Costo Efectividad del Tratamiento de Tumores Neuroendócrinos Pancreáticos Avanzados no Operables con Sunitinib en México.

PubMed

Muciño Ortega, Emilio; Chi-Chan, Alfredo; Peniche-Otero, Gustavo; Gutiérrez-Colín, Consuelo I; Herrera-Rojas, Joaquín; Galindo-Suárez, Rosa María

2012-12-01

Sunitinib had showed a substantial clinical benefit in patients with non-resectable pancreatic Neuroendocrine Tumors (NET). The objective of this study was to estimate the cost-effectiveness of sunitinib in the treatment of non-resectable pancreatic NET, from the perspective of the Social Security Mexican Institute (IMSS). A Markov model (2-week cycles) was used to estimate the health and economic consequences of sunitinib 37.5mg/day+best supportive care (BSC) regarding placebo+BSC (ten-years horizon, discount rate: 5%). Effectiveness measures were: overall survival (OS), progression-free survival (PFS) and quality adjusted life years (QALY). Resource utilization (BSC, adverse events management, medical follow-up) was estimated through a survey with Mexican oncologists (n=10). Unit costs of medication and medical resources were obtained from institutional sources. Sensitivity analyses were performed and acceptability curves were constructed. Sunitinib+BSC gained 0.49 years (PFS), 1.18 years (OS) and 0.70 QALY against placebo+BSC. Sunitinib+BSC increased medical direct costs (2011 US$) per patient in $20,854, which was driven by acquisition costs of sunitinib and medical follow up before progression. ICER's were $42,157, $17,662 and $29,808 per progression-free year, life-year and QALY gained, respectively, which remained robust through±25% changes in main parameters. At willingness to pay higher than $40,000, $22,400 and $37,600 sunitinib+BSC becomes the most cost-effective alternative in regards to PFS, OS and QALYs, respectively. At IMSS, sunitinib+BSC would provide substantial clinical benefits to patients suffering unresectable pancreatic NET, although the latter would increase medical costs of treatment and clinical follow up. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Experimental and Theoretical Studies of Atmosphereic Inorganic Chlorine Chemistry

NASA Technical Reports Server (NTRS)

Sander, Stanley P.; Friedl, Randall R.

1993-01-01

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

78 FR 61811 - National Domestic Violence Awareness Month, 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-04

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

What is Job Satisfaction?

ERIC Educational Resources Information Center

Locke. Edwin A.

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

Ten Years after "A Nation at Risk."

ERIC Educational Resources Information Center

Asayesh, Gelareh

1993-01-01

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

Social Programs That Work.

ERIC Educational Resources Information Center

Crane, Jonathan, Ed.

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

A plot twist: the continuing story of VCSELs at AOC

NASA Astrophysics Data System (ADS)

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

2005-03-01

During a year of substantial consolidation in the VCSEL industry, Honeywell sold their VCSEL Optical Products Division, which has now officially changed its name to Advanced Optical Components (AOC). Both manufacture and applied research continue, however. Some of the developments of the past year are discussed in this paper. They include advances in the understanding of VCSEL degradation physics, substantial improvements in long-wavelength VCSEL performance, and continuing progress in manufacturing technology. In addition, higher speed serial communications products, at 10 gigabits and particularly at 4 gigabits per second, have shown faster than predicted growth. We place these technologies and AOC's approach to them in a market perspective, along with other emerging applications.

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

PubMed

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

2017-04-01

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

Fibrosis progression in African Americans and Caucasian Americans with chronic hepatitis C.

PubMed

Terrault, Norah A; Im, Kelly; Boylan, Ross; Bacchetti, Peter; Kleiner, David E; Fontana, Robert J; Hoofnagle, Jay H; Belle, Steven H

2008-12-01

Prior studies suggest the rate of liver fibrosis progression is slower in African Americans (AAs) than Caucasian Americans (CAs) with chronic HCV infection. With a multi-state Markov model, fibrosis progression was evaluated in a well-characterized cohort of 143 AA and 157 CA adults with untreated chronic HCV genotype 1 infection. In subjects with a history of injection drug use, duration of infection was imputed from a fitted risk model rather than assumed to be the reported first year of use. The distribution of Ishak fibrosis stages was 0 (8.7%), 1/2 (55.7%), 3/4 (29.3%), and 5/6 (6.3%) and was similar in AAs and CAs (P = .22). After adjusting for biopsy adequacy, AAs had a 10% lower rate of fibrosis progression than did CAs, but the difference was not statistically significant (hazard ratio, 0.90; 95% confidence interval, 0.72-1.12). The overall 20-year estimates of probabilities of progression from stage 0 to stages 1/2, 3/4, and 5/6 were 59.3%, 28.8%, and 4.7%, respectively. The estimated median time from no fibrosis to cirrhosis was 79 years for the entire cohort and 74 and 83 years for CAs and AAs, respectively. In 3-variable models including race and biopsy adequacy, the factors significantly associated with fibrosis progression were age when infected, steatosis, ALT level, and necroinflammatory score. The rates of fibrosis progression were slow and did not appear to differ substantially between AAs and CAs.

