel approaches to finding compounds that are effective against multi-drug resistant bacteria, and that delay onset of resistance. One such strategy has been to link antibiotics to produce hybrids designed to overcome resistance mechanisms. The concept of dual-acting hybrid antibiotics was introduced and reviewed in this journal in 2010. In the present review the authors sought to discover how clinical candidates described had progressed, and to examine how the field has developed. In three sections the authors cover the clinical progress of hybrid antibiotics, novel agents produced from hybridisation of two or more small-molecule antibiotics, and novel agents produced from hybridisation of antibiotics with small-molecules that have complementary activity. Many key questions regarding dual-acting hybrid antibiotics remain to be answered, and the proposed benefits of this approach are yet to be demonstrated. While Cadazolid in particular continues to progress in the clinic, suggesting that there is promise in hybridisation through covalent linkage, it may be that properties other than antibacterial activity are key when choosing a partner molecule.
A Sharing Mind Map-Oriented Approach to Enhance Collaborative Mobile Learning with Digital Archiving Systems

ERIC Educational Resources Information Center

Chang, Jui-Hung; Chiu, Po-Sheng; Huang, Yueh-Min

2018-01-01

With the advances in mobile network technology, the use of portable devices and mobile networks for learning is not limited by time and space. Such use, in combination with appropriate learning strategies, can achieve a better effect. Despite the effectiveness of mobile learning, students' learning direction, progress, and achievement may differ.…
An Alternative Three-Level Model for Estimating SEIs and Their Stability.

ERIC Educational Resources Information Center

Mandeville, Garrett K.

After a brief review of recent research concerning school effectiveness, this paper proposes an approach to operationalizing school effectiveness that is based on the achievement of students in a school over a period of time. This three-level model does not follow a single cohort of students as they progress through school. Rather, it uses the…
Evolutionary space platform concept study. Volume 2, part A: SASP special emphasis trade studies

NASA Technical Reports Server (NTRS)

1982-01-01

Efforts are in progress to define an approach to provide a simple and cost effective solution to the problem of long duration space flight. This approach involves a Space Platform in low Earth orbit, which can be tended by the Space Shuttle and which will provide, for extended periods of time, stability, utilities and access for a variety of replaceable payloads. The feasibility of an evolutionary space system which would cost effectively support unmanned payloads in groups, using a Space Platform which provides centralized basic subsystems is addressed.
Rating competitors before tournament starts: How it's affecting team progression in a soccer tournament

NASA Astrophysics Data System (ADS)

Yusof, Muhammad Mat; Sulaiman, Tajularipin; Khalid, Ruzelan; Hamid, Mohamad Shukri Abdul; Mansor, Rosnalini

2014-12-01

In professional sporting events, rating competitors before tournament start is a well-known approach to distinguish the favorite team and the weaker teams. Various methodologies are used to rate competitors. In this paper, we explore four ways to rate competitors; least squares rating, maximum likelihood strength ratio, standing points in large round robin simulation and previous league rank position. The tournament metric we used to evaluate different types of rating approach is tournament outcome characteristics measure. The tournament outcome characteristics measure is defined by the probability that a particular team in the top 100q pre-tournament rank percentile progress beyond round R, for all q and R. Based on simulation result, we found that different rating approach produces different effect to the team. Our simulation result shows that from eight teams participate in knockout standard seeding, Perak has highest probability to win for tournament that use the least squares rating approach, PKNS has highest probability to win using the maximum likelihood strength ratio and the large round robin simulation approach, while Perak has the highest probability to win a tournament using previous league season approach.
A Life Participation Approach to Primary Progressive Aphasia Intervention.

PubMed

Rogalski, Emily J; Khayum, Becky

2018-07-01

Primary progressive aphasia (PPA) is a clinical neurodegenerative dementia syndrome characterized by deficits in spoken and written word retrieval, word usage, and/or word comprehension. Currently, there are no effective treatments to reverse or halt the underlying disease process; however, speech-language therapy may be helpful. The Communication Bridge Care Model was developed to address the unique communication and quality of life needs of individuals living with PPA. The core elements include person-centered care with dyadic instruction for disease education, and counseling, along with tailored levels of impairment- and compensatory-based communication strategy training. Our multicomponent approach incorporates guidance from the Life Participation Approach for Aphasia, including client-directed assessment and interventions that aim to maximize functional communication and participation in desired life activities. The direct and indirect use of technology is integrated into our tailored model of care to facilitate achievement of the client's functional goals. Here, we describe how to practically apply the Communication Bridge Care Model across treatment settings, including case examples from the Communication Bridge research study. This approach to care provides an opportunity to maximize communication effectiveness and quality of life for individuals living with PPA throughout the course of disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Modelling the Progression of Competitive Performance of an Academy's Soccer Teams.

PubMed

Malcata, Rita M; Hopkins, Will G; Richardson, Scott

2012-01-01

Progression of a team's performance is a key issue in competitive sport, but there appears to have been no published research on team progression for periods longer than a season. In this study we report the game-score progression of three teams of a youth talent-development academy over five seasons using a novel analytic approach based on generalised mixed modelling. The teams consisted of players born in 1991, 1992 and 1993; they played totals of 115, 107 and 122 games in Asia and Europe between 2005 and 2010 against teams differing in age by up to 3 years. Game scores predicted by the mixed model were assumed to have an over-dispersed Poisson distribution. The fixed effects in the model estimated an annual linear pro-gression for Aspire and for the other teams (grouped as a single opponent) with adjustment for home-ground advantage and for a linear effect of age difference between competing teams. A random effect allowed for different mean scores for Aspire and opposition teams. All effects were estimated as factors via log-transformation and presented as percent differences in scores. Inferences were based on the span of 90% confidence intervals in relation to thresholds for small factor effects of x/÷1.10 (+10%/-9%). Most effects were clear only when data for the three teams were combined. Older teams showed a small 27% increase in goals scored per year of age difference (90% confidence interval 13 to 42%). Aspire experienced a small home-ground advantage of 16% (-5 to 41%), whereas opposition teams experienced 31% (7 to 60%) on their own ground. After adjustment for these effects, the Aspire teams scored on average 1.5 goals per match, with little change in the five years of their existence, whereas their opponents' scores fell from 1.4 in their first year to 1.0 in their last. The difference in progression was trivial over one year (7%, -4 to 20%), small over two years (15%, -8 to 44%), but unclear over >2 years. In conclusion, the generalized mixed model has marginal utility for estimating progression of soccer scores, owing to the uncertainty arising from low game scores. The estimates are likely to be more precise and useful in sports with higher game scores. Key pointsA generalized linear mixed model is the approach for tracking game scores, key performance indicators or other measures of performance based on counts in sports where changes within and/or between games/seasons have to be considered.Game scores in soccer could be useful to track performance progression of teams, but hundreds of games are needed.Fewer games will be needed for tracking performance represented by counts with high scores, such as game scores in rugby or key performance indicators based on frequent events or player actions in any team sport.
Modelling the Progression of Competitive Performance of an Academy’s Soccer Teams

PubMed Central

Malcata, Rita M.; Hopkins, Will G; Richardson, Scott

2012-01-01

Progression of a team’s performance is a key issue in competitive sport, but there appears to have been no published research on team progression for periods longer than a season. In this study we report the game-score progression of three teams of a youth talent-development academy over five seasons using a novel analytic approach based on generalised mixed modelling. The teams consisted of players born in 1991, 1992 and 1993; they played totals of 115, 107 and 122 games in Asia and Europe between 2005 and 2010 against teams differing in age by up to 3 years. Game scores predicted by the mixed model were assumed to have an over-dispersed Poisson distribution. The fixed effects in the model estimated an annual linear pro-gression for Aspire and for the other teams (grouped as a single opponent) with adjustment for home-ground advantage and for a linear effect of age difference between competing teams. A random effect allowed for different mean scores for Aspire and opposition teams. All effects were estimated as factors via log-transformation and presented as percent differences in scores. Inferences were based on the span of 90% confidence intervals in relation to thresholds for small factor effects of x/÷1.10 (+10%/-9%). Most effects were clear only when data for the three teams were combined. Older teams showed a small 27% increase in goals scored per year of age difference (90% confidence interval 13 to 42%). Aspire experienced a small home-ground advantage of 16% (-5 to 41%), whereas opposition teams experienced 31% (7 to 60%) on their own ground. After adjustment for these effects, the Aspire teams scored on average 1.5 goals per match, with little change in the five years of their existence, whereas their opponents’ scores fell from 1.4 in their first year to 1.0 in their last. The difference in progression was trivial over one year (7%, -4 to 20%), small over two years (15%, -8 to 44%), but unclear over >2 years. In conclusion, the generalized mixed model has marginal utility for estimating progression of soccer scores, owing to the uncertainty arising from low game scores. The estimates are likely to be more precise and useful in sports with higher game scores. Key pointsA generalized linear mixed model is the approach for tracking game scores, key performance indicators or other measures of performance based on counts in sports where changes within and/or between games/seasons have to be considered.Game scores in soccer could be useful to track performance progression of teams, but hundreds of games are needed.Fewer games will be needed for tracking performance represented by counts with high scores, such as game scores in rugby or key performance indicators based on frequent events or player actions in any team sport. PMID:24149364
The role of exercise in amyotrophic lateral sclerosis.

PubMed

Chen, Amy; Montes, Jacqueline; Mitsumoto, Hiroshi

2008-08-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the motor nervous system. It causes progressive and cumulative physical disabilities in patients, and leads to eventual death due to respiratory muscle failure. The disease is diverse in its presentation, course, and progression. We do not yet fully understand the cause or causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. Currently, we rely on a multidisciplinary approach to symptomatically manage and care for patients who have ALS. In this article, the authors review the literature on the role of exercise in patients who have ALS, and briefly compare what is known about exercise in other neuromuscular diseases.
Direct Surgery of Previously Coiled Large Internal Carotid Ophthalmic Aneurysm for the Purpose of Optic Nerve Decompression

PubMed Central

Kawabata, Shuhei; Toyota, Shingo; Kumagai, Tetsuya; Goto, Tetsu; Mori, Kanji; Taki, Takuyu

2017-01-01

Background Progressive visual loss after coil embolization of a large internal carotid ophthalmic aneurysm has been widely reported. It is generally accepted that the primary strategy for this complication should be conservative, including steroid therapy; however, it is not well known as to what approach to take when the conservative therapy is not effective. Case Presentation We report a case of a 55-year-old female presenting with progressive visual loss after the coiling of a ruptured large internal carotid ophthalmic aneurysm. As the conservative therapy had not been effective, we performed neck clipping of the aneurysm with optic canal unroofing, anterior clinoidectomy, and partial removal of the embolized coils for the purpose of optic nerve decompression. After the surgery, the visual symptom was improved markedly. Conclusions It is suggested that direct surgery for the purpose of optic nerve decompression may be one of the options when conservative therapy is not effective for progressive visual disturbance after coil embolization. PMID:28229036
Trabecular morphometry by fractal signature analysis is a novel marker of osteoarthritis progression.

PubMed

Kraus, Virginia Byers; Feng, Sheng; Wang, ShengChu; White, Scott; Ainslie, Maureen; Brett, Alan; Holmes, Anthony; Charles, H Cecil

2009-12-01

To evaluate the effectiveness of using subchondral bone texture observed on a radiograph taken at baseline to predict progression of knee osteoarthritis (OA) over a 3-year period. A total of 138 participants in the Prediction of Osteoarthritis Progression study were evaluated at baseline and after 3 years. Fractal signature analysis (FSA) of the medial subchondral tibial plateau was performed on fixed flexion radiographs of 248 nonreplaced knees, using a commercially available software tool. OA progression was defined as a change in joint space narrowing (JSN) or osteophyte formation of 1 grade according to a standardized knee atlas. Statistical analysis of fractal signatures was performed using a new model based on correlating the overall shape of a fractal dimension curve with radius. Fractal signature of the medial tibial plateau at baseline was predictive of medial knee JSN progression (area under the curve [AUC] 0.75, of a receiver operating characteristic curve) but was not predictive of osteophyte formation or progression of JSN in the lateral compartment. Traditional covariates (age, sex, body mass index, knee pain), general bone mineral content, and joint space width at baseline were no more effective than random variables for predicting OA progression (AUC 0.52-0.58). The predictive model with maximum effectiveness combined fractal signature at baseline, knee alignment, traditional covariates, and bone mineral content (AUC 0.79). We identified a prognostic marker of OA that is readily extracted from a plain radiograph using FSA. Although the method needs to be validated in a second cohort, our results indicate that the global shape approach to analyzing these data is a potentially efficient means of identifying individuals at risk of knee OA progression.
A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-1-0654 TITLE: A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS...valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE Oct 2017 2. REPORT TYPE Annual 3. DATES COVERED 30...Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT
A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0653 TITLE: A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS...Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e...compare the gut microbiome of subjects with RMS and PPMS. Major Task 1: To seek and obtain HRPO approval Major Task 2: Identification and
A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0654 TITLE: A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS...Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Major Tasks and subtasks: Aim#1: To compare the gut microbiome of subjects with RMS and PPMS. Major Task 1: To seek and obtain HRPO approval Major

A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0652 TITLE: A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS...0652 A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...SOW, each Aim was subdivided into Major Tasks and subtasks: Aim#1: To compare the gut microbiome of subjects with RMS and PPMS. Major Task 1
Progress 28 supply vehicle approach

NASA Image and Video Library

2008-02-07

ISS016-E-027761 (7 Feb. 2008) --- Backdropped by a colorful Earth, an unpiloted Progress supply vehicle approaches the International Space Station. Progress 28 resupply craft launched at 7:03 a.m. (CST) on Feb. 5, 2008 from the Baikonur Cosmodrome in Kazakhstan to deliver more than 2.5 tons of food, fuel, oxygen and other supplies to the Expedition 16 crewmembers onboard the station. Progress automatically docked to the Pirs Docking Compartment at 8:30 a.m. (CST) on Feb. 7.
Progress 28 supply vehicle approach

NASA Image and Video Library

2008-02-07

ISS016-E-027815 (7 Feb. 2008) --- Backdropped by a colorful Earth, an unpiloted Progress supply vehicle approaches the International Space Station. Progress 28 resupply craft launched at 7:03 a.m. (CST) on Feb. 5, 2008 from the Baikonur Cosmodrome in Kazakhstan to deliver more than 2.5 tons of food, fuel, oxygen and other supplies to the Expedition 16 crewmembers onboard the station. Progress automatically docked to the Pirs Docking Compartment at 8:30 a.m. (CST) on Feb. 7.
Genetic Approaches to Study Meiosis and Meiosis-Specific Gene Expression in Saccharomyces cerevisiae.

PubMed

Kassir, Yona; Stuart, David T

2017-01-01

The budding yeast Saccharomyces cerevisiae has a long history as a model organism for studies of meiosis and the cell cycle. The popularity of this yeast as a model is in large part due to the variety of genetic and cytological approaches that can be effectively performed with the cells. Cultures of the cells can be induced to synchronously progress through meiosis and sporulation allowing large-scale gene expression and biochemical studies to be performed. Additionally, the spore tetrads resulting from meiosis make it possible to characterize the haploid products of meiosis allowing investigation of meiotic recombination and chromosome segregation. Here we describe genetic methods for analysis progression of S. cerevisiae through meiosis and sporulation with an emphasis on strategies for the genetic analysis of regulators of meiosis-specific genes.
Semiotics and the placebo effect.

PubMed

Miller, Franklin G; Colloca, Luana

2010-01-01

Despite substantial progress in elucidating its neurobiological mechanisms, theoretical understanding of the placebo effect is poorly developed. Application of the semiotic theory developed by the American philosopher Charles Peirce offers a promising account of placebo effects as involving the apprehension and response to signs. The semiotic approach dovetails with the various psychological mechanisms invoked to account for placebo effects, such as conditioning and expectation, and bridges the biological and cultural dimensions of this fascinating phenomenon.
Neuroprotective effects of phytochemicals on dopaminergic neuron cultures.

PubMed

Sandoval-Avila, S; Diaz, N F; Gómez-Pinedo, U; Canales-Aguirre, A A; Gutiérrez-Mercado, Y K; Padilla-Camberos, E; Marquez-Aguirre, A L; Díaz-Martínez, N E

2016-06-21

Parkinson's disease is a progressive neurodegenerative disorder characterised by a loss of dopaminergic neurons in the substantia nigra pars compacta, which results in a significant decrease in dopamine levels and consequent functional motor impairment. Although its aetiology is not fully understood, several pathogenic mechanisms, including oxidative stress, have been proposed. Current therapeutic approaches are based on dopamine replacement drugs; these agents, however, are not able to stop or even slow disease progression. Novel therapeutic approaches aimed at acting on the pathways leading to neuronal dysfunction and death are under investigation. In recent years, such natural molecules as polyphenols, alkaloids, and saponins have been shown to have a neuroprotective effect due to their antioxidant and anti-inflammatory properties. The aim of our review is to analyse the most relevant studies worldwide addressing the benefits of some phytochemicals used in in vitro models of Parkinson's disease. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.
[DIET CHARACTERISTICS IN PATIENTS WITH CHRONIC KIDNEY DISEASE].

PubMed

Bašić-Marković, N; Šutić, I; Popović, B; Marković, R; Vučak, J

2016-12-01

Because of the increasing number of patients, chronic kidney disease (CKD) has become a significant public health problem. As kidney function decreases, it is necessary to introduce certain dietary modifications. The aim was to investigate what is the appropriate approach to diet of CKD patients, which could contribute to slowing down progression of the disease. Dietary recommendations are individual for each patient, but also vary in the same patient depending on the stage of disease progression because special attention must be paid to appropriate intake of macronutrients (protein, carbohydrates and fats), micronutrients (sodium, potassium, calcium, phosphorus, zinc, selenium, various vitamins), and water. In newly diagnosed patients, it is necessary to assess their nutritional status and energy requirements. It has been shown that protein-energy malnutrition, muscle loss and cachexia are strong predictors of mortality in CKD. Comparing different dietary approaches in everyday life of patients suffering from CKD, it was found that the most effective diet is Mediterranean food style. Studies confirm that Mediterranean diet has a preventive effect on renal function and reduces progression of the disease. Preventive measures, correct identification and early intervention can increase survival of patients and improve their quality of life. Mediterranean diet tailored to individual stages of CKD has been confirmed as the best choice in CKD patients.
Metabolic enzymes dysregulation in heart failure: the prospective therapy.

PubMed

Parihar, Priyanka; Parihar, Mordhwaj Singh

2017-01-01

The heart failure accounts for the highest mortality rate all over the world. The development of preventive therapeutic approaches is still in their infancy. Owing to the extremely high energy demand of the heart, the bioenergetics pathways need to respond efficiently based on substrate availability. The metabolic regulation of such heart bioenergetics is mediated by various rate limiting enzymes involved in energy metabolism. Although all the pertinent mechanisms are not clearly understood, the progressive decline in the activity of metabolic enzymes leading to diminished ATP production is known to cause progression of the heart failure. Therefore, metabolic therapy that can maintain the appropriate activities of metabolic enzymes can be a promising approach for the prevention and treatment of the heart failure. The flavonoids that constitute various human dietary ingredients also effectively offer a variety of health benefits. The flavonoids target a variety of metabolic enzymes and facilitate effective management of the equilibrium between production and utilization of energy in the heart. This review discusses the broad impact of metabolic enzymes in the heart functions and explains how the dysregulated enzyme activity causes the heart failure. In addition, the prospects of targeting dysregulated metabolic enzymes by developing flavonoid-based metabolic approaches are discussed.
A Progressive Damage Model for unidirectional Fibre Reinforced Composites with Application to Impact and Penetration Simulation

NASA Astrophysics Data System (ADS)

Kerschbaum, M.; Hopmann, C.

2016-06-01

The computationally efficient simulation of the progressive damage behaviour of continuous fibre reinforced plastics is still a challenging task with currently available computer aided engineering methods. This paper presents an original approach for an energy based continuum damage model which accounts for stress-/strain nonlinearities, transverse and shear stress interaction phenomena, quasi-plastic shear strain components, strain rate effects, regularised damage evolution and consideration of load reversal effects. The physically based modelling approach enables experimental determination of all parameters on ply level to avoid expensive inverse analysis procedures. The modelling strategy, implementation and verification of this model using commercially available explicit finite element software are detailed. The model is then applied to simulate the impact and penetration of carbon fibre reinforced cross-ply specimens with variation of the impact speed. The simulation results show that the presented approach enables a good representation of the force-/displacement curves and especially well agreement with the experimentally observed fracture patterns. In addition, the mesh dependency of the results were assessed for one impact case showing only very little change of the simulation results which emphasises the general applicability of the presented method.
Site-level progression of periodontal disease during a follow-up period

PubMed Central

Morozumi, Toshiya; Nakagawa, Taneaki; Sugaya, Tsutomu; Kawanami, Masamitsu; Suzuki, Fumihiko; Takahashi, Keiso; Abe, Yuzo; Sato, Soh; Makino-Oi, Asako; Saito, Atsushi; Takano, Satomi; Minabe, Masato; Nakayama, Yohei; Ogata, Yorimasa; Kobayashi, Hiroaki; Izumi, Yuichi; Sugano, Naoyuki; Ito, Koichi; Sekino, Satoshi; Numabe, Yukihiro; Fukaya, Chie; Yoshinari, Nobuo; Fukuda, Mitsuo; Noguchi, Toshihide; Kono, Tomoo; Umeda, Makoto; Fujise, Osamu; Nishimura, Fusanori; Yoshimura, Atsutoshi; Hara, Yoshitaka; Nakamura, Toshiaki; Noguchi, Kazuyuki; Kakuta, Erika; Hanada, Nobuhiro; Takashiba, Shogo; Amitani, Yasuharu; Yoshie, Hiromasa

2017-01-01

Periodontal disease is assessed and its progression is determined via observations on a site-by-site basis. Periodontal data are complex and structured in multiple levels; thus, applying a summary statistical approach (i.e., the mean) for site-level evaluations results in loss of information. Previous studies have shown the availability of mixed effects modeling. However, clinically beneficial information on the progression of periodontal disease during the follow-up period is not available. We conducted a multicenter prospective cohort study. Using mixed effects modeling, we analyzed 18,834 sites distributed on 3,139 teeth in 124 patients, and data were collected 5 times over a 24-month follow-up period. The change in the clinical attachment level (CAL) was used as the outcome variable. The CAL at baseline was an important determinant of the CAL changes, which varied widely according to the tooth surface. The salivary levels of periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were affected by CAL progression. “Linear”- and “burst”-type patterns of CAL progression occurred simultaneously within the same patient. More than half of the teeth that presented burst-type progression sites also presented linear-type progression sites, and most of the progressions were of the linear type. Maxillary premolars and anterior teeth tended to show burst-type progression. The parameters identified in this study may guide practitioners in determining the type and extent of treatment needed at the site and patient levels. In addition, these results show that prior hypotheses concerning "burst" and "linear" theories are not valid. PMID:29206238
Suppression of mitochondrial respiration with auraptene inhibits the progression of renal cell carcinoma: involvement of HIF-1α degradation.

PubMed

Jang, Yunseon; Han, Jeongsu; Kim, Soo Jeong; Kim, Jungim; Lee, Min Joung; Jeong, Soyeon; Ryu, Min Jeong; Seo, Kang-Sik; Choi, Song-Yi; Shong, Minho; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

2015-11-10

Renal cell carcinoma (RCC) progression resulting from the uncontrolled migration and enhanced angiogenesis is an obstacle to effective therapeutic intervention. Tumor metabolism has distinctive feature called Warburg effect, which enhances the aerobic glycolysis rapidly supplying the energy for migration of tumor. To manipulate this metabolic change characteristic of aggressive tumors, we utilized the citrus extract, auraptene, known as a mitochondrial inhibitor, testing its anticancer effects against the RCC4 cell line. We found that auraptene impaired RCC4 cell motility through reduction of mitochondrial respiration and glycolytic pathway-related genes. It also strongly disrupted VEGF-induced angiogenesis in vitro and in vivo. Hypoxia-inducible factor 1a (HIF-1a), a key regulator of cancer metabolism, migration and angiogenesis that is stably expressed in RCCs by virtue of a genetic mutation in the von Hippel-Lindau (VHL) tumor-suppressor protein, was impeded by auraptene, which blocked HIF-1a translation initiation without causing cytotoxicity. We suggest that blockade HIF-1a and reforming energy metabolism with auraptene is an effective approach for suspension RCC progression.
Systematic Analysis of Cell Cycle Effects of Common Drugs Leads to the Discovery of a Suppressive Interaction between Gemfibrozil and Fluoxetine

PubMed Central

Hoose, Scott A.; Duran, Camille; Malik, Indranil; Eslamfam, Shabnam; Shasserre, Samantha C.; Downing, S. Sabina; Hoover, Evelyn M.; Dowd, Katherine E.; Smith, Roger; Polymenis, Michael

2012-01-01

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation. PMID:22567160
Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.

PubMed

Hoose, Scott A; Duran, Camille; Malik, Indranil; Eslamfam, Shabnam; Shasserre, Samantha C; Downing, S Sabina; Hoover, Evelyn M; Dowd, Katherine E; Smith, Roger; Polymenis, Michael

2012-01-01

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation.
Alternative Approach to Teaching Veterinary Anatomy: A Progress Report

ERIC Educational Resources Information Center

Hullinger, Ronald; Render, Gary F.

1975-01-01

Students in microscopic anatomy at Purdue University School of Veterinary Medicine selected a self-directed or teacher-directed approach to the course. Adoption of the experimental approach described here increased faculty time for evaluating student progress but was supportive of student development particularly in cognitive skills and affective…
An Improved Design Methodology for Modeling Thick-Section Composite Structures Using a Multiscale Approach

DTIC Science & Technology

2012-09-01

Technologies. Helius was developed as a user material subroutine for ABAQUS and ANSYS (9). Through an ABAQUS plug-in and graphical interface, a...incorporated into an ABAQUS subroutine and compared to experimental data. Xie and Biggers (18) look at the effect width-to-hole-diameter ratio on open- hole...smearing-unsmearing” approach, nonlinear anisotropy, and progressive failure analysis into ABAQUS . The subroutine UMAT is used to define the
Modeling Tumor Clonal Evolution for Drug Combinations Design.

PubMed

Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A

2016-03-01

Cancer is a clonal evolutionary process. This presents challenges for effective therapeutic intervention, given the constant selective pressure towards drug resistance. Mathematical modeling from population genetics, evolutionary dynamics, and engineering perspectives are being increasingly employed to study tumor progression, intratumoral heterogeneity, drug resistance, and rational drug scheduling and combinations design. In this review, we discuss promising opportunities these inter-disciplinary approaches hold for advances in cancer biology and treatment. We propose that quantitative modeling perspectives can complement emerging experimental technologies to facilitate enhanced understanding of disease progression and improved capabilities for therapeutic drug regimen designs.
The contribution of growth hormone to mammary neoplasia

PubMed Central

Perry, Jo K; Mohankumar, Kumarasamypet M; Emerald, B Starling; Mertani, Hichem C; Lobie, Peter E

2008-01-01

While the effects of growth hormone (GH) on longitudinal growth are well established, the observation that GH contributes to neoplastic progression is more recent. Accumulating literature implicates GH-mediated signal transduction in the development and progression of a wide range malignancies including breast cancer. Recently autocrine human GH been demonstrated to be an orthotopically expressed oncogene for the human mammary gland. This review will highlight recent evidence linking GH and mammary carcinoma and discuss GH-antagonism as a potential therapeutic approach for treatment of breast cancer. PMID:18253708
Remedying CERCLA`s natural resource damages provision: Incorporation of the public trust doctrine into natural resource damage actions

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

Chase, A.R.

When Congress enacted the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), it ushered in a sweeping approach to controlling the environmental effects of improper hazardous waste disposal. CERCLA`s cleanup provisions, which focus on removal and remediation of hazardous substances from inactive hazardous waste sites, have progressed through more than a decade of litigation and a great deal of public debate. However, CERCLA`s natural resource damage provisions have not shared this same degree of progress.
A spray flamelet/progress variable approach combined with a transported joint PDF model for turbulent spray flames

NASA Astrophysics Data System (ADS)

Hu, Yong; Olguin, Hernan; Gutheil, Eva

2017-05-01

A spray flamelet/progress variable approach is developed for use in spray combustion with partly pre-vaporised liquid fuel, where a laminar spray flamelet library accounts for evaporation within the laminar flame structures. For this purpose, the standard spray flamelet formulation for pure evaporating liquid fuel and oxidiser is extended by a chemical reaction progress variable in both the turbulent spray flame model and the laminar spray flame structures, in order to account for the effect of pre-vaporised liquid fuel for instance through use of a pilot flame. This new approach is combined with a transported joint probability density function (PDF) method for the simulation of a turbulent piloted ethanol/air spray flame, and the extension requires the formulation of a joint three-variate PDF depending on the gas phase mixture fraction, the chemical reaction progress variable, and gas enthalpy. The molecular mixing is modelled with the extended interaction-by-exchange-with-the-mean (IEM) model, where source terms account for spray evaporation and heat exchange due to evaporation as well as the chemical reaction rate for the chemical reaction progress variable. This is the first formulation using a spray flamelet model considering both evaporation and partly pre-vaporised liquid fuel within the laminar spray flamelets. Results with this new formulation show good agreement with the experimental data provided by A.R. Masri, Sydney, Australia. The analysis of the Lagrangian statistics of the gas temperature and the OH mass fraction indicates that partially premixed combustion prevails near the nozzle exit of the spray, whereas further downstream, the non-premixed flame is promoted towards the inner rich-side of the spray jet since the pilot flame heats up the premixed inner spray zone. In summary, the simulation with the new formulation considering the reaction progress variable shows good performance, greatly improving the standard formulation, and it provides new insight into the local structure of this complex spray flame.
Theoretical Methods of Domain Structures in Ultrathin Ferroelectric Films: A Review

PubMed Central

Liu, Jianyi; Chen, Weijin; Wang, Biao; Zheng, Yue

2014-01-01

This review covers methods and recent developments of the theoretical study of domain structures in ultrathin ferroelectric films. The review begins with an introduction to some basic concepts and theories (e.g., polarization and its modern theory, ferroelectric phase transition, domain formation, and finite size effects, etc.) that are relevant to the study of domain structures in ultrathin ferroelectric films. Basic techniques and recent progress of a variety of important approaches for domain structure simulation, including first-principles calculation, molecular dynamics, Monte Carlo simulation, effective Hamiltonian approach and phase field modeling, as well as multiscale simulation are then elaborated. For each approach, its important features and relative merits over other approaches for modeling domain structures in ultrathin ferroelectric films are discussed. Finally, we review recent theoretical studies on some important issues of domain structures in ultrathin ferroelectric films, with an emphasis on the effects of interfacial electrostatics, boundary conditions and external loads. PMID:28788198

McGraw-Hill Programmed Reading Evaluation.

ERIC Educational Resources Information Center

Norfolk Public Schools, VA.

One of the programs included in "Effective Reading Programs...," this program, begun in 1972, serves about 3,600 disadvantaged first through fourth grade students. The independent learning approach is featured in this program. Placement tests help teachers determine each child's needs, and diagnostic tests monitor student progress.…
Practical Strategies for Enhancing Doctoral Students' Preparedness to Teach

ERIC Educational Resources Information Center

Richards, K. Andrew R.; Sinelnikov, Oleg A.; Starck, Jenna R.

2018-01-01

Doctoral education programs in physical education teacher education have a responsibility to train aspiring faculty members to be effective researchers and good teachers. Using occupational socialization theory as a framework, this article proposes a progressive approach to helping physical education teacher education doctoral students gain…
Personality Type and Leadership Approach

ERIC Educational Resources Information Center

Adams, Dolly L.

2009-01-01

Effective leadership in public schools includes, but is not limited to being able to communicate goals, set expectations, monitor instructional progress, coordinate the curriculum, and supervise and evaluate faculty (Snowden & Gorton, 2002). All of these leadership skills are driven by a need for leaders to build collaborative rapport and…
Relaxation Techniques for Handicapped Children: A Review of Literature.

ERIC Educational Resources Information Center

Zipkin, Dvora

1985-01-01

The paper discusses four major relaxation training approaches used with handicapped children: progressive muscle relaxation, biofeedback, yoga, and mental relaxation, which includes guided fantasy, imagery, and meditation. Descriptions of these techniques, the effects of their use with various populations, and reviews of recent studies of their…
Students' perception of an integrated approach of teaching entire sequence of medicinal chemistry, pharmacology, and pharmacotherapeutics courses in PharmD curriculum.

PubMed

Islam, Mohammed A; Schweiger, Teresa A

2015-04-01

To develop an integrated approach of teaching medicinal chemistry, pharmacology, and pharmacotherapeutics and to evaluate students' perceptions of integration as they progress through the PharmD curriculum. Instructors from each discipline jointly mapped the course contents and sequenced the course delivery based on organ systems/disease states. Medicinal chemistry and pharmacology contents were integrated and aligned with respective pharmacotherapeutics contents to deliver throughout second and third year of the curriculum. In addition to classroom lectures, active learning strategies such as recitation, case studies, online-discussion boards, open book quizzes, and writing patient progress notes were incorporated to enhance student learning. Student learning was assessed by examination scores, patient progress notes, and writing assignments. The impact of course integration was evaluated by a Web-based survey. One hundred and sixty-nine students completed the survey. Students exhibited positive attitude toward the integrated approach of teaching medicinal chemistry, pharmacology, and therapeutics. The P3 and P4 students better appreciated the benefits of integration compared to P2 students (P < .05). Students perceived the course integration as an effective way of learning. This study supports course improvement and the viability of expanding the concept of integration to other courses in the curriculum. © The Author(s) 2014.
Treatment of secondary burn wound progression in contact burns-a systematic review of experimental approaches.

PubMed

Schmauss, Daniel; Rezaeian, Farid; Finck, Tom; Machens, Hans-Guenther; Wettstein, Reto; Harder, Yves

2015-01-01

After a burn injury, superficial partial-thickness burn wounds may progress to deep partial-thickness or full-thickness burn wounds, if kept untreated. This phenomenon is called secondary burn wound progression or conversion. Burn wound depth is an important determinant of patient morbidity and mortality. Therefore, reduction or even the prevention of secondary burn wound progression is one goal of the acute care of burned patients. The objective of this study was to review preclinical approaches evaluating therapies to reduce burn wound progression. A systematic review of experimental approaches in animals that aim at reducing or preventing secondary burn wound progression was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines. The selected references consist of all the peer-reviewed studies performed in vivo in animals and review articles published in English, German, Italian, Spanish, or French language relevant to the topic of secondary burn wound progression. We searched MEDLINE, Cochrane Library, and Google Scholar including all the articles published from the beginning of notations to the present. The search was conducted between May 3, 2012 and December 26, 2013. We included 29 experimental studies in this review, investigating agents that maintain or increase local perfusion conditions, as well as agents that exhibit an anti-coagulatory, an anti-inflammatory, or an anti-apoptotic property. Warm water, simvastatin, EPO, or cerium nitrate may represent particularly promising approaches for the translation into clinical use in the near future. This review demonstrates promising experimental approaches that might reduce secondary burn wound progression. Nevertheless, a translation into clinical application needs to confirm the results compiled in experimental animal studies.
Revisiting a Progressive Pedagogy. The Developmental-Interaction Approach. SUNY Series, Early Childhood Education: Inquiries and Insights.

ERIC Educational Resources Information Center

Nager, Nancy, Ed.; Shapiro, Edna K., Ed.

This book reviews the history of the developmental-interactive approach, a formulation rooted in developmental psychology and educational practice, progressively informing educational thinking since the early 20th century. The book describes and analyzes key assumptions and assesses the compatibility of new theoretical approaches, focuses on…
Health impact assessment in Australia: A review and directions for progress

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

Harris, Patrick, E-mail: patrick.harris@unsw.edu.a; Spickett, Jeff, E-mail: J.Spickett@curtin.edu.a

2011-07-15

This article provides an overview of Health Impact Assessment (HIA) within Australia. We discuss the development and current position of HIA and offer some directions for HIA's progression. Since the early 1990s HIA activity in Australia has increased and diversified in application and practice. This article first highlights the emergent streams of HIA practice across environmental, policy and health equity foci, and how these have developed within Australia. The article then provides summaries of current practice provided by each Australian state and territory. We then offer some insight into current issues that require further progression or resolution if HIA ismore » to progress effectively in Australia. This progress rests both on developing broad system support for HIA across government, led by the health sector, and developing system capacity to undertake, commission or review HIAs. We argue that a unified and clear HIA approach is required as a prerequisite to gaining the understanding and support for HIA in the public and private sectors and the wider community.« less
Ion-Sensitive Field-Effect Transistor for Biological Sensing

PubMed Central

Lee, Chang-Soo; Kim, Sang Kyu; Kim, Moonil

2009-01-01

In recent years there has been great progress in applying FET-type biosensors for highly sensitive biological detection. Among them, the ISFET (ion-sensitive field-effect transistor) is one of the most intriguing approaches in electrical biosensing technology. Here, we review some of the main advances in this field over the past few years, explore its application prospects, and discuss the main issues, approaches, and challenges, with the aim of stimulating a broader interest in developing ISFET-based biosensors and extending their applications for reliable and sensitive analysis of various biomolecules such as DNA, proteins, enzymes, and cells. PMID:22423205
Use of Acoustic Emission to Monitor Progressive Damage Accumulation in KEVLAR® 49 Composites

NASA Astrophysics Data System (ADS)

Waller, J. M.; Andrade, E.; Saulsberry, R. L.

2010-02-01

Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar® 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio <1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.
Global progress in prevention of cardiovascular disease

PubMed Central

2017-01-01

Although there is measurable global progress in prevention of cardiovascular disease (CVD), it has been highly uneven and inadequate, particularly in low- and middle-income countries. Voluntary global targets have helped to galvanize attention, resources and accountability on tobacco use, harmful use of alcohol, unhealthy diet and physical inactivity which are the major behavioural drivers of CVD. Many obstacles and challenges continue to impede the progress of cardiovascular prevention. The inclusion of noncommunicable diseases (NCDs) in the sustainable development agenda as a specific target, offers an unprecedented opportunity to further advance the global progress of cardiovascular prevention. In order to seize this opportunity, a paradigm shift is required in the way key challenges to cardiovascular prevention are addressed. Such an approach must provide leadership for intersectoral policy coherence, identify effective means of tackling commercial determinants of behavioural risk factors, use rights based arguments, enhance public engagement and ensure accountability. PMID:28529920
Novel Molecular Therapies for Heritable Skin Disorders

PubMed Central

Uitto, Jouni; Christiano, Angela M.; Irwin McLean, W. H.; McGrath, John A.

2013-01-01

Tremendous progress has been made in the past two decades in molecular genetics of heritable skin diseases, and pathogenic mutations have been identified in as many as 500 distinct human genes. This progress has resulted in improved diagnosis with prognostic implications, refined genetic counseling, and has formed the basis for prenatal and presymptomatic testing as well as preimplantation genetic diagnosis. However, there has been relatively little progress in developing effective and specific treatments for these often devastating diseases. Very recently, however, a number of novel molecular strategies, including gene therapy, cell-based approaches, and protein replacement therapy have been explored for treatment of these conditions. This overview will focus on the prototypic heritable blistering disorders, epidermolysis bullosa and related keratinopathies, in which significant progress has been recently made towards treatment, and illustrate how some of the translational research therapies have already entered the clinical arena. PMID:22158553
Breaking down the LMS Walls

ERIC Educational Resources Information Center

Hotrum, Michael

2005-01-01

The traditional packaging of electronic learning--the learning management system (LMS)--is progressively being regarded as a hindrance to effective online learning. Its design, functionality, complexity, price, and value are being questioned. A new generation of Web-based tools and approaches is evolving that are better suited to meet the need for…
A Randomized Clinical Trial of Alternative Stress Management Interventions in Persons with HIV Infection

ERIC Educational Resources Information Center

McCain, Nancy L.; Gray, D. Patricia; Elswick, R. K., Jr.; Robins, Jolynne W.; Tuck, Inez; Walter, Jeanne M.; Rausch, Sarah M.; Ketchum, Jessica McKinney

2008-01-01

Research in psychoneuroimmunology suggests that immunosuppression associated with perceived stress may contribute to disease progression in persons with HIV infection. While stress management interventions may enhance immune function, few alternative approaches have yet been tested. This randomized clinical trial was conducted to test effects of…
The Self-Systems: Facilitating Personal Well-Being Experiences at School

ERIC Educational Resources Information Center

Phan, Huy P.

2017-01-01

The focus of inquiry pertaining to quality learning and student well-being experiences at school has involved numerous studies, utilizing complex quantitative methodological approaches. In a similar vein, for consideration of research advancement, there has been extensive progress made regarding motivational tenets of effective learning and…
Assessing Change: Can Organizational Learning "Work" for Schools?

ERIC Educational Resources Information Center

Austin, Manila S.; Harkins, Debra A.

2008-01-01

Purpose: The purpose of this paper is to measure the effectiveness and practical utility of an organizational learning intervention for an organization that was not progressive, was not specifically chartered as a learning organization, and was situated in an urban, culturally diverse, and under-privileged community. Design/methodology/approach:…
Putting the Laboratory at the Center of Teaching Chemistry

ERIC Educational Resources Information Center

Bopegedera, A. M. R. P.

2011-01-01

This article describes an effective approach to teaching chemistry by bringing the laboratory to the center of teaching, to bring the excitement of discovery to the learning process. The lectures and laboratories are closely integrated to provide a holistic learning experience. The laboratories progress from verification to open-inquiry and…
Modular Access and Progression Routes: Support Issues and Student Directed Learning.

ERIC Educational Resources Information Center

Ward, Jill

1995-01-01

The effects of modularizing Access Courses provided by the University of Derby were examined for 299 adult students. No significant differences appeared in retention, but the modular approach had increased recruitment/retention of unskilled and lower achieving students. Students with lower entry qualifications had higher achievement than similar…
Some new approaches in hail suppression experiments

NASA Technical Reports Server (NTRS)

Browning, K. A.; Atlas, D.

1977-01-01

It is suggested that progress in hail suppression research requires simultaneous improvements in methods of evaluating seeding effects and in monitoring the physical structure of the hailstorm and the hail growth processes. On this basis a case is made for the extensive use of multiple Doppler radar and chemical tracer techniques.
Ongoing Data Collection for Measuring Child Progress.

ERIC Educational Resources Information Center

Stevens-Dominquez, Meave, Ed.; Stremel-Campbell, Kathleen, Ed.

Practical information is supplied that can be directly applied to early childhood projects and used for staff inservice in data collection procedures. This information assists in documenting the overall effectiveness of an approach and aids in making the frequent educational decisions to ensure the child is benefiting from instruction. Separate…

Managing Corporate Risk through Better Knowledge Management

ERIC Educational Resources Information Center

Neef, Dale

2005-01-01

Purpose: To explain how progressive companies are using a combination of knowledge and risk management (KRM) systems and techniques in order to help them to prevent, or respond most effectively to, ethical or reputation-damaging incidents. Design/methodology/approach: The paper explains KRM, develops a corporate integrity framework, and then…
Assessment of Environmental and Occupational Health Impacts in Munitions and Weapon Systems Development: A Phased Approach

DTIC Science & Technology

2010-12-01

Human Health Impacts of New Energetic Compounds. • Models – QSARs • In vitro toxicology • In vivo toxicology • Aligned with RDT&E level of...D.A.B.T. Health Effects Research Program Directorate of Toxicology Army Institute of Public Health UNCLASSIFIED Report Documentation Page Form...program. Early in the research stage models are primarily relied upon (e.g. QSAR approaches) and as the technology progresses, a greater reliance is
Planning in the Continuous Operations Environment of the International Space Station

NASA Technical Reports Server (NTRS)

Maxwell, Theresa; Hagopian, Jeff

1996-01-01

The continuous operation planning approach developed for the operations planning of the International Space Station (ISS) is reported on. The approach was designed to be a robust and cost-effective method. It separates ISS planning into two planning functions: long-range planning for a fixed length planning horizon which continually moves forward as ISS operations progress, and short-range planning which takes a small segment of the long-range plan and develops a detailed operations schedule. The continuous approach is compared with the incremental approach, the short and long-range planning functions are described, and the benefits and challenges of implementing a continuous operations planning approach for the ISS are summarized.
Developing Exemplar Interactive Multimedia Instruction for Unmanned Aircraft System Repairers

DTIC Science & Technology

2017-08-01

material and also compared the effectiveness of two different IMI design approaches used to progress the learner through the various training modules...instruction. For the Hydraulics Theory and Components, we compared the learner-controlled Interactive Multimedia Instruction and the designer ... Design Three UAS Repairer IMI modules were developed, and the effectiveness of each was compared to the current live instruction covering the
Optimal filter design with progressive genetic algorithm for local damage detection in rolling bearings

NASA Astrophysics Data System (ADS)

Wodecki, Jacek; Michalak, Anna; Zimroz, Radoslaw

2018-03-01

Harsh industrial conditions present in underground mining cause a lot of difficulties for local damage detection in heavy-duty machinery. For vibration signals one of the most intuitive approaches of obtaining signal with expected properties, such as clearly visible informative features, is prefiltration with appropriately prepared filter. Design of such filter is very broad field of research on its own. In this paper authors propose a novel approach to dedicated optimal filter design using progressive genetic algorithm. Presented method is fully data-driven and requires no prior knowledge of the signal. It has been tested against a set of real and simulated data. Effectiveness of operation has been proven for both healthy and damaged case. Termination criterion for evolution process was developed, and diagnostic decision making feature has been proposed for final result determinance.
Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease

PubMed Central

Hoban, Megan D.; Bauer, Daniel E.

2016-01-01

Effective medical management for sickle cell disease (SCD) remains elusive. As a prevalent and severe monogenic disorder, SCD has been long considered a logical candidate for gene therapy. Significant progress has been made in moving toward this goal. These efforts have provided substantial insight into the natural regulation of the globin genes and illuminated challenges for genetic manipulation of the hematopoietic system. The initial γ-retroviral vectors, next-generation lentiviral vectors, and novel genome engineering and gene regulation approaches each share the goal of preventing erythrocyte sickling. After years of preclinical studies, several clinical trials for SCD gene therapies are now open. This review focuses on progress made toward achieving gene therapy, the current state of the field, consideration of factors that may determine clinical success, and prospects for future development. PMID:26758916
Evaluation of a Region-of-Interest Approach for Detecting Progressive Glaucomatous Macular Damage on Optical Coherence Tomography.

PubMed

Wu, Zhichao; Weng, Denis S D; Thenappan, Abinaya; Ritch, Robert; Hood, Donald C

2018-04-01

To evaluate a manual region-of-interest (ROI) approach for detecting progressive macular ganglion cell complex (GCC) changes on optical coherence tomography (OCT) imaging. One hundred forty-six eyes with a clinical diagnosis of glaucoma or suspected glaucoma with macular OCT scans obtained at least 1 year apart were evaluated. Changes in the GCC thickness were identified using a manual ROI approach (ROI M ), whereby region(s) of observed or suspected glaucomatous damage were manually identified when using key features from the macular OCT scan on the second visit. Progression was also evaluated using the global GCC thickness and an automatic ROI approach (ROI A ), where contiguous region(s) that fell below the 1% lower normative limit and exceeded 288 μm 2 in size were evaluated. Longitudinal signal-to-noise ratios (SNRs) were calculated for progressive changes detected by each of these methods using individualized estimates of test-retest variability and age-related changes, obtained from 303 glaucoma and 394 healthy eyes, respectively. On average, the longitudinal SNR for the global thickness, ROI A and ROI M methods were -0.90 y -1 , -0.91 y -1 , and -1.03 y -1 , respectively, and was significantly more negative for the ROI M compared with the global thickness ( P = 0.003) and ROI A methods ( P = 0.021). Progressive glaucomatous macular GCC changes were optimally detected with a manual ROI approach. These findings suggests that an approach based on a qualitative evaluation of OCT imaging information and consideration of known patterns of damage can improve the detection of progressive glaucomatous macular damage.
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.
Conceptions of Progress: How Is Progress Perceived? Mainstream versus Alternative Conceptions of Progress

ERIC Educational Resources Information Center

Itay, Anat

2009-01-01

Progress is a powerful political concept, encompassing different and sometimes contradictory conceptions. This paper examines the results of a survey on progress conducted at the OECD World Forum entitled "Measuring and Fostering the Progress of Societies" held in Istanbul in June 2007. First, a distinction is drawn between the two approaches to…
Estimation of fatigue life using electromechanical impedance technique

NASA Astrophysics Data System (ADS)

Lim, Yee Yan; Soh, Chee Kiong

2010-04-01

Fatigue induced damage is often progressive and gradual in nature. Structures subjected to large number of fatigue load cycles will encounter the process of progressive crack initiation, propagation and finally fracture. Monitoring of structural health, especially for the critical components, is therefore essential for early detection of potential harmful crack. Recent advent of smart materials such as piezo-impedance transducer adopting the electromechanical impedance (EMI) technique and wave propagation technique are well proven to be effective in incipient damage detection and characterization. Exceptional advantages such as autonomous, real-time and online, remote monitoring may provide a cost-effective alternative to the conventional structural health monitoring (SHM) techniques. In this study, the main focus is to investigate the feasibility of characterizing a propagating fatigue crack in a structure using the EMI technique as well as estimating its remaining fatigue life using the linear elastic fracture mechanics (LEFM) approach. Uniaxial cyclic tensile load is applied on a lab-sized aluminum beam up to failure. Progressive shift in admittance signatures measured by the piezo-impedance transducer (PZT patch) corresponding to increase of loading cycles reflects effectiveness of the EMI technique in tracing the process of fatigue damage progression. With the use of LEFM, prediction of the remaining life of the structure at different cycles of loading is possible.
The Effects of 6 Months of Progressive High Effort Resistance Training Methods upon Strength, Body Composition, Function, and Wellbeing of Elderly Adults.