Current and innovative pain management techniques in total knee arthroplasty.

PubMed

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

2012-01-01

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

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

Code of Federal Regulations, 2010 CFR

2010-07-01

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

Knowledge Mobilisation in the Polish Education System

ERIC Educational Resources Information Center

Fazlagic, Jan; Erkol, Arif

2015-01-01

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

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

PubMed

Hazarika, Indrajit

2012-05-01

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

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

PubMed

Warner, Kenneth E; Tam, Jamie

2012-03-01

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

2016 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

Satyapal, Sunita

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

2010 Annual Progress Report: DOE Hydrogen Program

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

Not Available

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

2015 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

Popovich, Neil

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

2012 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

Not Available

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

(Photosynthesis in intact plants)

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

Not Available

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

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

ERIC Educational Resources Information Center

Rice, Jennifer King

2015-01-01

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

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

ERIC Educational Resources Information Center

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

2015-01-01

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

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

ERIC Educational Resources Information Center

Her Majesty's Inspectorate of Education, 2007

2007-01-01

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

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

ERIC Educational Resources Information Center

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

2018-01-01

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

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

ERIC Educational Resources Information Center

Teachman, Jay

2010-01-01

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

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

ERIC Educational Resources Information Center

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

2010-01-01

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

Profile of medical care costs in patients with amyotrophic lateral sclerosis in the Medicare programme and under commercial insurance.

PubMed

Meng, Lisa; Bian, Amy; Jordan, Scott; Wolff, Andrew; Shefner, Jeremy M; Andrews, Jinsy

2018-02-01

To determine amyotrophic lateral sclerosis (ALS)-associated costs incurred by patients covered by Medicare and/or commercial insurance before, during and after diagnosis and provide cost details. Costs were calculated from the Medicare Standard Analytical File 5% sample claims data from Parts A and B from 2009, 2010 and 2011 for ALS Medicare patients aged ≥70 years (monthly costs) and ≥65 years (costs associated with disability milestones). Commercial insurance patients aged 18-63 years were selected based on the data provided in the Coordination of Benefits field from Truven MarketScan® in 2008-2010. Monthly costs increased nine months before diagnosis, peaked during the index month (Medicare: $10,398; commercial: $9354) and decreased but remained high post-index. Costs generally shifted from outpatient to inpatient and private nursing after diagnosis; prescriptions and durable medical equipment costs were much higher for commercial patients post-diagnosis. Patients appeared to progress to disability milestones more rapidly as their disease progressed in severity (14.4 months to non-invasive ventilation [NIV] vs. 16.6 months to hospice), and their costs increased accordingly (NIV: $58,973 vs. hospice: $76,179). For newly diagnosed ALS patients in the U.S., medical costs are substantial and increase rapidly and substantially with each disability milestone.

Timely disclosure of progress in long-term cancer survival: the boomerang method substantially improved estimates in a comparative study.

PubMed

Brenner, Hermann; Jansen, Lina

2016-02-01

Monitoring cancer survival is a key task of cancer registries, but timely disclosure of progress in long-term survival remains a challenge. We introduce and evaluate a novel method, denoted "boomerang method," for deriving more up-to-date estimates of long-term survival. We applied three established methods (cohort, complete, and period analysis) and the boomerang method to derive up-to-date 10-year relative survival of patients diagnosed with common solid cancers and hematological malignancies in the United States. Using the Surveillance, Epidemiology and End Results 9 database, we compared the most up-to-date age-specific estimates that might have been obtained with the database including patients diagnosed up to 2001 with 10-year survival later observed for patients diagnosed in 1997-2001. For cancers with little or no increase in survival over time, the various estimates of 10-year relative survival potentially available by the end of 2001 were generally rather similar. For malignancies with strongly increasing survival over time, including breast and prostate cancer and all hematological malignancies, the boomerang method provided estimates that were closest to later observed 10-year relative survival in 23 of the 34 groups assessed. The boomerang method can substantially improve up-to-dateness of long-term cancer survival estimates in times of ongoing improvement in prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathways in Learning to Teach Elementary Science: Navigating Contexts, Roles, Affordances and Constraints