PubMed

Steele, James; Raubold, Kristin; Kemmler, Wolfgang; Fisher, James; Gentil, Paulo; Giessing, Jürgen

2017-01-01

The present study examined the progressive implementation of a high effort resistance training (RT) approach in older adults over 6 months and through a 6-month follow-up on strength, body composition, function, and wellbeing of older adults. Twenty-three older adults (aged 61 to 80 years) completed a 6-month supervised RT intervention applying progressive introduction of higher effort set end points. After completion of the intervention participants could choose to continue performing RT unsupervised until 6-month follow-up. Strength, body composition, function, and wellbeing all significantly improved over the intervention. Over the follow-up, body composition changes reverted to baseline values, strength was reduced though it remained significantly higher than baseline, and wellbeing outcomes were mostly maintained. Comparisons over the follow-up between those who did and those who did not continue with RT revealed no significant differences for changes in any outcome measure. Supervised RT employing progressive application of high effort set end points is well tolerated and effective in improving strength, body composition, function, and wellbeing in older adults. However, whether participants continued, or did not, with RT unsupervised at follow-up had no effect on outcomes perhaps due to reduced effort employed during unsupervised RT.
Effective properties of dispersed phase reinforced composite materials with perfect and imperfect interfaces

NASA Astrophysics Data System (ADS)

Han, Ru

This thesis focuses on the analysis of dispersed phase reinforced composite materials with perfect as well as imperfect interfaces using the Boundary Element Method (BEM). Two problems of interest are considered, namely, to determine the limitations in the use of effective properties and the analysis of failure progression at the inclusion-matrix interface. The effective moduli (effective Young's modulus, effective Poisson's ratio, effective shear modulus, and effective bulk modulus) of composite materials can be determined at the mesoscopic level using three-dimensional parallel BEM simulations. By comparing the mesoscopic BEM results and the macroscopic results based on effective properties, limitations in the effective property approach can be determined. Decohesion is an important failure mode associated with fiber-reinforced composite materials. Analysis of failure progression at the fiber-matrix interface in fiber-reinforced composite materials is considered using a softening decohesion model consistent with thermodynamic concepts. In this model, the initiation of failure is given directly by a failure criterion. Damage is interpreted by the development of a discontinuity of displacement. The formulation describing the potential development of damage is governed by a discrete decohesive constitutive equation. Numerical simulations are performed using the direct boundary element method. Incremental decohesion simulations illustrate the progressive evolution of debonding zones and the propagation of cracks along the interfaces. The effect of decohesion on the macroscopic response of composite materials is also investigated.
An Overview of Current Approaches Toward the Treatment and Prevention of West Nile Virus Infection.

PubMed

Acharya, Dhiraj; Bai, Fengwei

2016-01-01

The persistence of West Nile virus (WNV) infections throughout the USA since its inception in 1999 and its continuous spread throughout the globe calls for an urgent need of effective treatments and prevention measures. Although the licensing of several WNV vaccines for veterinary use provides a proof of concept, similar efforts on the development of an effective vaccine for humans remain still unsuccessful. Increased understanding of biology and pathogenesis of WNV together with recent technological advancements have raised hope that an effective WNV vaccine may be available in the near future. In addition, rapid progress in the structural and functional characterization of WNV and other flaviviral proteins have provided a solid base for the design and development of several classes of inhibitors as potential WNV therapeutics. Moreover, the therapeutic monoclonal antibodies demonstrate an excellent efficacy against WNV in animal models and represent a promising class of WNV therapeutics. However, there are some challenges as to the design and development of a safe and efficient WNV vaccine or therapeutic. In this chapter, we discuss the current approaches, progress, and challenges toward the development of WNV vaccines, therapeutic antibodies, and antiviral drugs.
Acceptance and Commitment Therapy and Contextual Behavioral Science: Examining the Progress of a Distinctive Model of Behavioral and Cognitive Therapy

PubMed Central

Hayes, Steven C.; Levin, Michael E.; Plumb-Vilardaga, Jennifer; Villatte, Jennifer L.; Pistorello, Jacqueline

2012-01-01

A number of recent authors have compared acceptance and commitment therapy (ACT) and traditional cognitive behavior therapy (CBT). The present article describes ACT as a distinct and unified model of behavior change, linked to a specific strategy of scientific development, which we term “contextual behavioral science.” We outline the empirical progress of ACT and describe its distinctive development strategy. A contextual behavioral science approach is an inductive attempt to build more adequate psychological systems based on philosophical clarity; the development of basic principles and theories; the development of applied theories linked to basic ones; techniques and components linked to these processes and principles; measurement of theoretically key processes; an emphasis on mediation and moderation in the analysis of applied impact; an interest in effectiveness, dissemination, and training; empirical testing of the research program across a broad range of areas and levels of analysis; and the creation of a more effective scientific and clinical community. We argue that this is a reasonable approach, focused on long-term progress, and that in broad terms it seems to be working. ACT is not hostile to traditional CBT, and is not directly buoyed by whatever weaknesses traditional CBT may have. ACT should be measured at least in part against its own goals as specified by its own developmental strategy. PMID:23611068
Acceptance and commitment therapy and contextual behavioral science: examining the progress of a distinctive model of behavioral and cognitive therapy.

PubMed

Hayes, Steven C; Levin, Michael E; Plumb-Vilardaga, Jennifer; Villatte, Jennifer L; Pistorello, Jacqueline

2013-06-01

A number of recent authors have compared acceptance and commitment therapy (ACT) and traditional cognitive behavior therapy (CBT). The present article describes ACT as a distinct and unified model of behavior change, linked to a specific strategy of scientific development, which we term "contextual behavioral science." We outline the empirical progress of ACT and describe its distinctive development strategy. A contextual behavioral science approach is an inductive attempt to build more adequate psychological systems based on philosophical clarity; the development of basic principles and theories; the development of applied theories linked to basic ones; techniques and components linked to these processes and principles; measurement of theoretically key processes; an emphasis on mediation and moderation in the analysis of applied impact; an interest in effectiveness, dissemination, and training; empirical testing of the research program across a broad range of areas and levels of analysis; and the creation of a more effective scientific and clinical community. We argue that this is a reasonable approach, focused on long-term progress, and that in broad terms it seems to be working. ACT is not hostile to traditional CBT, and is not directly buoyed by whatever weaknesses traditional CBT may have. ACT should be measured at least in part against its own goals as specified by its own developmental strategy. Copyright © 2011. Published by Elsevier Ltd.
Comparison of Statistical Approaches Dealing with Time-dependent Confounding in Drug Effectiveness Studies

PubMed Central

Karim, Mohammad Ehsanul; Petkau, John; Gustafson, Paul; Platt, Robert W.; Tremlett, Helen

2017-01-01

In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models (MSCMs) are frequently used to deal with such confounding. To avoid some of the problems of fitting MSCM, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding. We carry out simulation studies to assess the suitability of the sequential Cox approach for analyzing time-to-event data in the presence of a time-dependent covariate that may or may not be a time-dependent confounder. Results from these simulations revealed that the sequential Cox approach is not as effective as MSCM in addressing the time-dependent confounding. The sequential Cox approach was also found to be inadequate in the presence of a time-dependent covariate. We propose a modified version of the sequential Cox approach that correctly estimates the treatment effect in both of the above scenarios. All approaches are applied to investigate the impact of beta-interferon treatment in delaying disability progression in the British Columbia Multiple Sclerosis cohort (1995 – 2008). PMID:27659168
Comparison of statistical approaches dealing with time-dependent confounding in drug effectiveness studies.

PubMed

Karim, Mohammad Ehsanul; Petkau, John; Gustafson, Paul; Platt, Robert W; Tremlett, Helen

2018-06-01

In longitudinal studies, if the time-dependent covariates are affected by the past treatment, time-dependent confounding may be present. For a time-to-event response, marginal structural Cox models are frequently used to deal with such confounding. To avoid some of the problems of fitting marginal structural Cox model, the sequential Cox approach has been suggested as an alternative. Although the estimation mechanisms are different, both approaches claim to estimate the causal effect of treatment by appropriately adjusting for time-dependent confounding. We carry out simulation studies to assess the suitability of the sequential Cox approach for analyzing time-to-event data in the presence of a time-dependent covariate that may or may not be a time-dependent confounder. Results from these simulations revealed that the sequential Cox approach is not as effective as marginal structural Cox model in addressing the time-dependent confounding. The sequential Cox approach was also found to be inadequate in the presence of a time-dependent covariate. We propose a modified version of the sequential Cox approach that correctly estimates the treatment effect in both of the above scenarios. All approaches are applied to investigate the impact of beta-interferon treatment in delaying disability progression in the British Columbia Multiple Sclerosis cohort (1995-2008).
Modeling Tumor Clonal Evolution for Drug Combinations Design

PubMed Central

Zhao, Boyang; Hemann, Michael T.; Lauffenburger, Douglas A.

2016-01-01

Cancer is a clonal evolutionary process. This presents challenges for effective therapeutic intervention, given the constant selective pressure towards drug resistance. Mathematical modeling from population genetics, evolutionary dynamics, and engineering perspectives are being increasingly employed to study tumor progression, intratumoral heterogeneity, drug resistance, and rational drug scheduling and combinations design. In this review, we discuss promising opportunities these inter-disciplinary approaches hold for advances in cancer biology and treatment. We propose that quantitative modeling perspectives can complement emerging experimental technologies to facilitate enhanced understanding of disease progression and improved capabilities for therapeutic drug regimen designs. PMID:28435907
Direct laser writing of graphene electronics.

PubMed

El-Kady, Maher F; Kaner, Richard B

2014-09-23

One of the fundamental issues with graphene for logic applications is its lack of a band gap. In this issue of ACS Nano, Shim and colleagues introduce an effective approach for modulating the current flow in graphene by forming p-n junctions using lasers. The findings could lead to a new route for controlling the electronic properties of graphene-based devices. We highlight recent progress in the direct laser synthesis and patterning of graphene for numerous applications. We also discuss the challenges and opportunities in translating this remarkable progress toward the direct laser writing of graphene electronics at large scales.
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.

Managing the consequences of hospital cutbacks: the role of workforce reduction practices.

PubMed

Rondeau, K V; Wagar, T H

2001-01-01

In recent years, hospitals in Canada as elsewhere have witnessed unprecedented downsizing of their workforces. It is generally assumed that planned workforce reductions can have deleterious consequences on an organization's human resources. Scholars and practitioners alike have identified a number of humane or progressive approaches that are widely considered to be effective for organizations undergoing downsizing. This study examines the impact that workforce reduction approaches have on perceptions of organizational performance in a large sample of Canadian hospitals undergoing workforce reductions.
Use of Acoustic Emission to Monitor Progressive Damage Accumulation in Kevlar (R) 49 Composites

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.; Andrade, Eduardo

2009-01-01

Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar(Registeres TradeMark) 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio < 1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.
Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action

PubMed Central

Aung, Thazin Nwe; Qu, Zhipeng; Kortschak, R. Daniel; Adelson, David L.

2017-01-01

Many approaches to cancer management are often ineffective due to adverse reactions, drug resistance, or inadequate target specificity of single anti-cancer agents. In contrast, a combinatorial approach with the application of two or more anti-cancer agents at their respective effective dosages can achieve a synergistic effect that boosts cytotoxicity to cancer cells. In cancer, aberrant apoptotic pathways allow cells that should be killed to survive with genetic abnormalities, leading to cancer progression. Mutations in apoptotic mechanism arising during the treatment of cancer through cancer progression can consequently lead to chemoresistance. Natural compound mixtures that are believed to have multiple specific targets with minimal acceptable side-effects are now of interest to many researchers due to their cytotoxic and chemosensitizing activities. Synergistic interactions within a drug mixture enhance the search for potential molecular targets in cancer cells. Nonetheless, biased/flawed scientific evidence from natural products can suggest false positive therapeutic benefits during drug screening. In this review, we have taken these factors into consideration when discussing the evidence for these compounds and their synergistic therapeutic benefits in cancer. While there is limited evidence for clinical efficacy for these mixtures, in vitro data suggest that these preparations merit further investigation, both in vitro and in vivo. PMID:28304343
Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action.

PubMed

Aung, Thazin Nwe; Qu, Zhipeng; Kortschak, R Daniel; Adelson, David L

2017-03-17

Many approaches to cancer management are often ineffective due to adverse reactions, drug resistance, or inadequate target specificity of single anti-cancer agents. In contrast, a combinatorial approach with the application of two or more anti-cancer agents at their respective effective dosages can achieve a synergistic effect that boosts cytotoxicity to cancer cells. In cancer, aberrant apoptotic pathways allow cells that should be killed to survive with genetic abnormalities, leading to cancer progression. Mutations in apoptotic mechanism arising during the treatment of cancer through cancer progression can consequently lead to chemoresistance. Natural compound mixtures that are believed to have multiple specific targets with minimal acceptable side-effects are now of interest to many researchers due to their cytotoxic and chemosensitizing activities. Synergistic interactions within a drug mixture enhance the search for potential molecular targets in cancer cells. Nonetheless, biased/flawed scientific evidence from natural products can suggest false positive therapeutic benefits during drug screening. In this review, we have taken these factors into consideration when discussing the evidence for these compounds and their synergistic therapeutic benefits in cancer. While there is limited evidence for clinical efficacy for these mixtures, in vitro data suggest that these preparations merit further investigation, both in vitro and in vivo.
Understanding the P×S Aspect of Within-Person Variation: A Variance Partitioning Approach

PubMed Central

Lakey, Brian

2016-01-01

This article reviews a variance partitioning approach to within-person variation based on Generalizability Theory and the Social Relations Model. The approach conceptualizes an important part of within-person variation as Person × Situation (P×S) interactions: differences among persons in their profiles of responses across the same situations. The approach provided the first quantitative method for capturing within-person variation and demonstrated very large P×S effects for a wide range of constructs. These include anxiety, five-factor personality traits, perceived social support, leadership, and task performance. Although P×S effects are commonly very large, conceptual, and analytic obstacles have thwarted consistent progress. For example, how does one develop a psychological, versus purely statistical, understanding of P×S effects? How does one forecast future behavior when the criterion is a P×S effect? How can understanding P×S effects contribute to psychological theory? This review describes potential solutions to these and other problems developed in the course of conducting research on the P×S aspect of social support. Additional problems that need resolution are identified. PMID:26858661
Evaluation of a Region-of-Interest Approach for Detecting Progressive Glaucomatous Macular Damage on Optical Coherence Tomography

PubMed Central

Weng, Denis S. D.; Thenappan, Abinaya; Ritch, Robert; Hood, Donald C.

2018-01-01

Purpose To evaluate a manual region-of-interest (ROI) approach for detecting progressive macular ganglion cell complex (GCC) changes on optical coherence tomography (OCT) imaging. Methods One hundred forty-six eyes with a clinical diagnosis of glaucoma or suspected glaucoma with macular OCT scans obtained at least 1 year apart were evaluated. Changes in the GCC thickness were identified using a manual ROI approach (ROIM), whereby region(s) of observed or suspected glaucomatous damage were manually identified when using key features from the macular OCT scan on the second visit. Progression was also evaluated using the global GCC thickness and an automatic ROI approach (ROIA), where contiguous region(s) that fell below the 1% lower normative limit and exceeded 288 μm2 in size were evaluated. Longitudinal signal-to-noise ratios (SNRs) were calculated for progressive changes detected by each of these methods using individualized estimates of test–retest variability and age-related changes, obtained from 303 glaucoma and 394 healthy eyes, respectively. Results On average, the longitudinal SNR for the global thickness, ROIA and ROIM methods were −0.90 y−1, −0.91 y−1, and −1.03 y−1, respectively, and was significantly more negative for the ROIM compared with the global thickness (P = 0.003) and ROIA methods (P = 0.021). Conclusions Progressive glaucomatous macular GCC changes were optimally detected with a manual ROI approach. Translational Relevance These findings suggests that an approach based on a qualitative evaluation of OCT imaging information and consideration of known patterns of damage can improve the detection of progressive glaucomatous macular damage. PMID:29616153
Progress 14P approaches the ISS during Expedition 9

NASA Image and Video Library

2004-05-27

ISS009-E-08847 (27 May 2004) --- Backdropped by the blackness of space and Earths horizon, an unpiloted Progress supply vehicle approaches the International Space Station (ISS). The Progress 14 resupply craft launched at 7:34 a.m. (CDT) on May 25, 2004 from the Baikonur Cosmodrome in Kazakhstan to deliver 2 ½ tons of food, water, fuel and supplies to the Expedition 9 crewmembers onboard the Station. Progress docked to the aft port of the Zvezda Service Module at 8:55 a.m. (CDT) on May 27 as the two craft flew 230 statute miles above Central Asia.
Progress 14P approaches the ISS during Expedition 9

NASA Image and Video Library

2004-05-27

ISS009-E-08842 (27 May 2004) --- Backdropped by a blue and white Earth, an unpiloted Progress supply vehicle approaches the International Space Station (ISS). The Progress 14 resupply craft launched at 7:34 a.m. (CDT) on May 25, 2004 from the Baikonur Cosmodrome in Kazakhstan to deliver 2 ½ tons of food, water, fuel and supplies to the Expedition 9 crewmembers onboard the Station. Progress docked to the aft port of the Zvezda Service Module at 8:55 a.m. (CDT) on May 27 as the two craft flew 230 statute miles above Central Asia.
Rasch Analysis: A Primer for School Psychology Researchers and Practitioners

ERIC Educational Resources Information Center

Boone, William J.; Noltemeyer, Amity

2017-01-01

In order to progress as a field, school psychology research must be informed by effective measurement techniques. One approach to address the need for careful measurement is Rasch analysis. This technique can (a) facilitate the development of instruments that provide useful data, (b) provide data that can be used confidently for both descriptive…
The Relationship between Computer-Assisted Language Learning and Student Achievement on Language Tests

ERIC Educational Resources Information Center

Umstead, Lyubov

2013-01-01

The number of English Language Learners (ELLs) is rapidly growing. Teachers continue facing challenges in providing effective content instruction to ELLs while helping them learn English. New and improved approaches are necessary to meet the individual learning needs of this diverse group of students and help them progress academically while…
Social Learning Theory: Toward a Unified Approach of Pediatric Procedural Pain

ERIC Educational Resources Information Center

Page, Lynn Olson; Blanchette, Jennifer A.

2009-01-01

Undermanaged procedural pain has been shown to have short and long term effects on children. While significant progress regarding empirically supported treatments has been made, theoretical bases for the development and management of procedural pain are lacking. This paper examines the role of social learning theory in our current understanding of…
Exploring Relationships among TPACK Constructs and ICT Achievement among Trainee Teachers

ERIC Educational Resources Information Center

Khine, Myint Swe; Ali, Nagla; Afari, Ernest

2017-01-01

Teaching in the classroom today can no longer sustain the interest of students and be effective if the process involves traditional approach--teachers as sole provider of content information. In recent years technology has played a significant role in transforming education to more progressive and interactive activities. However the use of…
Educational Leadership Effectiveness: A Rasch Analysis

ERIC Educational Resources Information Center

Sinnema, Claire; Ludlow, Larry; Robinson, Viviane

2016-01-01

Purpose: The purposes of this paper are, first, to establish the psychometric properties of the ELP tool, and, second, to test, using a Rasch item response theory analysis, the hypothesized progression of challenge presented by the items included in the tool. Design/ Methodology/ Approach: Data were collected at two time points through a survey of…
Component-Based Approach for Educating Students in Bioinformatics

ERIC Educational Resources Information Center

Poe, D.; Venkatraman, N.; Hansen, C.; Singh, G.

2009-01-01

There is an increasing need for an effective method of teaching bioinformatics. Increased progress and availability of computer-based tools for educating students have led to the implementation of a computer-based system for teaching bioinformatics as described in this paper. Bioinformatics is a recent, hybrid field of study combining elements of…
Instantaneous progression reference frame for calculating pelvis rotations: Reliable and anatomically-meaningful results independent of the direction of movement.

PubMed

Kainz, Hans; Lloyd, David G; Walsh, Henry P J; Carty, Christopher P

2016-05-01

In motion analysis, pelvis angles are conventionally calculated as the rotations between the pelvis and laboratory reference frame. This approach assumes that the participant's motion is along the anterior-posterior laboratory reference frame axis. When this assumption is violated interpretation of pelvis angels become problematic. In this paper a new approach for calculating pelvis angles based on the rotations between the pelvis and an instantaneous progression reference frame was introduced. At every time-point, the tangent to the trajectory of the midpoint of the pelvis projected into the horizontal plane of the laboratory reference frame was used to define the anterior-posterior axis of the instantaneous progression reference frame. This new approach combined with the rotation-obliquity-tilt rotation sequence was compared to the conventional approach using the rotation-obliquity-tilt and tilt-obliquity-rotation sequences. Four different movement tasks performed by eight healthy adults were analysed. The instantaneous progression reference frame approach was the only approach that showed reliable and anatomically meaningful results for all analysed movement tasks (mean root-mean-square-differences below 5°, differences in pelvis angles at pre-defined gait events below 10°). Both rotation sequences combined with the conventional approach led to unreliable results as soon as the participant's motion was not along the anterior-posterior laboratory axis (mean root-mean-square-differences up to 30°, differences in pelvis angles at pre-defined gait events up to 45°). The instantaneous progression reference frame approach enables the gait analysis community to analysis pelvis angles for movements that do not follow the anterior-posterior axis of the laboratory reference frame. Copyright © 2016 Elsevier B.V. All rights reserved.
Envisioning the future of polymer therapeutics for brain disorders.

PubMed

Rodriguez-Otormin, Fernanda; Duro-Castano, Aroa; Conejos-Sánchez, Inmaculada; Vicent, María J

2018-06-14

The growing incidence of brain-related pathologies and the problems that undermine the development of efficient and effective treatments have prompted both researchers and the pharmaceutical industry to search for novel therapeutic alternatives. Polymer therapeutics (PT) display properties well suited to the treatment of neuro-related disorders, which help to overcome the many hidden obstacles on the journey to the central nervous system (CNS). The inherent features of PT, derived from drug(s) conjugation, in parallel with the progress in synthesis and analytical methods, the increasing knowledge in molecular basis of diseases, and collected clinical data through the last four decades, have driven the translation from "bench to bedside" for various biomedical applications. However, since the approval of Gliadel® wafers, little progress has been made in the CNS field, even though brain targeting represents an ever-growing challenge. A thorough assessment of the steps required for successful brain delivery via different administration routes and the consideration of the disease-specific hallmarks are essential to progress in the field. Within this review, we hope to summarize the latest developments, successes, and failures and discuss considerations on designs and strategies for PT in the treatment of CNS disorders. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease. © 2018 Wiley Periodicals, Inc.
Developing vascular and hypoxia based theranostics in solid tumors

NASA Astrophysics Data System (ADS)

Koonce, Nathan A.

Tissue hypoxia was recognized for its biological attenuating effects on ionizing radiation over a century ago and is a characteristic feature of many solid tumors. Clinical and experimental evidence indicates tumor hypoxia plays diverse and key roles in tumor progression, angiogenesis, and resistance to chemotherapy/radiotherapy. Hypoxia has known effects on progression and resistance to several standard treatment approaches and the significant history of study might suggest diagnostic imaging and therapeutic interventions would be routine in oncological practice. Curiously, this is not the case and the research results involved in this report will attempt to better understand and contribute to why this gap in knowledge exists and a rationale for harnessing the potential of detecting and targeting hypoxia. Despite the addition of oxygen and reversal of hypoxia being known as the best radiosensitizer, hypoxia remains unexploited in clinical cancer therapy. The studies reported herein detail development of a novel imaging technique to detect a subtype of tumor hypoxia, vascular hypoxia or hypoxemia, with a 17-fold increase (p<0.05) in uptake of pimonidazole targeted microbubbles observed compared to controls. This technique creates the potential to study the role of hypoxemia in progression and therapeutic response. Additionally, description of a nanoparticle-based therapy that targets tumor areas associated with tumor hypoxia and the tumor microenvironment in general is reported. TNF-loaded nanoparticles combined with radiotherapy resulted in a 5.25-fold growth delay that was found to be synergistic (p<0.05) and suggests clinical evaluation is warranted. An additional study to evaluate an approach to use thermal ablation of intratumoral hypoxia by an image-guided technique developed in our group is described along with a sequence dependence of radiation preceding ablation. A final study on the use of galectin-1 antagonist to significantly decrease (p<0.05) hypoxia in the tumor microenvironment by altering tumor vessel characteristics is illustrated in Chapter 5. Overall, this thesis details imaging approaches of tumor hypoxia and its detection, quantification and targeting in therapeutic approaches.
Interpreting null findings from trials of alcohol brief interventions.

PubMed

Heather, Nick

2014-01-01

The effectiveness of alcohol brief intervention (ABI) has been established by a succession of meta-analyses but, because the effects of ABI are small, null findings from randomized controlled trials are often reported and can sometimes lead to skepticism regarding the benefits of ABI in routine practice. This article first explains why null findings are likely to occur under null hypothesis significance testing (NHST) due to the phenomenon known as "the dance of the p-values." A number of misconceptions about null findings are then described, using as an example the way in which the results of the primary care arm of a recent cluster-randomized trial of ABI in England (the SIPS project) have been misunderstood. These misinterpretations include the fallacy of "proving the null hypothesis" that lack of a significant difference between the means of sample groups can be taken as evidence of no difference between their population means, and the possible effects of this and related misunderstandings of the SIPS findings are examined. The mistaken inference that reductions in alcohol consumption seen in control groups from baseline to follow-up are evidence of real effects of control group procedures is then discussed and other possible reasons for such reductions, including regression to the mean, research participation effects, historical trends, and assessment reactivity, are described. From the standpoint of scientific progress, the chief problem about null findings under the conventional NHST approach is that it is not possible to distinguish "evidence of absence" from "absence of evidence." By contrast, under a Bayesian approach, such a distinction is possible and it is explained how this approach could classify ABIs in particular settings or among particular populations as either truly ineffective or as of unknown effectiveness, thus accelerating progress in the field of ABI research.
Household structure vs. composition: Understanding gendered effects on educational progress in rural South Africa.

PubMed

Madhavan, Sangeetha; Myroniuk, Tyler W; Kuhn, Randall; Collinson, Mark A

2017-01-01

Demographers have long been interested in the relationship between living arrangements and gendered outcomes for children in sub-Saharan Africa. Most extant research conflates household structure with composition and has revealed little about the pathways that link these components to gendered outcomes. First, we offer a conceptual approach that differentiates structure from composition with a focus on gendered processes that operate in the household; and second, we demonstrate the value of this approach through an analysis of educational progress for boys and girls in rural South Africa. We use data from the 2002 round of the Agincourt Health and Demographic Surveillance System. Our analytical sample includes 22,997 children aged 6-18 who were neither parents themselves nor lived with a partner or partner's family. We employ ordinary least squares regression models to examine the effects of structure and composition on educational progress of girls and boys. The results suggest that non-nuclear structures are associated with similar negative effects for both boys and girls compared to children growing up in nuclear households. However, the presence of other kin in the absence of one or both parents results in gendered effects favouring boys. The absence of any gendered effects when using a household structure typology suggests that secular changes to attitudes about gender equity trump any specific gendered processes stemming from particular configurations. On the other hand, gendered effects that appear when one or both parents are absent show that traditional gender norms and/or resource constraints continue to favour boys. Despite the wealth of literature on household structure and children's educational outcomes in sub-Saharan Africa, the conceptual basis of these effects has not been well articulated. We have shown the value of unpacking household structure to better understand how gender norms and gendered resource allocations impact education.
Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease.

PubMed

Hoban, Megan D; Orkin, Stuart H; Bauer, Daniel E

2016-02-18

Effective medical management for sickle cell disease (SCD) remains elusive. As a prevalent and severe monogenic disorder, SCD has been long considered a logical candidate for gene therapy. Significant progress has been made in moving toward this goal. These efforts have provided substantial insight into the natural regulation of the globin genes and illuminated challenges for genetic manipulation of the hematopoietic system. The initial γ-retroviral vectors, next-generation lentiviral vectors, and novel genome engineering and gene regulation approaches each share the goal of preventing erythrocyte sickling. After years of preclinical studies, several clinical trials for SCD gene therapies are now open. This review focuses on progress made toward achieving gene therapy, the current state of the field, consideration of factors that may determine clinical success, and prospects for future development. © 2016 by The American Society of Hematology.

Integration of infrared thermography into various maintenance methodologies

NASA Astrophysics Data System (ADS)

Morgan, William T.

1993-04-01

Maintenance methodologies are in developmental stages throughout the world as global competitiveness drives all industries to improve operational efficiencies. Rapid progress in technical advancements has added an additional strain on maintenance organizations to progressively change. Accompanying needs for advanced training and documentation is the demand for utilization of various analytical instruments and quantitative methods. Infrared thermography is one of the primary elements of engineered approaches to maintenance. Current maintenance methodologies can be divided into six categories; Routine ('Breakdown'), Preventive, Predictive, Proactive, Reliability-Based, and Total Productive (TPM) maintenance. Each of these methodologies have distinctive approaches to achieving improved operational efficiencies. Popular though is that infrared thermography is a Predictive maintenance tool. While this is true, it is also true that it can be effectively integrated into each of the maintenance methodologies for achieving desired results. The six maintenance strategies will be defined. Infrared applications integrated into each will be composed in tabular form.
Determination of Fracture Parameters for Multiple Cracks of Laminated Composite Finite Plate

NASA Astrophysics Data System (ADS)

Srivastava, Amit Kumar; Arora, P. K.; Srivastava, Sharad Chandra; Kumar, Harish; Lohumi, M. K.

2018-04-01

A predictive method for estimation of stress state at zone of crack tip and assessment of remaining component lifetime depend on the stress intensity factor (SIF). This paper discusses the numerical approach for prediction of first ply failure load (FL), progressive failure load, SIF and critical SIF for multiple cracks configurations of laminated composite finite plate using finite element method (FEM). The Hashin and Chang failure criterion are incorporated in ABAQUS using subroutine approach user defined field variables (USDFLD) for prediction of progressive fracture response of laminated composite finite plate, which is not directly available in the software. A tensile experiment on laminated composite finite plate with stress concentration is performed to validate the numerically predicted subroutine results, shows excellent agreement. The typical results are presented to examine effect of changing the crack tip distance (S), crack offset distance (H), and stacking fiber angle (θ) on FL, and SIF .
Latent class analysis of diagnostic science assessment data using Bayesian networks

NASA Astrophysics Data System (ADS)

Steedle, Jeffrey Thomas

2008-10-01

Diagnostic science assessments seek to draw inferences about student understanding by eliciting evidence about the mental models that underlie students' reasoning about physical systems. Measurement techniques for analyzing data from such assessments embody one of two contrasting assessment programs: learning progressions and facet-based assessments. Learning progressions assume that students have coherent theories that they apply systematically across different problem contexts. In contrast, the facet approach makes no such assumption, so students should not be expected to reason systematically across different problem contexts. A systematic comparison of these two approaches is of great practical value to assessment programs such as the National Assessment of Educational Progress as they seek to incorporate small clusters of related items in their tests for the purpose of measuring depth of understanding. This dissertation describes an investigation comparing learning progression and facet models. Data comprised student responses to small clusters of multiple-choice diagnostic science items focusing on narrow aspects of understanding of Newtonian mechanics. Latent class analysis was employed using Bayesian networks in order to model the relationship between students' science understanding and item responses. Separate models reflecting the assumptions of the learning progression and facet approaches were fit to the data. The technical qualities of inferences about student understanding resulting from the two models were compared in order to determine if either modeling approach was more appropriate. Specifically, models were compared on model-data fit, diagnostic reliability, diagnostic certainty, and predictive accuracy. In addition, the effects of test length were evaluated for both models in order to inform the number of items required to obtain adequately reliable latent class diagnoses. Lastly, changes in student understanding over time were studied with a longitudinal model in order to provide educators and curriculum developers with a sense of how students advance in understanding over the course of instruction. Results indicated that expected student response patterns rarely reflected the assumptions of the learning progression approach. That is, students tended not to systematically apply a coherent set of ideas across different problem contexts. Even those students expected to express scientifically-accurate understanding had substantial probabilities of reporting certain problematic ideas. The learning progression models failed to make as many substantively-meaningful distinctions among students as the facet models. In statistical comparisons, model-data fit was better for the facet model, but the models were quite comparable on all other statistical criteria. Studying the effects of test length revealed that approximately 8 items are needed to obtain adequate diagnostic certainty, but more items are needed to obtain adequate diagnostic reliability. The longitudinal analysis demonstrated that students either advance in their understanding (i.e., switch to the more advanced latent class) over a short period of instruction or stay at the same level. There was no significant relationship between the probability of changing latent classes and time between testing occasions. In all, this study is valuable because it provides evidence informing decisions about modeling and reporting on student understanding, it assesses the quality of measurement available from short clusters of diagnostic multiple-choice items, and it provides educators with knowledge of the paths that student may take as they advance from novice to expert understanding over the course of instruction.
Integrative Genome Comparison of Primary and Metastatic Melanomas

PubMed Central

Feng, Bin; Nazarian, Rosalynn M.; Bosenberg, Marcus; Wu, Min; Scott, Kenneth L.; Kwong, Lawrence N.; Xiao, Yonghong; Cordon-Cardo, Carlos; Granter, Scott R.; Ramaswamy, Sridhar; Golub, Todd; Duncan, Lyn M.; Wagner, Stephan N.; Brennan, Cameron; Chin, Lynda

2010-01-01

A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes. PMID:20520718
Reconstructing Progressive Education

ERIC Educational Resources Information Center

Kaplan, Andy

2013-01-01

The work of Colonel Francis W. Parker, the man whom Dewey called "the father of progressive education," provides a starting point for reconstructing the loose ambiguities of progressive education into a coherent social and educational philosophy. Although progressives have claimed their approach is more humane and sensitive to children, we need…
Effect of Age on Complexity and Causality of the Cardiovascular Control: Comparison between Model-Based and Model-Free Approaches

PubMed Central

Porta, Alberto; Faes, Luca; Bari, Vlasta; Marchi, Andrea; Bassani, Tito; Nollo, Giandomenico; Perseguini, Natália Maria; Milan, Juliana; Minatel, Vinícius; Borghi-Silva, Audrey; Takahashi, Anielle C. M.; Catai, Aparecida M.

2014-01-01

The proposed approach evaluates complexity of the cardiovascular control and causality among cardiovascular regulatory mechanisms from spontaneous variability of heart period (HP), systolic arterial pressure (SAP) and respiration (RESP). It relies on construction of a multivariate embedding space, optimization of the embedding dimension and a procedure allowing the selection of the components most suitable to form the multivariate embedding space. Moreover, it allows the comparison between linear model-based (MB) and nonlinear model-free (MF) techniques and between MF approaches exploiting local predictability (LP) and conditional entropy (CE). The framework was applied to study age-related modifications of complexity and causality in healthy humans in supine resting (REST) and during standing (STAND). We found that: 1) MF approaches are more efficient than the MB method when nonlinear components are present, while the reverse situation holds in presence of high dimensional embedding spaces; 2) the CE method is the least powerful in detecting age-related trends; 3) the association of HP complexity on age suggests an impairment of cardiac regulation and response to STAND; 4) the relation of SAP complexity on age indicates a gradual increase of sympathetic activity and a reduced responsiveness of vasomotor control to STAND; 5) the association from SAP to HP on age during STAND reveals a progressive inefficiency of baroreflex; 6) the reduced connection from HP to SAP with age might be linked to the progressive exploitation of Frank-Starling mechanism at REST and to the progressive increase of peripheral resistances during STAND; 7) at REST the diminished association from RESP to HP with age suggests a vagal withdrawal and a gradual uncoupling between respiratory activity and heart; 8) the weakened connection from RESP to SAP with age might be related to the progressive increase of left ventricular thickness and vascular stiffness and to the gradual decrease of respiratory sinus arrhythmia. PMID:24586796
Immunological network signatures of cancer progression and survival

PubMed Central

2011-01-01

Background The immune contribution to cancer progression is complex and difficult to characterize. For example in tumors, immune gene expression is detected from the combination of normal, tumor and immune cells in the tumor microenvironment. Profiling the immune component of tumors may facilitate the characterization of the poorly understood roles immunity plays in cancer progression. However, the current approaches to analyze the immune component of a tumor rely on incomplete identification of immune factors. Methods To facilitate a more comprehensive approach, we created a ranked immunological relevance score for all human genes, developed using a novel strategy that combines text mining and information theory. We used this score to assign an immunological grade to gene expression profiles, and thereby quantify the immunological component of tumors. This immunological relevance score was benchmarked against existing manually curated immune resources as well as high-throughput studies. To further characterize immunological relevance for genes, the relevance score was charted against both the human interactome and cancer information, forming an expanded interactome landscape of tumor immunity. We applied this approach to expression profiles in melanomas, thus identifying and grading their immunological components, followed by identification of their associated protein interactions. Results The power of this strategy was demonstrated by the observation of early activation of the adaptive immune response and the diversity of the immune component during melanoma progression. Furthermore, the genome-wide immunological relevance score classified melanoma patient groups, whose immunological grade correlated with clinical features, such as immune phenotypes and survival. Conclusions The assignment of a ranked immunological relevance score to all human genes extends the content of existing immune gene resources and enriches our understanding of immune involvement in complex biological networks. The application of this approach to tumor immunity represents an automated systems strategy that quantifies the immunological component in complex disease. In so doing, it stratifies patients according to their immune profiles, which may lead to effective computational prognostic and clinical guides. PMID:21453479
A feature selection approach towards progressive vector transmission over the Internet

NASA Astrophysics Data System (ADS)

Miao, Ru; Song, Jia; Feng, Min

2017-09-01

WebGIS has been applied for visualizing and sharing geospatial information popularly over the Internet. In order to improve the efficiency of the client applications, the web-based progressive vector transmission approach is proposed. Important features should be selected and transferred firstly, and the methods for measuring the importance of features should be further considered in the progressive transmission. However, studies on progressive transmission for large-volume vector data have mostly focused on map generalization in the field of cartography, but rarely discussed on the selection of geographic features quantitatively. This paper applies information theory for measuring the feature importance of vector maps. A measurement model for the amount of information of vector features is defined based upon the amount of information for dealing with feature selection issues. The measurement model involves geometry factor, spatial distribution factor and thematic attribute factor. Moreover, a real-time transport protocol (RTP)-based progressive transmission method is then presented to improve the transmission of vector data. To clearly demonstrate the essential methodology and key techniques, a prototype for web-based progressive vector transmission is presented, and an experiment of progressive selection and transmission for vector features is conducted. The experimental results indicate that our approach clearly improves the performance and end-user experience of delivering and manipulating large vector data over the Internet.
Probabilistic structural analysis to quantify uncertainties associated with turbopump blades

NASA Technical Reports Server (NTRS)

Nagpal, Vinod K.; Rubinstein, Robert; Chamis, Christos C.

1988-01-01

A probabilistic study of turbopump blades has been in progress at NASA Lewis Research Center for over the last two years. The objectives of this study are to evaluate the effects of uncertainties in geometry and material properties on the structural response of the turbopump blades to evaluate the tolerance limits on the design. A methodology based on probabilistic approach was developed to quantify the effects of the random uncertainties. The results indicate that only the variations in geometry have significant effects.
Current and emerging challenges of field effect transistor based bio-sensing

NASA Astrophysics Data System (ADS)

Matsumoto, Akira; Miyahara, Yuji

2013-10-01

Field-effect-transistor (FET) based electrical signal transduction is an increasingly prevalent strategy for bio-sensing. This technique, often termed ``Bio-FETs'', provides an essentially label-free and real-time based bio-sensing platform effective for a variety of targets. This review highlights recent progress and challenges in the field. A special focus is on the comprehension of emerging nanotechnology-based approaches to facilitate signal-transduction and amplification. Some new targets of Bio-FETs and the future perspectives are also discussed.
Current and emerging challenges of field effect transistor based bio-sensing.

PubMed

Matsumoto, Akira; Miyahara, Yuji

2013-11-21

Field-effect-transistor (FET) based electrical signal transduction is an increasingly prevalent strategy for bio-sensing. This technique, often termed "Bio-FETs", provides an essentially label-free and real-time based bio-sensing platform effective for a variety of targets. This review highlights recent progress and challenges in the field. A special focus is on the comprehension of emerging nanotechnology-based approaches to facilitate signal-transduction and amplification. Some new targets of Bio-FETs and the future perspectives are also discussed.
A personalized and control systems engineering conceptual approach to target childhood anxiety in the contexts of cultural diversity.

PubMed

Pina, Armando A; Holly, Lindsay E; Zerr, Argero A; Rivera, Daniel E

2014-01-01

In the child and adolescent anxiety area, some progress has been made to develop evidence-based prevention protocols, but less is known about how to best target these problems in children and families of color. In general, data show differential program effects with some minority children benefiting significantly less. Our preliminary data, however, show promise and suggest cultural parameters to consider in the tailoring process beyond language and cultural symbols. It appears that a more focused approach to culture might help activate intervention components and its intended effects by focusing, for example, on the various facets of familismo when working with some Mexican parents. However, testing the effects and nuances of cultural adaption vis-à-vis a focused personalized approach is methodologically challenging. For this reason, we identify control systems engineering design methods and provide example scenarios relevant to our data and recent intervention work.
Gene Therapy for Parkinson's Disease

PubMed Central

Denyer, Rachel; Douglas, Michael R.

2012-01-01

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field. PMID:22619738
Gene therapy for Parkinson's disease.

PubMed

Denyer, Rachel; Douglas, Michael R

2012-01-01

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.
Medical treatment of lower urinary tract symptoms/benign prostatic hyperplasia: anything new in 2015.

PubMed

Schauer, Ingrid; Madersbacher, Stephan

2015-01-01

The purpose of this study is to provide an update on recent developments regarding the medical management of male lower urinary tract symptoms (LUTS). Silodosin improves storage/voiding symptoms and nocturia and is effective within the framework of a trial without a catheter. 5α-reductase inhibitors (5ARIs) are not associated with male breast cancer development. Alcohol consumption seems to increase the risk of high-grade prostate cancer under 5ARIs. The combination of α-blocker and 5ARIs remains a well established concept for benign prostatic hyperplasia/LUTS patients with an enhanced risk of disease progression. Tadalafil 5 mg/day monotherapy is a valid option particularly for men with LUTS and erectile dysfunction; the combination of Tadalafil 5 mg/day with a 5ARI is an interesting approach. The fixed-dose combination of α-blocker and antimuscarinic provides advantages regarding storage symptom improvement. This approach is currently primarily recommended as an add-on strategy. Mirabegron opens new horizons in the management of male LUTS and has no negative (but also no positive) urodynamic effects. Several encouraging novel approaches are currently in the experimental phase and might enhance our therapeutic armamentarium in the near future. The recent literature refines our knowledge on current therapeutic options and provides further evidence for an individualized, risk-adapted approach for male LUTS mainly depending on symptoms status, comorbidities (i.e. erectile dysfunction) and risk of disease progression.
Approaches to Vaccination Among Populations in Areas of Conflict

PubMed Central

Nnadi, Chimeremma; Etsano, Andrew; Uba, Belinda; Ohuabunwo, Chima; Melton, Musa; Nganda, Gatei wa; Esapa, Lisa; Bolu, Omotayo; Mahoney, Frank; Vertefeuille, John; Wiesen, Eric; Durry, Elias

2017-01-01

Vaccination is an important and cost-effective disease prevention and control strategy. Despite progress in vaccine development and immunization delivery systems worldwide, populations in areas of conflict (hereafter, “conflict settings”) often have limited or no access to lifesaving vaccines, leaving them at increased risk for morbidity and mortality related to vaccine-preventable disease. Without developing and refining approaches to reach and vaccinate children and other vulnerable populations in conflict settings, outbreaks of vaccine-preventable disease in these settings may persist and spread across subnational and international borders. Understanding and refining current approaches to vaccinating populations in conflict and humanitarian emergency settings may save lives. Despite major setbacks, the Global Polio Eradication Initiative has made substantial progress in vaccinating millions of children worldwide, including those living in communities affected by conflicts and other humanitarian emergencies. In this article, we examine key strategic and operational tactics that have led to increased polio vaccination coverage among populations living in diverse conflict settings, including Nigeria, Somalia, and Pakistan, and how these could be applied to reach and vaccinate populations in other settings across the world. PMID:28838202
Non-microbial approach for Helicobacter pylori as faster track to prevent gastric cancer than simple eradication

PubMed Central

Park, Sang-Ho; Kangwan, Napapan; Park, Jong-Min; Kim, Eun-Hee; Hahm, Ki Baik

2013-01-01

Although the International Agency for Research on Cancer declared Helicobacter pylori (H. pylori) as a definite human carcinogen in 1994, the Japanese Society for Helicobacter Research only recently (February 2013) adopted the position that H. pylori infection should be considered as an indication for either amelioration of chronic gastritis or for decreasing gastric cancer mortality. Japanese researchers have found that H. pylori eradication halts progressive mucosal damage and that successful eradication in patients with non-atrophic gastritis most likely prevents subsequent development of gastric cancer. However, those who have already developed atrophic gastritis/gastric atrophy retain potential risk factors for gastric cancer. Because chronic perpetuated progression of H. pylori-associated gastric inflammation is associated with increased morbidity culminating in gastric carcinogenesis, a non-microbial approach to treatment that provides long-term control of gastric inflammation through nutrients and other interventions may be an effective way to decrease this morbidity. This non-microbial approach might represent a new form of prerequisite “rescue” therapy that provides a quicker path to the prevention of gastric cancer as compared to simple eradication. PMID:24379623
The effect of improvisation-assisted desensitization, and music-assisted progressive muscle relaxation and imagery on reducing pianists' music performance anxiety.

PubMed

Kim, Youngshin

2008-01-01

The purpose of this study was to investigate the effects of two music therapy approaches, improvisation-assisted desensitization, and music-assisted progressive muscle relaxation and imagery on ameliorating the symptoms of music performance anxiety (MPA) among student pianists. Thirty female college pianists (N = 30) were randomly assigned to one of two conditions: (a) improvised music-assisted desensitization group (n = 15), or (b) music-assisted progressive muscle relaxation (PMR) and imagery group (n = 15). All participants received 6 weekly music therapy sessions according to their assigned group. Two lab performances were provided; one before and one after the 6 music therapy sessions, as the performance stimuli for MPA. All participants completed pretest and posttest measures that included four types of visual analogue scales (MPA, stress, tension, and comfort), the state portion of Spielberger's State-Trait Anxiety Inventory (STAI), and the Music Performance Anxiety Questionnaire (MPAQ) developed by Lehrer, Goldman, and Strommen (1990). Participants' finger temperatures were also measured. When results of the music-assisted PMR and imagery condition were compared from pretest to posttest, statistically significant differences occurred in 6 out of the 7 measures-MPA, tension, comfort, STAI, MPAQ, and finger temperature, indicating that the music-assisted PMR and imagery treatment was very successful in reducing MPA. For the improvisation-assisted desensitization condition, the statistically significant decreases in tension and STAI, with increases in finger temperature indicated that this approach was effective in managing MPA to some extent. When the difference scores for the two approaches were compared, there was no statistically significant difference between the two approaches for any of the seven measures. Therefore, no one treatment condition appeared more effective than the other. Although statistically significant differences were not found between the two groups, a visual analysis of mean difference scores revealed that the music-assisted PMR and imagery condition resulted in greater mean differences from pretest to posttest than the improvisation-assisted desensitization condition across all seven measures. This result may be due to the fact that all participants in the music-assisted PMR and imagery condition followed the procedure easily, while two of the 15 participants in the improvisation-assisted desensitization group had difficulty improvising.
Research progress on chemopreventive effects of phytochemicals on colorectal cancer and their mechanisms.