NASA Astrophysics Data System (ADS)

Smith, Deborah C.; Jang, Shinho

2011-12-01

This case study of a fifth-year elementary intern's pathway in learning to teach science focused on her science methods course, placement science teaching, and reflections as a first-year teacher. We studied the sociocultural contexts within which the intern learned, their affordances and constraints, and participants' perspectives on their roles and responsibilities, and her learning. Semi-structured interviews were conducted with all participants. Audiotapes of the science methods class, videotapes of her science teaching, and field notes were collected. Data were transcribed and searched for affordances or constraints within contexts, perspectives on roles and responsibilities, and how views of her progress changed. Findings show the intern's substantial progress, the ways in which affordances sometimes became constraints, and participants' sometimes contradictory perspectives.

State-Level Progress in Reducing the Black–White Infant Mortality Gap, United States, 1999–2013

PubMed Central

Goldfarb, Samantha Sittig; Wells, Brittny A.; Beitsch, Leslie; Levine, Robert S.; Rust, George

2017-01-01

Objectives. To assess state-level progress on eliminating racial disparities in infant mortality. Methods. Using linked infant birth–death files from 1999 to 2013, we calculated state-level 3-year rolling average infant mortality rates (IMRs) and Black–White IMR ratios. We also calculated percentage improvement and a projected year for achieving equality if current trend lines are sustained. Results. We found substantial state-level variation in Black IMRs (range = 6.6–13.8) and Black–White rate ratios (1.5–2.7), and also in percentage relative improvement in IMR (range = 2.7% to 36.5% improvement) and in Black–White rate ratios (from 11.7% relative worsening to 24.0% improvement). Thirteen states achieved statistically significant reductions in Black–White IMR disparities. Eliminating the Black–White IMR gap would have saved 64 876 babies during these 15 years. Eighteen states would achieve IMR racial equality by the year 2050 if current trends are sustained. Conclusions. States are achieving varying levels of progress in reducing Black infant mortality and Black–White IMR disparities. Public Health Implications. Racial equality in infant survival is achievable, but will require shifting our focus to determinants of progress and strategies for success. PMID:28323476

Assessing the Risk of Progression From Asymptomatic Left Ventricular Dysfunction to Overt Heart Failure: A Systematic Overview and Meta-Analysis.

PubMed

Echouffo-Tcheugui, Justin B; Erqou, Sebhat; Butler, Javed; Yancy, Clyde W; Fonarow, Gregg C

2016-04-01

This study sought to provide estimates of the risk of progression to overt heart failure (HF) from systolic or diastolic asymptomatic left ventricular dysfunction through a systematic review and meta-analysis. Precise population-based estimates on the progression from asymptomatic left ventricular dysfunction (or stage B HF) to clinical HF (stage C HF) remain limited, despite its prognostic and clinical implications. Pre-emptive intervention with neurohormonal modulation may attenuate disease progression. MEDLINE and EMBASE were systematically searched (until March 2015). Cohort studies reporting on the progression from asymptomatic left ventricular systolic dysfunction (ALVSD) or asymptomatic left ventricular diastolic dysfunction (ALVDD) to overt HF were included. Effect estimates (prevalence, incidence, and relative risk) were pooled using a random-effects model meta-analysis, separately for systolic and diastolic dysfunction, with heterogeneity assessed with the I(2) statistic. Thirteen reports based on 11 distinct studies of progression of ALVSD were included in the meta-analysis assessing a total of 25,369 participants followed for 7.9 years on average. The absolute risks of progression to HF were 8.4 per 100 person-years (95% confidence interval [CI]: 4.0 to 12.8 per 100 person-years) for those with ALVSD, 2.8 per 100 person-years (95% CI: 1.9 to 3.7 per 100 person-years) for those with ALVDD, and 1.04 per 100 person-years (95% CI: 0.0 to 2.2 per 100 person-years) without any ventricular dysfunction evident. The combined maximally adjusted relative risk of HF for ALVSD was 4.6 (95% CI: 2.2 to 9.8), and that of ALVDD was 1.7 (95% CI: 1.3 to 2.2). ALVSD and ALVDD are each associated with a substantial risk for incident HF indicating an imperative to develop effective intervention at these stages. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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

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

Not Available

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

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

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

Not Available

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

Industry benefits from recent genetic progress in sheep and beef populations.

PubMed

Amer, P R; Nieuwhof, G J; Pollott, G E; Roughsedge, T; Conington, J; Simm, G

2007-11-01

An analytical model that evaluates the benefits from 10 years of genetic improvement over a 20-year time frame was specified. Estimates of recent genetic trends in recorded traits, industry statistics and published estimates of the economic values of trait changes were used to parameterise the model for the UK sheep and beef industries. Despite rates of genetic change in the relevant performance-recorded breeding populations being substantially less than theoretical predictions, the financial benefits of genetic change were substantial. Over 20 years, the benefits from 10 years of genetic progress at recently achieved rates in recorded hill sheep, sheep crossing sire and sheep terminal sire breeding programmes was estimated to be £5.3, £1.0 and £11.5 million, respectively. If dissemination of genetic material is such that these rates of change are also realised across the entire ram breeding industry, the combined benefits would be £110.8 million. For beef cattle, genetic evaluation systems have been operating within all the major breeds for some years with quite widespread use of performance recording, and so genetic trends within the beef breeds were used as predictors of industry genetic change. Benefits from 10 years of genetic progress at recent rates of change, considering a 20-year time frame, in terminal sire beef breeds are expected to be £4.9 million. Benefits from genetic progress for growth and carcass characters in dual-purpose beef breeds were £18.2 million after subtraction of costs associated with a deterioration in calving traits. These benefits may be further offset by unfavourable associated changes in maternal traits. Additional benefits from identification and use of the best animals available from the breeding sector for commercial matings through performance recording and genetic evaluation could not be quantified. When benefits of genetic improvement were expressed on an annual present value basis and compared with lagged annual investment costs to achieve it, the internal rate of return (IRR) on the combined investment in sheep and beef cattle was 32%. Despite a much higher rate of participation in performance recording, the present value of benefits and the IRR were lower for beef cattle than for sheep. The implications of these results for future national and industry investment in genetic improvement infrastructure were discussed.

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

PubMed

Williams, M J; Lang-Lenton, M

2011-01-01

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

Effectiveness study of atropine for progressive myopia in Europeans.

PubMed

Polling, J R; Kok, R G W; Tideman, J W L; Meskat, B; Klaver, C C W

2016-07-01

PurposeRandomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a non-Asian country.MethodsAn effectiveness study was performed in Rotterdam, the Netherlands. Overall 77 children (mean age 10.3 years±2.3), of European (n=53), Asian (n=18), and African (n=6) descent with progressive myopia were prescribed atropine 0.5% eye drops daily. Both parents and children filled in a questionnaire regarding adverse events and adherence to therapy. A standardized eye examination including cycloplegic refraction and axial length was performed at baseline and 1, 4, and 12 months after initiation of therapy.ResultsMean spherical equivalent at baseline was -6.6D (±3.3). The majority (60/77, 78%) of children adhered to atropine treatment for 12 months; 11 of the 17 children who discontinued therapy did so within 1 month after the start of therapy. The most prominent reported adverse events were photophobia (72%), followed by reading problems (38%), and headaches (22%). The progression rate of spherical equivalent before treatment (-1.0D/year±0.7) diminished substantially during treatment (-0.1D/year±0.7) compared to those who ceased therapy (-0.5D/year±0.6; P=0.03).ConclusionsDespite the relatively high occurrence of adverse events, our study shows that atropine can be an effective and sustainable treatment for progressive high myopia in Europeans.

Review: Semen sexing - current state of the art with emphasis on bovine species.

PubMed

Vishwanath, R; Moreno, J F

2018-06-01

It is approaching three decades since the first public evidence of sex-sorting of semen. The technology has progressed considerably since then with a number of institutions and researchers collaborating to eventually bring this to application. The technical challenges have been quite substantial and in the early years the application was limited to only heifer inseminations. Comparable fertility of sex-sorted semen with conventional semen has been an aspirational benchmark for the industry for many years. Significant investment in research in the primary biology of sex-sorted sperm and associated sorting equipment ensured steady progress over the years and current methods particularly the new SexedULTRA-4M™ seems to have now mostly bridged this fertility gap. The dairy and beef industry have adopted this technology quite rapidly. Other animal industries are progressively testing it for application in their specific niches and environments. The current state of the art in the fundamentals of sex-sorting, the biology of the process as well as new developments in machinery are described in this review.

Controlling Tumor Progression with Cyclophosphamide, Vincristine, and Dacarbazine Treatment Improves Survival in Patients with Metastatic and Unresectable Malignant Pheochromocytomas/Paragangliomas.