PubMed

Yin, Teng-Fei; Wang, Min; Qing, Ying; Lin, Ying-Min; Wu, Dong

2016-08-21

Colorectal cancer (CRC) is a type of cancer with high morbidity and mortality rates worldwide and has become a global health problem. The conventional radiotherapy and chemotherapy regimen for CRC not only has a low cure rate but also causes side effects. Many studies have shown that adequate intake of fruits and vegetables in the diet may have a protective effect on CRC occurrence, possibly due to the special biological protective effect of the phytochemicals in these foods. Numerous in vitro and in vivo studies have demonstrated that phytochemicals play strong antioxidant, anti-inflammatory and anti-cancer roles by regulating specific signaling pathways and molecular markers to inhibit the occurrence and development of CRC. This review summarizes the progress on CRC prevention using the phytochemicals sulforaphane, curcumin and resveratrol, and elaborates on the specific underlying mechanisms. Thus, we believe that phytochemicals might provide a novel therapeutic approach for CRC prevention, but future clinical studies are needed to confirm the specific preventive effect of phytochemicals on cancer.
A school-based program implemented by community providers previously trained for the prevention of eating and weight-related problems in secondary-school adolescents: the MABIC study protocol.

PubMed

Sánchez-Carracedo, David; López-Guimerà, Gemma; Fauquet, Jordi; Barrada, Juan Ramón; Pàmias, Montserrat; Puntí, Joaquim; Querol, Mireia; Trepat, Esther

2013-10-12

The prevention of eating disorders and disordered eating are increasingly recognized as public health priorities. Challenges in this field included moving from efficacy to effectiveness and developing an integrated approach to the prevention of a broad spectrum of eating and weight-related problems. A previous efficacy trial indicated that a universal disordered eating prevention program, based on the social cognitive model, media literacy educational approach and cognitive dissonance theory, reduced risk factors for disordered eating, but it is unclear whether this program has effects under more real-world conditions. The main aim of this effectiveness trial protocol is to test whether this program has effects when incorporating an integrated approach to prevention and when previously-trained community providers implement the intervention. The research design involved a multi-center non-randomized controlled trial with baseline, post and 1-year follow-up measures. Six schools from the city of Sabadell (close to Barcelona) participated in the intervention group, and eleven schools from four towns neighboring Sabadell participated in the control group. A total of 174 girls and 180 boys in the intervention group, and 484 girls and 490 boys in the control group were registered in class lists prior to baseline. A total of 18 community providers, secondary-school class tutors, nurses from the Catalan Government's Health and School Program, and health promotion technicians from Sabadell City Council were trained and delivered the program. Shared risk factors of eating and weight-related problems were assessed as main measures. It will be vital for progress in disordered eating prevention to conduct effectiveness trials, which test whether interventions are effective when delivered by community providers under ecologically valid conditions, as opposed to tightly controlled research trials. The MABIC project will provide new contributions in this transition from efficacy to effectiveness and new data about progress in the integrated approach to prevention. Pending the results, the effectiveness trial meets the effectiveness standards set down by the Society for Prevention Research. This study will provide new evidence to improve and enhance disordered eating prevention programs. Current Controlled Trials ISRCTN47682626.

Learning of speckle statistics for in vivo and noninvasive characterization of cutaneous wound regions using laser speckle contrast imaging.

PubMed

Basak, Kausik; Dey, Goutam; Mahadevappa, Manjunatha; Mandal, Mahitosh; Sheet, Debdoot; Dutta, Pranab Kumar

2016-09-01

Laser speckle contrast imaging (LSCI) provides a noninvasive and cost effective solution for in vivo monitoring of blood flow. So far, most of the researches consider changes in speckle pattern (i.e. correlation time of speckle intensity fluctuation), account for relative change in blood flow during abnormal conditions. This paper introduces an application of LSCI for monitoring wound progression and characterization of cutaneous wound regions on mice model. Speckle images are captured on a tumor wound region at mice leg in periodic interval. Initially, raw speckle images are converted to their corresponding contrast images. Functional characterization begins with first segmenting the affected area using k-means clustering, taking wavelet energies in a local region as feature set. In the next stage, different regions in wound bed are clustered based on progressive and non-progressive nature of tissue properties. Changes in contrast due to heterogeneity in tissue structure and functionality are modeled using LSCI speckle statistics. Final characterization is achieved through supervised learning of these speckle statistics using support vector machine. On cross evaluation with mice model experiment, the proposed approach classifies the progressive and non-progressive wound regions with an average sensitivity of 96.18%, 97.62% and average specificity of 97.24%, 96.42% respectively. The clinical information yield with this approach is validated with the conventional immunohistochemistry result of wound to justify the ability of LSCI for in vivo, noninvasive and periodic assessment of wounds. Copyright © 2016 Elsevier Inc. All rights reserved.
Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030552 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.
Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030578 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.
Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030563 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.
Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030460 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.
Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030445 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.
Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030584 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.
Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030444 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.
Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030528 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.
Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer

PubMed Central

Martín, María Angeles; Goya, Luis; Ramos, Sonia

2016-01-01

Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to interfere at the three stages of cancer. Cocoa has been demonstrated to counteract oxidative stress and to have a potential capacity to interact with multiple carcinogenic pathways involved in inflammation, proliferation and apoptosis of initiated and malignant cells. Therefore, restriction of oxidative stress and/or prevention or delayed progression of cancer stages by cocoa antioxidant compounds has gained interest as an effective approach in colorectal cancer prevention. In this review, we look over different in vitro and in vivo studies that have identified potential targets and mechanisms whereby cocoa and their flavonoids could interfere with colonic cancer. In addition, evidence from human studies is also illustrated. PMID:28933386
A Deep Learning Approach to Neuroanatomical Characterisation of Alzheimer's Disease.

PubMed

Ambastha, Abhinit Kumar; Leong, Tze-Yun

2017-01-01

Alzheimer's disease (AD) is a neurological degenerative disorder that leads to progressive mental deterioration. This work introduces a computational approach to improve our understanding of the progression of AD. We use ensemble learning methods and deep neural networks to identify salient structural correlations among brain regions that degenerate together in AD; this provides an understanding of how AD progresses in the brain. The proposed technique has a classification accuracy of 81.79% for AD against healthy subjects using a single modality imaging dataset.
Progress 23 supply vehicle approach

NASA Image and Video Library

2006-10-26

ISS014-E-06544 (26 Oct. 2006) --- Backdropped by a blue and white Earth, an unpiloted Progress supply vehicle approaches the International Space Station. Progress docked to the aft port of the Zvezda Service Module at 9:29 a.m. (CDT) on Oct. 26. The spacecraft used the automated Kurs system to dock at the aft port of the Zvezda service module. Expedition 14 flight engineer Mikhail Tyurin stood by at the manual Toru docking system controls, but the automated system functioned as designed and manual intervention was not needed.
The Intensive Dysphagia Rehabilitation Approach Applied to Patients With Neurogenic Dysphagia: A Case Series Design Study.

PubMed

Malandraki, Georgia A; Rajappa, Akila; Kantarcigil, Cagla; Wagner, Elise; Ivey, Chandra; Youse, Kathleen

2016-04-01

To examine the effects of the Intensive Dysphagia Rehabilitation approach on physiological and functional swallowing outcomes in adults with neurogenic dysphagia. Intervention study; before-after trial with 4-week follow-up through an online survey. Outpatient university clinics. A consecutive sample of subjects (N=10) recruited from outpatient university clinics. All subjects were diagnosed with adult-onset neurologic injury or disease. Dysphagia diagnosis was confirmed through clinical and endoscopic swallowing evaluations. No subjects withdrew from the study. Participants completed the 4-week Intensive Dysphagia Rehabilitation protocol, including 2 oropharyngeal exercise regimens, a targeted swallowing routine using salient stimuli, and caregiver participation. Treatment included hourly sessions twice per week and home practice for approximately 45 min/d. Outcome measures assessed pre- and posttreatment included airway safety using an 8-point Penetration Aspiration Scale, lingual isometric pressures, self-reported swallowing-related quality of life (QOL), and level of oral intake. Also, patients were monitored for adverse dysphagia-related effects. QOL and adverse effects were also assessed at the 4-week follow-up (online survey). The Intensive Dysphagia Rehabilitation approach was effective in improving maximum and mean Penetration Aspiration Scale scores (P<.05, η(2)=.8146 and P<.05, η(2)=.799708, respectively) and level of oral intake (P<.005, Cohen d=-1.387). Of the 5 patients who were feeding tube dependent initially, 2 progressed to total oral nutrition, and 2 progressed to partial oral nutrition. One patient remained tube dependent. QOL was significantly improved at the 4-week follow-up (95% confidence interval, 6.38-14.5; P<.00), but not at the posttreatment. No adverse effects were observed/reported. The Intensive Dysphagia Rehabilitation approach was safe and improved physiological and some functional swallowing outcomes in our sample; however, further investigation is needed before it can be widely applied. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Progressively engaging: constructing nurse, patient, and family relationships in acute care settings.

PubMed

Segaric, Cheryl Ann; Hall, Wendy A

2015-02-01

In this grounded theory study, informed by symbolic interactionism, we explain how nurses, patients, and family members construct relationships in acute care settings, including managing effects of work environments. We recruited participants from 10 acute care units across four community hospitals in a Western Canadian city. From 33 hr of participant observation and 40 interviews with 13 nurses, 17 patients, and 10 family members, we constructed the basic social-psychological process of progressively engaging. Nurses, patients, and family members approached constructing relationships through levels of engagement, ranging from perspectives about "just doing the job" to "doing the job with heart." Progressively engaging involved three stages: focusing on tasks, getting acquainted, and building rapport. Workplace conditions and personal factors contributed or detracted from participants' movement through the stages of the process; with higher levels of engagement, participants experienced greater satisfaction and cooperation. Progressively engaging provides direction for how all participants in care can invest in relationships. © The Author(s) 2014.
Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, randomized clinical study

PubMed Central

2014-01-01

Background Progressive Supranuclear Palsy (PSP) is a sporadic and progressive neurodegenerative disease which belongs to the family of tauopathies and involves both cortical and subcortical structures. No effective therapy is to date available. Methods/design Autologous bone marrow (BM) mesenchymal stem cells (MSC) from patients affected by different type of parkinsonisms have shown their ability to improve the dopaminergic function in preclinical and clinical models. It is also possible to isolate and expand MSC from the BM of PSP patients with the same proliferation rate and immuphenotypic profile as MSC from healthy donors. BM MSC can be efficiently delivered to the affected brain regions of PSP patients where they can exert their beneficial effects through different mechanisms including the secretion of neurotrophic factors. Here we propose a randomized, placebo-controlled, double-blind phase I clinical trial in patients affected by PSP with MSC delivered via intra-arterial injection. Discussion To our knowledge, this is the first clinical trial to be applied in a no-option parkinsonism that aims to test the safety and to exploit the properties of autologous mesenchymal stem cells in reducing disease progression. The study has been designed to test the safety of this “first-in-man” approach and to preliminarily explore its efficacy by excluding the placebo effect. Trial registration NCT01824121 PMID:24438512
The Challenge of Induction! Introducing Engineering Students to Higher Education: A Task-Oriented Approach.

ERIC Educational Resources Information Center

Edward, Norrie; Middleton, June

2002-01-01

First-year engineering students at Robert Gordon University (Scotland) were presented with a task-oriented induction program. Students were divided into groups and assigned a facilitator, later personal tutor, to whom they could refer. Student reaction to the experience was very favorable. Effect on progression rates is yet to be determined. (AEF)
The Effect of Flexible Small Groups on Math Achievement in First Grade

ERIC Educational Resources Information Center

Benders, David; Craft, Tracy

2016-01-01

This action research study explores the Guided Math Approach to improving math scores for first grade students. Previous MAP (Measure of Academic Progress) scores were used to measure proficiency and students were placed in separate categories for appropriate instruction. This study reviewed math achievement scores on MAP test from a First grade…
Improvements in Intracorporeal Lithotripters for Percutaneous Nephrolithotomy

NASA Astrophysics Data System (ADS)

Kuo, Ramsay L.

2007-04-01

Percutaneous nephrolithotomy (PNL) is an effective minimally invasive surgical approach for the treatment of large renal stone burden. Intracorporeal lithotripters (ICL) are utilized during PNL to fragment calculi, with some devices capable of concurrently removing fragments as well. Much progress has been made in the design of ICL devices, resulting in potentially more efficient treatment of nephrolithiasis.
Students' Emotions as an Organizing Principle in the Social Work Curriculum

ERIC Educational Resources Information Center

Chung, Irene W.

2010-01-01

Students' frustration with the lack of measurable progress in their practice has always been a major obstacle for them in learning to use themselves differentially and to effect changes in their clients (Saari, 1986). This article discusses the author's approach to tending to students' emotions as a central component in organizing and teaching in…
The Utility of an Efficient Outcomes Assessment System at University Counseling Centers

ERIC Educational Resources Information Center

Kopta, S. Mark; Petrik, Megan L.; Saunders, Stephen M.; Mond, Michael; Hirsch, Glenn; Kadison, Richard; Raymond, Danielle

2014-01-01

Due to increased demands placed on university counseling centers (UCCs) in recent years, there is a need for these centers to enhance the efficiency and effectiveness of their psychological services. Regularly monitoring client progress is one approach to increase the likelihood of positive clinical outcomes. This article describes the use of the…

A Moveable Feast--A Progressive Approach to the Unit Operations Laboratory

ERIC Educational Resources Information Center

Conner, Wm. Curtis, Jr.; Hammond, Karl D.; Laurence, Robert L.

2011-01-01

The authors describe an alternative format for the senior laboratory in which students are allowed--indeed, expected--to communicate with previous groups and build on their results. The effect is a unit operations laboratory in which students are empowered to propose the experiments they wish to do and in which the cumulative experience of the…
The Effect of Systematic Academic Instruction on Behavioural and Academic Outcomes of Students with EBD

ERIC Educational Resources Information Center

van der Worp-van der Kamp, Lidy; Pijl, Sip Jan; Post, Wendy J.; Bijstra, Jan O.; van den Bosch, Els J.

2016-01-01

This study aims to assess the impact of systematic academic instruction on academic progress and behavioural problems of students with emotional and/or behavioural disorders (EBD) in special education. Earlier studies have noted the importance of a systematic approach as well as the significance of focusing on academic instruction instead of on…
Is physical exercise a multiple sclerosis disease modifying treatment?

PubMed

Motl, Robert W; Pilutti, Lara A

2016-08-01

There is consensus that exercise represents a behavioral approach for the restoration of function and management of symptoms among persons with multiple sclerosis (MS). The current paper provides a review on the topic of exercise and physical activity as MS-disease modifying treatments. Firstly, metrics for evaluating disease modification and progression in MS are described. Secondly, evidence for exercise as a MS-disease modifying therapy based on individual studies, literature reviews, and meta-analyses is summarized. Finally, the paper focuses on major limitations of the existing body of research. Expert commentary: Exercise and physical activity have been associated with reduced relapse rate, mobility disability and its progression, and lesion volume, and improved neuroperformance, particularly walking outcomes. This evidence provides a positive, yet preliminary, picture for exercise having possible effects on markers of disease modification and progression in MS.
Computational approach for deriving cancer progression roadmaps from static sample data

PubMed Central

Yao, Jin; Yang, Le; Chen, Runpu; Nowak, Norma J.

2017-01-01

Abstract As with any biological process, cancer development is inherently dynamic. While major efforts continue to catalog the genomic events associated with human cancer, it remains difficult to interpret and extrapolate the accumulating data to provide insights into the dynamic aspects of the disease. Here, we present a computational strategy that enables the construction of a cancer progression model using static tumor sample data. The developed approach overcame many technical limitations of existing methods. Application of the approach to breast cancer data revealed a linear, branching model with two distinct trajectories for malignant progression. The validity of the constructed model was demonstrated in 27 independent breast cancer data sets, and through visualization of the data in the context of disease progression we were able to identify a number of potentially key molecular events in the advance of breast cancer to malignancy. PMID:28108658
Progress testing in the medical curriculum: students' approaches to learning and perceived stress.

PubMed

Chen, Yan; Henning, Marcus; Yielder, Jill; Jones, Rhys; Wearn, Andy; Weller, Jennifer

2015-09-11

Progress Tests (PTs) draw on a common question bank to assess all students in a programme against graduate outcomes. Theoretically PTs drive deep approaches to learning and reduce assessment-related stress. In 2013, PTs were introduced to two year groups of medical students (Years 2 and 4), whereas students in Years 3 and 5 were taking traditional high-stakes assessments. Staged introduction of PTs into our medical curriculum provided a time-limited opportunity for a comparative study. The main purpose of the current study was to compare the impact of PTs on undergraduate medical students' approaches to learning and perceived stress with that of traditional high-stakes assessments. We also aimed to investigate the associations between approaches to learning, stress and PT scores. Undergraduate medical students (N = 333 and N = 298 at Time 1 and Time 2 respectively) answered the Revised Study Process Questionnaire (R-SPQ-2F) and the Perceived Stress Scale (PSS) at two time points to evaluate change over time. The R-SPQ-2F generated a surface approach and a deep approach score; the PSS generated an overall perceived stress score. We found no significant differences between the two groups in approaches to learning at either time point, and no significant changes in approaches to learning over time in either cohort. Levels of stress increased significantly at the end of the year (Time 2) for students in the traditional assessment cohort, but not in the PT cohort. In the PT cohort, surface approach to learning, but not stress, was a significant negative predictor of students' PT scores. While confirming an association between surface approaches to learning and lower PT scores, we failed to demonstrate an effect of PTs on approaches to learning. However, a reduction in assessment-associated stress is an important finding.
Nutrition and Cardiovascular Disease: Finding the Perfect Recipe for Cardiovascular Health

PubMed Central

Ravera, Alice; Carubelli, Valentina; Sciatti, Edoardo; Bonadei, Ivano; Gorga, Elio; Cani, Dario; Vizzardi, Enrico; Metra, Marco; Lombardi, Carlo

2016-01-01

The increasing burden of cardiovascular disease (CVD) despite the progress in management entails the need of more effective preventive and curative strategies. As dietary-associated risk is the most important behavioral factor influencing global health, it appears the best target in the challenge against CVD. Although for many years, since the formulation of the cholesterol hypothesis, a nutrient-based approach was attempted for CVD prevention and treatment, in recent years a dietary-based approach resulted more effective in reducing cardiovascular risk worldwide. After the publication of randomized trials on the remarkable effects of the Mediterranean diet and the Dietary Approach to Stop Hypertension (DASH) diet on CVD, new efforts were put on research about the effects of complex dietary interventions on CVD. The purpose of this paper is to review the evidence on dietary interventions in the prevention and disease modification of CVD, focusing on coronary artery disease and heart failure, the main disease responsible for the enormous toll taken by CVD worldwide. PMID:27314382
Nutrition and Cardiovascular Disease: Finding the Perfect Recipe for Cardiovascular Health.

PubMed

Ravera, Alice; Carubelli, Valentina; Sciatti, Edoardo; Bonadei, Ivano; Gorga, Elio; Cani, Dario; Vizzardi, Enrico; Metra, Marco; Lombardi, Carlo

2016-06-14

The increasing burden of cardiovascular disease (CVD) despite the progress in management entails the need of more effective preventive and curative strategies. As dietary-associated risk is the most important behavioral factor influencing global health, it appears the best target in the challenge against CVD. Although for many years, since the formulation of the cholesterol hypothesis, a nutrient-based approach was attempted for CVD prevention and treatment, in recent years a dietary-based approach resulted more effective in reducing cardiovascular risk worldwide. After the publication of randomized trials on the remarkable effects of the Mediterranean diet and the Dietary Approach to Stop Hypertension (DASH) diet on CVD, new efforts were put on research about the effects of complex dietary interventions on CVD. The purpose of this paper is to review the evidence on dietary interventions in the prevention and disease modification of CVD, focusing on coronary artery disease and heart failure, the main disease responsible for the enormous toll taken by CVD worldwide.
Improvement of Long-Jump Performance During Competition Using a Plyometric Exercise.

PubMed

Bogdanis, Gregory C; Tsoukos, Athanasios; Veligekas, Panagiotis

2017-02-01

To examine the acute effects of a conditioning plyometric exercise on long-jump performance during a simulated long-jump competition. Eight national-level track and field decathletes performed 6 long-jump attempts with a full approach run separated by 10-min recoveries. In the experimental condition subjects performed 3 rebound vertical jumps with maximal effort 3 min before the last 5 attempts, while the 1st attempt served as baseline. In the control condition the participants performed 6 long jumps without executing the conditioning exercise. Compared with baseline, long-jump performance progressively increased only in the experimental condition, from 3.0%, or 17.5 cm, in the 3rd attempt (P = .046, d = 0.56), to 4.8%, or 28.2 cm, in the 6th attempt (P = .0001, d = 0.84). The improvement in long-jump performance was due to a gradual increase in vertical takeoff velocity from the 3rd (by 8.7%, P = .0001, d = 1.82) to the 6th jump (by 17.7%, P = .0001, d = 4.38). Horizontal-approach velocity, takeoff duration, and horizontal velocity at takeoff were similar at all long-jump attempts in both conditions (P = .80, P = .36, and P = .15, respectively). Long-jump performance progressively improved during a simulated competition when a plyometric conditioning exercise was executed 3 min before each attempt. This improvement was due to a progressive increase in vertical velocity of takeoff, while there was no effect on the horizontal velocity.
Pseudo progression identification of glioblastoma with dictionary learning.

PubMed

Zhang, Jian; Yu, Hengyong; Qian, Xiaohua; Liu, Keqin; Tan, Hua; Yang, Tielin; Wang, Maode; Li, King Chuen; Chan, Michael D; Debinski, Waldemar; Paulsson, Anna; Wang, Ge; Zhou, Xiaobo

2016-06-01

Although the use of temozolomide in chemoradiotherapy is effective, the challenging clinical problem of pseudo progression has been raised in brain tumor treatment. This study aims to distinguish pseudo progression from true progression. Between 2000 and 2012, a total of 161 patients with glioblastoma multiforme (GBM) were treated with chemoradiotherapy at our hospital. Among the patients, 79 had their diffusion tensor imaging (DTI) data acquired at the earliest diagnosed date of pseudo progression or true progression, and 23 had both DTI data and genomic data. Clinical records of all patients were kept in good condition. Volumetric fractional anisotropy (FA) images obtained from the DTI data were decomposed into a sequence of sparse representations. Then, a feature selection algorithm was applied to extract the critical features from the feature matrix to reduce the size of the feature matrix and to improve the classification accuracy. The proposed approach was validated using the 79 samples with clinical DTI data. Satisfactory results were obtained under different experimental conditions. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.87 for a given dictionary with 1024 atoms. For the subgroup of 23 samples, genomics data analysis was also performed. Results implied further perspective on pseudo progression classification. The proposed method can determine pseudo progression and true progression with improved accuracy. Laboring segmentation is no longer necessary because this skillfully designed method is not sensitive to tumor location. Copyright © 2016 Elsevier Ltd. All rights reserved.
Twistor approach to string compactifications: A review

NASA Astrophysics Data System (ADS)

Alexandrov, Sergei

2013-01-01

We review a progress in obtaining the complete non-perturbative effective action of type II string theory compactified on a Calabi-Yau manifold. This problem is equivalent to understanding quantum corrections to the metric on the hypermultiplet moduli space. We show how all these corrections, which include D-brane and NS5-brane instantons, are incorporated in the framework of the twistor approach, which provides a powerful mathematical description of hyperkähler and quaternion-Kähler manifolds. We also present new insights on S-duality, quantum mirror symmetry, connections to integrable models and topological strings.
Students' Experiences of the Factors Affecting Their Study Progress: Differences in Study Profiles

ERIC Educational Resources Information Center

Hailikari, Telle; Tuononen, Tarja; Parpala, Anna

2018-01-01

Many factors influence students' progress in higher education. However, the students' own voices are seldom heard. Using a qualitative approach, the study explored students' own experiences of the factors that have influenced their studying. Research has indicated that students' experiences are often related to their approaches to learning.…
A Progressive Approach to Discrete Trial Teaching: Some Current Guidelines

ERIC Educational Resources Information Center

Leaf, Justin B.; Cihon, Joseph H.; Leaf, Ronald; McEachin, John; Taubman, Mitchell

2016-01-01

Discrete trial teaching (DTT) is one of the cornerstones of applied behavior analysis (ABA) based interventions. Conventionally, DTT is commonly implemented within a prescribed, fixed manner in which the therapist is governed by a strict set of rules. In contrast to conventional DTT, a progressive approach to DTT allows the therapist to remain…
Sex and Gender Differences in Prevention of Type 2 Diabetes.

PubMed

Harreiter, Jürgen; Kautzky-Willer, Alexandra

2018-01-01

Lifestyle intervention programs are effective in the prevention of type 2 diabetes mellitus (T2DM) in high risk populations. However, most studies only give limited information about the influence of sex and/or gender effectiveness of these interventions. So far, similar outcome was reported for diabetes progression and weight loss. Nevertheless, long-term data on cardiovascular outcome are sparse but favoring women regarding all-cause and cardiovascular mortality. In both men and women, sex hormone imbalances and reproductive disorders are associated with a higher risk of T2DM development. Diabetes prevention approaches are reported for polycystic ovary syndrome, gestational diabetes mellitus, and erectile dysfunction and are presented in this review. In the surgical treatment options for morbid obese patients, sex and gender differences are present. Choices and preferences of adherence to lifestyle and pharmacological interventions, expectations, treatment effects, and complications are influenced by sex or gender. In general, bariatric surgery is performed more often in women seeking medical/surgical help to lose weight. Men are older and have higher comorbidities and mortality rates and worse follow-up outcome after bariatric surgery. A more gender-sensitive clinical approach, as well as consideration of ethnicity may improve quality of life and increase health and life expectancy in men and women with a high risk for subsequent progression to T2DM.
Resonance Frequency Breathing Biofeedback to Reduce Symptoms of Subthreshold PTSD with an Air Force Special Tactics Operator: A Case Study.

PubMed

Petta, Lorene M

2017-06-01

The prevalence rates of post-traumatic stress disorder (PTSD) have been estimated to be several times higher in military populations compared to the national average. Special Tactics operators are a group that is more likely to avoid seeking psychological care due to the stigma and other consequences the diagnosis may have on their military careers. There is a need for more effective and less stigmatizing interventions to treat this population. Psychophysiological methods have been proven to be efficacious in treating PTSD, yet have received less attention as an adjunctive intervention. Resonance frequency (RF) biofeedback is a form of cardiorespiratory intervention that has shown promise as an effective treatment. The current case study examined the use of RF biofeedback in combination with other physiological and evidence-based methods as part of a comprehensive treatment approach. The client showed a significant drop from his initial scores on a screening assessment by the end of treatment, and demonstrated continued progress despite a 3-month break from the therapy. This author proposed that the synergistic effects of the multi-phased treatment approach contributed to the client's progress. Furthermore, a case was made for using multiple techniques when treating subthreshold PTSD and related symptoms within a treatment resistant population.
Progress in wet-coated organic light-emitting devices for lighting

NASA Astrophysics Data System (ADS)

Liu, Jie; Ye, Qing; Lewis, Larry N.; Duggal, Anil R.

2007-09-01

Here we present recent progress in developing efficient wet-coated organic light-emitting devices (OLEDs) for lighting applications. In particular, we describe a novel approach for building efficient wet-coated dye-doped blue phosphorescent devices. Further, a novel approach for achieving arbitrary emission patterning for OLEDs is discussed. This approach utilizes a photo-induced chemical doping strategy for selectively activating charge injection materials, thus enabling devices with arbitrary emission patterning. This approach may provide a simple, low cost path towards specialty lighting and signage applications for OLED technology.
Inhibition of prostate cancer osteoblastic progression with VEGF121/rGel, a single agent targeting osteoblasts, osteoclasts, and tumor neovasculature.

PubMed

Mohamedali, Khalid A; Li, Zhi Gang; Starbuck, Michael W; Wan, Xinhai; Yang, Jun; Kim, Sehoon; Zhang, Wendy; Rosenblum, Michael G; Navone, Nora M

2011-04-15

A hallmark of prostate cancer (PCa) progression is the development of osteoblastic bone metastases, which respond poorly to available therapies. We previously reported that VEGF(121)/rGel targets osteoclast precursors and tumor neovasculature. Here we tested the hypothesis that targeting nontumor cells expressing these receptors can inhibit tumor progression in a clinically relevant model of osteoblastic PCa. Cells from MDA PCa 118b, a PCa xenograft obtained from a bone metastasis in a patient with castrate-resistant PCa, were injected into the femurs of mice. Osteoblastic progression was monitored following systemic administration of VEGF(121)/rGel. VEGF(121)/rGel was cytotoxic in vitro to osteoblast precursor cells. This cytotoxicity was specific as VEGF(121)/rGel internalization into osteoblasts was VEGF(121) receptor driven. Furthermore, VEGF(121)/rGel significantly inhibited PCa-induced bone formation in a mouse calvaria culture assay. In vivo, VEGF(121)/rGel significantly inhibited the osteoblastic progression of PCa cells in the femurs of nude mice. Microcomputed tomographic analysis revealed that VEGF(121)/rGel restored the bone volume fraction of tumor-bearing femurs to values similar to those of the contralateral (non-tumor-bearing) femurs. VEGF(121)/rGel significantly reduced the number of tumor-associated osteoclasts but did not change the numbers of peritumoral osteoblasts. Importantly, VEGF(121)/rGel-treated mice had significantly less tumor burden than control mice. Our results thus indicate that VEGF(121)/rGel inhibits osteoblastic tumor progression by targeting angiogenesis, osteoclastogenesis, and bone formation. Targeting VEGF receptor (VEGFR)-1- or VEGFR-2-expressing cells is effective in controlling the osteoblastic progression of PCa in bone. These findings provide the basis for an effective multitargeted approach for metastatic PCa. ©2011 AACR.
Capturing transitions and trajectories: the role of socioeconomic status in later life disability.

PubMed

Taylor, Miles G

2010-11-01

Disability is conceptualized as a life course process and measured using either transitions or trajectories. Previous research does not simultaneously explore both aspects of disablement, accounting for timing and trajectory. The role of education is noted in disability research, but its independent effects over time have not been fully examined. I investigate the effects of education and income on disability onset and progression over a decade. I use a latent curve modeling approach with four waves of the Duke Established Populations for Epidemiologic Studies of the Elderly data to independently test the preventive and mediating effects education and income provide for disability. Education has a preventive effect for disability onset but no significant effect on progression once income is held constant. Income has both a preventive and mediating effect on disability, although preventive effects are stronger for education. Later life disability is measured here using both onset and trajectory. Findings are consistent with health research suggesting that education and income work through shared and independent mechanisms to affect disability over time. These findings also highlight the importance of modeling timing when studying health trajectories.
Synergistic Effects of GDNF and VEGF on Lifespan and Disease Progression in a Familial ALS Rat Model

PubMed Central

Krakora, Dan; Mulcrone, Patrick; Meyer, Michael; Lewis, Christina; Bernau, Ksenija; Gowing, Genevieve; Zimprich, Chad; Aebischer, Patrick; Svendsen, Clive N; Suzuki, Masatoshi

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. We have recently shown that human mesenchymal stem cells (hMSCs) modified to release glial cell line-derived neurotrophic factor (GDNF) decrease disease progression in a rat model of ALS when delivered to skeletal muscle. In the current study, we determined whether or not this effect could be enhanced by delivering GDNF in concert with other trophic factors. hMSC engineered to secrete GDNF (hMSC-GDNF), vascular endothelial growth factor (hMSC-VEGF), insulin-like growth factor-I (hMSC-IGF-I), or brain-derived neurotrophic factor (hMSC-BDNF), were prepared and transplanted bilaterally into three muscle groups. hMSC-GDNF and hMSC-VEGF prolonged survival and slowed the loss of motor function, but hMSC-IGF-I and hMSC-BDNF did not have any effect. We then tested the efficacy of a combined ex vivo delivery of GDNF and VEGF in extending survival and protecting neuromuscular junctions (NMJs) and motor neurons. Interestingly, the combined delivery of these neurotrophic factors showed a strong synergistic effect. These studies further support ex vivo gene therapy approaches for ALS that target skeletal muscle. PMID:23712039
Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

PubMed

Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U

2016-11-01

Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
p53 Restoration in Induction and Maintenance of Senescence: Differential Effects in Premalignant and Malignant Tumor Cells

PubMed Central

Harajly, Mohamad; Zalzali, Hasan; Nawaz, Zafar; Ghayad, Sandra E.; Ghamloush, Farah; Basma, Hussein; Zainedin, Samiha; Rabeh, Wissam; Jabbour, Mark; Tawil, Ayman; Badro, Danielle A.; Evan, Gerard I.

2015-01-01

The restoration of p53 has been suggested as a therapeutic approach in tumors. However, the timing of p53 restoration in relation to its efficacy during tumor progression still is unclear. We now show that the restoration of p53 in murine premalignant proliferating pineal lesions resulted in cellular senescence, while p53 restoration in invasive pineal tumors did not. The effectiveness of p53 restoration was not dependent on p19Arf expression but showed an inverse correlation with Mdm2 expression. In tumor cells, p53 restoration became effective when paired with either DNA-damaging therapy or with nutlin, an inhibitor of p53-Mdm2 interaction. Interestingly, the inactivation of p53 after senescence resulted in reentry into the cell cycle and rapid tumor progression. The evaluation of a panel of human supratentorial primitive neuroectodermal tumors (sPNET) showed low activity of the p53 pathway. Together, these data suggest that the restoration of the p53 pathway has different effects in premalignant versus invasive pineal tumors, and that p53 activation needs to be continually sustained, as reversion from senescence occurs rapidly with aggressive tumor growth when p53 is lost again. Finally, p53 restoration approaches may be worth exploring in sPNET, where the p53 gene is intact but the pathway is inactive in the majority of examined tumors. PMID:26598601

Impact of virtual learning environment (VLE): A technological approach to genetics teaching on high school students' content knowledge, self-efficacy and career goal aspirations

NASA Astrophysics Data System (ADS)

Kandi, Kamala M.

This study examines the effect of a technology-based instructional tool 'Geniverse' on the content knowledge gains, Science Self-Efficacy, Technology Self-Efficacy, and Career Goal Aspirations among 283 high school learners. The study was conducted in four urban high schools, two of which have achieved Adequate Yearly Progress (AYP) and two have not. Students in both types of schools were taught genetics either through Geniverse, a virtual learning environment or Dragon genetics, a paper-pencil activity embedded in traditional instructional method. Results indicated that students in all schools increased their knowledge of genetics using either type of instructional approach. Students who were taught using Geniverse demonstrated an advantage for genetics knowledge although the effect was small. These increases were more pronounced in the schools that had been meeting the AYP goal. The other significant effect for Geniverse was that students in the technology-enhanced classrooms increased in science Self-Efficacy while students in the non-technology enhanced classrooms decreased. In addition, students from Non-AYP schools showed an improvement in Science and Technology Self-Efficacy; however the effects were small. The implications of these results for the future use of technology-enriched classrooms were discussed. Keywords: Technology-based instruction, Self-Efficacy, career goals and Adequate Yearly Progress (AYP).
Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer

PubMed Central

Lei, Yifeng; Tang, Lixue; Xie, Yangzhouyun; Xianyu, Yunlei; Zhang, Lingmin; Wang, Peng; Hamada, Yoh; Jiang, Kai; Zheng, Wenfu; Jiang, Xingyu

2017-01-01

Pancreatic cancer is one of the deadliest human cancers, whose progression is highly dependent on the nervous microenvironment. The suppression of gene expression of nerve growth factor (NGF) may have great potential in pancreatic cancer treatment. Here we show that gold nanocluster-assisted delivery of siRNA of NGF (GNC–siRNA) allows efficient NGF gene silencing and pancreatic cancer treatment. The GNC–siRNA complex increases the stability of siRNA in serum, prolongs the circulation lifetime of siRNA in blood and enhances the cellular uptake and tumour accumulation of siRNA. The GNC–siRNA complex potently downregulates the NGF expression in Panc-1 cells and in pancreatic tumours, and effectively inhibits the tumour progression in three pancreatic tumour models (subcutaneous model, orthotopic model and patient-derived xenograft model) without adverse effects. Our study constitutes a straightforward but effective approach to inhibit pancreatic cancer via NGF knockdown, suggesting a promising therapeutic direction for pancreatic cancer. PMID:28440296
Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer

NASA Astrophysics Data System (ADS)

Lei, Yifeng; Tang, Lixue; Xie, Yangzhouyun; Xianyu, Yunlei; Zhang, Lingmin; Wang, Peng; Hamada, Yoh; Jiang, Kai; Zheng, Wenfu; Jiang, Xingyu

2017-04-01

Pancreatic cancer is one of the deadliest human cancers, whose progression is highly dependent on the nervous microenvironment. The suppression of gene expression of nerve growth factor (NGF) may have great potential in pancreatic cancer treatment. Here we show that gold nanocluster-assisted delivery of siRNA of NGF (GNC-siRNA) allows efficient NGF gene silencing and pancreatic cancer treatment. The GNC-siRNA complex increases the stability of siRNA in serum, prolongs the circulation lifetime of siRNA in blood and enhances the cellular uptake and tumour accumulation of siRNA. The GNC-siRNA complex potently downregulates the NGF expression in Panc-1 cells and in pancreatic tumours, and effectively inhibits the tumour progression in three pancreatic tumour models (subcutaneous model, orthotopic model and patient-derived xenograft model) without adverse effects. Our study constitutes a straightforward but effective approach to inhibit pancreatic cancer via NGF knockdown, suggesting a promising therapeutic direction for pancreatic cancer.
From Cheerleader to Coach: The Developmental Progression of Bedside Teachers in Giving Feedback to Early Learners.

PubMed

Wenrich, Marjorie D; Jackson, Molly Blackley; Maestas, Ramoncita R; Wolfhagen, Ineke H A P; Scherpbier, Albert J J

2015-11-01

Medical students learn clinical skills at the bedside from teaching clinicians, who often learn to teach by teaching. Little is known about the process of becoming an effective clinical teacher. Understanding how teaching skills and approaches change with experience may help tailor faculty development for new teachers. Focusing on giving feedback to early learners, the authors asked: What is the developmental progression of clinician-teachers as they learn to give clinical skills feedback to medical students? This qualitative study included longitudinal interviews with clinician-teachers over five years in a new clinical skills teaching program for preclinical medical students. Techniques derived from grounded theory were used for initial analyses. The current study focused on one theme identified in initial analyses: giving feedback to students. Transcript passages were organized by interview year, coded, and discussed in year clusters; thematic codes were compared and emergent codes developed. Themes related to giving feedback demonstrated a dyadic structure: characteristic of less experienced teachers versus characteristic of experienced teachers. Seven dominant dyadic themes emerged, including teacher as cheerleader versus coach, concern about student fragility versus understanding resilience, and focus on creating a safe environment versus challenging students within a safe environment. With consistent teaching, clinical teachers demonstrated progress in giving feedback to students in multiple areas, including understanding students' developmental trajectory and needs, developing tools and strategies, and adopting a dynamic, challenging, inclusive team approach. Ongoing teaching opportunities with targeted faculty development may help improve clinician-teachers' feedback skills and approaches.
Effective control of acute myeloid leukaemia and acute lymphoblastic leukaemia progression by telomerase specific adoptive T-cell therapy.

PubMed

Sandri, Sara; De Sanctis, Francesco; Lamolinara, Alessia; Boschi, Federico; Poffe, Ornella; Trovato, Rosalinda; Fiore, Alessandra; Sartori, Sara; Sbarbati, Andrea; Bondanza, Attilio; Cesaro, Simone; Krampera, Mauro; Scupoli, Maria T; Nishimura, Michael I; Iezzi, Manuela; Sartoris, Silvia; Bronte, Vincenzo; Ugel, Stefano

2017-10-20

Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice. In the present report, we show the ability of our approach to limit the progression of more aggressive leukemic pathologies, such as acute myeloid leukaemia (AML) and B-cell acute lymphoblastic leukaemia (B-ALL). Together, our findings demonstrate that TERT-based adoptive cell therapy is a concrete platform of T cell-mediated immunotherapy for leukaemia treatment.
Effective control of acute myeloid leukaemia and acute lymphoblastic leukaemia progression by telomerase specific adoptive T-cell therapy

PubMed Central

Lamolinara, Alessia; Boschi, Federico; Poffe, Ornella; Trovato, Rosalinda; Fiore, Alessandra; Sartori, Sara; Sbarbati, Andrea; Bondanza, Attilio; Cesaro, Simone; Krampera, Mauro; Scupoli, Maria T.; Nishimura, Michael I.; Iezzi, Manuela; Sartoris, Silvia; Bronte, Vincenzo; Ugel, Stefano

2017-01-01

Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice. In the present report, we show the ability of our approach to limit the progression of more aggressive leukemic pathologies, such as acute myeloid leukaemia (AML) and B-cell acute lymphoblastic leukaemia (B-ALL). Together, our findings demonstrate that TERT-based adoptive cell therapy is a concrete platform of T cell-mediated immunotherapy for leukaemia treatment. PMID:29152058
Nuclear Explosion Monitoring Advances and Challenges

NASA Astrophysics Data System (ADS)

Baker, G. E.

2015-12-01

We address the state-of-the-art in areas important to monitoring, current challenges, specific efforts that illustrate approaches addressing shortcomings in capabilities, and additional approaches that might be helpful. The exponential increase in the number of events that must be screened as magnitude thresholds decrease presents one of the greatest challenges. Ongoing efforts to exploit repeat seismic events using waveform correlation, subspace methods, and empirical matched field processing holds as much "game-changing" promise as anything being done, and further efforts to develop and apply such methods efficiently are critical. Greater accuracy of travel time, signal loss, and full waveform predictions are still needed to better locate and discriminate seismic events. Important developments include methods to model velocities using multiple types of data; to model attenuation with better separation of source, path, and site effects; and to model focusing and defocusing of surface waves. Current efforts to model higher frequency full waveforms are likely to improve source characterization while more effective estimation of attenuation from ambient noise holds promise for filling in gaps. Censoring in attenuation modeling is a critical problem to address. Quantifying uncertainty of discriminants is key to their operational use. Efforts to do so for moment tensor (MT) inversion are particularly important, and fundamental progress on the statistics of MT distributions is the most important advance needed in the near term in this area. Source physics is seeing great progress through theoretical, experimental, and simulation studies. The biggest need is to accurately predict the effects of source conditions on seismic generation. Uniqueness is the challenge here. Progress will depend on studies that probe what distinguishes mechanisms, rather than whether one of many possible mechanisms is consistent with some set of observations.
First steps in experimental cancer evolution

PubMed Central

Taylor, Tiffany B; Johnson, Louise J; Jackson, Robert W; Brockhurst, Michael A; Dash, Philip R

2013-01-01

Evolutionary processes play a central role in the development, progression and response to treatment of cancers. The current challenge facing researchers is to harness evolutionary theory to further our understanding of the clinical progression of cancers. Central to this endeavour will be the development of experimental systems and approaches by which theories of cancer evolution can be effectively tested. We argue here that the experimental evolution approach – whereby evolution is observed in real time and which has typically employed microorganisms – can be usefully applied to cancer. This approach allows us to disentangle the ecological causes of natural selection, identify the genetic basis of evolutionary changes and determine their repeatability. Cell cultures used in cancer research share many of the desirable traits that make microorganisms ideal for studying evolution. As such, experimental cancer evolution is feasible and likely to give great insight into the selective pressures driving the evolution of clinically destructive cancer traits. We highlight three areas of evolutionary theory with importance to cancer biology that are amenable to experimental evolution: drug resistance, social evolution and resource competition. Understanding the diversity, persistence and evolution of cancers is vital for treatment and drug development, and an experimental evolution approach could provide strategic directions and focus for future research. PMID:23745144
Time-based analysis of total cost of patient episodes: a case study of hip replacement.

PubMed

Peltokorpi, Antti; Kujala, Jaakko

2006-01-01

Healthcare in the public and private sectors is facing increasing pressure to become more cost-effective. Time-based competition and work-in-progress have been used successfully to measure and improve the efficiency of industrial manufacturing. Seeks to address this issue. Presents a framework for time based management of the total cost of a patient episode and apply it to the six sigma DMAIC-process development approach. The framework is used to analyse hip replacement patient episodes in Päijät-Häme Hospital District in Finland, which has a catchment area of 210,000 inhabitants and performs an average of 230 hip replacements per year. The work-in-progress concept is applicable to healthcare--notably that the DMAIC-process development approach can be used to analyse the total cost of patient episodes. Concludes that a framework, which combines the patient-in-process and the DMAIC development approach, can be used not only to analyse the total cost of patient episode but also to improve patient process efficiency. Presents a framework that combines patient-in-process and DMAIC-process development approaches, which can be used to analyse the total cost of a patient episode in order to improve patient process efficiency.
Imaging Genetics and Genomics in Psychiatry: A Critical Review of Progress and Potential.

PubMed

Bogdan, Ryan; Salmeron, Betty Jo; Carey, Caitlin E; Agrawal, Arpana; Calhoun, Vince D; Garavan, Hugh; Hariri, Ahmad R; Heinz, Andreas; Hill, Matthew N; Holmes, Andrew; Kalin, Ned H; Goldman, David

2017-08-01

Imaging genetics and genomics research has begun to provide insight into the molecular and genetic architecture of neural phenotypes and the neural mechanisms through which genetic risk for psychopathology may emerge. As it approaches its third decade, imaging genetics is confronted by many challenges, including the proliferation of studies using small sample sizes and diverse designs, limited replication, problems with harmonization of neural phenotypes for meta-analysis, unclear mechanisms, and evidence that effect sizes may be more modest than originally posited, with increasing evidence of polygenicity. These concerns have encouraged the field to grow in many new directions, including the development of consortia and large-scale data collection projects and the use of novel methods (e.g., polygenic approaches, machine learning) that enhance the quality of imaging genetic studies but also introduce new challenges. We critically review progress in imaging genetics and offer suggestions and highlight potential pitfalls of novel approaches. Ultimately, the strength of imaging genetics and genomics lies in their translational and integrative potential with other research approaches (e.g., nonhuman animal models, psychiatric genetics, pharmacologic challenge) to elucidate brain-based pathways that give rise to the vast individual differences in behavior as well as risk for psychopathology. Copyright © 2017 Society of Biological Psychiatry. All rights reserved.
Recent advances in collisional effects on spectra of molecular gases and their practical consequences

NASA Astrophysics Data System (ADS)

Hartmann, Jean-Michel; Tran, Ha; Armante, Raymond; Boulet, Christian; Campargue, Alain; Forget, François; Gianfrani, Livio; Gordon, Iouli; Guerlet, Sandrine; Gustafsson, Magnus; Hodges, Joseph T.; Kassi, Samir; Lisak, Daniel; Thibault, Franck; Toon, Geoffrey C.

2018-07-01

We review progress, since publication of the book ``Collisional effects on molecular spectra: Laboratory experiments and models, consequences for applications" (Elsevier, Amsterdam, 2008), on measuring, modeling and predicting the influence of pressure (ie of intermolecular collisions) on the spectra of gas molecules. We first introduce recently developed experimental techniques of high accuracy and sensitivity. We then complement the aforementioned book by presenting the theoretical approaches, results and data proposed (mostly) in the last decade on the topics of isolated line shapes, line-broadening and -shifting, line-mixing, the far wings and associated continua, and collision-induced absorption. Examples of recently demonstrated consequences of the progress in the description of spectral shapes for some practical applications (metrology, probing of gas media, climate predictions) are then given. Remaining issues and directions for future research are finally discussed.
Comparison of Statistical Approaches for Dealing With Immortal Time Bias in Drug Effectiveness Studies

PubMed Central

Karim, Mohammad Ehsanul; Gustafson, Paul; Petkau, John; Tremlett, Helen

2016-01-01

In time-to-event analyses of observational studies of drug effectiveness, incorrect handling of the period between cohort entry and first treatment exposure during follow-up may result in immortal time bias. This bias can be eliminated by acknowledging a change in treatment exposure status with time-dependent analyses, such as fitting a time-dependent Cox model. The prescription time-distribution matching (PTDM) method has been proposed as a simpler approach for controlling immortal time bias. Using simulation studies and theoretical quantification of bias, we compared the performance of the PTDM approach with that of the time-dependent Cox model in the presence of immortal time. Both assessments revealed that the PTDM approach did not adequately address immortal time bias. Based on our simulation results, another recently proposed observational data analysis technique, the sequential Cox approach, was found to be more useful than the PTDM approach (Cox: bias = −0.002, mean squared error = 0.025; PTDM: bias = −1.411, mean squared error = 2.011). We applied these approaches to investigate the association of β-interferon treatment with delaying disability progression in a multiple sclerosis cohort in British Columbia, Canada (Long-Term Benefits and Adverse Effects of Beta-Interferon for Multiple Sclerosis (BeAMS) Study, 1995–2008). PMID:27455963
A Professional Code of Ethics and Progress Report: One University's Approach to Addressing Disruptive Behaviors in the Classroom

ERIC Educational Resources Information Center

Murphy, Kelle L.