PubMed

Asai, Shiko; Katabami, Takuyuki; Tsuiki, Mika; Tanaka, Yasushi; Naruse, Mitsuhide

2017-04-01

Evidence has not been established to support that combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) improves survival in patients with malignant pheochromocytoma and paraganglioma (M-PPGL). To investigate the efficacy of CVD for this disease, we retrospectively analyzed data of 23 patients with metastatic and unresectable M-PPGL (mean age, 41.7 ± 15.4 years) who received at least 2 cycles of this regimen. The follow-up period after initiation of CVD ranged from 0.3 to 13.7 years, with a median of 3.3 years. CVD therapy achieved a complete tumor response (CR) in 1 patient (4%), a partial response (PR) in 5 (22%), stable disease (SD) in 5 (22%), and progressive disease (PD) in 13 (52%), respectively. All of the responders (CR and PR) but 6% of the non-responders (SD and PD) showed substantial biochemical improvement. The progression-free survival period in the responders was significantly longer than in the non-responders (p < 0.01). Although the overall survival and survival after the diagnosis of M-PPGL were longer in the responders than the non-responders, the difference was not statistically significant (p = 0.08). The progression-free and overall survival period were significantly longer in the non-progression group (CR, PR, and SD) than in the progression group (PD) (1.7 ± 3.3 vs. 0.3 ± 0.3 years, p < 0.01, and 4.6 ± 3.6 vs. 2.0 ± 3.7 years, p = 0.01, respectively). It is therefore suggested that CVD chemotherapy could be useful in controlling tumor progression and improving survival in patients with metastatic and progressive M-PPGL.

Magnetic bearings: Fifty years of progress

NASA Technical Reports Server (NTRS)

Swann, Michael K.

1993-01-01

Magnetic bearings are just beginning to be flown in spacecraft systems, but their development spans more than 50 years. The promise of completely noncontacting, unlubricated rotating systems operating at speeds substantially beyond the range of conventional bearings, and with no wear and virtually no vibration, has provided the incentive to develop magnetic bearing technology for many diverse applications. Earnshaw theorized in 1842 that stable magnetic suspension is not possible in all three spatial directions unless the magnetic field is actively controlled. Since that time, researchers have attempted to successfully support spinning rotors in a stable manner. Development of magnetic suspension systems over the past fifty years has included progress on both passive (permanent magnet) and active (electromagnet) systems. The improvements in bearing load capacity, stiffness, and damping characteristics are traced. The trends in rotor size, rotational kinetic energy, and improvements in active control systems capabilities are also reviewed. Implications of superconductivity on suspension system design and performance are discussed.

24 CFR 598.430 - Revocation of designation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... approval from HUD; (2) Has failed to make progress in implementing the strategic plan; or (3) Has not complied substantially with the strategic plan. (b) Letter of warning. Before revoking the designation of... complying substantially with, or has failed to make progress in implementing the strategic plan; and (2...

24 CFR 598.430 - Revocation of designation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... approval from HUD; (2) Has failed to make progress in implementing the strategic plan; or (3) Has not complied substantially with the strategic plan. (b) Letter of warning. Before revoking the designation of... complying substantially with, or has failed to make progress in implementing the strategic plan; and (2...

From Fancy to Reason: Scaling Deaf and Hearing Children's Understanding of Theory of Mind and Pretence

ERIC Educational Resources Information Center

Peterson, Candida C.; Wellman, Henry M.

2009-01-01

We examined deaf and hearing children's progression of steps in theory of mind (ToM) development including their understanding of social pretending. Ninety-three children (33 deaf; 60 hearing) aged 3-13 years were tested on a set of six closely matched ToM tasks. Results showed that deaf children were delayed substantially behind hearing children…

Karhunen-Loeve Analysis of SCIGN GPS Data

NASA Technical Reports Server (NTRS)

Rundle, John B.; Tiampo, Kristy; Gross, Susanna

2004-01-01

During the final year of this project, we made substantial progress on the proposed work. Specifically, we have continued the horizontal and vertical Karhunen-Loeve (KL) analysis of SCIGN data and implemented the study of a number of particular modes. In particular, we studied the spatial and temporal interactions of these modes in an effort to better understand and model the source of each signal.

Structural Integrity of Water Reactor Pressure Boundary Components.

DTIC Science & Technology

1979-12-31

fatigue crack growth is also on-going. Substantial progress in all three of the areas - fatigue data generation, fractography and micromechanism... Fractographie Examinations During the past year, there have been several fractographic studies and fractographically-related research efforts which have been...in the T-L orientation were characterized by a m icrostructural texture running parallel to the macroscopic crack propagation direction (Fig. 31). This

Missing data in forest ecology and management: advances in quantitative methods [Preface

Treesearch

Tara Barrett; Matti Maltomo

2012-01-01

In recent years, substantial progress has been made for handling missing data issues for applications in forest ecology and management, particularly in the area of imputation techniques. A session on this topic was held at the XXlll IUFRO World Congress in Seoul, South Korea, on August 23-28, 2010, resulting in this special issue of six papers that address recent...

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

PubMed

Devers, Kelly J

2011-02-01

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

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

PubMed

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

2017-02-03

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

Beneficial and detrimental role of adenosine signaling in diseases and therapy

PubMed Central

Liu, Hong

2015-01-01

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

Personalized predictive modeling for patients with Alzheimer's disease using an extension of Sullivan's life table model.

PubMed

Stallard, Eric; Kinosian, Bruce; Stern, Yaakov

2017-09-20

Alzheimer's disease (AD) progression varies substantially among patients, hindering calculation of residual total life expectancy (TLE) and its decomposition into disability-free life expectancy (DFLE) and disabled life expectancy (DLE) for individual patients with AD. The objective of the present study was to assess the accuracy of a new synthesis of Sullivan's life table (SLT) and longitudinal Grade of Membership (L-GoM) models that estimates individualized TLEs, DFLEs, and DLEs for patients with AD. If sufficiently accurate, such information could enhance the quality of important decisions in AD treatment and patient care. We estimated a new SLT/L-GoM model of the natural history of AD over 10 years in the Predictors 2 Study cohort: N = 229 with 6 fixed and 73 time-varying covariates over 21 examinations covering 11 measurement domains including cognitive, functional, behavioral, psychiatric, and other symptoms/signs. Total remaining life expectancy was censored at 10 years. Disability was defined as need for full-time care (FTC), the outcome most strongly associated with AD progression. All parameters were estimated via weighted maximum likelihood using data-dependent weights designed to ensure that the estimates of the prognostic subtypes were of high quality. Goodness of fit was tested/confirmed for survival and FTC disability for five relatively homogeneous subgroups defined to cover the range of patient outcomes over the 21 examinations. The substantial heterogeneity in initial patient presentation and AD progression was captured using three clinically meaningful prognostic subtypes and one terminal subtype exhibiting highly differentiated symptom severity on 7 of the 11 measurement domains. Comparisons of the observed and estimated survival and FTC disability probabilities demonstrated that the estimates were accurate for all five subgroups, supporting their use in AD life expectancy calculations. Mean 10-year TLE differed widely across subgroups: range 3.6-8.0 years, average 6.1 years. Mean 10-year DFLE differed relatively even more widely across subgroups: range 1.2-6.5 years, average 4.0 years. Mean 10-year DLE was relatively much closer: range 1.5-2.3 years, average 2.1 years. The SLT/L-GoM model yields accurate maximum likelihood estimates of TLE, DFLE, and DLE for patients with AD; it provides a realistic, comprehensive modeling framework for endpoint and resource use/cost calculations.

Effectiveness study of atropine for progressive myopia in Europeans

PubMed Central

Polling, J R; Kok, R G W; Tideman, J W L; Meskat, B; Klaver, C C W

2016-01-01

Purpose Randomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a non-Asian country. Methods An effectiveness study was performed in Rotterdam, the Netherlands. Overall 77 children (mean age 10.3 years±2.3), of European (n=53), Asian (n=18), and African (n=6) descent with progressive myopia were prescribed atropine 0.5% eye drops daily. Both parents and children filled in a questionnaire regarding adverse events and adherence to therapy. A standardized eye examination including cycloplegic refraction and axial length was performed at baseline and 1, 4, and 12 months after initiation of therapy. Results Mean spherical equivalent at baseline was −6.6D (±3.3). The majority (60/77, 78%) of children adhered to atropine treatment for 12 months; 11 of the 17 children who discontinued therapy did so within 1 month after the start of therapy. The most prominent reported adverse events were photophobia (72%), followed by reading problems (38%), and headaches (22%). The progression rate of spherical equivalent before treatment (−1.0D/year±0.7) diminished substantially during treatment (−0.1D/year±0.7) compared to those who ceased therapy (−0.5D/year±0.6; P=0.03). Conclusions Despite the relatively high occurrence of adverse events, our study shows that atropine can be an effective and sustainable treatment for progressive high myopia in Europeans. PMID:27101751

Semiparametric regression during 2003–2007*

PubMed Central

Ruppert, David; Wand, M.P.; Carroll, Raymond J.