2007-01-01

Educators in all disciplines are increasingly concerned about the disruptive behaviors often displayed by students in the college classroom. In order for physical education teacher education (PETE) candidates to learn effectively and become good educators, such behaviors must be addressed and modified. To do so, educators must first understand the…
Attention Training in Autism as a Potential Approach to Improving Academic Performance: A School-Based Pilot Study

ERIC Educational Resources Information Center

Spaniol, Mayra Muller; Shalev, Lilach; Kossyvaki, Lila; Mevorach, Carmel

2018-01-01

This study assessed the effectiveness of an attention intervention program (Computerized Progressive Attentional Training; CPAT) in improving academic performance of children with ASD. Fifteen 6-10 year olds with ASD attending a mainstream and a special school were assigned to an experimental (CPAT; n = 8) and active control (computer games; n =…
Instructional Systems Design and Preservice Teachers' Processes of Thinking, Teaching and Planning: What Do They Learn and How Do They Change?

ERIC Educational Resources Information Center

Moallem, Mahnaz; Applefield, James

This study explored the development and processes of thinking, planning, and decision making of two preservice teachers as they progressed through their teacher education program. The effects of training in the systems approach on two preservice teachers' thinking about instruction and on their actual instructional planning documents were…
Mineralocorticoid receptor blockade—a novel approach to fight hyperkalaemia in chronic kidney disease

PubMed Central

Ritz, E.; Pitt, B.

2013-01-01

Hyperkalaemia continues to be a major hazard of mineralocorticoid receptor blockade in an effort to retard the progression of chronic kidney disease (CKD). In cardiac patients on mineralocorticoid receptor blockade, RLY-5016 which captures K+ in the colon has been effective in reducing the risk of hyperkalaemia. This compound might be useful in CKD as well. PMID:26120440
Learners' Anxiety in Audiographic Conferences: A Discursive Psychology Approach to Emotion Talk

ERIC Educational Resources Information Center

de los Arcos, Beatriz; Coleman, James A.; Hampel, Regine

2009-01-01

Success and failure in language learning are partly determined by the learners' ability to regulate their emotions. Negative feelings are more likely to frustrate progress, while positive ones make the task of learning a second language (L2) a more effective experience. To date no significant body of research has been carried out into the role of…
Strategies for Digital Inclusion: Towards a Pedagogy for Embracing and Sustaining Student Diversity and Engagement with Online Learning

ERIC Educational Resources Information Center

Clarida, Baylie Hart; Bobeva, Milena; Hutchings, Maggie; Taylor, Jacqui

2016-01-01

This paper reports on the progress of a current PhD research study. The research study will evolve through four phases and eventually develop a conceptual framework for effective teaching and learning approaches that influence digital inclusion and exclusion of students from diverse backgrounds. It will also seek to identify differences in learner…
Linking Resources to Results: The Chicago Public Education Fund's Master Teacher Initiative. Principles for Effective Education Grantmaking. Case in Brief Number 1

ERIC Educational Resources Information Center

Grantmakers for Education, 2012

2012-01-01

"Linking Resources to Results" explores the deliberate approach--including specific goals, a clearly articulated grantmaking strategy and benchmarks for measuring progress--the Chicago Public Education Fund used to help the Chicago Public Schools recognize, reward and deploy high-quality teachers. The case study is intended to help…
Is It Just a Mole, or Is It More? | Center for Cancer Research

Cancer.gov

Fast and reliable tests that accurately detect and characterize cancer are a major goal in cancer research. At present, histological examination of the cells from a biopsy is the most cost-effective and widely used method for the diagnosis of melanoma. However, this traditional approach does not always reveal the extent of disease progression or adequately guide decisions

Nascent Entrepreneurship and the Developing Individual: Early Entrepreneurial Competence in Adolescence and Venture Creation Success during the Career

ERIC Educational Resources Information Center

Obschonka, Martin; Silbereisen, Rainer K.; Schmitt-Rodermund, Eva; Stuetzer, Michael

2011-01-01

What predicts a person's venture creation success over the course of the career, such as making progress in the venture creation process and multiple successful venture creations? Applying a life span approach of human development, this study examined the effect of early entrepreneurial competence in adolescence, which was gathered retrospectively…
Evolving targets for lipid-modifying therapy

PubMed Central

Do, Rose Q; Nicholls, Stephen J; Schwartz, Gregory G

2014-01-01

The pathogenesis and progression of atherosclerosis are integrally connected to the concentration and function of lipoproteins in various classes. This review examines existing and emerging approaches to modify low-density lipoprotein and lipoprotein (a), triglyceride-rich lipoproteins, and high-density lipoproteins, emphasizing approaches that have progressed to clinical evaluation. Targeting of nuclear receptors and phospholipases is also discussed. PMID:25172365
Patient Activities Planning and Progress Noting a Humanistic Integrated-Team Approach.

ERIC Educational Resources Information Center

Muilenburg, Ted

This document outlines a system for planning recreation therapy, documenting progress, and relating the entire process to a team approach which includes patient assessment and involvement. The recreation program is seen as therapeutic, closely related to the total medical treatment program. The model is designed so that it can be adapted to almost…
Ultrasound and Microbubble Guided Drug Delivery: Mechanistic Understanding and Clinical Implications

PubMed Central

Wang, Tzu-Yin; Wilson, Katheryne E.; Machtaler, Steven; Willmann, Jürgen K.

2014-01-01

Ultrasound mediated drug delivery using microbubbles is a safe and noninvasive approach for spatially localized drug administration. This approach can create temporary and reversible openings on cellular membranes and vessel walls (a process called “sonoporation”), allowing for enhanced transport of therapeutic agents across these natural barriers. It is generally believed that the sonoporation process is highly associated with the energetic cavitation activities (volumetric expansion, contraction, fragmentation, and collapse) of the microbubble. However, a thorough understanding of the process was unavailable until recently. Important progress on the mechanistic understanding of sonoporation and the corresponding physiological responses in vitro and in vivo has been made. Specifically, recent research shed light on the cavitation process of microbubbles and fluid motion during insonation of ultrasound, on the spatio-temporal interactions between microbubbles and cells or vessel walls, as well as on the temporal course of the subsequent biological effects. These findings have significant clinical implications on the development of optimal treatment strategies for effective drug delivery. In this article, current progress in the mechanistic understanding of ultrasound and microbubble mediated drug delivery and its implications for clinical translation is discussed. PMID:24372231
Computational wear simulation of patellofemoral articular cartilage during in vitro testing.

PubMed

Li, Lingmin; Patil, Shantanu; Steklov, Nick; Bae, Won; Temple-Wong, Michele; D'Lima, Darryl D; Sah, Robert L; Fregly, Benjamin J

2011-05-17

Though changes in normal joint motions and loads (e.g., following anterior cruciate ligament injury) contribute to the development of knee osteoarthritis, the precise mechanism by which these changes induce osteoarthritis remains unknown. As a first step toward identifying this mechanism, this study evaluates computational wear simulations of a patellofemoral joint specimen wear tested on a knee simulator machine. A multibody dynamic model of the specimen mounted in the simulator machine was constructed in commercial computer-aided engineering software. A custom elastic foundation contact model was used to calculate contact pressures and wear on the femoral and patellar articular surfaces using geometry created from laser scan and MR data. Two different wear simulation approaches were investigated--one that wore the surface geometries gradually over a sequence of 10 one-cycle dynamic simulations (termed the "progressive" approach), and one that wore the surface geometries abruptly using results from a single one-cycle dynamic simulation (termed the "non-progressive" approach). The progressive approach with laser scan geometry reproduced the experimentally measured wear depths and areas for both the femur and patella. The less costly non-progressive approach predicted deeper wear depths, especially on the patella, but had little influence on predicted wear areas. Use of MR data for creating the articular and subchondral bone geometry altered wear depth and area predictions by at most 13%. These results suggest that MR-derived geometry may be sufficient for simulating articular cartilage wear in vivo and that a progressive simulation approach may be needed for the patella and tibia since both remain in continuous contact with the femur. Copyright © 2011 Elsevier Ltd. All rights reserved.
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.
Tris-base buffer: a promising new inhibitor for cancer progression and metastasis.

PubMed

Ibrahim-Hashim, Arig; Abrahams, Dominique; Enriquez-Navas, Pedro M; Luddy, Kim; Gatenby, Robert A; Gillies, Robert J

2017-07-01

Neutralizing tumor external acidity with oral buffers has proven effective for the prevention and inhibition of metastasis in several cancer mouse models. Solid tumors are highly acidic as a result of high glycolysis combined with an inadequate blood supply. Our prior work has shown that sodium bicarbonate, imidazole, and free-base (but not protonated) lysine are effective in reducing tumor progression and metastasis. However, a concern in translating these results to clinic has been the presence of counter ions and their potential undesirable side effects (e.g., hypernatremia). In this work, we investigate tris(hydroxymethyl)aminomethane, (THAM or Tris), a primary amine with no counter ion, for its effects on metastasis and progression in prostate and pancreatic cancer in vivo models using MRI and bioluminescence imaging. At an ad lib concentration of 200 mmol/L, Tris effectively inhibited metastasis in both models and furthermore led to a decrease in the expression of the major glucose transporter, GLUT-1. Our results also showed that Tris-base buffer (pH 8.4) had no overt toxicity to C3H mice even at higher doses (400 mmol/L). In conclusion, we have developed a novel therapeutic approach to manipulate tumor extracellular pH (pHe) that could be readily adapted to a clinical trial. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
In situ sediment treatment using activated carbon: a demonstrated sediment cleanup technology.

PubMed

Patmont, Clayton R; Ghosh, Upal; LaRosa, Paul; Menzie, Charles A; Luthy, Richard G; Greenberg, Marc S; Cornelissen, Gerard; Eek, Espen; Collins, John; Hull, John; Hjartland, Tore; Glaza, Edward; Bleiler, John; Quadrini, James

2015-04-01

This paper reviews general approaches for applying activated carbon (AC) amendments as an in situ sediment treatment remedy. In situ sediment treatment involves targeted placement of amendments using installation options that fall into two general approaches: 1) directly applying a thin layer of amendments (which potentially incorporates weighting or binding materials) to surface sediment, with or without initial mixing; and 2) incorporating amendments into a premixed, blended cover material of clean sand or sediment, which is also applied to the sediment surface. Over the past decade, pilot- or full-scale field sediment treatment projects using AC-globally recognized as one of the most effective sorbents for organic contaminants-were completed or were underway at more than 25 field sites in the United States, Norway, and the Netherlands. Collectively, these field projects (along with numerous laboratory experiments) have demonstrated the efficacy of AC for in situ treatment in a range of contaminated sediment conditions. Results from experimental studies and field applications indicate that in situ sequestration and immobilization treatment of hydrophobic organic compounds using either installation approach can reduce porewater concentrations and biouptake significantly, often becoming more effective over time due to progressive mass transfer. Certain conditions, such as use in unstable sediment environments, should be taken into account to maximize AC effectiveness over long time periods. In situ treatment is generally less disruptive and less expensive than traditional sediment cleanup technologies such as dredging or isolation capping. Proper site-specific balancing of the potential benefits, risks, ecological effects, and costs of in situ treatment technologies (in this case, AC) relative to other sediment cleanup technologies is important to successful full-scale field application. Extensive experimental studies and field trials have shown that when applied correctly, in situ treatment via contaminant sequestration and immobilization using a sorbent material such as AC has progressed from an innovative sediment remediation approach to a proven, reliable technology. © 2014 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of SETAC.
Probabilistic structural analysis to quantify uncertainties associated with turbopump blades

NASA Technical Reports Server (NTRS)

Nagpal, Vinod K.; Rubinstein, Robert; Chamis, Christos C.

1987-01-01

A probabilistic study of turbopump blades has been in progress at NASA Lewis Research Center for over the last two years. The objectives of this study are to evaluate the effects of uncertainties in geometry and material properties on the structural response of the turbopump blades to evaluate the tolerance limits on the design. A methodology based on probabilistic approach has been developed to quantify the effects of the random uncertainties. The results of this study indicate that only the variations in geometry have significant effects.
Recent advances in understanding vitiligo.

PubMed

Manga, Prashiela; Elbuluk, Nada; Orlow, Seth J

2016-01-01

Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.
Research progress on osteoarthritis treatment mechanisms.

PubMed

Gu, Yun-Tao; Chen, Jian; Meng, Zhu-Long; Ge, Wan-Yu; Bian, Yang-Yang; Cheng, Shao-Wen; Xing, Chen-Kun; Yao, Jiang-Ling; Fu, Jian; Peng, Lei

2017-09-01

Osteoarthritis is a common disease and is frequently encountered in the older population; the incidence rises sharply with age. It is estimated that more than 360 million people suffer from OA. However, the pathogenesis of osteoarthritis remains unclear, and we cannot effectively prevent the progression of OA. The aim of this review was to explore the molecular markers and signaling pathways that induce chondrocyte apoptosis in OA. We searched, using the key words osteoarthritis, chondrocyte apoptosis, autophagy, endoplasmic reticulum stress, molecular targets, and biomarkers, in PubMed, Web of Science, and Google Scholar from 1994 to 2017. We also reviewed the signaling pathways and molecular markers associated with chondrocyte apoptosis and approaches aimed at inhibiting the apoptosis-inducing mechanism to at least delay the progression of cartilage degeneration in OA. This article provides an overview of targeted therapies and the related signaling pathways in OA. Copyright © 2017. Published by Elsevier Masson SAS.
Nineteenth century exercise clinics for the treatment of scoliosis.

PubMed

Elsaesser, S; Butler, A R

2014-01-01

Scoliosis is the abnormal lateral curvature and rotation of the spine. In the past this deformity has been linked with moral depravity, as in the case of Richard III. Treatment for scoliosis began with Hippocrates's use of boards and axial distortion. Today, bracing and surgery are used either to correct the deformity or to prevent further progression. In the past, however, exercise regimens have been used in the belief that strengthening back muscles would reduce curvature progression. This approach was pioneered by Per Henrik Ling in the early nineteenth century and was continued by his followers Mathius Roth and Franz Berwald and, most notably, by Gustav Zander. Even today a few clinics, particularly in Eastern Europe, still use exercise in the treatment of scoliosis. Whether it is effective remains debatable, but even if progression is not prevented the patient's general health will benefit from an exercise regimen.
Clearance of Hepatitis C Virus Prior to Lung Transplantation: A Case Report.

PubMed

Shafii, A E; Harris, D D; Baz, M

2017-09-01

Hepatitis C virus (HCV) continues to be considered a relative contraindication to lung transplantation due to concerns of progression of liver disease with the introduction of immunosuppression. Since the recent introduction of effective antiviral therapy for HCV, new approaches in the management of the HCV-positive recipient are being utilized in liver transplantation to clear HCV pre- and post-transplant. Herein, we report use of ledipasvir/sofosbuvir for HCV clearance prior to lung transplantation in a patient with usual interstitial pneumonia. Listing for transplant was delayed until completion of HCV treatment, and he subsequently required extracorporeal membrane oxygenation as a bridge to transplantation due to progressive hypoxia. With antiviral cure rates exceeding 90%, HCV should no longer be considered a relative contraindication to lung transplant, and timing of antiviral treatment should consider the progressive nature of the recipient's lung disease. Copyright © 2017 Elsevier Inc. All rights reserved.
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.
Optical effects produced by running onboard engines of low-earth-orbit spacecraft

NASA Astrophysics Data System (ADS)

Beletskiy, A. B.; Mihalev, A. V.; Hahinov, V. V.; Lebedev, V. P.

2016-12-01

This paper presents results of optical observations made during Radar-Progress Experiment performed on April 17, 2013 and July 30, 2014 after approach-correction engines (ACE) of Progress M-17M and Progress M-23M cargo spacecraft in the thermosphere had been started. A region of enhanced emission intensity was recorded during engine operation. This may have been related to the scatter of twilight solar emission along the cargo spacecraft exhaust and to the emergence of additional atomic oxygen [OI] emission at 630 nm. The maximum dimension of the observed emission region was ~330-350 km and ~250-270 km along and across the orbit respectively. For the first time after ACE had been started, an expansion rate of emission region was ~ 7 and ~ 3.5 km/s along and across the orbit respectively. The maximum intensity of the disturbance area for Progress M-17M is estimated as ~40-60 R at 2 nm. Progress M-23M Space Experiment recorded a minor disturbance of atmospheric [OI] 630.0 nm emissions, both in near and in far cargo spacecraft flight paths, which might have been associated with the ACE exhaust gas injection.
Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study

PubMed Central

Catanzaro, Daniele; Schäffer, Alejandro A.; Schwartz, Russell

2016-01-01

Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with Synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints. PMID:26353381
Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.

PubMed

Catanzaro, Daniele; Shackney, Stanley E; Schaffer, Alejandro A; Schwartz, Russell

2016-01-01

Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.
Defense Financial and Investment Review. Appendix 4. Part 1. Survey of Defense Procurement Personnel Results and Findings,

DTIC Science & Technology

1984-12-01

133 Flexible Progress Payment Model ...................... 146 Flow Down of Financing Provisions .................... 155 Use of...34 . . .. . -- .. . .. * "." . .. . . .. .. .. ". .’ . . Flexible Progress Payment Model A plurality (45%) of all respondents agreed that the flexible progress payment model is too...would result in higher prices to DoD. -; Flexible Progress Payment Model In addition to the standard progress payment approach to contract financing, DoD
A Construct-Modeling Approach to Develop a Learning Progression of How Students Understand the Structure of Matter

ERIC Educational Resources Information Center

Morell, Linda; Collier, Tina; Black, Paul; Wilson, Mark

2017-01-01

This paper builds on the current literature base about learning progressions in science to address the question, "What is the nature of the learning progression in the content domain of the structure of matter?" We introduce a learning progression in response to that question and illustrate a methodology, the Construct Modeling (Wilson,…
Alignment and the States: Three Approaches to Aligning the National Assessment of Educational Progress with State Assessments, Other Assessments, and Standards

ERIC Educational Resources Information Center

Vockley, Martha; Lang, Vockley

2009-01-01

Since 1969, the National Assessment of Educational Progress (NAEP) has been the common yardstick for measuring the progress of students' education over time across the country. Teachers, principals, parents, policymakers, and researchers all use NAEP results to assess progress and develop ways to improve education in America. To make the…

ENGINEERING NANO- AND MICRO-PARTICLES TO TUNE IMMUNITY

PubMed Central

Moon, James J.; Irvine, Darrell J.; Huang, Bonnie

2013-01-01

The immune system can be a cure or cause of disease, fulfilling a protective role in attacking cancer or pathogenic microbes but also causing tissue destruction in autoimmune disorders. Thus, therapies aimed to amplify or suppress immune reactions are of great interest. However, the complex regulation of the immune system, coupled with the potential systemic side effects associated with traditional systemic drug therapies, has presented a major hurdle for the development of successful immunotherapies,. Recent progress in the design of synthetic micro- and nano-particles that can target drugs, deliver imaging agents, or stimulate immune cells directly through their physical and chemical properties is leading to new approaches to deliver vaccines, promote immune responses against tumors, and suppress autoimmunity. In addition, novel strategies, such as the use of particle-laden immune cells as living targeting agents for drugs, are providing exciting new approaches for immunotherapy. This progress report describes recent advances in the design of micro- and nano-particles in immunotherapies and diagnostics. PMID:22641380
Using a systems biology approach to understand and study the mechanisms of metastasis.

PubMed

Ha, Ngoc-Han; Hunter, Kent W

2014-01-01

Metastasis remains the main cause for cancer-related deaths due to the lack of effective therapy. The clonal selection model has long been thought to be the primary mechanism of metastatic progression but many different mechanisms have been hypothesized for the progression from tumorigenesis to the successful dissemination and expansion of tumor cells at the secondary site. MicroRNAs, germline polymorphisms in combination with the tumor microenvironment are few of the different pathways to explain the metastatic cascade. Technological advances for high-throughput screening of cells such as expression profiling, next generation sequencing, as well as global network analyses have advanced the studies of these mechanisms. Combined with new insights into the various mechanisms of metastasis a systems biology approach has also been shown to be useful in identifying metastasis-specific gene signatures as well as predicting disease outcome. Furthermore, the results of these studies have been relevant for identifying biomarkers for metastatic disease. © 2013 Wiley Periodicals, Inc.
Priorities for research and control of cestode zoonoses in Asia

PubMed Central

2013-01-01

Globally, cestode zoonoses cause serious public health problems, particularly in Asia. Among all neglected zoonotic diseases, cestode zoonoses account for over 75% of global disability adjusted life years (DALYs) lost. An international symposium on cestode zoonoses research and control was held in Shanghai, China between 28th and 30th October 2012 in order to establish joint efforts to study and research effective approaches to control these zoonoses. It brought together 96 scientists from the Asian region and beyond to exchange ideas, report on progress, make a gap analysis, and distill prioritizing settings with a focus on the Asian region. Key objectives of this international symposium were to agree on solutions to accelerate progress towards decreasing transmission, and human mortality and morbidity caused by the three major cestode zoonoses (cystic echinococcosis, alveolar echinococcosis, and cysticercosis); to critically assess the potential to control these diseases; to establish a research and validation agenda on existing and new approaches; and to report on novel tools for the study and control of cestode zoonoses. PMID:23915395
Progressive 3D shape abstraction via hierarchical CSG tree

NASA Astrophysics Data System (ADS)

Chen, Xingyou; Tang, Jin; Li, Chenglong

2017-06-01

A constructive solid geometry(CSG) tree model is proposed to progressively abstract 3D geometric shape of general object from 2D image. Unlike conventional ones, our method applies to general object without the need for massive CAD models, and represents the object shapes in a coarse-to-fine manner that allows users to view temporal shape representations at any time. It stands in a transitional position between 2D image feature and CAD model, benefits from state-of-the-art object detection approaches and better initializes CAD model for finer fitting, estimates 3D shape and pose parameters of object at different levels according to visual perception objective, in a coarse-to-fine manner. Two main contributions are the application of CSG building up procedure into visual perception, and the ability of extending object estimation result into a more flexible and expressive model than 2D/3D primitive shapes. Experimental results demonstrate the feasibility and effectiveness of the proposed approach.
[Brain protection against cerebral ischemia].

PubMed

Kitagawa, Kazuo

2013-01-01

Previous clinical trials failed to show the benefit of several potentially protective drugs in acute ischemic stroke. However, there would be three main approaches for brain protection against stroke. The first is to develop a novel thrombolytic agent which is more efficient and safer than alteplase. Tenecteplase and desmoteplase are in progress as a new thrombolytic drug. The second strategy is to augment collateral circulation through leptomeningeal anastomosis. Administration of G-CSF could enhance arteriogenesis, but it takes several days to develop functional collateral. For this purpose, partial aortic balloon clumping or stimulation of pterygopalatine ganglion may be promising. The third one is to protect neurovascular unit against reperfusion injury. Brain hypothermia is the most effective strategy in experimental ischemia, and the clinical trial for hypothermia combined with thrombolysis therapy is in progress. Activation of endogenous protective response, as presented by ischemic tolerance, has focused on remote ischemic conditioning. Although the precise mechanisms of remote preconditioning remain unclear, intermittent limb ischemia is a safe approach. Remote ischemic conditioning is now investigated in acute patients with thrombolysis therapy.
Tumor heterogeneity and progression: conceptual foundations for modeling.

PubMed

Greller, L D; Tobin, F L; Poste, G

1996-01-01

A conceptual foundation for modeling tumor progression, growth, and heterogeneity is presented. The purpose of such models is to aid understanding, test ideas, formulate experiments, and to model cancer 'in machina' to address the dynamic features of tumor cell heterogeneity, progression, and growth. The descriptive capabilities of such an approach provides a consistent language for qualitatively reasoning about tumor behavior. This approach provides a schema for building conceptual models that combine three key phenomenological driving elements: growth, progression, and genetic instability. The growth element encompasses processes contributing to changes in tumor bulk and is distinct from progression per se. The progression element subsumes a broad collection of processes underlying phenotypic progression. The genetics elements represents heritable changes which potentially affect tumor character and behavior. Models, conceptual and mathematical, can be built for different tumor situations by drawing upon the interaction of these three distinct driving elements. These models can be used as tools to explore a diversity of hypotheses concerning dynamic changes in cellular populations during tumor progression, including the generation of intratumor heterogeneity. Such models can also serve to guide experimentation and to gain insight into dynamic aspects of complex tumor behavior.
When dementia progresses quickly: a practical approach to the diagnosis and management of rapidly progressive dementia.

PubMed

Day, Gregory S; Tang-Wai, David F

2014-01-01

Making a diagnosis of rapidly progressive dementia requires practical adaptation of the skills used to assess patients with chronic causes of cognitive impairment. An expedited assessment, commensurate with the accelerated pace of the disease, is required to identify the cause of symptoms amidst a myriad of possibilities. Features upon history, physical examination and cognitive assessment that support specific diagnoses are reviewed, and a stratified approach to testing is presented. The use of readily-accessible investigations is prioritized, acknowledging the implications and applications of novel diagnostic tests. The coordinated use of clinical and laboratory measures are promoted as a means of facilitating rapid evaluation, with the ultimate goal of identifying patients with potentially reversible causes of rapidly progressive dementia.
Summaries of press automation conference presented

NASA Astrophysics Data System (ADS)

Makhlin, A. Y.; Pokrovskaya, G. M.

1985-01-01

The automation and mechanization of cold and hot stamping were discussed. Problems in the comprehensive mechanization and automatio of stamping in machine building development were examined. Automation becomes effective when it is implemented in progressive manufacturing processes and a comprehensive approach to the solution of all problems, beginning with the delivery of initial materials and ending with the transportation of finished products to the warehouse. Production intensification and improvments of effectiveness of produced output through the comprehensive mechanization and automation of stamping operations are reported.
Targeted Therapy of Fn14-Positive Breast Tumors Using a TWEAK-Cytotoxin Fusion Protein or Noncovalent Complex

DTIC Science & Technology

2010-09-01

Task Summary: Construct expression plasmids, purify proteins, test proteins for cytotoxic effects on breast cancer cell lines. Progress: The majority...either Pseudomonas exotoxin PE38 protein or a recombinant form of a plant toxin named gelonin (denoted rGel) act as the cytotoxic cargo. We found that...ability to kill Fn14-positive breast cancer cells the cytotoxic effect was not impressive (see Annual Report). Another approach listed in this Aim was
Impact of universal interventions on social inequalities in physical activity among older adults: an equity-focused systematic review.

PubMed

Lehne, Gesa; Bolte, Gabriele

2017-02-10

Physical activity is one of the most important contributors to healthy aging. Public health strategies aiming to promote physical activity among older adults are increasingly being implemented. However, little is known about their impact on social inequalities. Purpose of the study was to analyze whether and how studies of interventions consider effects on social inequalities in physical activity among older adults. Nine electronic databases were searched to identify quantitative studies evaluating the effects of interventions on self-reported or objectively measured physical activity among the general population of older adults (≥50 years). English and German language peer-reviewed journal articles published between 2005 and 2015 were included. Using the PROGRESS-Plus framework, data on whether and how social factors were considered both for describing participants' baseline characteristics and for measuring intervention effects were systematically extracted. Studies examining differential intervention effects by at least one PROGRESS-Plus factor were quality assessed. Results were presented in narrative synthesis. Fifty-nine studies were included. Beside age and sex, 44 studies used at least 1 further PROGRESS-Plus factor for the description of participants' baseline characteristics. When measuring intervention effects, 22 studies considered PROGRESS-Plus factors as control variables. Eleven studies reported having analyzed potential effects on inequalities by testing interaction effects, stratifying effect analyses, or exploring associations between PROGRESS-Plus factors and increases in physical activity following an intervention. Effects were most often analyzed by gender/sex (n = 9) and age (n = 9), followed by education (n = 3), marital status (n = 2), and race/ethnicity (n = 2). Five studies pointed to gender/sex- or age-specific intervention effects, indicating that some interventions affect males and females, and younger and older individuals differently. Many studies evaluating the effects of interventions on physical activity among older adults have not exploited the potential for assessing effects on social inequalities so far. There is an urgent need for systematic application of appropriate methodological approaches and transparent reporting of social inequalities-related findings which can provide important indications for the design of those interventions most likely to be effective across all social groups of older adults. PROSPERO registration number: CRD42015025066.
[Research Progress of Carrion-breeding Phorid Flies for Post-mortem Interval Estimation in Forensic Medicine].

PubMed

Li, L; Feng, D X; Wu, J

2016-10-01

It is a difficult problem of forensic medicine to accurately estimate the post-mortem interval. Entomological approach has been regarded as an effective way to estimate the post-mortem interval. The developmental biology of carrion-breeding flies has an important position at the post-mortem interval estimation. Phorid flies are tiny and occur as the main or even the only insect evidence in relatively enclosed environments. This paper reviews the research progress of carrion-breeding phorid flies for estimating post-mortem interval in forensic medicine which includes their roles, species identification and age determination of immatures. Copyright© by the Editorial Department of Journal of Forensic Medicine.
Monitoring road safety development at regional level: A case study in the ASEAN region.

PubMed

Chen, Faan; Wang, Jianjun; Wu, Jiaorong; Chen, Xiaohong; Zegras, P Christopher

2017-09-01

Persistent monitoring of progress, evaluating the results of interventions and recalibrating to achieve continuous improvement over time is widely recognized as being crucial towards the successful development of road safety. In the ASEAN (Association of Southeast Asian Nations) region there is a lack of well-resourced teams that contain multidisciplinary safety professionals, and specialists in individual countries, who are able to carry out this work effectively. In this context, not only must the monitoring framework be effective, it must also be easy to use and adapt. This paper provides a case study that can be easily reproduced; based on an updated and refined Road Safety Development Index (RSDI), by means of the RSR (Rank-sum ratio)-based model, for monitoring/reporting road safety development at regional level. The case study was focused on the road safety achievements in eleven Southeast Asian countries; identifying the areas of poor performance, potential problems and delays. These countries are finally grouped into several classes based on an overview of their progress and achievements regarding to road safety. The results allow the policymakers to better understand their own road safety progress toward their desired impact; more importantly, these results enable necessary interventions to be made in a quick and timely manner. Keeping action plans on schedule if things are not progressing as desired. This would avoid 'reinventing the wheel' and trial and error approaches to road safety, making the implementation of action plans more effective. Copyright © 2017 Elsevier Ltd. All rights reserved.
Recent Evolution of Endoscopic Endonasal Surgery for Treatment of Pituitary Adenomas

PubMed Central

NISHIOKA, Hiroshi

2017-01-01

For the treatment of pituitary tumors, microscopic transsphenoidal surgery has been considered the “gold standard” since the late 1960s. Over the last two decades, however, a worldwide shift towards endoscopic endonasal surgery is in progress for many reasons. These include a wide panoramic view, improved illumination, an ability to look around anatomical corners using angled tip and, in addition, application to the extended approaches for parasellar tumors. Both endoscopic and microscopic approaches appear equally effective for nonfunctioning adenomas without significant suprasellar or lateral extensions, whereas the endoscopic approach may improve outcomes associated with the extent of resection and postoperative complications for larger tumors. Despite many theoretical benefits in the endoscopic surgery, remission rates of functioning adenomas do not substantially differ between the approaches in experienced hands. The endoscopic approach is a valid alternative to the microscopic approach for adenomas. The benefits will be more appreciated in the extended surgery for parasellar tumors. PMID:28239067
Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules.

PubMed

Dave, Vivek S; Gupta, Deepak; Yu, Monica; Nguyen, Phuong; Varghese Gupta, Sheeba

2017-02-01

The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds.
Design and implementation of a novel mechanical testing system for cellular solids.

PubMed

Nazarian, Ara; Stauber, Martin; Müller, Ralph

2005-05-01

Cellular solids constitute an important class of engineering materials encompassing both man-made and natural constructs. Materials such as wood, cork, coral, and cancellous bone are examples of cellular solids. The structural analysis of cellular solid failure has been limited to 2D sections to illustrate global fracture patterns. Due to the inherent destructiveness of 2D methods, dynamic assessment of fracture progression has not been possible. Image-guided failure assessment (IGFA), a noninvasive technique to analyze 3D progressive bone failure, has been developed utilizing stepwise microcompression in combination with time-lapsed microcomputed tomographic imaging (microCT). This method allows for the assessment of fracture progression in the plastic region, where much of the structural deformation/energy absorption is encountered in a cellular solid. Therefore, the goal of this project was to design and fabricate a novel micromechanical testing system to validate the effectiveness of the stepwise IGFA technique compared to classical continuous mechanical testing, using a variety of engineered and natural cellular solids. In our analysis, we found stepwise compression to be a valid approach for IGFA with high precision and accuracy comparable to classical continuous testing. Therefore, this approach complements the conventional mechanical testing methods by providing visual insight into the failure propagation mechanisms of cellular solids. (c) 2005 Wiley Periodicals, Inc.
How Hierarchical Topics Evolve in Large Text Corpora.

PubMed

Cui, Weiwei; Liu, Shixia; Wu, Zhuofeng; Wei, Hao

2014-12-01

Using a sequence of topic trees to organize documents is a popular way to represent hierarchical and evolving topics in text corpora. However, following evolving topics in the context of topic trees remains difficult for users. To address this issue, we present an interactive visual text analysis approach to allow users to progressively explore and analyze the complex evolutionary patterns of hierarchical topics. The key idea behind our approach is to exploit a tree cut to approximate each tree and allow users to interactively modify the tree cuts based on their interests. In particular, we propose an incremental evolutionary tree cut algorithm with the goal of balancing 1) the fitness of each tree cut and the smoothness between adjacent tree cuts; 2) the historical and new information related to user interests. A time-based visualization is designed to illustrate the evolving topics over time. To preserve the mental map, we develop a stable layout algorithm. As a result, our approach can quickly guide users to progressively gain profound insights into evolving hierarchical topics. We evaluate the effectiveness of the proposed method on Amazon's Mechanical Turk and real-world news data. The results show that users are able to successfully analyze evolving topics in text data.
Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy.

PubMed

Karuppagounder, Vengadeshprabhu; Arumugam, Somasundaram; Giridharan, Vijayasree V; Sreedhar, Remya; Bose, Rajendran J C; Vanama, Jyothi; Palaniyandi, Suresh S; Konishi, Tetsuya; Watanabe, Kenichi; Thandavarayan, Rajarajan A

2017-02-01

Diabetic cardiomyopathy (DCM) is described as impaired cardiac diastolic and systolic functions. Diabetes mellitus (DM), a related cardiovascular disease, has become one of the major causes of death in DM patients. Mortality in these diseases is 2 to 3 times higher than in non-DM patients with cardiovascular disease. The progression of DCM and the cellular and molecular perturbations associated with the pathogenesis are complex and multifactorial. Although considerable progress has been achieved, the molecular etiologies of DCM remain poorly understood. There is an expanding need for natural antidiabetic medicines that do not cause the side effects of modern drugs. Curcumin, a pleiotropic molecule, from Curcuma longa, is known to possess numerous impacts such as scavenging free radical, antioxidant, antitumor, and antiinflammatory activities. The reports from preclinical and clinical findings revealed that curcumin can reverse insulin resistance, hyperglycemia, obesity, and obesity-related metabolic diseases. The current review provides an updated overview of the possible molecular mechanism of DCM and multitarget approach of curcumin in alleviating DCM and diabetic complication. Additionally, we mentioned the approaches that are currently being implemented to improve the bioavailability of this promising natural product in diabetes therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.
Salivary biomarker development using genomic, proteomic and metabolomic approaches

PubMed Central

2012-01-01

The use of saliva as a diagnostic sample provides a non-invasive, cost-efficient method of sample collection for disease screening without the need for highly trained professionals. Saliva collection is far more practical and safe compared with invasive methods of sample collection, because of the infection risk from contaminated needles during, for example, blood sampling. Furthermore, the use of saliva could increase the availability of accurate diagnostics for remote and impoverished regions. However, the development of salivary diagnostics has required technical innovation to allow stabilization and detection of analytes in the complex molecular mixture that is saliva. The recent development of cost-effective room temperature analyte stabilization methods, nucleic acid pre-amplification techniques and direct saliva transcriptomic analysis have allowed accurate detection and quantification of transcripts found in saliva. Novel protein stabilization methods have also facilitated improved proteomic analyses. Although candidate biomarkers have been discovered using epigenetic, transcriptomic, proteomic and metabolomic approaches, transcriptomic analyses have so far achieved the most progress in terms of sensitivity and specificity, and progress towards clinical implementation. Here, we review recent developments in salivary diagnostics that have been accomplished using genomic, transcriptomic, proteomic and metabolomic approaches. PMID:23114182
Time to Dream: "Reflections on Paul Diederich and the Progressive American High School"

ERIC Educational Resources Information Center

O'Connor, John S.; Lessing, Avi D.

2015-01-01

In this essay, John S. O'Connor and Avi D. Lessing discuss the increasingly reductive and routinized nature of contemporary schools and the costs such an approach holds for students and teachers alike. The current approach is especially troublesome in light of the rich history of progressive voices, such as Paul Diederich, who have cautioned…
A Road Map for Learning Progressions Research in Geography

ERIC Educational Resources Information Center

Huynh, Niem Tu; Solem, Michael; Bednarz, Sarah Witham

2015-01-01

This article provides an overview of learning progressions (LP) and assesses the potential of this line of research to improve geography education. It presents the merits and limitations of three of the most common approaches used to conduct LP research and draws on one approach to propose a first draft of a LP on map reading and interpretation.…

Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis.

PubMed

Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

2017-08-01

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth: insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc . Furthermore, repair processes such as remyelination are incomplete. Experimental therapies that strive to improve metabolism within neurons and glia, e.g. , oligodendrocytes, could act to counter inadequate energy supplies and/or support remyelination. Most experimental approaches have been examined as standalone interventions; however, it is apparent that the biochemical steps being targeted are part of larger pathways, which are further intertwined with other metabolic pathways. Thus, the potential benefits of a tested intervention, or of an established therapy, e.g. , ocrelizumab, could be undermined by constraints on upstream and/or downstream steps. If correct, then this argues for a more comprehensive, multifaceted approach to therapy. Here we review experimental approaches to support neuronal and glial metabolism, and/or promote remyelination, which may have potential to lessen or delay progressive multiple sclerosis.
Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach.

PubMed

Zhai, Shiyan; Song, Genxin; Qin, Yaochen; Ye, Xinyue; Lee, Jay

2017-01-01

This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.
Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach

PubMed Central

Qin, Yaochen; Lee, Jay

2017-01-01

This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention. PMID:28950027
Human effects on ecological connectivity in aquatic ecosystems: Integrating scientific approaches to support management and mitigation.

PubMed

Crook, David A; Lowe, Winsor H; Allendorf, Frederick W; Erős, Tibor; Finn, Debra S; Gillanders, Bronwyn M; Hadwen, Wade L; Harrod, Chris; Hermoso, Virgilio; Jennings, Simon; Kilada, Raouf W; Nagelkerken, Ivan; Hansen, Michael M; Page, Timothy J; Riginos, Cynthia; Fry, Brian; Hughes, Jane M

2015-11-15

Understanding the drivers and implications of anthropogenic disturbance of ecological connectivity is a key concern for the conservation of biodiversity and ecosystem processes. Here, we review human activities that affect the movements and dispersal of aquatic organisms, including damming of rivers, river regulation, habitat loss and alteration, human-assisted dispersal of organisms and climate change. Using a series of case studies, we show that the insight needed to understand the nature and implications of connectivity, and to underpin conservation and management, is best achieved via data synthesis from multiple analytical approaches. We identify four key knowledge requirements for progressing our understanding of the effects of anthropogenic impacts on ecological connectivity: autecology; population structure; movement characteristics; and environmental tolerance/phenotypic plasticity. Structuring empirical research around these four broad data requirements, and using this information to parameterise appropriate models and develop management approaches, will allow for mitigation of the effects of anthropogenic disturbance on ecological connectivity in aquatic ecosystems. Copyright © 2015 Elsevier B.V. All rights reserved.
Obesity, Health at Every Size, and Public Health Policy

PubMed Central

2014-01-01

Obesity is associated with chronic diseases that may negatively affect individuals’ health and the sustainability of the health care system. Despite increasing emphasis on obesity as a major health care issue, little progress has been made in its treatment or prevention. Individual approaches to obesity treatment, largely composed of weight-loss dieting, have not proven effective. Little direct evidence supports the notion of reforms to the “obesogenic environment.” Both these individualistic and environmental approaches to obesity have important limitations and ethical implications. The low levels of success associated with these approaches may necessitate a new non–weight-centric public health strategy. Evidence is accumulating that a weight-neutral, nutrition- and physical activity–based, Health at Every Size (HAES) approach may be a promising chronic disease-prevention strategy. PMID:24328657
Obesity, health at every size, and public health policy.

PubMed

Bombak, Andrea

2014-02-01

Obesity is associated with chronic diseases that may negatively affect individuals' health and the sustainability of the health care system. Despite increasing emphasis on obesity as a major health care issue, little progress has been made in its treatment or prevention. Individual approaches to obesity treatment, largely composed of weight-loss dieting, have not proven effective. Little direct evidence supports the notion of reforms to the "obesogenic environment." Both these individualistic and environmental approaches to obesity have important limitations and ethical implications. The low levels of success associated with these approaches may necessitate a new non-weight-centric public health strategy. Evidence is accumulating that a weight-neutral, nutrition- and physical activity-based, Health at Every Size (HAES) approach may be a promising chronic disease-prevention strategy.
Re-rendezvous and approach of Progress 33P

NASA Image and Video Library

2009-07-12

ISS020-E-018056 (12 July 2009) --- An unpiloted ISS Progress 33 cargo craft approaches the International Space Station. On June 30, the Progress undocked from the station and was commanded into a parking orbit for its re-rendezvous with the ISS on July 12, approaching to within 10-15 meters of the Zvezda Service Module to test new automated rendezvous equipment mounted on Zvezda during a pair of spacewalks earlier this month by Gennady Padalka and Mike Barratt that will be used to guide the new Mini-Research Module-2 (MRM2) to an unpiloted docking to the zenith port of Zvezda later this year. MRM2 will serve as a new docking port for Russian spacecraft and an additional airlock for spacewalks conducted out of the Russian segment.
Cellular and molecular characterization of gametogenic progression in ex vivo cultured prepuberal mouse testes.

PubMed

Isoler-Alcaraz, J; Fernández-Pérez, D; Larriba, E; Del Mazo, J

2017-10-18

Recently, an effective testis culture method using a gas-liquid interphase, capable of differentiate male germ cells from neonatal spermatogonia to spermatozoa has been developed. Nevertheless, this methodology needs deep analyses that allow future experimental approaches in basic, pathologic and/or reprotoxicologic studies. Because of this, we characterized at cellular and molecular levels the entire in vitro spermatogenic progression, in order to understand and evaluate the characteristics that define the spermatogenic process in ex vivo cultured testes compared to the in vivo development. Testicular explants of CD1 mice aged 6 and 10 days post-partum were respectively cultured during 55 and 89 days. Cytological and molecular approaches were performed, analyzing germ cell proportion at different time culture points, meiotic markers immunodetecting synaptonemal complex protein SYCP3 by immunocytochemistry and the relative expression of different marker genes along the differentiation process by Reverse Transcription - quantitative Polymerase Chain Reaction. In addition, microRNA and piwi-interactingRNA profiles were also evaluated by Next Generation Sequencing and bioinformatic approaches. The method promoted and maintained the spermatogenic process during 89 days. At a cytological level we detected spermatogenic development delays of cultured explants compared to the natural in vivo process. The expression of different spermatogenic stages gene markers correlated with the proportion of different cell types detected in the cytological preparations. In vitro progression analysis of the different spermatogenic cell types, from both 6.5 dpp and 10.5 dpp testes explants, has revealed a relative delay in relation to in vivo process. The expression of the genes studied as biomarkers correlates with the cytologically and functional detected progression and differential expression identified in vivo. After a first analysis of deep sequencing data it has been observed that as long as cultures progress, the proportion of microRNAs declined respect to piwi-interactingRNAs levels that increased, showing a similar propensity than which happens in in vivo spermatogenesis. Our study allows to improve and potentially to control the ex vivo spermatogenesis development, opening new perspectives in the reproductive biology fields including male fertility.
Recent Progress in Treating Protein-Ligand Interactions with Quantum-Mechanical Methods.

PubMed

Yilmazer, Nusret Duygu; Korth, Martin

2016-05-16

We review the first successes and failures of a "new wave" of quantum chemistry-based approaches to the treatment of protein/ligand interactions. These approaches share the use of "enhanced", dispersion (D), and/or hydrogen-bond (H) corrected density functional theory (DFT) or semi-empirical quantum mechanical (SQM) methods, in combination with ensemble weighting techniques of some form to capture entropic effects. Benchmark and model system calculations in comparison to high-level theoretical as well as experimental references have shown that both DFT-D (dispersion-corrected density functional theory) and SQM-DH (dispersion and hydrogen bond-corrected semi-empirical quantum mechanical) perform much more accurately than older DFT and SQM approaches and also standard docking methods. In addition, DFT-D might soon become and SQM-DH already is fast enough to compute a large number of binding modes of comparably large protein/ligand complexes, thus allowing for a more accurate assessment of entropic effects.
The potential of prison-based democratic therapeutic communities.

PubMed

Bennett, Jamie; Shuker, Richard

2017-03-13

Purpose The purpose of this paper is to describe the work of HMP Grendon, the only prison in the UK to operate entirely as a series of democratic therapeutic communities and to summarise the research of its effectiveness. Design/methodology/approach The paper is both descriptive, providing an overview of the work of a prison-based therapeutic community, and offers a literature review regarding evidence of effectiveness. Findings The work of HMP Grendon has a wide range of positive benefits including reduced levels of disruption in prison, reduced self-harm, improved well-being, an environment that is experienced as more humane and reduced levels of reoffending. Originality/value The work of HMP Grendon offers a well established and evidenced approach to managing men who have committed serious violent and sexually violent offences. It also promotes and embodies a progressive approach to managing prisons rooted in the welfare tradition.
Oncology Modeling for Fun and Profit! Key Steps for Busy Analysts in Health Technology Assessment.

PubMed

Beca, Jaclyn; Husereau, Don; Chan, Kelvin K W; Hawkins, Neil; Hoch, Jeffrey S

2018-01-01

In evaluating new oncology medicines, two common modeling approaches are state transition (e.g., Markov and semi-Markov) and partitioned survival. Partitioned survival models have become more prominent in oncology health technology assessment processes in recent years. Our experience in conducting and evaluating models for economic evaluation has highlighted many important and practical pitfalls. As there is little guidance available on best practices for those who wish to conduct them, we provide guidance in the form of 'Key steps for busy analysts,' who may have very little time and require highly favorable results. Our guidance highlights the continued need for rigorous conduct and transparent reporting of economic evaluations regardless of the modeling approach taken, and the importance of modeling that better reflects reality, which includes better approaches to considering plausibility, estimating relative treatment effects, dealing with post-progression effects, and appropriate characterization of the uncertainty from modeling itself.
The Effect of Fiber Strength Stochastics and Local Fiber Volume Fraction on Multiscale Progressive Failure of Composites

NASA Technical Reports Server (NTRS)

Ricks, Trenton M.; Lacy, Jr., Thomas E.; Bednarcyk, Brett A.; Arnold, Steven M.

2013-01-01

Continuous fiber unidirectional polymer matrix composites (PMCs) can exhibit significant local variations in fiber volume fraction as a result of processing conditions that can lead to further local differences in material properties and failure behavior. In this work, the coupled effects of both local variations in fiber volume fraction and the empirically-based statistical distribution of fiber strengths on the predicted longitudinal modulus and local tensile strength of a unidirectional AS4 carbon fiber/ Hercules 3502 epoxy composite were investigated using the special purpose NASA Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC); local effective composite properties were obtained by homogenizing the material behavior over repeating units cells (RUCs). The predicted effective longitudinal modulus was relatively insensitive to small (8%) variations in local fiber volume fraction. The composite tensile strength, however, was highly dependent on the local distribution in fiber strengths. The RUC-averaged constitutive response can be used to characterize lower length scale material behavior within a multiscale analysis framework that couples the NASA code FEAMAC and the ABAQUS finite element solver. Such an approach can be effectively used to analyze the progressive failure of PMC structures whose failure initiates at the RUC level. Consideration of the effect of local variations in constituent properties and morphologies on progressive failure of PMCs is a central aspect of the application of Integrated Computational Materials Engineering (ICME) principles for composite materials.
Interpreting Null Findings from Trials of Alcohol Brief Interventions

PubMed Central

Heather, Nick

2014-01-01

The effectiveness of alcohol brief intervention (ABI) has been established by a succession of meta-analyses but, because the effects of ABI are small, null findings from randomized controlled trials are often reported and can sometimes lead to skepticism regarding the benefits of ABI in routine practice. This article first explains why null findings are likely to occur under null hypothesis significance testing (NHST) due to the phenomenon known as “the dance of the p-values.” A number of misconceptions about null findings are then described, using as an example the way in which the results of the primary care arm of a recent cluster-randomized trial of ABI in England (the SIPS project) have been misunderstood. These misinterpretations include the fallacy of “proving the null hypothesis” that lack of a significant difference between the means of sample groups can be taken as evidence of no difference between their population means, and the possible effects of this and related misunderstandings of the SIPS findings are examined. The mistaken inference that reductions in alcohol consumption seen in control groups from baseline to follow-up are evidence of real effects of control group procedures is then discussed and other possible reasons for such reductions, including regression to the mean, research participation effects, historical trends, and assessment reactivity, are described. From the standpoint of scientific progress, the chief problem about null findings under the conventional NHST approach is that it is not possible to distinguish “evidence of absence” from “absence of evidence.” By contrast, under a Bayesian approach, such a distinction is possible and it is explained how this approach could classify ABIs in particular settings or among particular populations as either truly ineffective or as of unknown effectiveness, thus accelerating progress in the field of ABI research. PMID:25076917
Nanotechnology Approaches to Improving Cancer Immunotherapy.