2010-01-01

Semiparametric regression is a fusion between parametric regression and nonparametric regression that integrates low-rank penalized splines, mixed model and hierarchical Bayesian methodology – thus allowing more streamlined handling of longitudinal and spatial correlation. We review progress in the field over the five-year period between 2003 and 2007. We find semiparametric regression to be a vibrant field with substantial involvement and activity, continual enhancement and widespread application. PMID:20305800

A longitudinal study of GAD65 and ICA512 autoantibodies during the progression to type 1 diabetes in Diabetes Prevention Trial-Type 1 (DPT-1) participants.

PubMed

Sosenko, Jay M; Skyler, Jay S; Palmer, Jerry P; Krischer, Jeffrey P; Cuthbertson, David; Yu, Liping; Schatz, Desmond A; Orban, Tihamer; Eisenbarth, George

2011-11-01

We examined changes in GAD65 and ICA-512 autoantibodies (GADA and IA-2A) during progression to type 1 diabetes (T1D). Diabetes Prevention Trial-Type 1 (DPT-1) participants were assessed for changes in positivity and titers of GADA and IA-2A during the progression to T1D. Among 99 progressors to T1D with GADA and IA-2A measurements at baseline and diagnosis (mean interval = 3.3 ± 1.5 years), GADA positivity changed little and GADA titers decreased (P < 0.01). In contrast, both IA-2A positivity and titers increased substantially (P < 0.001). Even among those positive at baseline, IA-2A titers increased from baseline to diagnosis (n = 57; P < 0.001), whereas GADA titers decreased (n = 80; P < 0.01). The same patterns of change were also evident among those positive for both autoantibodies (n = 48) at baseline. IA-2A titers increase during the years before the diagnosis of T1D, even among those positive for IA-2A. In contrast, GADA titers tend to decline during those years.

Frequency of Educational Computer Use as a Longitudinal Predictor of Educational Outcome in Young People with Specific Language Impairment

PubMed Central

Durkin, Kevin; Conti-Ramsden, Gina

2012-01-01

Computer use draws on linguistic abilities. Using this medium thus presents challenges for young people with Specific Language Impairment (SLI) and raises questions of whether computer-based tasks are appropriate for them. We consider theoretical arguments predicting impaired performance and negative outcomes relative to peers without SLI versus the possibility of positive gains. We examine the relationship between frequency of computer use (for leisure and educational purposes) and educational achievement; in particular examination performance at the end of compulsory education and level of educational progress two years later. Participants were 49 young people with SLI and 56 typically developing (TD) young people. At around age 17, the two groups did not differ in frequency of educational computer use or leisure computer use. There were no associations between computer use and educational outcomes in the TD group. In the SLI group, after PIQ was controlled for, educational computer use at around 17 years of age contributed substantially to the prediction of educational progress at 19 years. The findings suggest that educational uses of computers are conducive to educational progress in young people with SLI. PMID:23300610

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

Kahl, S.B.

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

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

PubMed Central

Leo, Seo-Wei; Young, Terri L.

2011-01-01

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

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

PubMed

López Mongil, Rosa; López Trigo, José Antonio

2016-06-01

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

The application of the diabetes prevention trial-type 1 risk score for identifying a preclinical state of type 1 diabetes.

PubMed

Sosenko, Jay M; Skyler, Jay S; Mahon, Jeffrey; Krischer, Jeffrey P; Beam, Craig A; Boulware, David C; Greenbaum, Carla J; Rafkin, Lisa E; Cowie, Catherine; Cuthbertson, David; Palmer, Jerry P

2012-07-01

We assessed the utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for identifying individuals who are highly likely to progress to type 1 diabetes (T1D) within 2 years. The DPTRS was previously developed from Diabetes Prevention Trial-Type 1 (DPT-1) data and was subsequently validated in the TrialNet Natural History Study (TNNHS). DPTRS components included C-peptide and glucose indexes from oral glucose tolerance testing, along with age and BMI. The cumulative incidence of T1D was determined after DPTRS thresholds were first exceeded and after the first occurrences of glucose abnormalities. The 2-year risks after the 9.00 DPTRS threshold was exceeded were 0.88 and 0.77 in DPT-1 (n = 90) and the TNNHS (n = 69), respectively. In DPT-1, the 2-year risks were much lower after dysglycemia first occurred (0.37; n = 306) and after a 2-h glucose value between 190 and 199 mg/dL was first reached (0.64; n = 59). Among those who developed T1D in DPT-1, the 9.00 threshold was exceeded 0.81 ± 0.53 years prior to the conventional diagnosis. Postchallenge C-peptide levels were substantially higher (P = 0.001 for 30 min; P < 0.001 for other time points) when the 9.00 threshold was first exceeded compared with the levels at diagnosis. A DPTRS threshold of 9.00 identifies individuals who are very highly likely to progress to the conventional diagnosis of T1D within 2 years and, thus, are essentially in a preclinical diabetic state. The 9.00 threshold is exceeded well before diagnosis, when stimulated C-peptide levels are substantially higher.