PubMed

Hagan, C Tilden; Medik, Yusra B; Wang, Andrew Z

2018-01-01

Cancer immunotherapy is a powerful, growing treatment approach to cancer that can be combined with chemotherapy, radiotherapy, and oncosurgery. Modulating the immune system to enhance anticancer response by several strategies has yielded improved cancer survival. Despite this progress, the success rate for immunotherapy has been below expectations due to unpredictable efficacy and off-target side effects from systemic dosing. Nanotechnology offers numerous different materials and targeting properties to overcome many of these challenges in immunotherapy. In this chapter, we review current immunotherapy and its challenges as well as the latest nanotechnology applications in cancer immunotherapy. © 2018 Elsevier Inc. All rights reserved.
Racing of the biological pacemaker.

PubMed

Yu, Han-Gang

2009-01-01

Over the past decade, rapid progress in the molecular studies of cardiac ion channels and stem cells biology has led to efforts to create a biological pacemaker to supplement the widely-used electronic pacemaker. We will review the main concepts of cardiac pacemaker activities in different heart regions and the approaches to design a working biological pacemaker. We will focus on how to use the gene- and cell-based approaches to meet the requirements of a working biological pacemaker. Possible future development and precautions for creation of an effective biological pacemaker superior to the electronic counterpart are also discussed along with recent patents.
Systemic Problems: A perspective on stem cell aging and rejuvenation.

PubMed

Conboy, Irina M; Conboy, Michael J; Rebo, Justin

2015-10-01

This review provides balanced analysis of the advances in systemic regulation of young and old tissue stem cells and suggests strategies for accelerating development of therapies to broadly combat age-related tissue degenerative pathologies. Many highlighted recent reports on systemic tissue rejuvenation combine parabiosis with a "silver bullet" putatively responsible for the positive effects. Attempts to unify these papers reflect the excitement about this experimental approach and add value in reproducing previous work. At the same time, defined molecular approaches, which are "beyond parabiosis" for the rejuvenation of multiple old organs represent progress toward attenuating or even reversing human tissue aging.
Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

The lab is interested in understanding the regulation of RNA localization by cancer-associated proteins and the contribution of localized RNAs to tumor progression. The work relies on a variety of cell biological, microscopical and biochemical approaches in 2D and 3D cell culture systems. Some of the current projects aim to investigate the effect of the mechanical properties of the extracellular matrix on RNA localization, and the coupling between RNA localization and translation using single-molecule imaging approaches. This research program is funded by the NIH Intramural Research Program and is supported by state-of-the-art facilities on the NIH campus.
The tortuous road to an ideal CGRP function blocker for the treatment of migraine.

PubMed

Davis, Carl D; Xu, Cen

2008-01-01

The critical role of Calcitonin Gene-Related Peptide (CGRP) in migraine has been validated, with two small molecule CGRP antagonists BIBN4096BS and MK-0974 demonstrating efficacy in the reversal of acute migraine attack. Multiple approaches have been taken to find the ideal agent that most effectively inhibits CGRP's function. Here, we have summarized the progress made in recent years, including the identification and optimization of an orally bioavailable small molecule CGRP receptor antagonist. We also describe other interventions such as scavenging of CGRP itself. The advantages and disadvantages of these distinct approaches are discussed.
The Impact of Aphasia Camp Participation on Quality of Life: A Primary Progressive Aphasia Perspective.

PubMed

Kim, Esther S; Figeys, Mathieu; Hubbard, H Isabel; Wilson, Carlee

2018-07-01

Individuals with primary progressive aphasia (PPA) and their caregivers are at risk for decreased quality of life (QoL) due to their progressive condition. Aphasia camps are an intervention that can improve QoL, yet individuals with PPA are underrepresented at aphasia camps relative to those with poststroke aphasia. The purpose of this exploratory case study was to examine the effect of participation in aphasia camp on the QoL of a couple impacted by PPA. The Living with Aphasia: Framework for Outcome Measurement (A-FROM) was used to guide a semistructured interview with an individual with PPA and her spouse, both of whom had attended the Alberta Aphasia Camp for 4 years. Conventional content analysis with an inductive approach was used to analyze results. Concepts that emerged from the interview were organized into pre-camp, during, and post-camp categories. Aspects of camp that had an effect on post-camp QoL for this couple with PPA included expanding social connections and introduction to new activities. Personal characteristics exhibited by the couple had an impact on their experience of aphasia camp and how they incorporated their experiences into their everyday lives post-camp. Aphasia camps are a participation-based service approach that can benefit people with aphasia regardless of etiology. A consideration of personal factors of potential campers with PPA, and the provision of PPA-specific resources, is recommended for programs such as aphasia camps that incorporate participants with mixed etiologies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Provider Agreement in the Assessment of Glaucoma Progression within a Team Model.

PubMed

Shah, Saumya; Choo, Clara; Odden, Jamie; Zhao, Bingying; Fang, Chengbo; Schornack, Muriel; Stalboerger, Gina; Bennett, Jeffrey R; Khanna, Cheryl L

2018-06-04

Glaucoma specialists and optometrists who work in a team model at a single institution utilize a common definition of glaucoma progression and treatment algorithm. The purpose of this study was to assess the consistency of agreement in identifying glaucoma progression among glaucoma specialists and optometrists of one team. 399 eyes of 200 patients age 18 or older with glaucoma were enrolled over two years. Clinical data, disc photographs, OCT, and visual fields were independently reviewed by two masked optometrists and two masked fellowship-trained glaucoma specialists. Each eye was judged as progression or no-progression of glaucomatous disease. The following were assessed: (1) agreement among optometrists; (2) agreement among glaucoma specialists; and (3) agreement among optometrists and glaucoma specialists. The frequency of use of testing modality to determine progression was also studied. Kappa statistics were used to evaluate agreements. Optometrists agreed with each other for 74.2% of the eyes assessed (κ=0.42), whereas glaucoma specialists agreed with each other for 78.7% of eyes (κ=0.39). All four providers agreed with each other for 54.4% of the eyes evaluated (κ=0.37). Providers had the highest agreement when the progression decision was based on disc hemorrhage (92%) and the lowest agreement when based on OCT progression analysis (36%). Compared to optometrists, glaucoma specialists used OCT (P= <0.01) more frequently to determine disease progression. Fair to moderate agreement levels were found among providers in their assessment of glaucoma progression, suggesting that a team approach to glaucoma management may be effective. Further work is needed to investigate ways to optimize consistency within the glaucoma team.

Impact of Virtual Learning Environment (VLE): A Technological Approach to Genetics Teaching on High School Students' Content Knowledge, Self-Efficacy and Career Goal Aspirations

ERIC Educational Resources Information Center

Kandi, Kamala M.

2013-01-01

This study examines the effect of a technology-based instructional tool "Geniverse" on the content knowledge gains, Science Self-Efficacy, Technology Self-Efficacy, and Career Goal Aspirations among 283 high school learners. The study was conducted in four urban high schools, two of which have achieved Adequate Yearly Progress (AYP) and…
Response to Intervention A Systematic Process to Increase Learning Outcomes for All Students. Guidance Document for New Mexico Schools

ERIC Educational Resources Information Center

New Mexico Public Education Department, 2006

2006-01-01

Response to Intervention (RtI) is the practice of providing high-quality instruction and interventions to meet student needs and monitor progress in order to ensure effectiveness of instruction and/or interventions. RtI is an integrated service delivery approach for all students and should be applied to decisions in general, remedial, and special…
Alternative School Education: Using Web-Based Curriculum Programs to Assist At-Risk Students with High School Credit Recovery in Select East Central Indiana Schools

ERIC Educational Resources Information Center

Robbins, William Shane

2011-01-01

"We know that education can be an arduous process. Countries use different approaches based on societal acceptances, but effective education always requires enormous efforts. Whether success is achieved, depends on the development of a rigorous and progressive curriculum, while at the same time providing all students the opportunity to…
Effect of 5E Learning Model on Academic Achievement, Attitude and Science Process Skills: Meta-Analysis Study

ERIC Educational Resources Information Center

Cakir, Nevin Kozcu

2017-01-01

Today, with the development of science and technology and its rapid progress, the importance attached to science education has increased. This increase in interest has led to the development of the methods, techniques, and approaches that enable the students to be active, question and construct knowledge. The 5E learning model is one of them, and…
Transport properties of porous media from the microstructure

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

Torquato, S.

The determination of the effective transport properties of a random porous medium remains a challenging area of research because the properties depend on the microstructure in a highly complex fashion. This paper reviews recent theoretical and experimental progress that we have made on various aspects of this problem. A unified approach is taken to characterize the microstructure and the seemingly disparate properties of the medium.
The Effects of Varying Group Size on the Reading Recovery Approach to Preventive Early Intervention

ERIC Educational Resources Information Center

Iversen, Sandra; Tunmer, William E.; Chapman, James W.

2005-01-01

The purpose of this study was to determine whether an early intervention program based on the Reading Recovery (RR) format could be developed for pairs of struggling readers that would allow them to make accelerated progress similar to that experienced in the 1-to-1 RR tutorial. A preliminary pilot study showed that the RR lesson format could be…
Etiologic Field Effect: Reappraisal of the Field Effect Concept in Cancer Predisposition and Progression

PubMed Central

Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Fuchs, Charles S; Beck, Andrew H; Giovannucci, Edward; Ogino, Shuji

2014-01-01

The term “field effect” (also known as field defect, field cancerization, or field carcinogenesis) has been used to describe a field of cellular and molecular alteration, which predisposes to the development of neoplasms within that territory. We explore an expanded, integrative concept, “etiologic field effect”, which asserts that various etiologic factors (the exposome including dietary, lifestyle, environmental, microbial, hormonal, and genetic factors) and their interactions (the interactome) contribute to a tissue microenvironmental milieu that constitutes a “field of susceptibility” to neoplasia initiation, evolution, and progression. Importantly, etiological fields predate the acquisition of molecular aberrations commonly considered to indicate presence of filed effect. Inspired by molecular pathological epidemiology (MPE) research, which examines the influence of etiologic factors on cellular and molecular alterations during disease course, an etiologically-focused approach to field effect can: 1) broaden the horizons of our inquiry into cancer susceptibility and progression at molecular, cellular, and environmental levels, during all stages of tumor evolution; 2) embrace host-environment-tumor interactions (including gene-environment interactions) occurring in the tumor microenvironment; and, 3) help explain intriguing observations, such as shared molecular features between bilateral primary breast carcinomas, and between synchronous colorectal cancers, where similar molecular changes are absent from intervening normal colon. MPE research has identified a number of endogenous and environmental exposures which can influence not only molecular signatures in the genome, epigenome, transcriptome, proteome, metabolome and interactome, but also host immunity and tumor behavior. We anticipate that future technological advances will allow the development of in vivo biosensors capable of detecting and quantifying “etiologic field effect” as abnormal network pathology patterns of cellular and microenvironmental responses to endogenous and exogenous exposures. Through an “etiologic field effect” paradigm, and holistic systems pathology (systems biology) approaches to cancer biology, we can improve personalized prevention and treatment strategies for precision medicine. PMID:24925058
Pathways Theory of Progression through Higher Education

ERIC Educational Resources Information Center

Robinson, Rosalie A.; Bornholt, Laurel J.

2007-01-01

This paper is concerned with the pathways students take through their studies at university. A critique of current research demands a fresh approach to explaining student progression, in particular within Australian higher education. To date, theories of student progression commonly consider the fit of the person to the university environment…
Using the Pragmatic Progressive Philosophy in Adult Education

ERIC Educational Resources Information Center

Ellis, Marsha L.

2012-01-01

Using a pragmatic approach of progressive philosophy when educating adult learners utilizes the knowledge of history, to connect reality with current experiences through facilitated learning. The purpose of this paper is an attempt to show how adult education that uses a pragmatic progressive philosophy encompasses adult experiences,…
Decision-Making Accuracy of CBM Progress-Monitoring Data

ERIC Educational Resources Information Center

Hintze, John M.; Wells, Craig S.; Marcotte, Amanda M.; Solomon, Benjamin G.

2018-01-01

This study examined the diagnostic accuracy associated with decision making as is typically conducted with curriculum-based measurement (CBM) approaches to progress monitoring. Using previously published estimates of the standard errors of estimate associated with CBM, 20,000 progress-monitoring data sets were simulated to model student reading…
A school-based program implemented by community providers previously trained for the prevention of eating and weight-related problems in secondary-school adolescents: the MABIC study protocol

PubMed Central

2013-01-01

Background The prevention of eating disorders and disordered eating are increasingly recognized as public health priorities. Challenges in this field included moving from efficacy to effectiveness and developing an integrated approach to the prevention of a broad spectrum of eating and weight-related problems. A previous efficacy trial indicated that a universal disordered eating prevention program, based on the social cognitive model, media literacy educational approach and cognitive dissonance theory, reduced risk factors for disordered eating, but it is unclear whether this program has effects under more real-world conditions. The main aim of this effectiveness trial protocol is to test whether this program has effects when incorporating an integrated approach to prevention and when previously-trained community providers implement the intervention. Methods/design The research design involved a multi-center non-randomized controlled trial with baseline, post and 1-year follow-up measures. Six schools from the city of Sabadell (close to Barcelona) participated in the intervention group, and eleven schools from four towns neighboring Sabadell participated in the control group. A total of 174 girls and 180 boys in the intervention group, and 484 girls and 490 boys in the control group were registered in class lists prior to baseline. A total of 18 community providers, secondary-school class tutors, nurses from the Catalan Government’s Health and School Program, and health promotion technicians from Sabadell City Council were trained and delivered the program. Shared risk factors of eating and weight-related problems were assessed as main measures. Discussion It will be vital for progress in disordered eating prevention to conduct effectiveness trials, which test whether interventions are effective when delivered by community providers under ecologically valid conditions, as opposed to tightly controlled research trials. The MABIC project will provide new contributions in this transition from efficacy to effectiveness and new data about progress in the integrated approach to prevention. Pending the results, the effectiveness trial meets the effectiveness standards set down by the Society for Prevention Research. This study will provide new evidence to improve and enhance disordered eating prevention programs. Trial registration Current Controlled Trials ISRCTN47682626 PMID:24118981
The perioperative period and promotion of cancer metastasis: New outlooks on mediating mechanisms and immune involvement

PubMed Central

Neeman, Elad; Ben-Eliyahu, Shamgar

2012-01-01

Surgery for the removal of a primary tumor presents an opportunity to eradicate cancer or arrest its progression, but is also believed to promote the outbreak of pre-existing micrometastases and the initiation of new metastases. These deleterious effects of surgery are mediated through various mechanisms, including psychological and physiological neuroendocrine and paracrine stress responses elicited by surgery. In this review we (i) describe the many risk factors that arise during the perioperative period, acting synergistically to make this short timeframe critical for determining long-term cancer recurrence, (ii) present newly identified potent immunocyte populations that can destroy autologous tumor cells that were traditionally considered immune-resistant, thus invigorating the notion of immune-surveillance against cancer metastasis, (iii) describe in vivo evidence in cancer patients that support a role for anti-cancer immunity, (iv) indicate neuroendocrine and paracrine mediating mechanisms of stress- and surgery-induced promotion of cancer progression, focusing on the prominent role of catecholamines and prostaglandins through their impact on anti-cancer immunity, and through direct effects on the malignant tissue and its surrounding, (v) discuss the impact of different anesthetic approaches and other intra-operative procedures on immunity and cancer progression, and (vi) suggest prophylactic measures against the immunosuppressive and cancer promoting effects of surgery. PMID:22504092
Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

PubMed

Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

2014-06-01

Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.
Overlap between age-at-onset and disease-progression determinants in Huntington disease.

PubMed

Aziz, N Ahmad; van der Burg, Jorien M M; Tabrizi, Sarah J; Landwehrmeyer, G Bernhard

2018-05-09

A fundamental but still unresolved issue regarding Huntington disease (HD) pathogenesis is whether the factors that determine age at onset are the same as those that govern disease progression. Because elucidation of this issue is crucial for the development as well as optimal timing of administration of novel disease-modifying therapies, we aimed to assess the extent of overlap between age-at-onset and disease-progression determinants in HD. Using observational data from Enroll-HD, the largest cohort of patients with HD worldwide, in this study we present, validate, and apply an intuitive method based on linear mixed-effect models to quantify the variability in the rate of disease progression in HD. A total of 3,411 patients with HD met inclusion criteria. We found that (1) about two-thirds of the rate of functional, motor, and cognitive progression in HD is determined by the same factors that also determine age at onset, with CAG repeat-dependent mechanisms having by far the largest effect; (2) although expanded HTT CAG repeat size had a large influence on average body weight, the rate of weight loss was largely independent of factors that determine age at onset in HD; and (3) about one-third of the factors that determine the rate of functional, motor, and cognitive progression are different from those that govern age at onset and need further elucidation. Our findings imply that targeting of CAG repeat-dependent mechanisms, for example through gene-silencing approaches, is likely to affect the rate of functional, motor, and cognitive impairment, but not weight loss, in manifest HD mutation carriers. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Design of combination angiotensin receptor blocker and angiotensin-converting enzyme inhibitor for treatment of diabetic nephropathy (VA NEPHRON-D).

PubMed

Fried, Linda F; Duckworth, William; Zhang, Jane Hongyuan; O'Connor, Theresa; Brophy, Mary; Emanuele, Nicholas; Huang, Grant D; McCullough, Peter A; Palevsky, Paul M; Seliger, Stephen; Warren, Stuart R; Peduzzi, Peter

2009-02-01

Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can slow the progression of diabetic nephropathy. Even with ACEI or ARB treatment, the proportion of patients who progress to end-stage renal disease (ESRD) remains high. Interventions that achieve more complete blockade of the renin-angiotensin system, such as combination ACEI and ARB, might be beneficial. This approach may decrease progression of nondiabetic kidney disease. In diabetic nephropathy, combination therapy decreases proteinuria, but its effect in slowing progression is unknown. In addition, the potential for hyperkalemia may limit the utility of combined therapy in this population. VA NEPHRON-D is a randomized, double-blind, multicenter clinical trial to assess the effect of combination losartan and lisinopril, compared with losartan alone, on the progression of kidney disease in 1850 patients with diabetes and overt proteinuria. The primary endpoints are time to (1) reduction in estimated GFR (eGFR) of > 50% (if baseline < 60 ml/min/1.73 m(2)); (2) reduction in eGFR of 30 ml/min/1.73 m(2) (if baseline > or = 60 ml/min/1.73 m(2)); (3) progression to ESRD (need for dialysis, renal transplant, or eGFR < 15 ml/min/1.73 m(2)); or (4) death. The secondary endpoint is time to change in eGFR or ESRD. Tertiary endpoints are cardiovascular events, slope of change in eGFR, and change in albuminuria at 1 yr. Specific safety endpoints are serious hyperkalemia (potassium > 6 mEq/L, requiring admission, emergency room visit, or dialysis), all-cause mortality, and other serious adverse events. This paper discusses the design and key methodological issues that arose during the planning of the study.
Phytoremediation of heavy metal polluted soils and water: Progresses and perspectives*

PubMed Central

Lone, Mohammad Iqbal; He, Zhen-li; Stoffella, Peter J.; Yang, Xiao-e

2008-01-01

Environmental pollution affects the quality of pedosphere, hydrosphere, atmosphere, lithosphere and biosphere. Great efforts have been made in the last two decades to reduce pollution sources and remedy the polluted soil and water resources. Phytoremediation, being more cost-effective and fewer side effects than physical and chemical approaches, has gained increasing popularity in both academic and practical circles. More than 400 plant species have been identified to have potential for soil and water remediation. Among them, Thlaspi, Brassica, Sedum alfredii H., and Arabidopsis species have been mostly studied. It is also expected that recent advances in biotechnology will play a promising role in the development of new hyperaccumulators by transferring metal hyperaccumulating genes from low biomass wild species to the higher biomass producing cultivated species in the times to come. This paper attempted to provide a brief review on recent progresses in research and practical applications of phytoremediation for soil and water resources. PMID:18357623
The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy.

PubMed

Magalhães, Andreia P; Azevedo, Nuno F; Pereira, Maria O; Lopes, Susana P

2016-02-01

The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.
2015 update on the diagnosis and management of neoplastic pericardial disease.

PubMed

Lestuzzi, Chiara; Berretta, Massimiliano; Tomkowski, Witold

2015-04-01

The best approach in diagnosis and treatment of neoplastic pericardial disease has not been defined yet. The authors report the most recent literature about the new diagnostic techniques that are useful to improve the diagnosis. The literature about the therapeutic options is critically reviewed, in order to give suggestions of use to the clinical practice. Pericardial effusion may require urgent drainage; the solid component, however, becomes predominant in some cases. Neoplastic pericardial disease should be assessed following oncologic criteria evaluation of the neoplastic burden; outcome classified as complete or partial response, stable or progressive disease and - in cases with progression - event-free survival. Systemic chemotherapy may be effective in lymphomas and possibly in breast carcinomas. Intrapericardial chemotherapy with systemic chemotherapy is the treatment of choice in lung cancer. Pericardial window with systemic chemotherapy is also effective in preventing the accumulation of large amount of fluid.
Can the Adoption of Informal Approaches to Learning Music in School Music Lessons Promote Musical Progression?

ERIC Educational Resources Information Center

Hallam, Susan; Creech, Andrea; McQueen, Hilary

2017-01-01

The aim of this research was to explore the impact of the adoption of the Musical Futures approach on the musical progression of students in Musical Futures' Champion schools. The research took place over three years in three phases with 733 students and 28 music teachers completing questionnaires. Data from the interviews with 39 staff and focus…
A "Fear" Studies Perspective and Critique: Analyzing English and Stengel's Progressive Study of Fear and Learning in "Education Theory." Technical Paper No. 37

ERIC Educational Resources Information Center

Fisher, R. Michael

2011-01-01

The author critiques the progressive approach of two contemporary educational philosophers (English and Stengel) on the topic of fear and learning. Using a postmodern integral approach, this article examines the tendency of reductionism, individualism, and psychologism as part of a hegemonic liberalism and modernism in discourses on fear and…

Sex and Gender Differences in Prevention of Type 2 Diabetes

PubMed Central

Harreiter, Jürgen; Kautzky-Willer, Alexandra

2018-01-01

Lifestyle intervention programs are effective in the prevention of type 2 diabetes mellitus (T2DM) in high risk populations. However, most studies only give limited information about the influence of sex and/or gender effectiveness of these interventions. So far, similar outcome was reported for diabetes progression and weight loss. Nevertheless, long-term data on cardiovascular outcome are sparse but favoring women regarding all-cause and cardiovascular mortality. In both men and women, sex hormone imbalances and reproductive disorders are associated with a higher risk of T2DM development. Diabetes prevention approaches are reported for polycystic ovary syndrome, gestational diabetes mellitus, and erectile dysfunction and are presented in this review. In the surgical treatment options for morbid obese patients, sex and gender differences are present. Choices and preferences of adherence to lifestyle and pharmacological interventions, expectations, treatment effects, and complications are influenced by sex or gender. In general, bariatric surgery is performed more often in women seeking medical/surgical help to lose weight. Men are older and have higher comorbidities and mortality rates and worse follow-up outcome after bariatric surgery. A more gender-sensitive clinical approach, as well as consideration of ethnicity may improve quality of life and increase health and life expectancy in men and women with a high risk for subsequent progression to T2DM. PMID:29780358
Investigating Interventions in Alzheimer's Disease with Computer Simulation Models

PubMed Central

Proctor, Carole J.; Boche, Delphine; Gray, Douglas A.; Nicoll, James A. R.

2013-01-01

Progress in the development of therapeutic interventions to treat or slow the progression of Alzheimer's disease has been hampered by lack of efficacy and unforeseen side effects in human clinical trials. This setback highlights the need for new approaches for pre-clinical testing of possible interventions. Systems modelling is becoming increasingly recognised as a valuable tool for investigating molecular and cellular mechanisms involved in ageing and age-related diseases. However, there is still a lack of awareness of modelling approaches in many areas of biomedical research. We previously developed a stochastic computer model to examine some of the key pathways involved in the aggregation of amyloid-beta (Aβ) and the micro-tubular binding protein tau. Here we show how we extended this model to include the main processes involved in passive and active immunisation against Aβ and then demonstrate the effects of this intervention on soluble Aβ, plaques, phosphorylated tau and tangles. The model predicts that immunisation leads to clearance of plaques but only results in small reductions in levels of soluble Aβ, phosphorylated tau and tangles. The behaviour of this model is supported by neuropathological observations in Alzheimer patients immunised against Aβ. Since, soluble Aβ, phosphorylated tau and tangles more closely correlate with cognitive decline than plaques, our model suggests that immunotherapy against Aβ may not be effective unless it is performed very early in the disease process or combined with other therapies. PMID:24098635
Sex differences and the role of dopamine receptors in the reward-enhancing effects of nicotine and bupropion.

PubMed

Barrett, Scott T; Geary, Trevor N; Steiner, Amy N; Bevins, Rick A

2017-01-01

Nicotine and bupropion have been demonstrated to enhance the value of other reinforcers, and this may partially account for nicotine reward and dependence. Evidence suggests that the sexes differ in their sensitivity to the primary and secondary reinforcing effects of nicotine and nicotine-associated stimuli. Whether the sexes also differ in sensitivity to the reward-enhancing effects of nicotine (and bupropion) is yet unclear. The present study evaluated potential sex differences in the enhancement effects of nicotine and bupropion using a reinforcer demand approach. Furthermore, we sought to investigate the role that D1- and D2-type dopamine receptors play in the reward-enhancing effects of nicotine and bupropion. Demand for sensory reinforcement was assessed in male and female rats responding on a progression of fixed ratio schedules. The effects of nicotine and 10 or 20 mg/kg bupropion on reinforcer demand were assessed within subjects. Subsequently, the effects of SCH-23390 and eticlopride were assessed on the enhancing effects of nicotine and bupropion on progressive ratio responding. Nicotine and bupropion enhanced demand metrics of reinforcement value in both sexes. Females were more sensitive to the enhancement effects of bupropion assessed by reinforcer demand and progressive ratio performance. D2-like dopamine receptor antagonism by eticlopride attenuated the enhancement effects of bupropion, but not of nicotine. Nicotine and bupropion both enhance reinforcement value in both sexes, though females may be more sensitive to the reward-enhancing effects of bupropion. D2- and possibly D1-type receptors appear to be involved in the reward-enhancing effects of bupropion, but not necessarily nicotine.
A cost-effectiveness comparison between early surgery and non-surgical approach for incidental papillary thyroid microcarcinoma.

PubMed

Lang, Brian Hung-Hin; Wong, Carlos K H

2015-09-01

The issue of whether all incidental papillary thyroid microcarcinoma (PTMC) should be managed by early surgery (ES) has been questioned and there is a growing acceptance that a non-surgical approach (NSA) might be more appropriate. We conducted a cost-effectiveness analysis comparing the two strategies in managing incidental PTMC. Our base case was a hypothetical 40-year-old female diagnosed with a unifocal intra-thyroidal 9 mm PTMC. The PTMC was considered suitable for either strategy. A Markov decision tree model was constructed to compare the estimated cost-effectiveness between ES and NSA after 20 years. Outcome probabilities, utilities and costs were derived from the literature. The threshold for cost-effectiveness was set at USD 50,000/quality-adjusted life year (QALY). A further analysis was done for patients < 40 and ≥ 40 years. Sensitivity and threshold analyses were used to examine model uncertainty. Each patient who adopted NSA over ES cost an extra USD 682.54 but gained an additional 0.260 QALY. NSA was cost saving (i.e. less costly and more effective) up to 16 years from diagnosis and remained cost-effective from 17 years onward. In the sensitivity analysis, NSA remained cost-effective regardless of patient age (< 40 and ≥ 40 years), complications, rates of progression, year cycle and discount rate. In the threshold analysis, none of the scenarios that could have changed the conclusion appeared clinically likely. For a selected group of incidental PTMC, adopting NSA was not only cost saving in the initial 16 years but also remained cost effective thereafter. This was irrespective of patient age, complication rate or rate of PTMC progression. © 2015 European Society of Endocrinology.
Is art therapy a reliable tool for rehabilitating people suffering from brain/mental diseases?

PubMed

Mirabella, Giovanni

2015-04-01

Whether art therapy can be an effective rehabilitative treatment for people with brain or mental diseases (e.g., dementia, Alzheimer's disease, Parkinson's disease, autism, schizophrenia) is a long-standing and highly debated issue. On the one hand, several observational studies and anecdotal evidence enthusiastically support the effectiveness of arts-based therapy. On the other hand, few rigorous clinical investigations have been performed, and there is too little empirical evidence to allow a full assessment of the risks and benefits of this intervention. Nevertheless, there is a progressively increasing demand for the development of appropriate complementary therapies to improve the personal and social lives of patients with neurodegenerative diseases. This is because conventional medical treatments are aimed at alleviating symptoms but cannot arrest or reverse the degenerative process. Thus, as disease progresses and adverse effects emerge, patients' quality of life dramatically decreases; when this occurs patients seek different forms of intervention. Art therapy is a potentially appealing treatment because of its more holistic approach to healthcare. However, as with any medicine, its effects must be tested by using standard, rigorous scientific approaches. This report describes the current state of research into art therapy and outlines many key factors that future research should consider, all of which are directly or indirectly related to the neural mechanism underlying behavioral changes: brain plasticity. Artistic performance could promote some form of brain plasticity that, to some extent, might compensate for the brain damage caused by the disease.
The comparative cost-effectiveness of an equity-focused approach to child survival, health, and nutrition: a modelling approach.

PubMed

Carrera, Carlos; Azrack, Adeline; Begkoyian, Genevieve; Pfaffmann, Jerome; Ribaira, Eric; O'Connell, Thomas; Doughty, Patricia; Aung, Kyaw Myint; Prieto, Lorena; Rasanathan, Kumanan; Sharkey, Alyssa; Chopra, Mickey; Knippenberg, Rudolf

2012-10-13

Progress on child mortality and undernutrition has seen widening inequities and a concentration of child deaths and undernutrition in the most deprived communities, threatening the achievement of the Millennium Development Goals. Conversely, a series of recent process and technological innovations have provided effective and efficient options to reach the most deprived populations. These trends raise the possibility that the perceived trade-off between equity and efficiency no longer applies for child health--that prioritising services for the poorest and most marginalised is now more effective and cost effective than mainstream approaches. We tested this hypothesis with a mathematical-modelling approach by comparing the cost-effectiveness in terms of child deaths and stunting events averted between two approaches (from 2011-15 in 14 countries and one province): an equity-focused approach that prioritises the most deprived communities, and a mainstream approach that is representative of current strategies. We combined some existing models, notably the Marginal Budgeting for Bottlenecks Toolkit and the Lives Saved Tool, to do our analysis. We showed that, with the same level of investment, disproportionately higher effects are possible by prioritising the poorest and most marginalised populations, for averting both child mortality and stunting. Our results suggest that an equity-focused approach could result in sharper decreases in child mortality and stunting and higher cost-effectiveness than mainstream approaches, while reducing inequities in effective intervention coverage, health outcomes, and out-of-pocket spending between the most and least deprived groups and geographic areas within countries. Our findings should be interpreted with caution due to uncertainties around some of the model parameters and baseline data. Further research is needed to address some of these gaps in the evidence base. Strategies for improving child nutrition and survival, however, should account for an increasing prioritisation of the most deprived communities and the increased use of community-based interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.
A Priori Analysis of a Compressible Flamelet Model using RANS Data for a Dual-Mode Scramjet Combustor

NASA Technical Reports Server (NTRS)

Quinlan, Jesse R.; Drozda, Tomasz G.; McDaniel, James C.; Lacaze, Guilhem; Oefelein, Joseph

2015-01-01

In an effort to make large eddy simulation of hydrocarbon-fueled scramjet combustors more computationally accessible using realistic chemical reaction mechanisms, a compressible flamelet/progress variable (FPV) model was proposed that extends current FPV model formulations to high-speed, compressible flows. Development of this model relied on observations garnered from an a priori analysis of the Reynolds-Averaged Navier-Stokes (RANS) data obtained for the Hypersonic International Flight Research and Experimentation (HI-FiRE) dual-mode scramjet combustor. The RANS data were obtained using a reduced chemical mechanism for the combustion of a JP-7 surrogate and were validated using avail- able experimental data. These RANS data were then post-processed to obtain, in an a priori fashion, the scalar fields corresponding to an FPV-based modeling approach. In the current work, in addition to the proposed compressible flamelet model, a standard incompressible FPV model was also considered. Several candidate progress variables were investigated for their ability to recover static temperature and major and minor product species. The effects of pressure and temperature on the tabulated progress variable source term were characterized, and model coupling terms embedded in the Reynolds- averaged Navier-Stokes equations were studied. Finally, results for the novel compressible flamelet/progress variable model were presented to demonstrate the improvement attained by modeling the effects of pressure and flamelet boundary conditions on the combustion.
Semantic Feature Training in Combination with Transcranial Direct Current Stimulation (tDCS) for Progressive Anomia

PubMed Central

Hung, Jinyi; Bauer, Ashley; Grossman, Murray; Hamilton, Roy H.; Coslett, H. B.; Reilly, Jamie

2017-01-01

We examined the effectiveness of a 2-week regimen of a semantic feature training in combination with transcranial direct current stimulation (tDCS) for progressive naming impairment associated with primary progressive aphasia (N = 4) or early onset Alzheimer’s Disease (N = 1). Patients received a 2-week regimen (10 sessions) of anodal tDCS delivered over the left temporoparietal cortex while completing a language therapy that consisted of repeated naming and semantic feature generation. Therapy targets consisted of familiar people, household items, clothes, foods, places, hygiene implements, and activities. Untrained items from each semantic category provided item level controls. We analyzed naming accuracies at multiple timepoints (i.e., pre-, post-, 6-month follow-up) via a mixed effects logistic regression and individual differences in treatment responsiveness using a series of non-parametric McNemar tests. Patients showed advantages for naming trained over untrained items. These gains were evident immediately post tDCS. Trained items also showed a shallower rate of decline over 6-months relative to untrained items that showed continued progressive decline. Patients tolerated stimulation well, and sustained improvements in naming accuracy suggest that the current intervention approach is viable. Future implementation of a sham control condition will be crucial toward ascertaining whether neurostimulation and behavioral treatment act synergistically or alternatively whether treatment gains are exclusively attributable to either tDCS or the behavioral intervention. PMID:28559805
Big data and data repurposing - using existing data to answer new questions in vascular dementia research.

PubMed

Doubal, Fergus N; Ali, Myzoon; Batty, G David; Charidimou, Andreas; Eriksdotter, Maria; Hofmann-Apitius, Martin; Kim, Yun-Hee; Levine, Deborah A; Mead, Gillian; Mucke, Hermann A M; Ritchie, Craig W; Roberts, Charlotte J; Russ, Tom C; Stewart, Robert; Whiteley, William; Quinn, Terence J

2017-04-17

Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group's experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9 th International Congress on Vascular Dementia (Ljubljana, 16-18 th October 2015). We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use.
Comprehensive analysis of the functional microRNA–mRNA regulatory network identifies miRNA signatures associated with glioma malignant progression

PubMed Central

Li, Yongsheng; Xu, Juan; Chen, Hong; Bai, Jing; Li, Shengli; Zhao, Zheng; Shao, Tingting; Jiang, Tao; Ren, Huan; Kang, Chunsheng; Li, Xia

2013-01-01

Glioma is the most common and fatal primary brain tumour with poor prognosis; however, the functional roles of miRNAs in glioma malignant progression are insufficiently understood. Here, we used an integrated approach to identify miRNA functional targets during glioma malignant progression by combining the paired expression profiles of miRNAs and mRNAs across 160 Chinese glioma patients, and further constructed the functional miRNA–mRNA regulatory network. As a result, most tumour-suppressive miRNAs in glioma progression were newly discovered, whose functions were widely involved in gliomagenesis. Moreover, three miRNA signatures, with different combinations of hub miRNAs (regulations≥30) were constructed, which could independently predict the survival of patients with all gliomas, high-grade glioma and glioblastoma. Our network-based method increased the ability to identify the prognostic biomarkers, when compared with the traditional method and random conditions. Hsa-miR-524-5p and hsa-miR-628-5p, shared by these three signatures, acted as protective factors and their expression decreased gradually during glioma progression. Functional analysis of these miRNA signatures highlighted their critical roles in cell cycle and cell proliferation in glioblastoma malignant progression, especially hsa-miR-524-5p and hsa-miR-628-5p exhibited dominant regulatory activities. Therefore, network-based biomarkers are expected to be more effective and provide deep insights into the molecular mechanism of glioma malignant progression. PMID:24194606
Documenting progress: hand therapy treatment shift from biomechanical to occupational adaptation.

PubMed

Jack, Jada; Estes, Rebecca I

2010-01-01

The investment of time and self to develop therapeutic relationships with clients appears incongruent with today's time-constrained health care system, yet bridging the gap of these incongruencies is the challenge therapists face to provide high-quality, client-centered, occupation-based treatment. This case report illustrates a shift in approach from biomechanical to occupational adaptation (OA) in an orthopedic outpatient clinic. The progress of a client with lupus-related arthritis who was 6 days postsurgery is documented. The intervention initially used a biomechanical frame of reference, but when little progress had been made at 10 weeks after surgery, a shift was made to the more client-centered OA approach. The Canadian Occupational Performance Measure was administered, and an OA approach was initiated. On reassessment, clinically important improvements were documented in all functional tasks addressed. An OA approach provides the bridge between the application of clinical expertise, client-centered, occupation-based therapy and the time constraints placed by payer sources.
Computational integration of nanoscale physical biomarkers and cognitive assessments for Alzheimer’s disease diagnosis and prognosis

PubMed Central

Yue, Tao; Jia, Xinghua; Petrosino, Jennifer; Sun, Leming; Fan, Zhen; Fine, Jesse; Davis, Rebecca; Galster, Scott; Kuret, Jeff; Scharre, Douglas W.; Zhang, Mingjun

2017-01-01

With the increasing prevalence of Alzheimer’s disease (AD), significant efforts have been directed toward developing novel diagnostics and biomarkers that can enhance AD detection and management. AD affects the cognition, behavior, function, and physiology of patients through mechanisms that are still being elucidated. Current AD diagnosis is contingent on evaluating which symptoms and signs a patient does or does not display. Concerns have been raised that AD diagnosis may be affected by how those measurements are analyzed. Unbiased means of diagnosing AD using computational algorithms that integrate multidisciplinary inputs, ranging from nanoscale biomarkers to cognitive assessments, and integrating both biochemical and physical changes may provide solutions to these limitations due to lack of understanding for the dynamic progress of the disease coupled with multiple symptoms in multiscale. We show that nanoscale physical properties of protein aggregates from the cerebral spinal fluid and blood of patients are altered during AD pathogenesis and that these properties can be used as a new class of “physical biomarkers.” Using a computational algorithm, developed to integrate these biomarkers and cognitive assessments, we demonstrate an approach to impartially diagnose AD and predict its progression. Real-time diagnostic updates of progression could be made on the basis of the changes in the physical biomarkers and the cognitive assessment scores of patients over time. Additionally, the Nyquist-Shannon sampling theorem was used to determine the minimum number of necessary patient checkups to effectively predict disease progression. This integrated computational approach can generate patient-specific, personalized signatures for AD diagnosis and prognosis. PMID:28782028
Caprylic Triglyceride as a Novel Therapeutic Approach to Effectively Improve the Performance and Attenuate the Symptoms Due to the Motor Neuron Loss in ALS Disease

PubMed Central

Zhao, Wei; Varghese, Merina; Vempati, Prashant; Dzhun, Anastasiya; Cheng, Alice; Wang, Jun; Lange, Dale; Bilski, Amanda; Faravelli, Irene; Pasinetti, Giulio Maria

2012-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients. PMID:23145119
Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease.

PubMed

Zhao, Wei; Varghese, Merina; Vempati, Prashant; Dzhun, Anastasiya; Cheng, Alice; Wang, Jun; Lange, Dale; Bilski, Amanda; Faravelli, Irene; Pasinetti, Giulio Maria

2012-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients.
Blunt impact as deterrent: human approach-avoidance behaviors and other stress responses studied within a paintball gaming context

NASA Astrophysics Data System (ADS)

Short, Kenneth R.; Bergen, Michael T.; DeMarco, Robert M.; Chua, Florence B.; Servatius, Richard J.

2006-05-01

Blunt impact munitions are often used by civilian law enforcement and in military operations on urban terrain (MOUT) missions to dissuade individuals and groups from approaching valued assets. The use of blunt munitions (rubber-ball or sponge) is predicated on their effectiveness as aversive stimuli; the effectiveness is weighed against the risk of serious injury or death. However, little empirical evidence supports effectiveness. Here, we use a paintball gaming context to study the effects of blunt impact on performance and approach behaviors. Volunteers individually traversed a course in which targets offer the opportunity to gain for accuracy. While completing the targeting task, subjects were bombarded with paintballs, which progressively became more numerous and the impact more intense as the subjects neared goal locations. Initial data suggest that over 30 blunt impacts by paintballs delivered at 280 ft/sec over 30 to 100 ft are insufficient to overcome intrinsic and extrinsic approach motivations or impair targeting or advance performance in an overwhelming majority of subjects. Our apparent ceiling effect was surprising. A sub-comparison of the few subjects who stopped the game before the end with those who did not suggests that personality factors influence the effectiveness of blunt impact as a deterrent. While paintballs differ from traditional blunt impact munitions on a number of physical characteristics, impact that was sufficient to repeatedly bruise volunteers was not an effective deterrent.
The capability approach: a guiding framework to improve population health and the attainment of the Sustainable Developmental Goals.

PubMed

Hirani, Shela Akbar Ali; Richter, Solina

2017-02-21

The world is progressing in terms of communication, innovative technology and cure of various diseases through advanced pharmacological preparations. Unfortunately, populations are still struggling with ill-health, disabilities, poverty, hunger, inequality, gender disparities and conflicts. Several questions come to mind in this regard: why are prosperity, health, peace and progress not evenly distributed and what is the best approach to address the issues associated with population health? The capability approach may offer a possible model. This approach is a blend of 5 key concepts: capabilities, functioning, agency, endowment, and conversion factors. It proposes an innovative approach to examine and enhance the quality of life and wellbeing of individuals. This reflective paper provides an overview of the capability approach, critically analyses population health from the theoretical lens of the capability approach and highlights the relevance of this approach to achieving the Sustainable Developmental Goals.
Characterizing risk assessments for the development of occupational exposure limits for engineered nanomaterials.

PubMed

Schulte, P A; Kuempel, E D; Drew, N M

2018-06-01

The commercialization of engineered nanomaterials (ENMs) began in the early 2000's. Since then the number of commercial products and the number of workers potentially exposed to ENMs is growing, as is the need to evaluate and manage the potential health risks. Occupational exposure limits (OELs) have been developed for some of the first generation of ENMs. These OELs have been based on risk assessments that progressed from qualitative to quantitative as nanotoxicology data became available. In this paper, that progression is characterized. It traces OEL development through the qualitative approach of general groups of ENMs based primarily on read-across with other materials to quantitative risk assessments for nanoscale particles including titanium dioxide, carbon nanotubes and nanofibers, silver nanoparticles, and cellulose nanocrystals. These represent prototypic approaches to risk assessment and OEL development for ENMs. Such substance-by-substance efforts are not practical given the insufficient data for many ENMs that are currently being used or potentially entering commerce. Consequently, categorical approaches are emerging to group and rank ENMs by hazard and potential health risk. The strengths and limitations of these approaches are described, and future derivations and research needs are discussed. Critical needs in moving forward with understanding the health effects of the numerous EMNs include more standardized and accessible quantitative data on the toxicity and physicochemical properties of ENMs. Published by Elsevier Inc.
Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.

PubMed

Kabu, Shushi; Gao, Yue; Kwon, Brian K; Labhasetwar, Vinod

2015-12-10

Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI. Copyright © 2015 Elsevier B.V. All rights reserved.
Microenvironmental acidosis in carcinogenesis and metastases: new strategies in prevention and therapy.

PubMed

Fais, Stefano; Venturi, Giulietta; Gatenby, Bob

2014-12-01

Much effort is currently devoted to developing patient-specific cancer therapy based on molecular characterization of tumors. In particular, this approach seeks to identify driver mutations that can be blocked through small molecular inhibitors. However, this approach is limited by extensive intratumoral genetic heterogeneity, and, not surprisingly, even dramatic initial responses are typically of limited duration as resistant tumor clones rapidly emerge and proliferate. We propose an alternative approach based on observations that while tumor evolution produces genetic divergence, it is also associated with striking phenotypic convergence that loosely correspond to the well-known cancer "hallmarks". These convergent properties can be described as driver phenotypes and may be more consistently and robustly expressed than genetic targets. To this purpose, it is necessary to identify strategies that are critical for cancer progression and metastases, and it is likely that these driver phenotypes will be closely related to cancer "hallmarks". It appears that an antiacidic approach, by targetting a driver phenotype in tumors, may be thought as a future strategy against tumors in either preventing the occurrence of cancer or treating tumor patients with multiple aims, including the improvement of efficacy of existing therapies, possibly reducing their systemic side effects, and controlling tumor growth, progression, and metastasis. This may be achieved with existing molecules such as proton pump inhibitors (PPIs) and buffers such as sodium bicarbonate, citrate, or TRIS.
E-Learning Personalization Using Triple-Factor Approach in Standard-Based Education

NASA Astrophysics Data System (ADS)

Laksitowening, K. A.; Santoso, H. B.; Hasibuan, Z. A.

2017-01-01

E-Learning can be a tool in monitoring learning process and progress towards the targeted competency. Process and progress on every learner can be different one to another, since every learner may have different learning type. Learning type itself can be identified by taking into account learning style, motivation, and knowledge ability. This study explores personalization for learning type based on Triple-Factor Approach. Considering that factors in Triple-Factor Approach are dynamic, the personalization system needs to accommodate the changes that may occurs. Originated from the issue, this study proposed personalization that guides learner progression dynamically towards stages of their learning process. The personalization is implemented in the form of interventions that trigger learner to access learning contents and discussion forums more often as well as improve their level of knowledge ability based on their state of learning type.

The Historiography of Gender and Progressive Education in the United States

ERIC Educational Resources Information Center

Weiler, Kathleen

2006-01-01

This article examines the feminist historiography of the progressive education movement over the past 25 years using the Foucauldian conception of genealogy and the theoretical approach of critical feminism. Gender has largely been ignored as a significant category of historical analysis in the historiography of progressive education in the United…
National Disability Policy: A Progress Report

ERIC Educational Resources Information Center

National Council on Disability, 2009

2009-01-01

In recent years, the National Council on Disability (NCD) Progress Report has been a retrospective review and analysis of Federal programs for people with disabilities. For this Progress Report, NCD members have chosen to depart from a retrospective approach, and, instead, will focus on the current status of the quality of life of people with…
Boyd Henry Bode, John Dewey, and the Problem of Subject Matters

ERIC Educational Resources Information Center

Watras, Joseph

2016-01-01

World War I marked an important turning point in progressive education. With the founding of the Progressive Education Association (PEA) in 1919 advocates had an organization that stood against pedagogical formalism. This essay provides a discussion of this new approach to education, the possibilities of the contributions progressive schools made…
RandomForest4Life: a Random Forest for predicting ALS disease progression.

PubMed

Hothorn, Torsten; Jung, Hans H

2014-09-01

We describe a method for predicting disease progression in amyotrophic lateral sclerosis (ALS) patients. The method was developed as a submission to the DREAM Phil Bowen ALS Prediction Prize4Life Challenge of summer 2012. Based on repeated patient examinations over a three- month period, we used a random forest algorithm to predict future disease progression. The procedure was set up and internally evaluated using data from 1197 ALS patients. External validation by an expert jury was based on undisclosed information of an additional 625 patients; all patient data were obtained from the PRO-ACT database. In terms of prediction accuracy, the approach described here ranked third best. Our interpretation of the prediction model confirmed previous reports suggesting that past disease progression is a strong predictor of future disease progression measured on the ALS functional rating scale (ALSFRS). We also found that larger variability in initial ALSFRS scores is linked to faster future disease progression. The results reported here furthermore suggested that approaches taking the multidimensionality of the ALSFRS into account promise some potential for improved ALS disease prediction.
An innovative outcome-based care and procurement model of hemophilia management.

PubMed

Gringeri, Alessandro; Doralt, Jennifer; Valentino, Leonard A; Crea, Roberto; Reininger, Armin J

2016-06-01

Hemophilia is a rare bleeding disorder associated with spontaneous and post-traumatic bleeding. Each hemophilia patient requires a personalized approach to episodic or prophylactic treatment, but self-management can be challenging for patients, and avoidable bleeding may occur. Patient-tailored care may provide more effective prevention of bleeding, which in turn, may decrease the likelihood of arthropathy and associated chronic pain, missed time from school or work, and progressive loss of mobility. A strategy is presented here aiming to reduce or eliminate bleeding altogether through a holistic approach based on individual patient characteristics. In an environment of budget constraints, this approach would link procurement to patient outcome, adding incentives for all stakeholders to strive for optimal care and, ultimately, a bleed-free world.
Computational Simulation of Continuous Fiber-Reinforced Ceramic Matrix Composites Behavior

NASA Technical Reports Server (NTRS)

Murthy, Pappu L. N.; Chamis, Christos C.; Mital, Subodh K.

1996-01-01

This report describes a methodology which predicts the behavior of ceramic matrix composites and has been incorporated in the computational tool CEMCAN (CEramic Matrix Composite ANalyzer). The approach combines micromechanics with a unique fiber substructuring concept. In this new concept, the conventional unit cell (the smallest representative volume element of the composite) of the micromechanics approach is modified by substructuring it into several slices and developing the micromechanics-based equations at the slice level. The methodology also takes into account nonlinear ceramic matrix composite (CMC) behavior due to temperature and the fracture initiation and progression. Important features of the approach and its effectiveness are described by using selected examples. Comparisons of predictions and limited experimental data are also provided.
Effects of Alcohol on Tumor Growth, Metastasis, Immune Response, and Host Survival

PubMed Central

Meadows, Gary G.; Zhang, Hui

2015-01-01

Most research involving alcohol and cancer concerns the relationship between alcohol consumption and cancer risk and the mechanisms of carcinogenesis. This review relates the amount and duration of alcohol intake in humans and in animal models of cancer to tumor growth, angiogenesis, invasion, metastasis, immune response, and host survival in specific types and subtypes of cancer. Research on the influence of alcohol drinking on human cancer patients is limited. Although there is more information in animal models of cancer, many aspects still are ill defined. More research is needed to define the mechanisms that underlie the role of alcohol on cancer progression in both animals and humans. Activation of the immune system can play a positive role in keeping cancer under control, but this also can facilitate cancer progression. Additionally, a functional immune system is required for cancer patients to achieve an optimal response to conventional chemotherapy. Insight into the underlying mechanisms of these interactions could lead to effective immunotherapeutic approaches to treat alcoholics with cancer. Defining the epigenetic mechanisms that modulate cancer progression also has great potential for the development of new treatment options not only for treating alcoholics with cancer but also for treating other alcohol-induced diseases. PMID:26695753
Global and 3D Spatial Assessment of Neuroinflammation in Rodent Models of Multiple Sclerosis

PubMed Central

Gupta, Shashank; Utoft, Regine; Hasseldam, Henrik; Schmidt-Christensen, Anja; Hannibal, Tine Dahlbaek; Hansen, Lisbeth; Fransén-Pettersson, Nina; Agarwal-Gupta, Noopur; Rozell, Björn; Andersson, Åsa; Holmberg, Dan

2013-01-01

Multiple Sclerosis (MS) is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS). T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE) animal models for the disease. A technology for quantitative and 3 dimensional (3D) spatial assessment of inflammation in this and other CNS inflammatory conditions is much needed. Here we present a procedure for 3D spatial assessment and global quantification of the development of neuroinflammation based on Optical Projection Tomography (OPT). Applying this approach to the analysis of rodent models of MS, we provide global quantitative data of the major inflammatory component as a function of the clinical course. Our data demonstrates a strong correlation between the development and progression of neuroinflammation and clinical disease in several mouse and a rat model of MS refining the information regarding the spatial dynamics of the inflammatory component in EAE. This method provides a powerful tool to investigate the effect of environmental and genetic forces and for assessing the therapeutic effects of drug therapy in animal models of MS and other neuroinflammatory/neurodegenerative disorders. PMID:24124545
Ulcerative proctitis: an update on the pharmacotherapy and management.

PubMed

Gecse, Krisztina B; Lakatos, Peter L

2014-08-01

Ulcerative colitis (UC) presents as proctitis in approximately a quarter of the patients. It may progress into left-sided or extensive colitis in up to 50% of cases upon long-term follow-up. Currently available data on ulcerative proctitis are summarized and critically reviewed. Extensive literature search (MEDLINE) was performed to identify relevant articles up to March 2014. The short-term goal of the treatment in UC is to induce remission, whereas long-term goals are to maintain remission and prevent disease progression. Topically administered 5-aminosalicylates (5-ASA) and corticosteroids are effective in the treatment of proctitis, although they seem to be underused in everyday practice. Locally administered 5-ASA preparations are more effective than oral compounds. The combination of topical and oral 5-ASA and steroids should be considered for escalation of treatment. Refractory patients should be re-evaluated to exclude for compliance failures, infections or proximal disease extent. True refractory or steroid-dependent patients may require immunomodulators or biological therapy. Alternative medicine can be used complementarily, while experimental approaches are reserved for patients failing conventional medication. Proctocolectomy may be the last resort of treatment. Upon long-term, 5-ASA maintenance treatment is indicated in all UC cases to prevent relapse and disease progression.
Novel Applications of Radionuclide Imaging in Peripheral Vascular Disease

PubMed Central

Stacy, Mitchel R.; Sinusas, Albert J.

2015-01-01

Peripheral vascular disease (PVD) is a progressive atherosclerotic disease that leads to stenosis or occlusion of blood vessels supplying the lower extremities. Current diagnostic imaging techniques commonly focus on evaluation of anatomy or blood flow at the macrovascular level and do not permit assessment of the underlying pathophysiology associated with disease progression or treatment response. Molecular imaging with radionuclide-based approaches, such as PET and SPECT, can offer novel insight into PVD by providing non-invasive assessment of biological processes such as angiogenesis and atherosclerosis. This review discusses emerging radionuclide-based imaging approaches that have potential clinical applications in the evaluation of PVD progression and treatment. PMID:26590787
Economic evaluations of trastuzumab in HER2-positive metastatic breast cancer: a systematic review and critique.

PubMed

Parkinson, Bonny; Pearson, Sallie-Anne; Viney, Rosalie

2014-01-01

Published economic evaluations of trastuzumab for the treatment of HER2-positive metastatic breast cancer have arrived at different conclusions regarding the cost-effectiveness of trastuzumab, despite comparative efficacy being demonstrated by a small set of randomised controlled trials (RCTs). This article aims to provide insight into the quality of the evaluations and explore the possible drivers of the conflicting conclusions. A systematic literature review was conducted to identify all published economic evaluations that compared the incremental costs and outcomes of trastuzumab versus a comparator. Fifteen economic evaluations were identified. In the evaluations that estimated efficacy using an RCT, the key drivers of the conclusions regarding cost-effectiveness were: the approach used to estimate overall survival in the control group given crossover to trastuzumab following progression in the trials; the inclusion of treatment beyond progression; inclusion of wastage due to unused vial portions, adverse events, and the cost of HER2 testing. Four evaluations used non-randomised approaches to estimate efficacy, thus introducing the potential for confounding. As a result these evaluations reported relatively optimistic estimates of comparative effectiveness. Finally the evaluations used different thresholds to determine whether treatment with trastuzumab was cost-effective. There were numerous drivers of the different conclusions regarding the cost-effectiveness of trastuzumab, many of which are due to judgements made by the authors when translating data from RCTs. Many of the potential drivers were not identified by the published systematic reviews of economic evaluations and perhaps more remain unidentified because of inconsistent and limited reporting.
Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression.

PubMed

Feng, Shu; Shao, Longjiang; Yu, Wendong; Gavine, Paul; Ittmann, Michael

2012-07-15

Extensive correlative studies in human prostate cancer as well as studies in vitro and in mouse models indicate that fibroblast growth factor receptor (FGFR) signaling plays an important role in prostate cancer progression. In this study, we used a probe compound for an FGFR inhibitor, which potently inhibits FGFR-1-3 and significantly inhibits FGFR-4. The purpose of this study is to determine whether targeting FGFR signaling from all four FGFRs will have in vitro activities consistent with inhibition of tumor progression and will inhibit tumor progression in vivo. Effects of AZ8010 on FGFR signaling and invasion were analyzed using immortalized normal prostate epithelial (PNT1a) cells and PNT1a overexpressing FGFR-1 or FGFR-4. The effect of AZ8010 on invasion and proliferation in vitro was also evaluated in prostate cancer cell lines. Finally, the impact of AZ8010 on tumor progression in vivo was evaluated using a VCaP xenograft model. AZ8010 completely inhibits FGFR-1 and significantly inhibits FGFR-4 signaling at 100 nmol/L, which is an achievable in vivo concentration. This results in marked inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and invasion in PNT1a cells expressing FGFR-1 and FGFR-4 and all prostate cancer cell lines tested. Treatment in vivo completely inhibited VCaP tumor growth and significantly inhibited angiogenesis and proliferation and increased cell death in treated tumors. This was associated with marked inhibition of ERK phosphorylation in treated tumors. Targeting FGFR signaling is a promising new approach to treating aggressive prostate cancer.
Consideration of Rat Chronic Progressive Nephropathy in Regulatory Evaluations for Carcinogenicity

PubMed Central

Hard, Gordon C.

2013-01-01

Chronic progressive nephropathy (CPN) is a spontaneous renal disease of rats which can be a serious confounder in toxicology studies. It is a progressive disease with known physiological factors that modify disease progression, such as high dietary protein. The weight of evidence supports an absence of a renal counterpart in humans. There is extensive evidence that advanced CPN, particularly end-stage kidney, is a risk factor for development of a background incidence of atypical tubule hyperplasia and renal tubule tumors (RTT). The likely cause underlying this association with tubule neoplasia is the long-term increased tubule cell proliferation that occurs throughout CPN progression. As a variety of chemicals are able to exacerbate CPN, there is a potential for those exacerbating the severity up to and including end-stage kidney to cause a marginal increase in RTT and their precursor lesions. Extensive statistical analysis of National Toxicology Program studies shows a strong correlation between high-grade CPN, especially end-stage CPN, and renal tumor development. CPN as a mode of action (MOA) for rat RTT has received attention from regulatory authorities only recently. In the absence of toxic effects elsewhere, this does not constitute a carcinogenic effect of the chemical but can be addressed through a proposed MOA approach for regulatory purposes to reach a decision that RTT, developing as a result of CPN exacerbation in rats, have no relevance for human risk assessment. Guidelines are proposed for evaluation of exacerbation of CPN and RTT as a valid MOA for a given chemical. PMID:23104430
Distinguishing between statistical significance and practical/clinical meaningfulness using statistical inference.

PubMed

Wilkinson, Michael

2014-03-01

Decisions about support for predictions of theories in light of data are made using statistical inference. The dominant approach in sport and exercise science is the Neyman-Pearson (N-P) significance-testing approach. When applied correctly it provides a reliable procedure for making dichotomous decisions for accepting or rejecting zero-effect null hypotheses with known and controlled long-run error rates. Type I and type II error rates must be specified in advance and the latter controlled by conducting an a priori sample size calculation. The N-P approach does not provide the probability of hypotheses or indicate the strength of support for hypotheses in light of data, yet many scientists believe it does. Outcomes of analyses allow conclusions only about the existence of non-zero effects, and provide no information about the likely size of true effects or their practical/clinical value. Bayesian inference can show how much support data provide for different hypotheses, and how personal convictions should be altered in light of data, but the approach is complicated by formulating probability distributions about prior subjective estimates of population effects. A pragmatic solution is magnitude-based inference, which allows scientists to estimate the true magnitude of population effects and how likely they are to exceed an effect magnitude of practical/clinical importance, thereby integrating elements of subjective Bayesian-style thinking. While this approach is gaining acceptance, progress might be hastened if scientists appreciate the shortcomings of traditional N-P null hypothesis significance testing.
Energy conservation for pasteurizer apparatus

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

Huling, J.K.

In the pasteurizing of beverages in closed containers, the containers arrive generally in a chilled state and are progressively raised in temperature approaching the pasteurizing temperature and, after being pasteurized for an appropriate time, are progressively cooled down. Apparatus of this type is provided with a source of chilled water which is available for use when skips occur in the supply of the containers, the chilled water being accumulated from the incoming containers and from common outside sources. The accumulated water in its chilled state saves substantial amounts of energy by eliminating mechanical or other means to produce the chillmore » effect, and such source of water is constantly available under control which senses the presence of a skip in the supply of containers.« less
Designing and measuring the progress and impact of health research capacity strengthening initiatives

PubMed Central

2015-01-01

Strengthening capacity in poorer countries to generate multi-disciplinary health research and to utilise research findings, is one of the most effective ways of advancing the countries' health and development. This paper explores current knowledge about how to design health research capacity strengthening (RCS) programmes and how to measure their progress and impact. It describes a systematic, evidence-based approach for designing such programmes and highlights some of the key challenges that will be faced in the next 10 years. These include designing and implementing common frameworks to facilitate comparisons among capacity strengthening projects, and developing monitoring indicators that can capture their interactions with knowledge users and their impact on changes in health systems. PMID:28281707
Spatial distribution of nuclei in progressive nucleation: Modeling and application

NASA Astrophysics Data System (ADS)

Tomellini, Massimo

2018-04-01

Phase transformations ruled by non-simultaneous nucleation and growth do not lead to random distribution of nuclei. Since nucleation is only allowed in the untransformed portion of space, positions of nuclei are correlated. In this article an analytical approach is presented for computing pair-correlation function of nuclei in progressive nucleation. This quantity is further employed for characterizing the spatial distribution of nuclei through the nearest neighbor distribution function. The modeling is developed for nucleation in 2D space with power growth law and it is applied to describe electrochemical nucleation where correlation effects are significant. Comparison with both computer simulations and experimental data lends support to the model which gives insights into the transition from Poissonian to correlated nearest neighbor probability density.
Electroencephalogram and Alzheimer's Disease: Clinical and Research Approaches

PubMed Central

Tsolaki, Anthoula; Kazis, Dimitrios; Kompatsiaris, Ioannis; Kosmidou, Vasiliki; Tsolaki, Magda

2014-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by cognitive deficits, problems in activities of daily living, and behavioral disturbances. Electroencephalogram (EEG) has been demonstrated as a reliable tool in dementia research and diagnosis. The application of EEG in AD has a wide range of interest. EEG contributes to the differential diagnosis and the prognosis of the disease progression. Additionally such recordings can add important information related to the drug effectiveness. This review is prepared to form a knowledge platform for the project entitled “Cognitive Signal Processing Lab,” which is in progress in Information Technology Institute in Thessaloniki. The team tried to focus on the main research fields of AD via EEG and recent published studies. PMID:24868482
Do the Hard Things First: A Randomized Controlled Trial Testing the Effects of Exemplar Selection on Generalization Following Therapy for Grammatical Morphology

ERIC Educational Resources Information Center

Van Horne, Amanda Jean Owen; Fey, Marc; Curran, Maura

2017-01-01

Purpose: Complexity-based approaches to treatment have been gaining popularity in domains such as phonology and aphasia but have not yet been tested in child morphological acquisition. In this study, we examined whether beginning treatment with easier-to-inflect (easy first) or harder-to-inflect (hard first) verbs led to greater progress in the…
Frontiers of Engineering: Reports on Leading-Edge Engineering from the 2008 Symposium

DTIC Science & Technology

2009-07-07

article, we review recent progress on a highly 61 ROLL PRINTING OF CRYSTALliNE NANOWIRES efficient, scalable approach for the ordered, unifonn...NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medicine The National Academy of Sciences is a private, nonprofit, self...target delivery of a therapy to a particular physiological system, minimizing systemic side effects. Talks in the session provided an overview of

Use of a Tier 3 Evidence-Based Intervention with Progress Monitoring, Formative Assessment, and Student Goal-Setting: An Evaluation of the Immediate and Long-Term Effects on Student Reading Achievement

ERIC Educational Resources Information Center

McMasters, Angela B.

2011-01-01

Early identification and intervention for students at risk for reading failure is essential to establish the foundational skills necessary for students to become skilled readers. The focus on evidence-based practices and data-driven decision making leads educators to consider additional instructional approaches, such as formative assessment (FA)…
High-Throughput Functional Validation of Progression Drivers in Lung Adenocarcinoma

DTIC Science & Technology

2013-09-01

2) a novel molecular barcoding approach that facilitates cost- effective detection of driver events following in vitro and in vivo functional screens...aberration construction pipeline, which we named High-Throughput 3 Mutagenesis and Molecular Barcoding (HiTMMoB; Fig.1). We have therefore been able...lentiviral vector specially constructed for this project. This vector is compatible with our flexible molecular barcoding technology (Fig. 1), thus each
A Network Pharmacology Approach to Understanding the Mechanisms of Action of Traditional Medicine: Bushenhuoxue Formula for Treatment of Chronic Kidney Disease

PubMed Central

Zheng, Xiao-yong; Cao, Dong-sheng; Ye, Fa-qing; Xiang, Zheng

2014-01-01

Traditional Chinese medicine (TCM) has unique therapeutic effects for complex chronic diseases. However, for the lack of an effective systematic approach, the research progress on the effective substances and pharmacological mechanism of action has been very slow. In this paper, by incorporating network biology, bioinformatics and chemoinformatics methods, an integrated approach was proposed to systematically investigate and explain the pharmacological mechanism of action and effective substances of TCM. This approach includes the following main steps: First, based on the known drug targets, network biology was used to screen out putative drug targets; Second, the molecular docking method was used to calculate whether the molecules from TCM and drug targets related to chronic kidney diseases (CKD) interact or not; Third, according to the result of molecular docking, natural product-target network, main component-target network and compound-target network were constructed; Finally, through analysis of network characteristics and literature mining, potential effective multi-components and their synergistic mechanism were putatively identified and uncovered. Bu-shen-Huo-xue formula (BSHX) which was frequently used for treating CKD, was used as the case to demonstrate reliability of our proposed approach. The results show that BSHX has the therapeutic effect by using multi-channel network regulation, such as regulating the coagulation and fibrinolytic balance, and the expression of inflammatory factors, inhibiting abnormal ECM accumulation. Tanshinone IIA, rhein, curcumin, calycosin and quercetin may be potential effective ingredients of BSHX. This research shows that the integration approach can be an effective means for discovering active substances and revealing their pharmacological mechanisms of TCM. PMID:24598793
Inhibition of prostate cancer osteoblastic progression with VEGF121/rGel, a single agent targeting osteoblasts, osteoclasts, and tumor neovasculature

PubMed Central

Mohamedali, Khalid A.; Li, Zhi Gang; Starbuck, Michael W.; Wan, Xinhai; Yang, Jun; Kim, Sehoon; Zhang, Wendy; Rosenblum, Michael G.; Navone, Nora M.

2011-01-01

Purpose A hallmark of prostate cancer (PCa) progression is the development of osteoblastic bone metastases, which respond poorly to available therapies. We previously reported that VEGF121/rGel targets osteoclast precursors and tumor neovasculature. Here we tested the hypothesis that targeting non-tumor cells expressing these receptors can inhibit tumor progression in a clinically relevant model of osteoblastic PCa. Experimental Design Cells from MDA PCa 118b, a PCa xenograft obtained from a bone metastasis in a patient with castrate-resistant PCa, were injected into the femurs of mice. Osteoblastic progression was monitored following systemic administration of VEGF121/rGel. Results VEGF121/rGel was cytotoxic in vitro to osteoblast precursor cells. This cytotoxicity was specific as VEGF121/rGel internalization into osteoblasts was VEGF121 receptor driven. Furthermore, VEGF121/rGel significantly inhibited PCa-induced bone formation in a mouse calvaria culture assay. In vivo, VEGF121/rGel significantly inhibited the osteoblastic progression of PCa cells in the femurs of nude mice. Microcomputed tomography analysis revealed that VEGF121/rGel restored the bone volume fraction of tumor-bearing femurs to values similar to those of the contralateral (non–tumor bearing) femurs. VEGF121/rGel significantly reduced the number of tumor-associated osteoclasts but did not change the numbers of peritumoral osteoblasts. Importantly, VEGF121/rGel-treated mice had significantly less tumor burden than control mice. Our results thus indicate that VEGF121/rGel inhibits osteoblastic tumor progression by targeting angiogenesis, osteoclastogenesis, and bone formation. Conclusions Targeting VEGFR-1 – or VEGFR-2–expressing cells is effective in controlling the osteoblastic progression of PCa in bone. These findings provide the basis for an effective multitargeted approach for metastatic PCa. PMID:21343372
Patterns of Progressive Ganglion Cell-Inner Plexiform Layer Thinning in Glaucoma Detected by OCT.

PubMed

Shin, Joong Won; Sung, Kyung Rim; Park, Sun-Won

2018-04-25

To investigate the spatial characteristics and patterns of progressive macular ganglion cell-inner plexiform layer (GCIPL) thinning in glaucomatous eyes assessed by OCT Guided Progression Analysis (GPA). Longitudinal, retrospective, observational study. Two hundred ninety-two eyes of 192 patients with primary open-angle glaucoma with a mean follow-up of 6.0 years (range, 3.2-8.1 years) were included. Macular GCIPL imaging and visual field (VF) examination were performed at 6-month intervals for 3 years or more. Progressive GCIPL thinning was evaluated by a Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) GPA device. Spatial characteristics of progressive GCIPL thinning were assessed by the GCIPL thickness change map. The pattern of progressive GCIPL thinning was evaluated by comparing the baseline GCIPL thickness deviation map and the final GCIPL thickness change map. Visual field progression was determined by Early Manifest Glaucoma Trial criteria and linear regression of the VF index. Spatial characteristics and patterns of progressive GCIPL thinning. Seventy-two eyes of 62 participants (24.7% [72/292]) showed progressive GCIPL thinning in the GCIPL thickness change map. Progressive GCIPL thinning was detected most frequently (25.0%) at 2.08 mm from the fovea, and it extended in an arcuate shape in the inferotemporal region (250°-339°). Compared with the baseline GCIPL defects, the progressive GCIPL thinning extended toward the fovea and optic disc. The most common pattern of progressive GCIPL thinning was widening of GCIPL defects (42 eyes [58.3%]), followed by deepening of GCIPL defects (19 eyes [26.4%]) and newly developed GCIPL defects (15 eyes [20.8%]). Visual field progression was accompanied by progressive GCIPL thinning in 41 of 72 eyes (56.9%). Progressive GCIPL thinning preceded (61.0% [25/41]) or occurred concomitantly with (21.9% [9/41]) VF progression. The use of OCT GPA maps offers an effective approach to evaluate the topographic patterns of progressive GCIPL thinning in glaucomatous eyes. Progression of GCIPL thinning occurred before apparent progression on standard automated perimetry in most glaucomatous eyes. Understanding specific patterns and sequences of macular damage may provide important insights in the monitoring of glaucomatous progression. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Treatment of progressive multiple sclerosis: what works, what does not, and what is needed.

PubMed

Feinstein, Anthony; Freeman, Jenny; Lo, Albert C

2015-02-01

Disease-modifying drugs have mostly failed as treatments for progressive multiple sclerosis. Management of the disease therefore solely aims to minimise symptoms and, if possible, improve function. The degree to which this approach is based on empirical data derived from studies of progressive disease or whether treatment decisions are based on what is known about relapsing-remitting disease remains unclear. Symptoms rated as important by patients with multiple sclerosis include balance and mobility impairments, weakness, reduced cardiovascular fitness, ataxia, fatigue, bladder dysfunction, spasticity, pain, cognitive deficits, depression, and pseudobulbar affect; a comprehensive literature search shows a notable paucity of studies devoted solely to these symptoms in progressive multiple sclerosis, which translates to few proven therapeutic options in the clinic. A new strategy that can be used in future rehabilitation trials is therefore needed, with the adoption of approaches that look beyond single interventions to concurrent, potentially synergistic, treatments that maximise what remains of neural plasticity in patients with progressive multiple sclerosis. Copyright © 2015 Elsevier Ltd. All rights reserved.
Evidence-based interventions for preventing substance use disorders in adolescents.

PubMed

Griffin, Kenneth W; Botvin, Gilbert J

2010-07-01

Substantial progress has been made in developing prevention programs for adolescent drug abuse. The most effective interventions target salient risk and protective factors at the individual, family, and community levels and are guided by relevant psychosocial theories regarding the etiology of substance use and abuse. This article reviews the epidemiology, etiologic risk and protective factors, and evidence-based approaches that have been found to be most effective in preventing adolescent substance use and abuse. Exemplary school- and family-based prevention programs for universal (everyone in population), selected (members of at-risk groups), and indicated (at-risk individuals) target populations are reviewed, along with model community-based prevention approaches. Challenges remain in widely disseminating evidence-based prevention programs into schools, families, and communities. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Evidence-Based Interventions for Preventing Substance Use Disorders in Adolescents

PubMed Central

Griffin, Kenneth W.; Botvin, Gilbert J.

2010-01-01

Synopsis Substantial progress has been made in developing prevention programs for adolescent drug abuse. The most effective interventions target salient risk and protective factors at the individual, family, and/or community levels and are guided by relevant psychosocial theories regarding the etiology of substance use and abuse. This article reviews the epidemiology, etiologic risk and protective factors, and evidence-based approaches that have been found to be most effective in preventing adolescent substance use and abuse. Exemplary school and family-based prevention programs for universal (everyone in population), selected (members of at-risk groups), and indicated (at-risk individuals) target populations are reviewed, along with model community-based prevention approaches. Challenges remain in widely disseminating evidence-based prevention programs into schools, families, and communities. PMID:20682218
Modeling Creep Effects in Advanced SiC/SiC Composites

NASA Technical Reports Server (NTRS)

Lang, Jerry; DiCarlo, James

2006-01-01

Because advanced SiC/SiC composites are projected to be used for aerospace components with large thermal gradients at high temperatures, efforts are on-going at NASA Glenn to develop approaches for modeling the anticipated creep behavior of these materials and its subsequent effects on such key composite properties as internal residual stress, proportional limit stress, ultimate tensile strength, and rupture life. Based primarily on in-plane creep data for 2D panels, this presentation describes initial modeling progress at applied composite stresses below matrix cracking for some high performance SiC/SiC composite systems recently developed at NASA. Studies are described to develop creep and rupture models using empirical, mechanical analog, and mechanistic approaches, and to implement them into finite element codes for improved component design and life modeling
Targeting myeloid-derived suppressor cells for cancer immunotherapy.

PubMed

Liu, Yijun; Wei, Guowei; Cheng, Wesley A; Dong, Zhenyuan; Sun, Han; Lee, Vincent Y; Cha, Soung-Chul; Smith, D Lynne; Kwak, Larry W; Qin, Hong

2018-05-31

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with an immune suppressive phenotype. They represent a critical component of the immune suppressive niche described in cancer, where they support immune escape and tumor progression through direct effects on both the innate and adaptive immune responses, largely by contributing to maintenance of a high oxidative stress environment. The number of MDSCs positively correlates with protumoral activity, and often diminishes the effectiveness of immunotherapies, which is particularly problematic with the emergence of personalized medicine. Approaches targeting MDSCs showed promising results in preclinical studies and are under active investigation in clinical trials in combination with various immune checkpoint inhibitors. In this review, we discuss MDSC targets and therapeutic approaches targeting MDSC that have the aim of enhancing the existing tumor therapies.
Modeling and Simulation of Nanoindentation

NASA Astrophysics Data System (ADS)

Huang, Sixie; Zhou, Caizhi

2017-11-01

Nanoindentation is a hardness test method applied to small volumes of material which can provide some unique effects and spark many related research activities. To fully understand the phenomena observed during nanoindentation tests, modeling and simulation methods have been developed to predict the mechanical response of materials during nanoindentation. However, challenges remain with those computational approaches, because of their length scale, predictive capability, and accuracy. This article reviews recent progress and challenges for modeling and simulation of nanoindentation, including an overview of molecular dynamics, the quasicontinuum method, discrete dislocation dynamics, and the crystal plasticity finite element method, and discusses how to integrate multiscale modeling approaches seamlessly with experimental studies to understand the length-scale effects and microstructure evolution during nanoindentation tests, creating a unique opportunity to establish new calibration procedures for the nanoindentation technique.
Improving comprehension in adolescents with severe receptive language impairments: a randomized control trial of intervention for coordinating conjunctions.

PubMed

Ebbels, Susan H; Marić, Nataša; Murphy, Aoife; Turner, Gail

2014-01-01

Little evidence exists for the effectiveness of therapy for children with receptive language difficulties, particularly those whose difficulties are severe and persistent. To establish the effectiveness of explicit speech and language therapy with visual support for secondary school-aged children with language impairments focusing on comprehension of coordinating conjunctions in a randomized control trial with an assessor blind to group status. Fourteen participants (aged 11;3-16;1) with severe RELI (mean standard scores: CELF4 ELS = 48, CELF4 RLS = 53 and TROG-2 = 57), but higher non-verbal (Matrices = 83) and visual perceptual skills (Test of Visual Perceptual Skills (TVPS) = 86) were randomly assigned to two groups: therapy versus waiting controls. In Phase 1, the therapy group received eight 30-min individual sessions of explicit teaching with visual support (Shape Coding) with their usual SLT. In Phase 2, the waiting controls received the same therapy. The participants' comprehension was tested pre-, post-Phase 1 and post-Phase 2 therapy on (1) a specific test of the targeted conjunctions, (2) the TROG-2 and (3) a test of passives. After Phase 1, the therapy group showed significantly more progress than the waiting controls on the targeted conjunctions (d = 1.6) and overall TROG-2 standard score (d = 1.4). The two groups did not differ on the passives test. After Phase 2, the waiting controls made similar progress to those in the original therapy group, who maintained their previous progress. Neither group showed progress on passives. When the two groups were combined, significant progress was found on the specific conjunctions (d = 1.3) and TROG-2 raw (d = 1.1) and standard scores (d = 0.9). Correlations showed no measures taken (including Matrices and TVPS) correlated significantly with progress on the targeted conjunctions or the TROG-2. Four hours of Shape Coding therapy led to significant gains on comprehension of coordinating conjunctions which were maintained after 4 months. Given the significant progress at a group level and the lack of reliable predictors of progress, this approach could be offered to other children with similar difficulties to the participants. However, the intervention was delivered one-to-one by speech and language therapists, thus the effectiveness of this therapy method with other methods of delivery remains to be evaluated. © 2013 Royal College of Speech and Language Therapists.
Research progress of surfactant

NASA Astrophysics Data System (ADS)

Zheng, Minyi; Mo, Lingyun; Qin, Ruqiong; Liang, Liying; Zhang, Fan

2017-01-01

With the rapid development of surfactant and the large growing use of the materials, the safety of surfactant may be a problem that draw worldwide attention. The surfactant can be discharged into environment through various approach and may cause toxic effects in organism. This paper reviews the environmental effects of surfactant materials for plants and animals, and raises some questions by describing the results of environmental toxicology. We put it that it is a great significant of promote the sustainable development of surfactant industry through a comprehensive understanding of surfactant environmental safety.
Nicotine and Tobacco as Substances of Abuse in Children and Adolescents.

PubMed

Siqueira, Lorena M

2017-01-01

Nicotine is the primary pharmacologic component of tobacco, and users of tobacco products seek out its effects. The highly addictive nature of nicotine is responsible for its widespread use and difficulty with quitting. This technical report focuses on nicotine and discusses the stages of use in progression to dependence on nicotine-containing products; the physiologic characteristics, neurobiology, metabolism, pharmacogenetics, and health effects of nicotine; and acute nicotine toxicity. Finally, some newer approaches to cessation are noted. Copyright © 2017 by the American Academy of Pediatrics.
Machine learning-based method for personalized and cost-effective detection of Alzheimer's disease.

PubMed

Escudero, Javier; Ifeachor, Emmanuel; Zajicek, John P; Green, Colin; Shearer, James; Pearson, Stephen

2013-01-01

Diagnosis of Alzheimer's disease (AD) is often difficult, especially early in the disease process at the stage of mild cognitive impairment (MCI). Yet, it is at this stage that treatment is most likely to be effective, so there would be great advantages in improving the diagnosis process. We describe and test a machine learning approach for personalized and cost-effective diagnosis of AD. It uses locally weighted learning to tailor a classifier model to each patient and computes the sequence of biomarkers most informative or cost-effective to diagnose patients. Using ADNI data, we classified AD versus controls and MCI patients who progressed to AD within a year, against those who did not. The approach performed similarly to considering all data at once, while significantly reducing the number (and cost) of the biomarkers needed to achieve a confident diagnosis for each patient. Thus, it may contribute to a personalized and effective detection of AD, and may prove useful in clinical settings.
Face Aging Effect Simulation Using Hidden Factor Analysis Joint Sparse Representation.

PubMed

Yang, Hongyu; Huang, Di; Wang, Yunhong; Wang, Heng; Tang, Yuanyan

2016-06-01

Face aging simulation has received rising investigations nowadays, whereas it still remains a challenge to generate convincing and natural age-progressed face images. In this paper, we present a novel approach to such an issue using hidden factor analysis joint sparse representation. In contrast to the majority of tasks in the literature that integrally handle the facial texture, the proposed aging approach separately models the person-specific facial properties that tend to be stable in a relatively long period and the age-specific clues that gradually change over time. It then transforms the age component to a target age group via sparse reconstruction, yielding aging effects, which is finally combined with the identity component to achieve the aged face. Experiments are carried out on three face aging databases, and the results achieved clearly demonstrate the effectiveness and robustness of the proposed method in rendering a face with aging effects. In addition, a series of evaluations prove its validity with respect to identity preservation and aging effect generation.
A Bayesian Network Approach to Modeling Learning Progressions and Task Performance. CRESST Report 776

ERIC Educational Resources Information Center

West, Patti; Rutstein, Daisy Wise; Mislevy, Robert J.; Liu, Junhui; Choi, Younyoung; Levy, Roy; Crawford, Aaron; DiCerbo, Kristen E.; Chappel, Kristina; Behrens, John T.

2010-01-01

A major issue in the study of learning progressions (LPs) is linking student performance on assessment tasks to the progressions. This report describes the challenges faced in making this linkage using Bayesian networks to model LPs in the field of computer networking. The ideas are illustrated with exemplar Bayesian networks built on Cisco…
[Individual Progress Program for the Extremely Gifted Student in the Greater Seattle Area.

ERIC Educational Resources Information Center

Norsen, Barbara G.; Wick, Christine

The Individual Progress Program (IPP) is an approach designed to serve extremely advanced gifted students (grades 1 through 9) in the Seattle area. IPP is intended to meet students' unmet educational needs by allowing them to progress at their own accelerated pace through a broadly based curriculum while also pursuing interest areas. The program…
Progressive Education and the Case of a Bilingual Palestinian-Arab and Jewish Co-Existence School in Israel

ERIC Educational Resources Information Center

Arar, Khalid; Massry-Herzalah, Asmahan

2017-01-01

The purpose of this paper is to exemplify a "grass-roots" change based on Dewey's experimental progressive education model employed in the "Bridge over the Valley" bilingual school, a Palestinian-Arab and Jewish school in Israel. In order to identify the progressive "approach" underlying this change, the…
Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

NASA Astrophysics Data System (ADS)

Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

Management of sexual problems: the approach of mindfulness.

PubMed

Vilarinho, Sandra

2017-11-01

During the last 10 years mindfulness has been progressively integrated into protocols for the management of sexual problems. The purpose of this study is to systematize potential benefits of mindfulness in sexual well-being (considering mind, emotion, and body), and to shortly review current applications and effectiveness of mindfulness-based interventions to the treatment of sexual problems. The majority of evidence available focuses on women's sexual desire and arousal problems, although there are also preliminary findings for the effectiveness of mindfulness-based interventions in enhancing other components of the sexual response. Relationship issues, sexual pain, sexual abuse, and sexual distress have also revealed to benefit from mindfulness-based interventions. The practice of mindfulness is a promising clinical approach with encouraging results for women's sexual problems. Further empirical research with different populations and greater methodological rigour is still needed to clarify the effectiveness of mindfulness as a specific component and the mechanisms contributing to therapeutic change.
Environmental Engineering Approaches toward Sustainable Management of Spider Mites.

PubMed

Suzuki, Takeshi

2012-10-26

Integrated pest management (IPM), which combines physical, biological, and chemical control measures to complementary effect, is one of the most important approaches to environmentally friendly sustainable agriculture. To expand IPM, we need to develop new pest control measures, reinforce existing measures, and investigate interactions between measures. Continued progress in the development of environmental control technologies and consequent price drops have facilitated their integration into plant production and pest control. Here I describe environmental control technologies for the IPM of spider mites through: (1) the disturbance of photoperiod-dependent diapause by artificial light, which may lead to death in seasonal environments; (2) the use of ultraviolet radiation to kill or repel mites; and (3) the use of water vapor control for the long-term cold storage of commercially available natural enemies. Such environmental control technologies have great potential for the efficient control of spider mites through direct physical effects and indirect effects via natural enemies.
Environmental Engineering Approaches toward Sustainable Management of Spider Mites

PubMed Central

Suzuki, Takeshi

2012-01-01

Integrated pest management (IPM), which combines physical, biological, and chemical control measures to complementary effect, is one of the most important approaches to environmentally friendly sustainable agriculture. To expand IPM, we need to develop new pest control measures, reinforce existing measures, and investigate interactions between measures. Continued progress in the development of environmental control technologies and consequent price drops have facilitated their integration into plant production and pest control. Here I describe environmental control technologies for the IPM of spider mites through: (1) the disturbance of photoperiod-dependent diapause by artificial light, which may lead to death in seasonal environments; (2) the use of ultraviolet radiation to kill or repel mites; and (3) the use of water vapor control for the long-term cold storage of commercially available natural enemies. Such environmental control technologies have great potential for the efficient control of spider mites through direct physical effects and indirect effects via natural enemies. PMID:26466730
The evaluation of clinical and cost outcomes associated with earlier initiation of insulin in patients with type 2 diabetes mellitus.

PubMed

Smolen, Harry J; Murphy, Daniel R; Gahn, James C; Yu, Xueting; Curtis, Bradley H

2014-09-01

The treatment for patients with type 2 diabetes mellitus (T2DM) follows a stepwise progression. As a treatment loses its effectiveness, it is typically replaced with a more complex and frequently more costly treatment. Eventually this progression leads to the use of basal insulin typically with concomitant treatments (e.g., metformin, a GLP-1 RA [glucagon-like peptide-1 receptor agonist], a TZD [thiazolidinedione] or a DPP-4i [dipeptidyl peptidase 4 inhibitor]) and, ultimately, to basal-bolus insulin in some forms. As the cost of oral antidiabetics (OADs) and noninsulin injectables have approached, and in some cases exceeded, the cost of insulin, we reexamined the placement of insulin in T2DM treatment progression. Our hypothesis was that earlier use of insulin produces clinical and cost benefits due to its superior efficacy and treatment scalability at an acceptable cost when considered over a 5-year period. To (a) estimate clinical and payer cost outcomes of initiating insulin treatment for patients with T2DM earlier in their treatment progression and (b) estimate clinical and payer cost outcomes resulting from delays in escalating treatment for T2DM when indicated by patient hemoglobin A1c levels. We developed a Monte Carlo microsimulation model to estimate patients reaching target A1c, diabetes-related complications, mortality, and associated costs under various treatment strategies for newly diagnosed patients with T2DM. Treatment efficacies were modeled from results of randomized clinical trials, including the time and rate of A1c drift. A typical treatment progression was selected based on the American Diabetes Association and the European Association for the Study of Diabetes guidelines as the standard of care (SOC). Two treatment approaches were evaluated: two-stage insulin (basal plus antidiabetics followed by biphasic plus metformin) and single-stage insulin (biphasic plus metformin). For each approach, we analyzed multiple strategies. For each analysis, treatment steps were sequentially and cumulatively removed from the SOC until only the insulin steps remained. Delays in escalating treatment were evaluated by increasing the minimum time on a treatment within each strategy. The analysis time frame was 5 years. Relative to SOC, the two-stage insulin approach resulted in 0.10% to 1.79% more patients achieving target A1c (<7.0%), at incremental costs of $95 to $3,267. (The ranges are due to the different strategies within the approach.) With the single-stage approach, 0.50% to 2.63% more patients achieved the target A1c compared with SOC at an incremental cost of -$1,642 to $1,177. Major diabetes-related complications were reduced by 0.38% to 17.46% using the two-stage approach and 0.72% to 25.92% using the single-stage approach. Severe hypoglycemia increased by 17.97% to 60.43% using the two-stage approach and 6.44% to 68.87% using the single-stage approach. In the base case scenario, the minimum time on a specific treatment was 3 months. When the minimum time on each treatment was increased to 12 months (i.e., delayed), patients reaching A1c targets were reduced by 57%, complications increased by 13% to 76%, and mortality increased by 8% over 5 years when compared with the base case for the SOC. However, severe hypoglycemic events were reduced by 83%. As insulin was advanced earlier in therapy in the two-stage and single-stage approaches, patients reaching their A1c targets increased, severe hypoglycemic events increased, and diabetes-related complications and mortality decreased. Cost savings were estimated for 3 (of 4) strategies in the single-stage approach. Delays in treatment escalation substantially reduced patients reaching target A1c levels and increased the occurrence of major nonhypoglycemic diabetic complications. With the exception of substantial increases in severe hypoglycemic events, earlier use of insulin mitigates the clinical consequences of these delays.
A Cluster Randomized Controlled Trial of an Adolescent HIV Prevention Program among Bahamian Youth: Effect at 12 Months Post-Intervention

PubMed Central

Chen, Xinguang; Lunn, Sonya; Deveaux, Lynette; Li, Xioaming; Brathwaite, Nanika; Cottrell, Lesley; Stanton, Bonita

2014-01-01

Background Behavioral interventions based on the Protection Motivation Theory (PMT) have been demonstrated to reduce HIV risk behavior among mid- and older adolescents in different settings across the globe but have not been evaluated among Caribbean nations and have received limited evaluation among pre-adolescents. Objective To determine 1) the effectiveness among pre-adolescents in The Bahamas of a PMT-based HIV prevention program “Focus on Youth in the Caribbean” (FOYC) and 2) the role of the targeted PMT constructs in intervention effect. Methods 1,360 sixth grade youth (10-11 years of age) from 15 urban schools in New Providence, The Bahamas were randomized by school to receive either FOYC or a control condition. Data collected at baseline, six and 12 months post intervention were analyzed. A five-step scheme was used to assess sexual behavior progression, ranging from “1” = “a virgin without intention to have sex” to” 5″ = “having sex without a condom”. Group-based trajectory analysis was utilized in assessing the program effect. Results Two sexual behavior progression patterns were detected: slow progressors and quick progressors. Receiving FOYC reduced the likelihood for adolescents to become quick progressors (adjusted OR = 0.77, 95% CI: 0.64-1.00). The observed effectiveness was especially impacted by a subset of the targeted PMT constructs. Conclusion FOYC effectively delays sexual risk among Bahamian pre-adolescents. The group-based trajectory analysis provides an analytical approach for assessing interventions among adolescents with low rates and diverse progression patterns of sexual activity. PMID:19116781
In-Situ NDE Characterization of Kevlar and Carbon Composite Micromechanics for Improved COPV Health Monitoring

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.

2009-01-01

This project is a subtask of a multi-center project to advance the state-of-the-art by developing NDE techniques that are capable of evaluating stress rupture (SR) degradation in Kevlar/epoxy (K/Ep) composite overwrapped pressure vessels (COPVs), and damage progression in carbon/epoxy (C/Ep) COPVs. In this subtask, acoustic emission (AE) data acquired during intermittent load hold tensile testing of K/Ep and C/Ep composite tow materials-of-construction used in COPV fabrication were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of composite tow was gained by monitoring AE event rate, energy, source location, and frequency. Source location based on arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to background and grip noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio < 1.0) with damage accumulation.
Intricate interplay between astrocytes and motor neurons in ALS

PubMed Central

Phatnani, Hemali P.; Guarnieri, Paolo; Friedman, Brad A.; Carrasco, Monica A.; Muratet, Michael; O’Keeffe, Sean; Nwakeze, Chiamaka; Pauli-Behn, Florencia; Newberry, Kimberly M.; Meadows, Sarah K.; Tapia, Juan Carlos; Myers, Richard M.; Maniatis, Tom

2013-01-01

ALS results from the selective and progressive degeneration of motor neurons. Although the underlying disease mechanisms remain unknown, glial cells have been implicated in ALS disease progression. Here, we examine the effects of glial cell/motor neuron interactions on gene expression using the hSOD1G93A (the G93A allele of the human superoxide dismutase gene) mouse model of ALS. We detect striking cell autonomous and nonautonomous changes in gene expression in cocultured motor neurons and glia, revealing that the two cell types profoundly affect each other. In addition, we found a remarkable concordance between the cell culture data and expression profiles of whole spinal cords and acutely isolated spinal cord cells during disease progression in the G93A mouse model, providing validation of the cell culture approach. Bioinformatics analyses identified changes in the expression of specific genes and signaling pathways that may contribute to motor neuron degeneration in ALS, among which are TGF-β signaling pathways. PMID:23388633
Targeting the GM-CSF receptor for the treatment of CNS autoimmunity

PubMed Central

Ifergan, Igal; Davidson, Todd S.; Kebir, Hania; Xu, Dan; Palacios-Macapagal, Daphne; Cann, Jennifer; Rodgers, Jane M.; Hunter, Zoe N.; Pittet, Camille L.; Beddow, Sara; Jones, Clare A.; Prat, Alexandre; Sleeman, Matthew A.; Miller, Stephen D.

2017-01-01

In multiple sclerosis (MS), there is a growing interest in inhibiting the pro-inflammatory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to evaluate the therapeutic potential and underlying mechanisms of GM-CSF receptor alpha (Rα) blockade in animal models of MS. We show that GM-CSF signaling inhibition at peak of chronic experimental autoimmune encephalomyelitis (EAE) results in amelioration of disease progression. Similarly, GM-CSF Rα blockade in relapsing-remitting (RR)-EAE model prevented disease relapses and inhibited T cell responses specific for both the inducing and spread myelin peptides, while reducing activation of mDCs and inflammatory monocytes. In situ immunostaining of lesions from human secondary progressive MS (SPMS), but not primary progressive MS patients shows extensive recruitment of GM-CSF Rα+ myeloid cells. Collectively, this study reveals a pivotal role of GM-CSF in disease relapses and the benefit of GM-CSF Rα blockade as a potential novel therapeutic approach for treatment of RRMS and SPMS. PMID:28641926
Targeting the GM-CSF receptor for the treatment of CNS autoimmunity.

PubMed

Ifergan, Igal; Davidson, Todd S; Kebir, Hania; Xu, Dan; Palacios-Macapagal, Daphne; Cann, Jennifer; Rodgers, Jane M; Hunter, Zoe N; Pittet, Camille L; Beddow, Sara; Jones, Clare A; Prat, Alexandre; Sleeman, Matthew A; Miller, Stephen D

2017-11-01

In multiple sclerosis (MS), there is a growing interest in inhibiting the pro-inflammatory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to evaluate the therapeutic potential and underlying mechanisms of GM-CSF receptor alpha (Rα) blockade in animal models of MS. We show that GM-CSF signaling inhibition at peak of chronic experimental autoimmune encephalomyelitis (EAE) results in amelioration of disease progression. Similarly, GM-CSF Rα blockade in relapsing-remitting (RR)-EAE model prevented disease relapses and inhibited T cell responses specific for both the inducing and spread myelin peptides, while reducing activation of mDCs and inflammatory monocytes. In situ immunostaining of lesions from human secondary progressive MS (SPMS), but not primary progressive MS patients shows extensive recruitment of GM-CSF Rα + myeloid cells. Collectively, this study reveals a pivotal role of GM-CSF in disease relapses and the benefit of GM-CSF Rα blockade as a potential novel therapeutic approach for treatment of RRMS and SPMS. Copyright © 2017 Elsevier Ltd. All rights reserved.
Country actions to meet UN commitments on non-communicable diseases: a stepwise approach.

PubMed

Bonita, Ruth; Magnusson, Roger; Bovet, Pascal; Zhao, Dong; Malta, Deborah C; Geneau, Robert; Suh, Il; Thankappan, Kavumpurathu Raman; McKee, Martin; Hospedales, James; de Courten, Maximilian; Capewell, Simon; Beaglehole, Robert

2013-02-16

Strong leadership from heads of state is needed to meet national commitments to the UN political declaration on non-communicable diseases (NCDs) and to achieve the goal of a 25% reduction in premature NCD mortality by 2025 (the 25 by 25 goal). A simple, phased, national response to the political declaration is suggested, with three key steps: planning, implementation, and accountability. Planning entails mobilisation of a multisectoral response to develop and support the national action plan, and to build human, financial, and regulatory capacity for change. Implementation of a few priority and feasible cost-effective interventions for the prevention and treatment of NCDs will achieve the 25 by 25 goal and will need only few additional financial resources. Accountability incorporates three dimensions: monitoring of progress, reviewing of progress, and appropriate responses to accelerate progress. A national NCD commission or equivalent, which is independent of government, is needed to ensure that all relevant stakeholders are held accountable for the UN commitments to NCDs. Copyright © 2013 Elsevier Ltd. All rights reserved.
Cutaneous progressive angiomatosis on the muzzle of a dog, treated by laser photocoagulation therapy.

PubMed

Olivieri, Lara; Nardini, Giordano; Pengo, Graziano; Abramo, Francesca

2010-10-01

A 10-year old, female, cocker spaniel was presented with a bleeding lesion on the muzzle and nasal planum observed initially as a small raised nodule at 1 year of age. This became clinically more pronounced at 5 years of age, progressively enlarged thereafter and was diagnosed initially as a vascular tumour. On clinical examination, multiple confluent nodules of variable diameter (0.5-1.5 cm) deformed the outline of the nose. Histological examination revealed a progressive angiomatosis with multifocal infiltrative growth of increased dermal vascularization with different sized and type of anastomosing vessels lined by a monolayer of reactive endothelium, often arranged as papillary projections into the lumina. Partial nosectomy, the first therapeutic approach, was unsuccessful and the lesion relapsed within 6 months. However, subsequent laser photocoagulation therapy provided a good cosmetic outcome, no relapse 1 year later, and appeared to provide an effective alternative to ablation surgery. © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.
Progressive Fracture of Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon

2001-01-01

This report includes the results of a research in which the COmposite Durability STRuctural ANalysis (CODSTRAN) computational simulation capabilities were augmented and applied to various structures for demonstration of the new features and verification. The first chapter of this report provides an introduction to the computational simulation or virtual laboratory approach for the assessment of damage and fracture progression characteristics in composite structures. The second chapter outlines the details of the overall methodology used, including the failure criteria and the incremental/iterative loading procedure with the definitions of damage, fracture, and equilibrium states. The subsequent chapters each contain an augmented feature of the code and/or demonstration examples. All but one of the presented examples contains laminated composite structures with various fiber/matrix constituents. For each structure simulated, damage initiation and progression mechanisms are identified and the structural damage tolerance is quantified at various degradation stages. Many chapters contain the simulation of defective and defect free structures to evaluate the effects of existing defects on structural durability.
Recent progresses in gene delivery-based bone tissue engineering.

PubMed

Lu, Chia-Hsin; Chang, Yu-Han; Lin, Shih-Yeh; Li, Kuei-Chang; Hu, Yu-Chen

2013-12-01

Gene therapy has converged with bone engineering over the past decade, by which a variety of therapeutic genes have been delivered to stimulate bone repair. These genes can be administered via in vivo or ex vivo approach using either viral or nonviral vectors. This article reviews the fundamental aspects and recent progresses in the gene therapy-based bone engineering, with emphasis on the new genes, viral vectors and gene delivery approaches. © 2013.
From novice to master surgeon: improving feedback with a descriptive approach to intraoperative assessment.

PubMed

Huang, Emily; Wyles, Susannah M; Chern, Hueylan; Kim, Edward; O'Sullivan, Patricia

2016-07-01

A developmental and descriptive approach to assessing trainee intraoperative performance was explored. Semistructured interviews with 20 surgeon educators were recorded, transcribed, deidentified, and analyzed using a grounded theory approach to identify emergent themes. Two researchers independently coded the transcripts. Emergent themes were also compared to existing theories of skill acquisition. Surgeon educators characterized intraoperative surgical performance as an integrated practice of multiple skill categories and included anticipating, planning for contingencies, monitoring progress, self-efficacy, and "working knowledge." Comments concerning progression through stages, broadly characterized as "technician," "anatomist," "anticipator," "strategist," and "executive," formed a narrative about each stage of development. The developmental trajectory with narrative, descriptive profiles of surgeons working toward mastery provide a standardized vocabulary for communicating feedback, while fostering reflection on trainee progress. Viewing surgical performance as integrated practice rather than the conglomerate of isolated skills enhances authentic assessment. Copyright © 2015 Elsevier Inc. All rights reserved.
Rethinking traditional methods for measuring intellectual capital.

PubMed

Corso, John A

2007-01-01

Historically, approaches to measuring intellectual capital have included both conventional accounting-based measures, such as variants of the market-to-book ratio, and more progressive measures, such as the measurement of intangible assets found in approaches such as the Balanced Scorecard and Human Resource Accounting. As greater emphasis is placed on intellectual capital and its various aspects in the continually growing service and knowledge economy, the use of assessment instruments to inventory the alignment, balance, and variety of intellectual capacities and metrics that assess the effectiveness of succession planning may represent new directions in which organizations can head in the measurement of this important construct.
Killing the hypnozoite – drug discovery approaches to prevent relapse in Plasmodium vivax

PubMed Central

Campo, Brice; Vandal, Omar; Wesche, David L.; Burrows, Jeremy N.

2015-01-01

The eradication of malaria will only be possible if effective, well-tolerated medicines kill hypnozoites in vivax and ovale malaria, and thus prevent relapses in patients. Despite progress in the 8-aminoquinoline series, with tafenoquine in Phase III showing clear benefits over primaquine, the drug discovery challenge to identify hypnozoiticidal or hypnozoite-activating compounds has been hampered by the dearth of biological tools and assays, which in turn has been limited by the immense scientific and logistical challenges associated with accessing relevant human tissue and sporozoites. This review summarises the existing drug discovery series and approaches concerning the goal to block relapse. PMID:25891812
Killing the hypnozoite--drug discovery approaches to prevent relapse in Plasmodium vivax.

PubMed

Campo, Brice; Vandal, Omar; Wesche, David L; Burrows, Jeremy N

2015-05-01

The eradication of malaria will only be possible if effective, well-tolerated medicines kill hypnozoites in vivax and ovale malaria, and thus prevent relapses in patients. Despite progress in the 8-aminoquinoline series, with tafenoquine in Phase III showing clear benefits over primaquine, the drug discovery challenge to identify hypnozoiticidal or hypnozoite-activating compounds has been hampered by the dearth of biological tools and assays, which in turn has been limited by the immense scientific and logistical challenges associated with accessing relevant human tissue and sporozoites. This review summarises the existing drug discovery series and approaches concerning the goal to block relapse.
Nanoparticle Approaches against Bacterial Infections

PubMed Central

Gao, Weiwei; Thamphiwatana, Soracha; Angsantikul, Pavimol; Zhang, Liangfang

2014-01-01

Despite the wide success of antibiotics, the treatment of bacterial infection still faces significant challenges, particularly the emergence of antibiotic resistance. As a result, nanoparticle drug delivery platforms including liposomes, polymeric nanoparticles, dendrimers, and various inorganic nanoparticles have been increasingly exploited to enhance the therapeutic effectiveness of existing antibiotics. This review focuses on areas where nanoparticle approaches hold significant potential to advance the treatment of bacterial infection. These areas include targeted antibiotic delivery, environmentally responsive antibiotic delivery, combinatorial antibiotic delivery, nanoparticle-enabled antibacterial vaccination, and nanoparticle-based bacterial detection. In each area we highlight the innovative antimicrobial nanoparticle platforms and review their progress made against bacterial infections. PMID:25044325
PACE4 inhibitors and their peptidomimetic analogs block prostate cancer tumor progression through quiescence induction, increased apoptosis and impaired neovascularisation

PubMed Central

Levesque, Christine; Couture, Frédéric; Kwiatkowska, Anna; Desjardins, Roxane; Guérin, Brigitte; Neugebauer, Witold A.; Day, Robert

2015-01-01

Prostate cancer is the leading cancer in North American men. Current pharmacological treatments are limited to anti-androgen strategies and the development of new therapeutic approaches remains a challenge. As a fundamentally new approach, we propose the inhibition of PACE4, a member of the proprotein convertases family of enzymes, as a therapeutic target in prostate cancer. We developed an inhibitor named the Multi-Leu peptide, with potent in vitro anti-proliferative effects. However, the Multi-Leu peptide has not been tested under in vivo conditions and its potency under such conditions is most likely limited, due to the labile characteristics of peptides in general. Using a peptidomimetic approach, we modified the initial scaffold, generating the analog Ac-[DLeu]LLLRVK-Amba, which demonstrates increased inhibitory potency and stability. The systemic administration of this peptidomimetic significantly inhibits tumor progression in the LNCaP xenograft model of prostate cancer by inducing tumor cell quiescence, increased apoptosis and neovascularization impairment. Pharmacokinetic and biodistribution profiles of this inhibitor confirm adequate tumor delivery properties of the compound. We conclude that PACE4 peptidomimetic inhibitors could result in stable and potent drugs for a novel therapeutic strategy for prostate cancer. PMID:25682874
Will genomic selection be a practical method for plant breeding?

PubMed

Nakaya, Akihiro; Isobe, Sachiko N

2012-11-01

Genomic selection or genome-wide selection (GS) has been highlighted as a new approach for marker-assisted selection (MAS) in recent years. GS is a form of MAS that selects favourable individuals based on genomic estimated breeding values. Previous studies have suggested the utility of GS, especially for capturing small-effect quantitative trait loci, but GS has not become a popular methodology in the field of plant breeding, possibly because there is insufficient information available on GS for practical use. In this review, GS is discussed from a practical breeding viewpoint. Statistical approaches employed in GS are briefly described, before the recent progress in GS studies is surveyed. GS practices in plant breeding are then reviewed before future prospects are discussed. Statistical concepts used in GS are discussed with genetic models and variance decomposition, heritability, breeding value and linear model. Recent progress in GS studies is reviewed with a focus on empirical studies. For the practice of GS in plant breeding, several specific points are discussed including linkage disequilibrium, feature of populations and genotyped markers and breeding scheme. Currently, GS is not perfect, but it is a potent, attractive and valuable approach for plant breeding. This method will be integrated into many practical breeding programmes in the near future with further advances and the maturing of its theory.

Study design and data analysis considerations for the discovery of prognostic molecular biomarkers: a case study of progression free survival in advanced serous ovarian cancer.

PubMed

Qin, Li-Xuan; Levine, Douglas A

2016-06-10

Accurate discovery of molecular biomarkers that are prognostic of a clinical outcome is an important yet challenging task, partly due to the combination of the typically weak genomic signal for a clinical outcome and the frequently strong noise due to microarray handling effects. Effective strategies to resolve this challenge are in dire need. We set out to assess the use of careful study design and data normalization for the discovery of prognostic molecular biomarkers. Taking progression free survival in advanced serous ovarian cancer as an example, we conducted empirical analysis on two sets of microRNA arrays for the same set of tumor samples: arrays in one set were collected using careful study design (that is, uniform handling and randomized array-to-sample assignment) and arrays in the other set were not. We found that (1) handling effects can confound the clinical outcome under study as a result of chance even with randomization, (2) the level of confounding handling effects can be reduced by data normalization, and (3) good study design cannot be replaced by post-hoc normalization. In addition, we provided a practical approach to define positive and negative control markers for detecting handling effects and assessing the performance of a normalization method. Our work showcased the difficulty of finding prognostic biomarkers for a clinical outcome of weak genomic signals, illustrated the benefits of careful study design and data normalization, and provided a practical approach to identify handling effects and select a beneficial normalization method. Our work calls for careful study design and data analysis for the discovery of robust and translatable molecular biomarkers.
Improved object optimal synthetic description, modeling, learning, and discrimination by GEOGINE computational kernel

NASA Astrophysics Data System (ADS)

Fiorini, Rodolfo A.; Dacquino, Gianfranco

2005-03-01

GEOGINE (GEOmetrical enGINE), a state-of-the-art OMG (Ontological Model Generator) based on n-D Tensor Invariants for n-Dimensional shape/texture optimal synthetic representation, description and learning, was presented in previous conferences elsewhere recently. Improved computational algorithms based on the computational invariant theory of finite groups in Euclidean space and a demo application is presented. Progressive model automatic generation is discussed. GEOGINE can be used as an efficient computational kernel for fast reliable application development and delivery in advanced biomedical engineering, biometric, intelligent computing, target recognition, content image retrieval, data mining technological areas mainly. Ontology can be regarded as a logical theory accounting for the intended meaning of a formal dictionary, i.e., its ontological commitment to a particular conceptualization of the world object. According to this approach, "n-D Tensor Calculus" can be considered a "Formal Language" to reliably compute optimized "n-Dimensional Tensor Invariants" as specific object "invariant parameter and attribute words" for automated n-Dimensional shape/texture optimal synthetic object description by incremental model generation. The class of those "invariant parameter and attribute words" can be thought as a specific "Formal Vocabulary" learned from a "Generalized Formal Dictionary" of the "Computational Tensor Invariants" language. Even object chromatic attributes can be effectively and reliably computed from object geometric parameters into robust colour shape invariant characteristics. As a matter of fact, any highly sophisticated application needing effective, robust object geometric/colour invariant attribute capture and parameterization features, for reliable automated object learning and discrimination can deeply benefit from GEOGINE progressive automated model generation computational kernel performance. Main operational advantages over previous, similar approaches are: 1) Progressive Automated Invariant Model Generation, 2) Invariant Minimal Complete Description Set for computational efficiency, 3) Arbitrary Model Precision for robust object description and identification.
Progressive transmission of secured images with authentication using decompositions into monovariate functions

NASA Astrophysics Data System (ADS)

Leni, Pierre-Emmanuel; Fougerolle, Yohan D.; Truchetet, Frédéric

2014-05-01

We propose a progressive transmission approach of an image authenticated using an overlapping subimage that can be removed to restore the original image. Our approach is different from most visible watermarking approaches that allow one to later remove the watermark, because the mark is not directly introduced in the two-dimensional image space. Instead, it is rather applied to an equivalent monovariate representation of the image. Precisely, the approach is based on our progressive transmission approach that relies on a modified Kolmogorov spline network, and therefore inherits its advantages: resilience to packet losses during transmission and support of heterogeneous display environments. The marked image can be accessed at any intermediate resolution, and a key is needed to remove the mark to fully recover the original image without loss. Moreover, the key can be different for every resolution, and the images can be globally restored in case of packet losses during the transmission. Our contributions lie in the proposition of decomposing a mark (an overlapping image) and an image into monovariate functions following the Kolmogorov superposition theorem; and in the combination of these monovariate functions to provide a removable visible "watermarking" of images with the ability to restore the original image using a key.
Mesoscale Models of Fluid Dynamics

NASA Astrophysics Data System (ADS)

Boghosian, Bruce M.; Hadjiconstantinou, Nicolas G.

During the last half century, enormous progress has been made in the field of computational materials modeling, to the extent that in many cases computational approaches are used in a predictive fashion. Despite this progress, modeling of general hydrodynamic behavior remains a challenging task. One of the main challenges stems from the fact that hydrodynamics manifests itself over a very wide range of length and time scales. On one end of the spectrum, one finds the fluid's "internal" scale characteristic of its molecular structure (in the absence of quantum effects, which we omit in this chapter). On the other end, the "outer" scale is set by the characteristic sizes of the problem's domain. The resulting scale separation or lack thereof as well as the existence of intermediate scales are key to determining the optimal approach. Successful treatments require a judicious choice of the level of description which is a delicate balancing act between the conflicting requirements of fidelity and manageable computational cost: a coarse description typically requires models for underlying processes occuring at smaller length and time scales; on the other hand, a fine-scale model will incur a significantly larger computational cost.
Surgical innovation and quality assurance: Can we have both?

PubMed

Georgeson, Keith

2015-06-01

Innovation is the major force for progress in pediatric surgery. Most of the progress in surgery has evolved secondary to novel approaches developed by surgeons confronted with difficult pathologic conditions. Up to the present time, most surgical innovation has been practiced with few rules for guidance. Innovation to make surgical procedures more effective and less morbid is highly desirable. However, the absence of oversight has the potential to lead to unbridled human experimentation. The quality improvement movement in medicine is attempting to improve outcomes using evidence-based clinical pathways. Quality improvement aims to decrease the variation in therapeutic approaches by scientifically defining best practices. There is a significant potential for autonomous surgical innovators to clash with well-meaning proponents of quality improvement. A suggested remedy to encourage surgical innovators while protecting patients from unintended harm is for institutions to develop Surgical Innovation Committees to evaluate and give oversight to the early application of new techniques and devices. Scientific evaluation under the auspices of an IRB should follow when feasible. Copyright © 2015 Elsevier Inc. All rights reserved.
Generation and analysis of correlated pairs of photons on board a nanosatellite

NASA Astrophysics Data System (ADS)

Chandrasekara, R.; Tang, Z.; Tan, Y. C.; Cheng, C.; Sha, L.; Hiang, G. C.; Oi, D.; Ling, A.

2016-10-01

Progress in quantum computers and their threat to conventional public key infrastructure is driving new forms of encryption. Quantum Key Distribution (QKD) using entangled photons is a promising approach. A global QKD network can be achieved using satellites equipped with optical links. Despite numerous proposals, actual experimental work demonstrating relevant entanglement technology in space is limited due to the prohibitive cost of traditional satellite development. To make progress, we have designed a photon pair source that can operate on modular spacecraft called CubeSats. We report the in-orbit operation of the photon pair source on board an orbiting CubeSat and demonstrate pair generation and polarisation correlation under space conditions. The in-orbit polarisation correlations are compatible with ground-based tests, validating our design. This successful demonstration is a major experimental milestone towards a space-based quantum network. Our approach provides a cost-effective method for proving the space-worthiness of critical components used in entangled photon technology. We expect that it will also accelerate efforts to probe the overlap between quantum and relativistic models of physics.
Dynamic and Progressive Control of DNA Origami Conformation by Modulating DNA Helicity with Chemical Adducts.

PubMed

Chen, Haorong; Zhang, Hanyu; Pan, Jing; Cha, Tae-Gon; Li, Shiming; Andréasson, Joakim; Choi, Jong Hyun

2016-05-24

DNA origami has received enormous attention for its ability to program complex nanostructures with a few nanometer precision. Dynamic origami structures that change conformation in response to environmental cues or external signals hold great promises in sensing and actuation at the nanoscale. The reconfiguration mechanism of existing dynamic origami structures is mostly limited to single-stranded hinges and relies almost exclusively on DNA hybridization or strand displacement. Here, we show an alternative approach by demonstrating on-demand conformation changes with DNA-binding molecules, which intercalate between base pairs and unwind DNA double helices. The unwinding effect modulates the helicity mismatch in DNA origami, which significantly influences the internal stress and the global conformation of the origami structure. We demonstrate the switching of a polymerized origami nanoribbon between different twisting states and a well-constrained torsional deformation in a monomeric origami shaft. The structural transformation is shown to be reversible, and binding isotherms confirm the reconfiguration mechanism. This approach provides a rapid and reversible means to change DNA origami conformation, which can be used for dynamic and progressive control at the nanoscale.
Multiple player tracking in sports video: a dual-mode two-way bayesian inference approach with progressive observation modeling.

PubMed

Xing, Junliang; Ai, Haizhou; Liu, Liwei; Lao, Shihong

2011-06-01

Multiple object tracking (MOT) is a very challenging task yet of fundamental importance for many practical applications. In this paper, we focus on the problem of tracking multiple players in sports video which is even more difficult due to the abrupt movements of players and their complex interactions. To handle the difficulties in this problem, we present a new MOT algorithm which contributes both in the observation modeling level and in the tracking strategy level. For the observation modeling, we develop a progressive observation modeling process that is able to provide strong tracking observations and greatly facilitate the tracking task. For the tracking strategy, we propose a dual-mode two-way Bayesian inference approach which dynamically switches between an offline general model and an online dedicated model to deal with single isolated object tracking and multiple occluded object tracking integrally by forward filtering and backward smoothing. Extensive experiments on different kinds of sports videos, including football, basketball, as well as hockey, demonstrate the effectiveness and efficiency of the proposed method.
A qualitative exploration of student perceptions of the impact of progress tests on learning and emotional wellbeing.

PubMed

Yielder, Jill; Wearn, Andy; Chen, Yan; Henning, Marcus A; Weller, Jennifer; Lillis, Steven; Mogol, Vernon; Bagg, Warwick

2017-08-29

Progress testing was introduced to the MBChB programme at the University of Auckland in 2013. As there has been a focus in published literature on aspects relating to the format or function of progress tests, the purpose of this study was to explore a qualitative student perspective on the introduction of progress testing and its impact on approaches to learning and perceived stress. This article presents the qualitative aspects of a longitudinal evaluation study. The qualitative data were derived from eight focus groups of Year 2-5 medical students in the University of Auckland medical programme. Two themes, 'Impact on Learning' and 'Emotional Wellbeing' and their subthemes offered insight into student perceptions and behaviour. Students described a variety of learning responses to progress testing that clustered around the employment of a range of learning strategies based on their experience of sitting progress tests and their individualised feedback. A range of emotional responses were also expressed, with some finding progress tests stressful, while others enjoyed not needing to intensively cram before the tests. Progress tests appear to influence the approach of students to their learning. They employ a mix of learning strategies, shaped by their performance, individualised feedback and the learning environment. While students expressed some stress and anxiety with respect to sitting progress tests, this form of testing was viewed by these students as no worse, and sometimes better than traditional assessments.
Man Versus Machine Part 2: Comparison of Radiologists' Interpretations and NeuroQuant Measures of Brain Asymmetry and Progressive Atrophy in Patients With Traumatic Brain Injury.

PubMed

Ross, David E; Ochs, Alfred L; DeSmit, Megan E; Seabaugh, Jan M; Havranek, Michael D

2015-01-01

This study is an expanded version of an earlier study, which compared NeuroQuant measures of MRI brain volume with the radiologist's traditional approach in outpatients with mild or moderate traumatic brain injury. NeuroQuant volumetric analyses were compared with the radiologists' interpretations. NeuroQuant found significantly higher rates of atrophy (50.0%), abnormal asymmetry (83.3%), and progressive atrophy (70.0%) than the radiologists (12.5%, 0% and 0%, respectively). Overall, NeuroQuant was more sensitive for detecting at least one sign of atrophy, abnormal asymmetry, or progressive atrophy (95.8%) than the traditional radiologist's approach (12.5%).
Diet and prostate cancer - a holistic approach to management.

PubMed

Cheetham, Philippa J; Katz, Aaron E

2011-10-01

There is now increasing evidence from epidemiologic surveys and from laboratory, intervention, and case-control studies that diet and lifestyle plays a crucial role in prostate cancer biology and tumorigenesis. This applies to both the development and progression of prostate cancer, although in many cases the specific initiating factors in the diet are poorly understood. Conversely, many nutrients and herbs also show significant promise in helping to treat prostate cancer by slowing progression and reducing recurrence, ultimately reducing the risk of morbidity and mortality from the disease. Furthermore for all grades of prostate cancer, nutritional interventions complement conventional treatment to improve response and quality of life. Slowing or even reversing the progression of, high-grade prostate intraepithelial neoplasia [HGPIN]). with chemo-preventative agents could be the best primary defense against prostate cancer, preventing it from occurring in the first place. The information given in this review about prostate cancer chemoprevention summarizes the key evidence for the role of different dietary components and their effect on prostate cancer prevention and progression. Most nutritional chemoprevention agents also have the added benefit of being beneficial for the cardiovascular system, bone health and for the prevention of other cancers.
Developing a response to family violence in primary health care: the New Zealand experience.

PubMed

Gear, Claire; Koziol-McLain, Jane; Wilson, Denise; Clark, Faye

2016-08-20

Despite primary health care being recognised as an ideal setting to effectively respond to those experiencing family violence, responses are not widely integrated as part of routine health care. A lack of evidence testing models and approaches for health sector integration, alongside challenges of transferability and sustainability, means the best approach in responding to family violence is still unknown. The Primary Health Care Family Violence Responsiveness Evaluation Tool was developed as a guide to implement a formal systems-led response to family violence within New Zealand primary health care settings. Given the difficulties integrating effective, sustainable responses to family violence, we share the experience of primary health care sites that embarked on developing a response to family violence, presenting the enablers, barriers and resources required to maintain, progress and sustain family violence response development. In this qualitative descriptive study data were collected from two sources. Firstly semi-structured focus group interviews were conducted during 24-month follow-up evaluation visits of primary health care sites to capture the enablers, barriers and resources required to maintain, progress and sustain a response to family violence. Secondly the outcomes of a group activity to identify response development barriers and implementation strategies were recorded during a network meeting of primary health care professionals interested in family violence prevention and intervention; findings were triangulated across the two data sources. Four sites, representing three PHOs and four general practices participated in the focus group interviews; 35 delegates from across New Zealand attended the network meeting representing a wider perspective on family violence response development within primary health care. Enablers and barriers to developing a family violence response were identified across four themes: 'Getting started', 'Building effective relationships', 'Sourcing funding' and 'Shaping a national approach to family violence'. The strong commitment of key people dedicated to addressing family violence is essential for response sustainability and would be strengthened by prioritising family violence response as a national health target with dedicated resourcing. Further analysis of the health care system as a complex adaptive system may provide insight into effective approaches to response development and health system integration.
Targets for future clinical trials in Huntington's disease: what's in the pipeline?

PubMed

Wild, Edward J; Tabrizi, Sarah J

2014-09-15

The known genetic cause of Huntington's disease (HD) has fueled considerable progress in understanding its pathobiology and the development of therapeutic approaches aimed at correcting specific changes linked to the causative mutation. Among the most promising is reducing expression of mutant huntingtin protein (mHTT) with RNA interference or antisense oligonucleotides; human trials are now being planned. Zinc-finger transcriptional repression is another innovative method to reduce mHTT expression. Modulation of mHTT phosphorylation, chaperone upregulation, and autophagy enhancement represent attempts to alter cellular homeostasis to favor removal of mHTT. Inhibition of histone deacetylases (HDACs) remains of interest; recent work affirms HDAC4 as a target but questions the assumed centrality of its catalytic activity in HD. Phosphodiesterase inhibition, aimed at restoring synaptic function, has progressed rapidly to human trials. Deranged cellular signaling provides several tractable targets, but specificity and complexity are challenges. Restoring neurotrophic support in HD remains a key potential therapeutic approach. with several approaches being pursued, including brain-derived neurotrophic factor (BDNF) mimesis through tyrosine receptor kinase B (TrkB) agonism and monoclonal antibodies. An increasing understanding of the role of glial cells in HD has led to several new therapeutic avenues, including kynurenine monooxygenase inhibition, immunomodulation by laquinimod, CB2 agonism, and others. The complex metabolic derangements in HD remain under study, but no clear therapeutic strategy has yet emerged. We conclude that many exciting therapeutics are progressing through the development pipeline, and combining a better understanding of HD biology in human patients, with concerted medicinal chemistry efforts, will be crucial for bringing about an era of effective therapies. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Deleterious effects of net clogging on the quantification of stream drift

USGS Publications Warehouse

Muehlbauer, Jeffrey D.; Kennedy, Theodore A.; Copp, Adam J.; Sabol, Thomas

2017-01-01

Drift studies are central to stream and river ecological research. However, a fundamental aspect of quantifying drift — how net clogging affects the accuracy of results — has been widely ignored. Utilizing approaches from plankton and suspended sediment studies in oceanography and hydrology, we examined the rate and dynamics of net clogging across a range of conditions. We found that nets clog nonlinearly over time and that suspended solid concentrations and net mesh size exerted a strong effect on clogging rates. Critically, net clogging introduced unpredictable biases in resultant data due to the inaccuracies in water volume estimates introduced by progressive clogging. This renders the widespread approach to linearly “correct” for clogging inadequate. Using a meta-analysis of 77 drift studies spanning 25 years, we demonstrate that the detrimental effects of net clogging are routinely unappreciated, even though the results of most of these studies were likely affected by clogging. We close by describing an approach for avoiding net clogging, which will increase the accuracy and reproducibility of results in future freshwater, lotic drift studies.
An overview of the treatment of Tourette's disorder and tics.

PubMed

Párraga, Humberto C; Harris, Kara M; Párraga, Karen L; Balen, George M; Cruz, Cristina

2010-08-01

The aim of this study was to review the efficacy of various treatments for Tourette's disorder (TD) and tics. This study is a historical review of the treatment modalities prior to the advent of neuroleptics. A review of double-blind and placebo-controlled clinical trials and open studies on the use of neuroleptics and selected reports was also carried out. The literature review reveals that the treatment of TD and tics has evolved from an early history of marginally effective approaches to the advent of neuroleptics, which started a new era in TD and tic treatment, with a significantly broader range of effectiveness. Although progress has been made, the literature review nevertheless reveals a great deal of confusion as related to the clinical heterogeneity of TD and tics, differences in populations, medication-dose combinations, and outcomes. However, a role for a limited number of pharmacologic agents, combined with psychosocial approaches, has been identified. There is a need for studies in larger, diagnostically homogenous samples and for the use of more sophisticated methodology, to identify intelligible models that would allow the development of more effective treatment approaches.
A Personalized Approach in Progressive Multiple Sclerosis: The Current Status of Disease Modifying Therapies (DMTs) and Future Perspectives

PubMed Central

D’Amico, Emanuele; Patti, Francesco; Zanghì, Aurora; Zappia, Mario

2016-01-01

Using the term of progressive multiple sclerosis (PMS), we considered a combined population of persons with secondary progressive MS (SPMS) and primary progressive MS (PPMS). These forms of MS cannot be challenged with efficacy by the licensed therapy. In the last years, several measures of risk estimation were developed for predicting clinical course in MS, but none is specific for the PMS forms. Personalized medicine is a therapeutic approach, based on identifying what might be the best therapy for an individual patient, taking into account the risk profile. We need to achieve more accurate estimates of useful predictors in PMS, including unconventional and qualitative markers which are not yet currently available or practicable routine diagnostics. The evaluation of an individual patient is based on the profile of disease activity.Within the neurology field, PMS is one of the fastest-moving going into the future. PMID:27763513
[Cancer immunotherapy. Importance of overcoming immune suppression].

PubMed

Malvicini, Mariana; Puchulo, Guillermo; Matar, Pablo; Mazzolini, Guillermo

2010-01-01

Increasing evidence indicates that the immune system is involved in the control of tumor progression. Effective antitumor immune response depends on the interaction between several components of the immune system, including antigen-presenting cells and different T cell subsets. However, tumor cells develop a number of mechanisms to escape recognition and elimination by the immune system. In this review we discuss these mechanisms and address possible therapeutic approaches to overcome the immune suppression generated by tumors.
Current applications and future potential for bioinorganic chemistry in the development of anticancer drugs

PubMed Central

van Rijt, Sabine H.; Sadler, Peter J.

2010-01-01

This review illustrates notable recent progress in the field of medicinal bioinorganic chemistry with many new approaches to the design of innovative metal-based anticancer drugs emerging. Current research addressing the problems associated with platinum drugs has focused on other metal-based therapeutics that have different modes of action, and on prodrug and targeting strategies in an effort to diminish the side-effects of cisplatin chemotherapy. PMID:19782150
Psoriasis

PubMed Central

Di Meglio, Paola; Villanova, Federica; Nestle, Frank O.

2014-01-01

Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life. PMID:25085957
Multimodal Approach to Testing the Acute Effects of Mild Traumatic Brain Injury (mTBI)

DTIC Science & Technology

2015-03-01

included several key staff changes, a major instrument acquisition, repairs and upgrades to the MEG , combined with substantial progress with patient...patients to non-head trauma controls in the first days after injury. Multiple modalities of behavioral, electrophysiological, and most strikingly, MEG ...changes were found. The MEG of all mTBI patients had delta activity in the frontal lobes that was absent in all controls. A scientific abstract on

Recent Progresses in Ab-Initio Studies of Low-Energy Few-Nucleon Reactions of Astrophysical Interest

NASA Astrophysics Data System (ADS)

Marcucci, Laura E.

2017-03-01

We review the most recent theoretical studies of nuclear reactions of astrophysical interest involving few-nucleon systems. In particular, we focus on the radiative capture of protons by deuterons in the energy range of interest for Big Bang Nucleosynthesis. Related to this, we will discuss also the most recent calculation of tritium β -decay. Two frameworks will be considered, the conventional and the chiral effective field theory approach.
Management and Rehabilitation of Joint Disease in Sport Horses.

PubMed

Contino, Erin K

2018-05-21

Joint disease is one of the most common issues effecting sport horses. Because there is no cure for joint disease, treatment goals surround slowing progression of the disease, minimizing pain, increasing function, and optimizing performance. Accomplishing these goals often requires a multimodal approach that combines systemic medications or supplements; intra-articular therapies, such as corticosteroids or biologics; management considerations; and physical therapy exercises. Copyright © 2018 Elsevier Inc. All rights reserved.
Feel the Progress: Second-Year Students' Reflections on Their First-Year Experience

ERIC Educational Resources Information Center

Hailikari, Telle; Kordts-Freudinger, Robert; Postareff, Liisa

2016-01-01

The aim of the present study was to explore first-year students' academic emotions and how they relate to their study progress. A mixed-method approach was used. The data consisted of deep interviews with 43 students. The number of their study credits was used as an indicator of their study progress. The results revealed that students expressed a…
John Woolman and Ethical Progress in Kitcher's Pragmatic Naturalism.

PubMed

Barresi, John

2017-01-01

The development of John Woolman’s views on slavery plays an important evidentiary role in Philip Kitcher’s recent book, The ethical project (Kitcher 2011). In this work Kitcher takes what he calls a “pragmatic naturalist” approach to ethics and claims that the discovery of ethical truth plays no role in the emergence of ethical progress. To support his view, he argues that Woolman’s contribution was not due to his discovery of an ethical truth about slavery, not previously known, but due to his sensitivity to slavery and his influence on others, which contributed to collective progressive change in moral norms involving slavery. While not disputing Kitcher’s ethical theory, I argue that personal discoveries of a moral psychological nature made by Woolman served both as insights and motivations for his contribution. Thus, even if there are no such things as independent ethical truths that can be discovered by individuals, a fully naturalistic approach to ethical progress requires that we make room not only for group-level progressive evolution of norms, but also for individual discoveries of a moral psychological nature that can sometimes cause an individual to play a significant initiating role in progressive ethical transitions that occur at a group level.
[Nutritional approaches to modulate oxidative stress that induce Alzheimer's disease. Nutritional approaches to prevent Alzheimer's disease].

PubMed

Lara, Humberto Herman; Alanís-Garza, Eduardo Javier; Estrada Puente, María Fernanda; Mureyko, Lucía Liliana; Alarcón Torres, David Alejandro; Ixtepan Turrent, Liliana

2015-01-01

Alzheimer's disease is the most common cause of dementia in the world; symptoms first appear after age 65 and have a progressive evolution. Expecting an increase on its incidence and knowing there is currently no cure for Alzheimer's disease, it is a necessity to prevent progression. The change in diet due to globalization may explain the growth of the incidence in places such as Japan and Mediterranean countries, which used to have fewer incidences. There is a direct correlation between disease progression and the increased intake of alcohol, saturated fats, and red meat. Therefore, we find obesity and higher serum levels in cholesterol due to saturated fat as a result. A way to decrease the progression of Alzheimer's is through a diet rich in polipheno/es (potent antioxidants), unsaturated fats (monounsaturated and polyunsaturated), fish, vegetable fa t, fruits with low glycemic index, and a moderate consumption of red wine. Through this potent antioxidant diet we accomplish the prevention of dementia and the progression of Alzheimer's disease. This article emphasizes the food and other components that have been demonstrated to decrease the oxidative stress related to these progressive diseases.
Conventional medical management of inflammatory bowel disease.

PubMed

Burger, Daniel; Travis, Simon

2011-05-01

Conventional therapies for ulcerative colitis and Crohn's disease (CD) include aminosalicylates, corticosteroids, thiopurines, methotrexate, and anti-tumor necrosis factor agents. A time-structured approach is required for appropriate management. Traditional step-up therapy has been partly replaced during the last decade by potent drugs and top-down therapies, with an accelerated step-up approach being the most appropriate in the majority of patients. When patients are diagnosed with CD or ulcerative colitis, physicians should consider the probable pattern of disease progression so that effective therapy is not delayed. This can be achieved by setting arbitrary time limits for administration of biological therapies, changing therapy from mesalamine in patients with active ulcerative colitis, or using rescue therapy for acute severe colitis. In this review, we provide algorithms with a time-structured approach for guidance of therapy. Common mistakes in conventional therapy include overprescription of mesalamine for CD; inappropriate use of steroids (for perianal CD, when there is sepsis, or for maintenance); delayed introduction or underdosing with azathioprine, 6-mercaptopurine, or methotrexate; and failure to consider timely surgery. The paradox of anti-tumor necrosis factor therapy is that although it too is used inappropriately (when patients have sepsis or fibrostenotic strictures) or too frequently (for diseases that would respond to less-potent therapy), it is also often introduced too late in disease progression. Conventional drugs are the mainstay of current therapy for inflammatory bowel diseases, but drug type, timing, and context must be optimized to manage individual patients effectively. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
Vulvar field resection: novel approach to the surgical treatment of vulvar cancer based on ontogenetic anatomy.

PubMed

Höckel, Michael; Schmidt, Katja; Bornmann, Karoline; Horn, Lars-Christian; Dornhöfer, Nadja

2010-10-01

Current local treatment of vulvar cancer is wide tumor excision and radical vulvectomy based on functional anatomy established from the adult and on the view of radial progressive tumor permeation. Standard surgery is associated with a considerable local failure rate and severe disturbance of the patients' body image. Vulvar field resection (VFR) is based on ontogenetic anatomy and on the concept of local tumor spread within permissive compartments. VFR combined with anatomical reconstruction (AR) is proposed as a new surgical approach to the treatment of vulvar cancer. A prospective trial was launched to test the compartment theory for vulvar cancer and to assess safety and effectiveness of the new therapy. In 54 consecutive patients 46 tumors were locally confined to the tissue compartment differentiated from the vulvar anlage. The 8 tumors having transgressed into adjacent tissue compartments of different embryonic origins exhibited signs of advanced malignant progression. 38 patients with vulvar cancer, stages T1-3 were treated with VFR and AR. The perioperative complication rate was low. At 19 (3-50) months follow-up no patient failed locally. 33 patients estimated their body image as undisturbed. Vulvar cancer permeates within ontogenetic tissue compartments and surgical treatment with VFR and AR appears to be safe and effective. Patients should benefit from the new approach as local tumor control is high and the preserved tissue can be successfully used for restoration of vulvar form and function. Confirmatory trials with more patients and longer follow-up are suggested. Copyright © 2010 Elsevier Inc. All rights reserved.
The GHSG Approach to Treating Hodgkin's Lymphoma.

PubMed

Bröckelmann, Paul J; Engert, Andreas

2015-09-01

Hodgkin's lymphoma (HL) is a relatively rare disease accounting for 15 % of all lymphoma. This disease has developed from an incurable disease to the adult malignancy with the most favorable prognosis. With current therapeutic approaches consisting of polychemo- and small-field radiotherapy, up to 80 % of all patients can be cured long term. In refractory or relapsed HL, intensified treatment including high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is associated with progression-free survival (PFS) of 50 %. Evaluation of novel drugs in multiple relapsed or refractory cases, better treatment options for elderly patients and reducing treatment-related side effects are the main focus of current research. Recent clinical developments and future approaches in the treatment of HL will be discussed in this review.
Should development of Alzheimer's disease-specific intravenous immunoglobulin be considered?

PubMed

Loeffler, David A

2014-12-05

Recent phase II and III studies with intravenous immunoglobulin (IVIG) in patients with Alzheimer's disease (AD) did not find evidence for the slowing of AD progression compared to placebo-treated patients, in contrast to encouraging results in pilot studies. An additional phase III trial is ongoing. If negative results are found, then further AD studies with IVIG are unlikely unless a manufacturer opts for a trial with high-dose IVIG, which would increase its anti-inflammatory effects but also the risk for adverse events. An alternative approach could be an AD-specific IVIG, supplementing IVIG with higher concentrations of selected antibodies purified from it or produced via recombinant polyclonal antibody technology. These antibodies could include those to amyloid-beta (Aβ, tau protein, inflammatory cytokines, complement activation proteins, and the receptor for advanced glycation end products. IgG fragment crystallizable (Fc) fragments containing terminal sialic acid could be added to increase anti-inflammatory effects. While this product might be more effective in slowing AD clinical progression than current IVIG, there are difficulties with this approach. Preclinical studies would be required to determine which of the antibodies of interest for supplementing current IVIG (for example, antibodies to phosphorylated or oligomeric tau) are actually present (and, therefore, available for purification) in IVIG, and the effects of the product in mouse models of AD. An Investigational New Drug application for an AD-specific IVIG would require United States Food and Drug Administration approval. If the drug would be found to benefit AD patients, meeting the increased demand for IVIG would be challenging.
Environmental Enrichment Extends Photoreceptor Survival and Visual Function in a Mouse Model of Retinitis Pigmentosa

PubMed Central

Barone, Ilaria; Novelli, Elena; Piano, Ilaria; Gargini, Claudia; Strettoi, Enrica

2012-01-01

Slow, progressive rod degeneration followed by cone death leading to blindness is the pathological signature of all forms of human retinitis pigmentosa (RP). Therapeutic schemes based on intraocular delivery of neuroprotective agents prolong the lifetime of photoreceptors and have reached the stage of clinical trial. The success of these approaches depends upon optimization of chronic supply and appropriate combination of factors. Environmental enrichment (EE), a novel neuroprotective strategy based on enhanced motor, sensory and social stimulation, has already been shown to exert beneficial effects in animal models of various disorders of the CNS, including Alzheimer and Huntington disease. Here we report the results of prolonged exposure of rd10 mice, a mutant strain undergoing progressive photoreceptor degeneration mimicking human RP, to such an enriched environment from birth. By means of microscopy of retinal tissue, electrophysiological recordings, visual behaviour assessment and molecular analysis, we show that EE considerably preserves retinal morphology and physiology as well as visual perception over time in rd10 mutant mice. We find that protective effects of EE are accompanied by increased expression of retinal mRNAs for CNTF and mTOR, both factors known as instrumental to photoreceptor survival. Compared to other rescue approaches used in similar animal models, EE is highly effective, minimally invasive and results into a long-lasting retinal protection. These results open novel perspectives of research pointing to environmental strategies as useful tools to extend photoreceptor survival. PMID:23209820
Signal detection in global mean temperatures after "Paris": an uncertainty and sensitivity analysis

NASA Astrophysics Data System (ADS)

Visser, Hans; Dangendorf, Sönke; van Vuuren, Detlef P.; Bregman, Bram; Petersen, Arthur C.

2018-02-01

In December 2015, 195 countries agreed in Paris to hold the increase in global mean surface temperature (GMST) well below 2.0 °C above pre-industrial levels and to pursue efforts to limit the temperature increase to 1.5 °C. Since large financial flows will be needed to keep GMSTs below these targets, it is important to know how GMST has progressed since pre-industrial times. However, the Paris Agreement is not conclusive as regards methods to calculate it. Should trend progression be deduced from GCM simulations or from instrumental records by (statistical) trend methods? Which simulations or GMST datasets should be chosen, and which trend models? What is pre-industrial and, finally, are the Paris targets formulated for total warming, originating from both natural and anthropogenic forcing, or do they refer to anthropogenic warming only? To find answers to these questions we performed an uncertainty and sensitivity analysis where datasets and model choices have been varied. For all cases we evaluated trend progression along with uncertainty information. To do so, we analysed four trend approaches and applied these to the five leading observational GMST products. We find GMST progression to be largely independent of various trend model approaches. However, GMST progression is significantly influenced by the choice of GMST datasets. Uncertainties due to natural variability are largest in size. As a parallel path, we calculated GMST progression from an ensemble of 42 GCM simulations. Mean progression derived from GCM-based GMSTs appears to lie in the range of trend-dataset combinations. A difference between both approaches appears to be the width of uncertainty bands: GCM simulations show a much wider spread. Finally, we discuss various choices for pre-industrial baselines and the role of warming definitions. Based on these findings we propose an estimate for signal progression in GMSTs since pre-industrial.
Comparison of Statistical Approaches for Dealing With Immortal Time Bias in Drug Effectiveness Studies.

PubMed

Karim, Mohammad Ehsanul; Gustafson, Paul; Petkau, John; Tremlett, Helen

2016-08-15

In time-to-event analyses of observational studies of drug effectiveness, incorrect handling of the period between cohort entry and first treatment exposure during follow-up may result in immortal time bias. This bias can be eliminated by acknowledging a change in treatment exposure status with time-dependent analyses, such as fitting a time-dependent Cox model. The prescription time-distribution matching (PTDM) method has been proposed as a simpler approach for controlling immortal time bias. Using simulation studies and theoretical quantification of bias, we compared the performance of the PTDM approach with that of the time-dependent Cox model in the presence of immortal time. Both assessments revealed that the PTDM approach did not adequately address immortal time bias. Based on our simulation results, another recently proposed observational data analysis technique, the sequential Cox approach, was found to be more useful than the PTDM approach (Cox: bias = -0.002, mean squared error = 0.025; PTDM: bias = -1.411, mean squared error = 2.011). We applied these approaches to investigate the association of β-interferon treatment with delaying disability progression in a multiple sclerosis cohort in British Columbia, Canada (Long-Term Benefits and Adverse Effects of Beta-Interferon for Multiple Sclerosis (BeAMS) Study, 1995-2008). © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
IMPACT OF OBESITY ON DEVELOPMENT AND PROGRESSION OF MAMMARY TUMORS IN PRECLINICAL MODELS OF BREAST CANCER

PubMed Central

Cleary, Margot P.

2013-01-01

Overweight and/or obesity are known risk factors for postmenopausal breast cancer. More recently increased body weight has also been associated with poor prognosis for both pre- and postmenopausal breast cancer. This relationship has primarily been identified through epidemiological studies. Additional information from in vitro studies has also been produced in attempts to delineate mechanisms of action for the association of obesity and body weight and breast cancer. This approach has identified potential growth factors such as insulin, leptin, estrogen and IGF-I which are reported to be modulated by body weight changes. However, in vitro studies are limited in scope and frequently use non-physiological concentrations of growth factors, while long follow-up is needed for human studies. Preclinical animal models provide an intermediary approach to investigate the impact of body weight and potential growth factors on mammary/breast tumor development and progression. Here results of a number of studies addressing this issue are presented. In the majority of the studies either genetically-obese or diet-induced obese rodent models have been used to investigate spontaneous, transgenic and carcinogen-induced mammary tumor development. To study tumor progression the major focus has been allograft studies in mice with either genetic or dietary-induced obesity. In general, obesity has been demonstrated to shorten mammary tumor latency and to impact tumor pathology. However, in rodents with defects in leptin and other growth factors the impact of obesity is not as straightforward. Future studies using more physiologically relevant obesity models and clearly distinguishing diet composition from body weight effects will be important in continuing to understand the factors associated with body weight’s impact on the mammary/breast cancer development and progression. PMID:24122258
Unified Approach to the Biomechanics of Dental Implantology

NASA Technical Reports Server (NTRS)

Grenoble, D. E.; Knoell, A. C.

1973-01-01

The human need for safe and effective dental implants is well-recognized. Although many implant designs have been tested and are in use today, a large number have resulted in clinical failure. These failures appear to be due to biomechanical effects, as well as biocompatibility and surgical factors. A unified approach is proposed using multidisciplinary systems technology, for the study of the biomechanical interactions between dental implants and host tissues. The approach progresses from biomechanical modeling and analysis, supported by experimental investigations, through implant design development, clinical verification, and education of the dental practitioner. The result of the biomechanical modeling, analysis, and experimental phases would be the development of scientific design criteria for implants. Implant designs meeting these criteria would be generated, fabricated, and tested in animals. After design acceptance, these implants would be tested in humans, using efficient and safe surgical and restorative procedures. Finally, educational media and instructional courses would be developed for training dental practitioners in the use of the resulting implants.
Multiple intracerebroventricular injections of human umbilical cord mesenchymal stem cells delay motor neurons loss but not disease progression of SOD1G93A mice.

PubMed

Sironi, Francesca; Vallarola, Antonio; Violatto, Martina Bruna; Talamini, Laura; Freschi, Mattia; De Gioia, Roberta; Capelli, Chiara; Agostini, Azzurra; Moscatelli, Davide; Tortarolo, Massimo; Bigini, Paolo; Introna, Martino; Bendotti, Caterina

2017-12-01

Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection. This prompted us to assess the effect of repeated ICV injections of hUC-MSCs on disease progression in SOD1G93A mice. Although no transplanted cells migrated to the spinal cord, a partial but significant protection of motor neurons (MNs) was found in the lumbar spinal cord of hUC-MSCs-treated SOD1G93A mice, accompanied by a shift from a pro-inflammatory (IL-6, IL-1β) to anti-inflammatory (IL-4, IL-10) and neuroprotective (IGF-1) environment in the lumbar spinal cord, probably linked to the activation of p-Akt survival pathway in both motor neurons and reactive astrocytes. However, this treatment neither prevented the muscle denervation nor delayed the disease progression of mice, emphasizing the growing evidence that protecting the motor neuron perikarya is not sufficient to delay the ALS progression. Copyright © 2017. Published by Elsevier B.V.
The smell of environmental change: Using floral scent to explain shifts in pollinator attraction1

PubMed Central

Burkle, Laura A.; Runyon, Justin B.

2017-01-01

As diverse environmental changes continue to influence the structure and function of plant–pollinator interactions across spatial and temporal scales, we will need to enlist numerous approaches to understand these changes. Quantitative examination of floral volatile organic compounds (VOCs) is one approach that is gaining popularity, and recent work suggests that floral VOCs hold substantial promise for better understanding and predicting the effects of environmental change on plant–pollinator interactions. Until recently, few ecologists were employing chemical approaches to investigate mechanisms by which components of environmental change may disrupt these essential mutualisms. In an attempt to make these approaches more accessible, we summarize the main field, laboratory, and statistical methods involved in capturing, quantifying, and analyzing floral VOCs in the context of changing environments. We also highlight some outstanding questions that we consider to be highly relevant to making progress in this field. PMID:28690928
'Mendelian randomization': an approach for exploring causal relations in epidemiology.

PubMed

Gupta, V; Walia, G K; Sachdeva, M P

2017-04-01

To assess the current status of Mendelian randomization (MR) approach in effectively influencing the observational epidemiology for examining causal relationships. Narrative review on studies related to principle, strengths, limitations, and achievements of MR approach. Observational epidemiological studies have repeatedly produced several beneficiary associations which were discarded when tested by standard randomized controlled trials (RCTs). The technique which is more feasible, highly similar to RCTs, and has the potential to establish a causal relationship between modifiable exposures and disease outcomes is known as MR. The technique uses genetic variants related to modifiable traits/exposures as instruments for detecting causal and directional associations with outcomes. In the last decade, the approach of MR has methodologically developed and progressed to a stage of high acceptance among the epidemiologists and is gradually expanding the landscape of causal relationships in non-communicable chronic diseases. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Vitrification in human and domestic animal embryology: work in progress.

PubMed

Vajta, Gábor

2013-01-01

According to the analysis of papers published in major international journals, rapidly increasing application of vitrification is one of the greatest achievements in domestic animal and especially human embryology during the first decade of our century. This review highlights factors supporting or hampering this progress, summarises results achieved with vitrification and outlines future tasks to fully exploit the benefits of this amazing approach that has changed or will change many aspects of laboratory (and also clinical) embryology. Supporting factors include the simplicity, cost efficiency and convincing success of vitrification compared with other approaches in all species and developmental stages in mammalian embryology, while causes that slow down the progress are mostly of human origin: inadequate tools and solutions, superficial teaching, improper application and unjustified concerns resulting in legal restrictions. Elimination of these hindrances seems to be a slower process and more demanding task than meeting the biological challenge. A key element of future progress will be to pass the pioneer age, establish a consensus regarding biosafety requirements, outline the indispensable features of a standard approach and design fully-automated vitrification machines executing all phases of the procedure, including equilibration, cooling, warming and dilution steps.
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
DNA and histone methylation in gastric carcinogenesis

PubMed Central

Calcagno, Danielle Queiroz; Gigek, Carolina Oliveira; Chen, Elizabeth Suchi; Burbano, Rommel Rodriguez; Smith, Marília de Arruda Cardoso

2013-01-01

Epigenetic alterations contribute significantly to the development and progression of gastric cancer, one of the leading causes of cancer death worldwide. Epigenetics refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA, and these changes lead to transcriptional activation or silencing of the gene. Over the years, the study of epigenetic processes has increased, and novel therapeutic approaches that target DNA methylation and histone modifications have emerged. A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment. Here, we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome. PMID:23482412

HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression.

PubMed

Keith, Brian; Johnson, Randall S; Simon, M Celeste

2011-12-15

Hypoxia-inducible factors (HIFs) are broadly expressed in human cancers, and HIF1α and HIF2α were previously suspected to promote tumour progression through largely overlapping functions. However, this relatively simple model has now been challenged in light of recent data from various approaches that reveal unique and sometimes opposing activities of these HIFα isoforms in both normal physiology and disease. These effects are mediated in part through the regulation of unique target genes, as well as through direct and indirect interactions with important oncoproteins and tumour suppressors, including MYC and p53. As HIF inhibitors are currently undergoing clinical evaluation as cancer therapeutics, a more thorough understanding of the unique roles performed by HIF1α and HIF2α in human neoplasia is warranted.
Oral feeding readiness assessment in premature infants.

PubMed

Gennattasio, Annmarie; Perri, Elizabeth A; Baranek, Donna; Rohan, Annie

2015-01-01

Oral feeding readiness is a complex concept. More evidence is needed on how to approach beginning oral feedings in premature hospitalized infants. This article provides a review of literature related to oral feeding readiness in the premature infant and strategies for promoting safe and efficient progression to full oral intake. Oral feeding readiness assessment tools, clinical pathways, and feeding advancement protocols have been developed to assist with oral feeding initiation and progression. Recognition and support of oral feeding readiness may decrease length of hospital stay and have a positive impact on reducing healthcare costs. Supporting effective cue-based oral feeding through use of rigorous assessment or evidence-based care guidelines can also optimize the hospital experience for infants and caregivers, which, in turn, can promote attachment and parent satisfaction.
G Protein-coupled Estrogen Receptor Protects from Atherosclerosis

PubMed Central

Meyer, Matthias R.; Fredette, Natalie C.; Howard, Tamara A.; Hu, Chelin; Ramesh, Chinnasamy; Daniel, Christoph; Amann, Kerstin; Arterburn, Jeffrey B.; Barton, Matthias; Prossnitz, Eric R.

2014-01-01

Coronary atherosclerosis and myocardial infarction in postmenopausal women have been linked to inflammation and reduced nitric oxide (NO) formation. Natural estrogen exerts protective effects on both processes, yet also displays uterotrophic activity. Here, we used genetic and pharmacologic approaches to investigate the role of the G protein-coupled estrogen receptor (GPER) in atherosclerosis. In ovary-intact mice, deletion of gper increased atherosclerosis progression, total and LDL cholesterol levels and inflammation while reducing vascular NO bioactivity, effects that were in some cases aggravated by surgical menopause. In human endothelial cells, GPER was expressed on intracellular membranes and mediated eNOS activation and NO formation, partially accounting for estrogen-mediated effects. Chronic treatment with G-1, a synthetic, highly selective small molecule agonist of GPER, reduced postmenopausal atherosclerosis and inflammation without uterotrophic effects. In summary, this study reveals an atheroprotective function of GPER and introduces selective GPER activation as a novel therapeutic approach to inhibit postmenopausal atherosclerosis and inflammation in the absence of uterotrophic activity. PMID:25532911
Technology for return of planetary samples, 1977

NASA Technical Reports Server (NTRS)

1978-01-01

Recent progress on the development of a basic warning system (BWS) proposed to assess the biohazard of a Mars sample returned to earth, an earth orbiting spacecraft, or to a moon base was presented. The BWS package consists of terrestrial microorganisms representing major metabolic pathways. A vital processes component of the BWS will examine the effects of a Mars sample at terrestrial atmospheric conditions while a hardy organism component will examine the effects of a Mars sample under conditions approaching those of the Martian environment. Any deleterious insult on terrestrial metabolism effected by the Mars sample could be indicated long before the sample reached earth proximity.
Integrative medical therapy: examination of meditation's therapeutic and global medicinal outcomes via nitric oxide (review).

PubMed

Stefano, George B; Esch, Tobias

2005-10-01

Relaxation techniques are part of the integrative medicine movement that is of growing importance for mainstream medicine. Complementary medical therapies have the potential to affect many physiological systems. Repeatedly studies show the benefits of the placebo response and relaxation techniques in the treatment of hypertension, cardiac arrhythmias, chronic pain, insomnia, anxiety and mild and moderate depression, premenstrual syndrome, and infertility. In itself, relaxation is characterized by a decreased metabolism, heart rate, blood pressure, and rate of breathing as well as an increase in skin temperature. Relaxation approaches, such as progressive muscle relaxation, autogenic training, meditation and biofeedback, are effective in lowering systolic and diastolic blood pressure in hypertensive patients by a significant margin. Given this association with changes in vascular tone, we have hypothesized that nitric oxide, a demonstrated vasodilator substance, contribute to physiological activity of relaxation approaches. We examined the scientific literature concerning the disorders noted earlier for their nitric oxide involvement in an attempt to provide a molecular rationale for the positive effects of relaxation approaches, which are physiological and cognitive process. We conclude that constitutive nitric oxide may crucially contribute to potentially beneficial outcomes and effects in diverse pathologies, exerting a global healing effect.
Novel approaches based on ultrasound for treatment of wastewater containing potassium ferrocyanide.

PubMed

Jawale, Rajashree H; Tandale, Akash; Gogate, Parag R

2017-09-01

Industrial wastewaters containing biorefractory compounds like cyanide offer significant environmental problems attributed to the fact that the conventional methods have limited effectiveness and hence developing efficient treatment approaches is an important requirement. The present work investigates the use of novel treatment approach of ultrasound (US) combined with advanced oxidation techniques for the degradation of potassium ferrocyanide (KFC) for the first time. An ultrasonic bath equipped with longitudinal horn (1kW rated power and 25kHz frequency) has been used. The effect of initial pH (2-9) on the progress of degradation has been investigated initially and subsequently using the optimized pH, effect of addition of hydrogen peroxide (ratio of KFC:H 2 O 2 varied over the range of 1:0.5-1:5) and TiO 2 in the presence of H 2 O 2 (1:1 ratio by weight of TiO 2 ) as process intensifying approach has been studied. Combination of ultrasonic irradiation with ozone (O 3 ) (100-400mg/h) and ultraviolet irradiation (UV) has also been investigated. Use of combination of US with H 2 O 2, H 2 O 2 +TiO 2 and ozone resulted in extent of KFC degradation as 54.2%, 74.82% and 82.41% respectively. Combination of US with both UV and ozone was established to be the best approach yielding 92.47% degradation. The study also focused on establishing kinetic rate constants for all the treatment approaches which revealed that all the approaches followed first order kinetic mechanism with higher rate constants for the combination approaches. Overall, it has been conclusively established that ultrasound based combined treatment schemes are very effective for the treatment of KFC containing wastewaters. Copyright © 2017 Elsevier B.V. All rights reserved.
The Future of Progressive Education

ERIC Educational Resources Information Center

Hayes, William

2008-01-01

What David J. Ferrero has called "the Hundred Year's War between "progressives" and "traditionalists"" continues unabated in the twenty-first century. Undoubtedly, current initiatives in public education favor those who support traditional approaches, yet many critics believe inflexible state tests are restricting…
Anti-inflammatory effects of flavonoids in neurodegenerative disorders.

PubMed

Spagnuolo, Carmela; Moccia, Stefania; Russo, Gian Luigi

2018-06-10

Neuroinflammation is one of the main mechanisms involved in the progression of several neurodegenerative diseases, such as Parkinson, Alzheimer, multiple sclerosis, amyotrophic lateral sclerosis and others. The activation of microglia is the main feature of neuroinflammation, promoting the release of pro-inflammatory cytokines and resulting in the progressive neuronal cell death. Natural compounds, such as flavonoids, possess neuroprotective potential probably related to their ability to modulate the inflammatory responses involved in neurodegenerative diseases. In fact, pure flavonoids (e.g., quercetin, genistein, hesperetin, epigallocatechin-3-gallate) or enriched-extracts, can reduce the expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2), down-regulate inflammatory markers and prevent neural damage. This anti-inflammatory activity is primarily related to the regulation of microglial cells, mediated by their effects on MAPKs and NF-κB signalling pathways, as demonstrated by in vivo and in vitro data. The present work reviews the role of inflammation in neurodegenerative diseases, highlighting the potential therapeutic effects of flavonoids as a promising approach to develop innovative neuroprotective strategy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Core principles of assessment in competency-based medical education.

PubMed

Lockyer, Jocelyn; Carraccio, Carol; Chan, Ming-Ka; Hart, Danielle; Smee, Sydney; Touchie, Claire; Holmboe, Eric S; Frank, Jason R

2017-06-01

The meaningful assessment of competence is critical for the implementation of effective competency-based medical education (CBME). Timely ongoing assessments are needed along with comprehensive periodic reviews to ensure that trainees continue to progress. New approaches are needed to optimize the use of multiple assessors and assessments; to synthesize the data collected from multiple assessors and multiple types of assessments; to develop faculty competence in assessment; and to ensure that relationships between the givers and receivers of feedback are appropriate. This paper describes the core principles of assessment for learning and assessment of learning. It addresses several ways to ensure the effectiveness of assessment programs, including using the right combination of assessment methods and conducting careful assessor selection and training. It provides a reconceptualization of the role of psychometrics and articulates the importance of a group process in determining trainees' progress. In addition, it notes that, to reach its potential as a driver in trainee development, quality care, and patient safety, CBME requires effective information management and documentation as well as ongoing consideration of ways to improve the assessment system.
An alternative approach to modelling HbA1c trajectories in patients with type 2 diabetes mellitus.

PubMed

McEwan, Phil; Bennett, Hayley; Qin, Lei; Bergenheim, Klas; Gordon, Jason; Evans, Marc

2017-05-01

Time-dependent HbA1c trajectories in health economic models of type 2 diabetes mellitus (T2DM) are typically informed by the UK Prospective Diabetes Study (UKPDS). However, this approach may not accurately predict HbA1c progression in patients who do not conform to the demographic profile of the original UKPDS cohort. This study aimed to develop an alternative mathematical model (MM) to simulate HbA1c progression in T2DM. A systematic literature review identified studies, published between 2005 and 2015, that reported HbA1c in adult T2DM patients over a minimum duration of 18 months. Pooled data from eligible studies were used to develop an alternative MM equation for HbA1c progression, which was then contrasted with the UKPDS 68 progression equation in illustrative scenarios. A total of 68 studies were eligible for data extraction (mean follow-up time 4.1 years). HbA1c progression was highly heterogeneous across studies, varying with baseline HbA1c, treatment group and patient age. The MM equation was fitted with parameters for mean baseline HbA1c (8.3%), initial change in HbA1c (-0.62%) and upper quartile of maximum observed HbA1c (9.3%). Differences in HbA1c trajectories between the MM and UKPDS approaches altered the timing of therapy escalation in illustrative scenarios. The MM represents an alternative approach to simulate HbA1c trajectories in T2DM models, as UKPDS data may not adequately reflect the heterogeneity of HbA1c profiles observed in clinical studies. However, the choice of approach should ultimately be determined by the characteristics of individual patients under consideration and the clinical face validity of the modelled trajectories. © 2016 John Wiley & Sons Ltd.
Proof Construction: Adolescent Development from Inductive to Deductive Problem-Solving Strategies.

ERIC Educational Resources Information Center

Foltz, Carol; And Others

1995-01-01

Studied 100 adolescents' approaches to problem-solving proofs and reasoning competence tasks. Found that a formal level of reasoning competence is associated with a deductive approach. Results support the notion of a cognitive development progression from an inductive approach to a deductive approach. (ETB)
Cost-effectiveness of the Decipher Genomic Classifier to Guide Individualized Decisions for Early Radiation Therapy After Prostatectomy for Prostate Cancer.

PubMed

Lobo, Jennifer M; Trifiletti, Daniel M; Sturz, Vanessa N; Dicker, Adam P; Buerki, Christine; Davicioni, Elai; Cooperberg, Matthew R; Karnes, R Jeffrey; Jenkins, Robert B; Den, Robert B; Showalter, Timothy N

2017-06-01

Controversy exists regarding the effectiveness of early adjuvant versus salvage radiation therapy after prostatectomy for prostate cancer. Estimates of prostate cancer progression from the Decipher genomic classifier (GC) could guide informed decision-making and improve the outcomes for patients. We developed a Markov model to compare the costs and quality-adjusted life years (QALYs) associated with GC-based treatment decisions regarding adjuvant therapy after prostatectomy with those of 2 control strategies: usual care (determined from patterns of care studies) and the alternative of 100% adjuvant radiation therapy. Using the bootstrapping method of sampling with replacement, the cases of 10,000 patients were simulated during a 10-year time horizon, with each subject having individual estimates for cancer progression (according to GC findings) and noncancer mortality (according to age). GC-based care was more effective and less costly than 100% adjuvant radiation therapy and resulted in cost savings up to an assay cost of $11,402. Compared with usual care, GC-based care resulted in more QALYs. Assuming a $4000 assay cost, the incremental cost-effectiveness ratio was $90,833 per QALY, assuming a 7% usage rate of adjuvant radiation therapy. GC-based care was also associated with a 16% reduction in the percentage of patients with distant metastasis at 5 years compared with usual care. The Decipher GC could be a cost-effective approach for genomics-driven cancer treatment decisions after prostatectomy, with improvements in estimated clinical outcomes compared with usual care. The individualized decision analytic framework applied in the present study offers a flexible approach to estimate the potential utility of genomic assays for personalized cancer medicine. Copyright © 2016 Elsevier Inc. All rights reserved.
Posttraumatic Stress Disorder: Five Vicious Cycles that Inhibit Effective Treatment.

PubMed

Ghaffarzadegan, Navid; Larson, Richard C

2015-01-01

Despite a wide range of studies and medical progress, it seems that we are far from significantly mitigating the problem of posttraumatic stress disorder (PTSD). The problem has major social and behavioral components. Developing innovative and effective policies requires a broad scope of analysis and consideration of the highly interconnected social, behavioral, and medical variables. In this article, we take a systems approach and offer an illustrative causal loop diagram which includes individual and social dynamics. Based on the map, we discuss 5 major barriers for effective interventions in PTSD. These barriers work as vicious cycles in the system, reduce effectiveness and therefore value of PTSD treatment. We also discuss policy implications of this perspective.
Non-pharmacological techniques for pain management in neonates.

PubMed

Golianu, Brenda; Krane, Elliot; Seybold, Jeannie; Almgren, Chris; Anand, K J S

2007-10-01

Significant progress in understanding the physiology, clinical correlates, and consequences of neonatal pain have resulted in greater attention to pain management during neonatal intensive care. A number of nonpharmacological therapies have been investigated, including nonnutritive sucking, with and without sucrose use, swaddling or facilitated tucking, kangaroo care, music therapy, and multi-sensorial stimulation. Although the efficacy of these approaches is clearly evident, they cannot provide analgesia for moderate or severe pain in the neonate. Further, some of these therapies cannot be effectively applied to all populations of critically ill neonates. Acupuncture, an ancient practice in Chinese medicine, has gained increasing popularity for symptom control among adults and older children. Acupuncture may provide an effective nonpharmacological approach for the treatment of pain in neonates, even moderate or severe pain, and should be considered for inclusion in a graduated multidisciplinary algorithm for neonatal pain management.
16 Weeks of Progressive Barefoot Running Training Changes Impact Force and Muscle Activation in Habitual Shod Runners

PubMed Central

Mezêncio, Bruno; Amadio, Alberto Carlos; Serrão, Julio Cerca

2016-01-01

Short-term effects of barefoot and simulated barefoot running have been widely discussed in recent years. Consequences of adopting barefoot running for a long period, including as a training approach, still remain unknown. The present study evaluated the influence of 16 weeks of progressive barefoot running training on impact force and muscle activation in habitual shod runners. Six habitual shod runners (3 men and 3 women, 29.5 ± 7.3 years) were tested barefoot (BF) and shod (SH), before and after 16 weeks of progressive barefoot running training. Tests consisted of running on instrumented treadmill at 9 km/h, for 10 minutes in each experimental condition. Nine data acquisitions (10 s) of vertical ground reaction force (VGRF) and electromyographic (EMG) signal were conducted in each experimental condition for each test. BF training was effective to alter VGRF and EMG parameters of running in habitual shod runners, regardless of footwear condition (SH or BF). The magnitude of first peak of VGRF (Fy1) and the impulse of the first 50 ms decreased after training for BF and SH (p<0.01). The activation reduced from PRE to POST training for four muscles in BF running (p<0.001), whereas only muscle gastrocnemius lateralis decreased significantly its activation (p<0.01) in SH running. A 16-week progressive barefoot running training seems to be an effective training strategy to reduce impact force, improve shock attenuation and to decrease muscle activation intensity, not only in BF running, but also in SH running, although BF condition seems to be more influenced by BF training. PMID:27907069
Evaluative studies in nuclear medicine research. Progress report, October 1, 1979-June 30, 1980

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

Potchen, E.J.

Effort since the last progress report (September 1979) has been directed toward assessing the potential short and long term benefits of continued development and application and medical research of emission computed tomograhy (ECT). This report contains a review of existing ECT technology, including functional descriptions of current and proposed image systems, for both sngle-photon ECT (SPECT) and positron ECT (PECT) approaches. Medical research and clinical topics to which ECT has been, or may be, applied are presented. One such area of investigation involves the effects of stroke. The application of ECT to laboratory research, and to clinical diagnosis and prognosis,more » of stroke may result in improved management of the disease. An illustration of the potential savings in the cost of management of stroke due to the effects of applied ECT research is included. The results represent a compilation of data collected from conversations with, and conference presentations by, ECT users, researchers and image system designers, and from a review of the literature.« less
Structure-based view on [PSI(+)] prion properties.

PubMed

Bondarev, Stanislav A; Zhouravleva, Galina A; Belousov, Mikhail V; Kajava, Andrey V

2015-01-01

Yeast [PSI(+)] prion is one of the most suitable and well characterized system for the investigation of the prion phenomenon. However, until recently, the lack of data on the 3D arrangement of Sup35p prion fibrils hindered progress in this area. The recent arrival in this field of new experimental techniques led to the parallel and in-register superpleated β-structure as a consensus model for Sup35p fibrils. Here, we analyzed the effect of amino acid substitutions of the Sup35 protein through the prism of this structural model. Application of a newly developed computational approach, called ArchCandy, gives us a better understanding of the effect caused by mutations on the fibril forming potential of Sup35 protein. This bioinformatics tool can be used for the design of new mutations with desired modification of prion properties. Thus, we provide examples of how today, having progress toward elucidation of the structural arrangement of Sup35p fibrils, researchers can advance more efficiently to a better understanding of prion [PSI(+)] stability and propagation.
Targeting tumor-associated macrophages by anti-tumor Chinese materia medica.

PubMed

Pu, Wei-Ling; Sun, Li-Kang; Gao, Xiu-Mei; Rüegg, Curzio; Cuendet, Muriel; Hottiger, Micheal O; Zhou, Kun; Miao, Lin; Zhang, Yun-Sha; Gebauer, Margaret

2017-10-01

Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.
Multiscale Modelling of Cancer Progression and Treatment Control: The Role of Intracellular Heterogeneities in Chemotherapy Treatment

NASA Astrophysics Data System (ADS)

Chaplain, Mark A. J.; Powathil, Gibin G.

Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.
Multiscale Modelling of Cancer Progression and Treatment Control: The Role of Intracellular Heterogeneities in Chemotherapy Treatment

NASA Astrophysics Data System (ADS)

Chaplain, Mark A. J.; Powathil, Gibin G.

2015-04-01

Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.

Monitoring Progress in Child Poverty Reduction: Methodological Insights and Illustration to the Case Study of Bangladesh

ERIC Educational Resources Information Center

Roche, Jose Manuel

2013-01-01

Important steps have been taken at international summits to set up goals and targets to improve the wellbeing of children worldwide. Now the world also has more and better data to monitor progress. This paper presents a new approach to monitoring progress in child poverty reduction based on the Alkire and Foster adjusted headcount ratio and an…
Ischemic diabetic retinopathy as a possible prognostic factor for chronic kidney disease progression

PubMed Central

Lee, W J; Sobrin, L; Kang, M H; Seong, M; Kim, Y J; Yi, J-H; Miller, J W; Cho, H Y

2014-01-01

Purpose To assess the value of diabetic retinopathy (DR) severity as a possible predictive prognostic factor for the progression of chronic kidney disease (CKD). Patients and methods Retrospective cohort study. Patients (51) who were initially diagnosed with DR and CKD were enrolled and their medical records were evaluated. The following ophthalmic factors were assessed by fluorescein angiography at the initial visit: area of capillary nonperfusion, presence of neovascularization and vitreous hemorrhage, and DR grade. The effect of these factors on CKD progression over the 2-year period of the study, defined as doubling of serum creatinine or the development of end-stage renal disease requiring dialysis or renal transplant, was evaluated. Results The study included 51 patients with DR and CKD; of these, 11 patients (21.6%) were found to have proliferative DR (PDR) and seven patients (13.7%) had high-risk PDR at baseline. Patients with ischemic DR, who showed extensive capillary nonperfusion (≥10 optic disc areas) in the retina, had a greater risk for CKD progression (hazard ratio=6.64; P=0.002). Conclusion We found that extensive capillary nonperfusion in the retina greatly increased the risk of progression of CKD in patients with DR. This suggests that the retina and the kidney may have shared risk factors for microvascular disease secondary to diabetes mellitus, and emphasizes the need for a team approach to diabetes care. PMID:24993319
MIF and D-DT are potential disease severity modifiers in male MS subjects

PubMed Central

Benedek, Gil; Meza-Romero, Roberto; Jordan, Kelley; Zhang, Ying; Nguyen, Ha; Kent, Gail; Li, Jia; Siu, Edwin; Frazer, Jenny; Piecychna, Marta; Du, Xin; Sreih, Antoine; Leng, Lin; Wiedrick, Jack; Caillier, Stacy J.; Offner, Halina; Oksenberg, Jorge R.; Yadav, Vijayshree; Bourdette, Dennis; Bucala, Richard; Vandenbark, Arthur A.

2017-01-01

Little is known about mechanisms that drive the development of progressive multiple sclerosis (MS), although inflammatory factors, such as macrophage migration inhibitory factor (MIF), its homolog D-dopachrome tautomerase (D-DT), and their common receptor CD74 may contribute to disease worsening. Our findings demonstrate elevated MIF and D-DT levels in males with progressive disease compared with relapsing-remitting males (RRMS) and female MS subjects, with increased levels of CD74 in females vs. males with high MS disease severity. Furthermore, increased MIF and D-DT levels in males with progressive disease were significantly correlated with the presence of two high-expression promoter polymorphisms located in the MIF gene, a −794CATT5–8 microsatellite repeat and a −173 G/C SNP. Conversely, mice lacking MIF or D-DT developed less-severe signs of experimental autoimmune encephalomyelitis, a murine model of MS, thus implicating both homologs as copathogenic contributors. These findings indicate that genetically controlled high MIF expression (and D-DT) promotes MS progression in males, suggesting that these two factors are sex-specific disease modifiers and raising the possibility that aggressive anti-MIF treatment of clinically isolated syndrome or RRMS males with a high-expresser genotype might slow or prevent the onset of progressive MS. Additionally, selective targeting of MIF:CD74 signaling might provide an effective, trackable therapeutic approach for MS subjects of both sexes. PMID:28923927
How to treat Parkinson's disease in 2013.

PubMed

Worth, Paul F

2013-02-01

Parkinson's disease is a common, progressive, debilitating disease with substantial physical, psychological and social implications. Pharmacological management is complex and should be individualised according to the needs of the patient. In early disease, treatment is generally highly effective, but medication becomes increasingly inadequate in controlling motor fluctuations and dyskinesias as the disease progresses. Non-motor symptoms, especially depression and dementia, require a holistic, multidisciplinary approach to maximise quality of life for patients and their carers. For the future, the ideal solution remains neuroprotection and restoration. Progress has been hampered by the lack of animal models that reflect the widespread brain pathology presumed to cause both motor and non-motor symptoms of PD in humans. Currently, agents are undergoing clinical trials in early, mildly affected patients, such as the plant-derived substance PYM50028 (Cogane), which promotes expression of endogenous neural growth factors and has shown promise in vitro and in animal models. Gene-therapy trials in progress rely on the viral vectors used to deliver the enzymatic machinery required for dopamine synthesis to the striatum. As PD progresses, adequate control of motor symptoms depends increasingly on continuous drug delivery, and greater physiological stimulation of dopamine receptors may help to prevent the development of LIDs and motor fluctuations. Efforts thus are afoot to develop better delivery systems for levodopa, and a new sustained-release formulation is in development.
Net benefits: assessing the effectiveness of clinical networks in Australia through qualitative methods

PubMed Central

2012-01-01

Background In the 21st century, government and industry are supplementing hierarchical, bureaucratic forms of organization with network forms, compatible with principles of devolved governance and decentralization of services. Clinical networks are employed as a key health policy approach to engage clinicians in improving patient care in Australia. With significant investment in such networks in Australia and internationally, it is important to assess their effectiveness and sustainability as implementation mechanisms. Methods In two purposively selected, musculoskeletal clinical networks, members and stakeholders were interviewed to ascertain their perceptions regarding key factors relating to network effectiveness and sustainability. We adopted a three-level approach to evaluating network effectiveness: at the community, network, and member levels, across the network lifecycle. Results Both networks studied are advisory networks displaying characteristics of the ‘enclave’ type of non-hierarchical network. They are hybrids of the mandated and natural network forms. In the short term, at member level, both networks were striving to create connectivity and collaboration of members. Over the short to medium term, at network level, both networks applied multi-disciplinary engagement in successfully developing models of care as key outputs, and disseminating information to stakeholders. In the long term, at both community and network levels, stakeholders would measure effectiveness by the broader statewide influence of the network in changing and improving practice. At community level, in the long term, stakeholders acknowledged both networks had raised the profile, and provided a ‘voice’ for musculoskeletal conditions, evidencing some progress with implementation of the network mission while pursuing additional implementation strategies. Conclusions This research sheds light on stakeholders’ perceptions of assessing clinical network effectiveness at community, network, and member levels during the network’s timeline, and on the role of networks and their contribution. Overall, stakeholders reported positive momentum and useful progress in network growth and development, and saw their networks as providing valuable mechanisms for meeting instrumental goals and pursuing collaborative interests. Network forms can prove their utility in addressing ‘wicked problems,’ and these Australian clinical networks present a practical approach to the difficult issue of clinician engagement in state-level implementation of best practice for improving patient care and outcomes. PMID:23122000
Frontal Mucocele Extended Orbita and Endoscopic Marsupialization Technique.

PubMed

Erdogan, Banu Atalay; Unlu, Nazmiye; Aydin, Sedat; Avci, Hakan

2018-06-01

Mucocele is benign, slow-growing, mucous-filled cystic lesions that arise in the paranasal sinuses. It causes progressive distension of the bony walls and induces compressive symptoms. Surgical treatment of paranasal sinus mucoceles includes endoscopic approach or external approach. The authors report a patient of frontal mucocele who presented with a history of progressive unilateral protrusion. Computed tomography scan revealed a large mucocele of the frontal sinus with orbital extension on the same side. He was successfully treated with endoscopic marsupialization without any serious complications.
Why health care corruption needs a new approach.

PubMed

Radin, Dagmar

2016-07-01

While corruption has been at the center of academic studies and on the agenda of international organizations for a couple of decades, in the health care sector corruption has not generated much interest or progress. At the centre of this issue is the lack of an interdisciplinary approach, which is warranted given the complexity of the issue and the lack of cooperation between STET scientifically rigorous academics and policy-makers, leaving room for more cooperation and progress. © The Author(s) 2015.
Walking impairment in patients with multiple sclerosis: exercise training as a treatment option.

PubMed

Motl, Robert W; Goldman, Myla D; Benedict, Ralph H B

2010-11-16

Multiple sclerosis (MS) is a chronic disease of the central nervous system that culminates in the progression of physical and cognitive disability over time. Walking impairment is a ubiquitous feature of MS and a sentinel characteristic of the later or advanced stages of the disease. This paper presents a conceptual rationale along with empirical evidence for exercise training as a rehabilitation approach for managing walking impairment and improving walking function in persons with MS. Conceptually, MS is associated with a decrease in physical activity, which, in turn, can result in deconditioning across multiple domains of physiological functioning. The resulting deconditioning feeds back and further drives physical inactivity until a threshold is reached that likely initiates the progression of walking impairment in MS. Empirically, physical activity and exercise training have been associated with beneficial effects on walking function in persons with MS. This is based on cross-sectional, longitudinal, and experimental research that included diversity in the breadth of measures of walking, persons with MS, and exercise/physical activity characteristics. Of particular importance, future researchers might consider examining the combinatory effects of exercise training plus pharmacological agents on walking mobility in MS. Collectively, exercise training and physical activity might hold significant potential for the management of progressive mobility disability in MS.
How can mathematical models advance tuberculosis control in high HIV prevalence settings?

PubMed

Houben, R M G J; Dowdy, D W; Vassall, A; Cohen, T; Nicol, M P; Granich, R M; Shea, J E; Eckhoff, P; Dye, C; Kimerling, M E; White, R G

2014-05-01

Existing approaches to tuberculosis (TB) control have been no more than partially successful in areas with high human immunodeficiency virus (HIV) prevalence. In the context of increasingly constrained resources, mathematical modelling can augment understanding and support policy for implementing those strategies that are most likely to bring public health and economic benefits. In this paper, we present an overview of past and recent contributions of TB modelling in this key area, and suggest a way forward through a modelling research agenda that supports a more effective response to the TB-HIV epidemic, based on expert discussions at a meeting convened by the TB Modelling and Analysis Consortium. The research agenda identified high-priority areas for future modelling efforts, including 1) the difficult diagnosis and high mortality of TB-HIV; 2) the high risk of disease progression; 3) TB health systems in high HIV prevalence settings; 4) uncertainty in the natural progression of TB-HIV; and 5) combined interventions for TB-HIV. Efficient and rapid progress towards completion of this modelling agenda will require co-ordination between the modelling community and key stakeholders, including advocates, health policy makers, donors and national or regional finance officials. A continuing dialogue will ensure that new results are effectively communicated and new policy-relevant questions are addressed swiftly.
The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis

PubMed Central

Holloman, Jameson P; Ho, Calvin C; Hukki, Arushi; Huntley, Jennifer L; Gallicano, G Ian

2013-01-01

This article examines the current use and future implications of stem cell therapy in treating Multiple Sclerosis (MS). MS is the most common neurological disease in young adults, affecting approximately two million people worldwide. Currently there is no cure for MS. The standard treatment of MS involves disease-modifying drugs, which work to alleviate the symptoms of MS. However, these drugs carry adverse side effects and are ineffective in preventing disease progression in many MS patients. Hematopoietic stem cell transplantation (HSCT) was first used in 1995 to treat patients with severe rapidly progressing MS. The HSCT treatment protocol has evolved into a less intense conditioning regimen that is currently demonstrating efficacy in treating patients with variable disease severity—with best results in early-stage rapidly progressing MS patients with active CNS inflammation. Mesenchymal stem cell therapy (MSCT) is an experimental stem cell therapy currently undergoing clinical trials. Animal models and early clinical trials have shown promise that MSCT might be a low risk treatment to precipitate neuroregeneration and immunomodulation in MS patients. Specifically, neuroprogenitor and placental-derived mesenchymal stem cells offer the best hope for a practical treatment for MS. Stem cell therapy, and perhaps a combinatorial therapeutic approach, holds promise for a better treatment for MS. PMID:23862098
Wind Power Electricity: The Bigger the Turbine, The Greener the Electricity?

PubMed Central

2012-01-01

Wind energy is a fast-growing and promising renewable energy source. The investment costs of wind turbines have decreased over the years, making wind energy economically competitive to conventionally produced electricity. Size scaling in the form of a power law, experience curves and progress rates are used to estimate the cost development of ever-larger turbines. In life cycle assessment, scaling and progress rates are seldom applied to estimate the environmental impacts of wind energy. This study quantifies whether the trend toward larger turbines affects the environmental profile of the generated electricity. Previously published life cycle inventories were combined with an engineering-based scaling approach as well as European wind power statistics. The results showed that the larger the turbine is, the greener the electricity becomes. This effect was caused by pure size effects of the turbine (micro level) as well as learning and experience with the technology over time (macro level). The environmental progress rate was 86%, indicating that for every cumulative production doubling, the global warming potential per kWh was reduced by 14%. The parameters, hub height and rotor diameter were identified as Environmental Key Performance Indicators that can be used to estimate the environmental impacts for a generic turbine. PMID:22475003
Wind power electricity: the bigger the turbine, the greener the electricity?

PubMed

Caduff, Marloes; Huijbregts, Mark A J; Althaus, Hans-Joerg; Koehler, Annette; Hellweg, Stefanie

2012-05-01

Wind energy is a fast-growing and promising renewable energy source. The investment costs of wind turbines have decreased over the years, making wind energy economically competitive to conventionally produced electricity. Size scaling in the form of a power law, experience curves and progress rates are used to estimate the cost development of ever-larger turbines. In life cycle assessment, scaling and progress rates are seldom applied to estimate the environmental impacts of wind energy. This study quantifies whether the trend toward larger turbines affects the environmental profile of the generated electricity. Previously published life cycle inventories were combined with an engineering-based scaling approach as well as European wind power statistics. The results showed that the larger the turbine is, the greener the electricity becomes. This effect was caused by pure size effects of the turbine (micro level) as well as learning and experience with the technology over time (macro level). The environmental progress rate was 86%, indicating that for every cumulative production doubling, the global warming potential per kWh was reduced by 14%. The parameters, hub height and rotor diameter were identified as Environmental Key Performance Indicators that can be used to estimate the environmental impacts for a generic turbine. © 2012 American Chemical Society
Statistical variation in progressive scrambling

NASA Astrophysics Data System (ADS)

Clark, Robert D.; Fox, Peter C.

2004-07-01

The two methods most often used to evaluate the robustness and predictivity of partial least squares (PLS) models are cross-validation and response randomization. Both methods may be overly optimistic for data sets that contain redundant observations, however. The kinds of perturbation analysis widely used for evaluating model stability in the context of ordinary least squares regression are only applicable when the descriptors are independent of each other and errors are independent and normally distributed; neither assumption holds for QSAR in general and for PLS in particular. Progressive scrambling is a novel, non-parametric approach to perturbing models in the response space in a way that does not disturb the underlying covariance structure of the data. Here, we introduce adjustments for two of the characteristic values produced by a progressive scrambling analysis - the deprecated predictivity (Q_s^{ast^2}) and standard error of prediction (SDEP s * ) - that correct for the effect of introduced perturbation. We also explore the statistical behavior of the adjusted values (Q_0^{ast^2} and SDEP 0 * ) and the sensitivity to perturbation (d q 2/d r yy ' 2). It is shown that the three statistics are all robust for stable PLS models, in terms of the stochastic component of their determination and of their variation due to sampling effects involved in training set selection.
Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression.

PubMed

Wu, Lijun; Zhang, Xu; Zhang, Bin; Shi, Hui; Yuan, Xiao; Sun, Yaoxiang; Pan, Zhaoji; Qian, Hui; Xu, Wenrong

2016-09-01

Exosomes are nano-sized membrane vesicles secreted by both normal and cancer cells. Emerging evidence indicates that cancer cells derived exosomes contribute to cancer progression through the modulation of tumor microenvironment. However, the effects of exosomes derived from gastric cancer cells on macrophages are not well understood. In this study, we investigated the biological role of gastric cancer cells derived exosomes in the activation of macrophages. We demonstrated that gastric cancer cells derived exosomes activated macrophages to express increased levels of proinflammatory factors, which in turn promoted tumor cell proliferation and migration. In addition, gastric cancer cells derived exosomes remarkably upregulated the phosphorylation of NF-κB in macrophages. Inhibiting the activation of NF-κB reversed the upregulation of proinflammatory factors in macrophages and blocked their promoting effects on gastric cancer cells. Moreover, we found that gastric cancer cells derived exosomes could also activate macrophages from human peripheral blood monocytes through the activation of NF-κB. In conclusion, our results suggest that gastric cancer cells derived exosomes stimulate the activation of NF-κB pathway in macrophages to promote cancer progression, which provides a potential therapeutic approach for gastric cancer by interfering with the interaction between exosomes and macrophages in tumor microenvironment.
Elucidating the ensemble of functionally-relevant transitions in protein systems with a robotics-inspired method.

PubMed

Molloy, Kevin; Shehu, Amarda

2013-01-01

Many proteins tune their biological function by transitioning between different functional states, effectively acting as dynamic molecular machines. Detailed structural characterization of transition trajectories is central to understanding the relationship between protein dynamics and function. Computational approaches that build on the Molecular Dynamics framework are in principle able to model transition trajectories at great detail but also at considerable computational cost. Methods that delay consideration of dynamics and focus instead on elucidating energetically-credible conformational paths connecting two functionally-relevant structures provide a complementary approach. Effective sampling-based path planning methods originating in robotics have been recently proposed to produce conformational paths. These methods largely model short peptides or address large proteins by simplifying conformational space. We propose a robotics-inspired method that connects two given structures of a protein by sampling conformational paths. The method focuses on small- to medium-size proteins, efficiently modeling structural deformations through the use of the molecular fragment replacement technique. In particular, the method grows a tree in conformational space rooted at the start structure, steering the tree to a goal region defined around the goal structure. We investigate various bias schemes over a progress coordinate for balance between coverage of conformational space and progress towards the goal. A geometric projection layer promotes path diversity. A reactive temperature scheme allows sampling of rare paths that cross energy barriers. Experiments are conducted on small- to medium-size proteins of length up to 214 amino acids and with multiple known functionally-relevant states, some of which are more than 13Å apart of each-other. Analysis reveals that the method effectively obtains conformational paths connecting structural states that are significantly different. A detailed analysis on the depth and breadth of the tree suggests that a soft global bias over the progress coordinate enhances sampling and results in higher path diversity. The explicit geometric projection layer that biases the exploration away from over-sampled regions further increases coverage, often improving proximity to the goal by forcing the exploration to find new paths. The reactive temperature scheme is shown effective in increasing path diversity, particularly in difficult structural transitions with known high-energy barriers.
Consensus–based approach to develop a measurement framework and identify a core set of indicators to track implementation and progress towards effective coverage of facility–based Kangaroo Mother Care

PubMed Central

Guenther, Tanya; Moxon, Sarah; Valsangkar, Bina; Wetzel, Greta; Ruiz, Juan; Kerber, Kate; Blencowe, Hannah; Dube, Queen; Vani, Shashi N; Vivio, Donna; Magge, Hema; De Leon–Mendoza, Socorro; Patterson, Janna; Mazia, Goldy

2017-01-01

Background As efforts to scale up the delivery of Kangaroo Mother Care (KMC) in facilities are increasing, a standardized approach to measure implementation and progress towards effective coverage is needed. Here, we describe a consensus–based approach to develop a measurement framework and identify a core set of indicators for monitoring facility–based KMC that would be feasible to measure within existing systems. Methods The KMC measurement framework and core list of indicators were developed through: 1) scoping exercise to identify potential indicators through literature review and requests from researchers and program implementers; and 2) face–to–face consultations with KMC and measurement experts working at country and global levels to review candidate indicators and finalize selection and definitions. Results The KMC measurement framework includes two main components: 1) service readiness, based on the WHO building blocks framework; and 2) service delivery action sequence covering identification, service initiation, continuation to discharge, and follow–up to graduation. Consensus was reached on 10 core indicators for KMC, which were organized according to the measurement framework. We identified 4 service readiness indicators, capturing national level policy for KMC, availability of KMC indicators in HMIS, costed operational plans for KMC and availability of KMC services at health facilities with inpatient maternity services. Six indicators were defined for service delivery, including weighing of babies at birth, identification of those ≤2000 g, initiation of facility–based KMC, monitoring the quality of KMC, status of babies at discharge from the facility and levels of follow–up (according to country–specific protocol). Conclusions These core KMC indicators, identified with input from a wide range of global and country–level KMC and measurement experts, can aid efforts to strengthen monitoring systems and facilitate global tracking of KMC implementation. As data collection systems advance, we encourage program managers and evaluators to document their experiences using this framework to measure progress and allow indicator refinement, with the overall aim of working towards sustainable, country–led data systems. PMID:29057074
Consensus-based approach to develop a measurement framework and identify a core set of indicators to track implementation and progress towards effective coverage of facility-based Kangaroo Mother Care.

PubMed

Guenther, Tanya; Moxon, Sarah; Valsangkar, Bina; Wetzel, Greta; Ruiz, Juan; Kerber, Kate; Blencowe, Hannah; Dube, Queen; Vani, Shashi N; Vivio, Donna; Magge, Hema; De Leon-Mendoza, Socorro; Patterson, Janna; Mazia, Goldy

2017-12-01

As efforts to scale up the delivery of Kangaroo Mother Care (KMC) in facilities are increasing, a standardized approach to measure implementation and progress towards effective coverage is needed. Here, we describe a consensus-based approach to develop a measurement framework and identify a core set of indicators for monitoring facility-based KMC that would be feasible to measure within existing systems. The KMC measurement framework and core list of indicators were developed through: 1) scoping exercise to identify potential indicators through literature review and requests from researchers and program implementers; and 2) face-to-face consultations with KMC and measurement experts working at country and global levels to review candidate indicators and finalize selection and definitions. The KMC measurement framework includes two main components: 1) service readiness, based on the WHO building blocks framework; and 2) service delivery action sequence covering identification, service initiation, continuation to discharge, and follow-up to graduation. Consensus was reached on 10 core indicators for KMC, which were organized according to the measurement framework. We identified 4 service readiness indicators, capturing national level policy for KMC, availability of KMC indicators in HMIS, costed operational plans for KMC and availability of KMC services at health facilities with inpatient maternity services. Six indicators were defined for service delivery, including weighing of babies at birth, identification of those ≤2000 g, initiation of facility-based KMC, monitoring the quality of KMC, status of babies at discharge from the facility and levels of follow-up (according to country-specific protocol). These core KMC indicators, identified with input from a wide range of global and country-level KMC and measurement experts, can aid efforts to strengthen monitoring systems and facilitate global tracking of KMC implementation. As data collection systems advance, we encourage program managers and evaluators to document their experiences using this framework to measure progress and allow indicator refinement, with the overall aim of working towards sustainable, country-led data systems.
Ionic liquids: Promising green solvents for lignocellulosic biomass utilization

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

Yoo, Chang Geun; Pu, Yunqiao; Ragauskas, Arthur J.

Ionic liquids are effective solvents/media for the utilization of lignocellulosic biomass. The unique properties of ionic liquids enable them to effectively dissolve and/or convert the biomass into various types of products. This review aims to cover the latest progress achieved in applications of ionic liquids on biomass conversion and analysis. Specifically, several recently developed approaches on how to overcome current challenges on the use of ionic liquids in the biomass conversion were highlighted. Here, recent studies addressing the potential applications of ionic liquids for the production of novel biomass-derived chemicals and materials were also discussed.
Gene therapy for arthritis

PubMed Central

Traister, Russell S.

2008-01-01

Arthritis is among the leading causes of disability in the developed world. There remains no cure for this disease and the current treatments are only modestly effective at slowing the disease's progression and providing symptomatic relief. The clinical effectiveness of current treatment regimens has been limited by short half-lives of the drugs and the requirement for repeated systemic administration. Utilizing gene transfer approaches for the treatment of arthritis may overcome some of the obstacles associated with current treatment strategies. The present review examines recent developments in gene therapy for arthritis. Delivery strategies, gene transfer vectors, candidate genes, and safety are also discussed. PMID:18176779
Translating supportability requirements into design reality

NASA Astrophysics Data System (ADS)

Buche, J.; Cohen, I.

1986-10-01

This paper explores some of the principal issues in the integration of supportability into the design process. Roles of the contractor's design, supportability and management specialists and their government counterparts are discussed as they relate to logistics influence in design. Methods and processes by which weapon system logistics and readiness requirements are established, assessed, allocated to system elements and translated into specific design features are described. Tradeoff consideration, an approach to effective tradeoff criteria, and the progress of supportability issues through the program phases are identified with particular emphasis on the necessity for developing and maintaining an effective audit trail.

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