Recent advances in anti-neutrophil cytoplasmic antibody-associated vasculitis

PubMed Central

Lazarus, B.; John, G. T.; O’Callaghan, C.; Ranganathan, D.

2016-01-01

Anti-neutrophil cytoplasmic antibody-associated vasculitis is an uncommon inflammatory disease of small to medium-sized vessels that frequently presents with rapidly progressive glomerulonephritis and renal failure though it can affect any organ system. If untreated, the vast majority of patients will die within a year. Current treatments improve prognosis but affected patients remain at a substantially higher risk of death and adverse outcomes. We review the classification of the disease, our understanding of the pathogenesis and epidemiology, and propose future directions for research. We also evaluate the evidence supporting established treatment regimens and the progress of clinical trials for newer treatments to inform the design of future studies. PMID:27051131

Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64).

PubMed

Adler, Amanda I; Stevens, Richard J; Manley, Sue E; Bilous, Rudy W; Cull, Carole A; Holman, Rury R

2003-01-01

The progression of nephropathy from diagnosis of type 2 diabetes has not been well described from a single population. This study sought to describe the development and progression through the stages of microalbuminuria, macroalbuminuria, persistently elevated plasma creatinine or renal replacement therapy (RRT), and death. Using observed and modeled data from 5097 subjects in the UK Prospective Diabetes Study, we measured the annual probability of transition from stage to stage (incidence), prevalence, cumulative incidence, ten-year survival, median duration per stage, and risk of death from all-causes or cardiovascular disease. From diagnosis of diabetes, progression to microalbuminuria occurred at 2.0% per year, from microalbuminuria to macroalbuminuria at 2.8% per year, and from macroalbuminuria to elevated plasma creatinine (>or=175 micromol/L) or renal replacement therapy at 2.3% per year. Ten years following diagnosis of diabetes, the prevalence of microalbuminuria was 24.9%, of macroalbuminuria was 5.3%, and of elevated plasma creatinine or RRT was 0.8%. Patients with elevated plasma creatinine or RRT had an annual death rate of 19.2% (95% confidence interval, CI, 14.0 to 24.4%). There was a trend for increasing risk of cardiovascular death with increasing nephropathy (P < 0.0001), with an annual rate of 0.7% for subjects in the stage of no nephropathy, 2.0% for those with microalbuminuria, 3.5% for those with macroalbuminuria, and 12.1% with elevated plasma creatinine or RRT. Individuals with macroalbuminuria were more likely to die in any year than to develop renal failure. The proportion of patients with type 2 diabetes who develop microalbuminuria is substantial with one quarter affected by 10 years from diagnosis. Relatively fewer patients develop macroalbuminuria, but in those who do, the death rate exceeds the rate of progression to worse nephropathy.

Pancreatic islet transplantation, what has been achieved since Edmonton break-through.

PubMed

Witkowski, Piotr; Zakai, Shama Bader; Rana, Abbas; Sledzinski, Zbigniew; Hardy, Mark A

2006-01-01

It has been 6 years since the Edmonton group published their outstanding results with pancreatic islet transplantation patients, demonstrating one-year insulin independence of 100% with type I diabetics. In order to assess what has been achieved for past six years we analyzed the actual state of islet transplantation, based on the updated summary of results from Edmonton and compare this experience with combined results from 19 institutions in North America as reported to the Collaborative Islet Transplant Registry (CITR). CITR data have largely substantiated the reproducibility of the Edmonton procedure. Complete insulin-independence was achieved in more then 55% of patients 1 year after transplant, but this state has not been sustained permanently. Although only 10% of patients remained insulin-free after 5 years, more then 80% of them had still detectable levels of C peptide and substantially improved glycemic control without episodes of hypoglycemia. Even though currently, the islet graft is still not a remedy for every brittle diabetic, islet transplantation has already obtained "nonresearch" status in Canada and is close to having a biological license status approved by the FDA in the United States that would further stimulate progress in the field.

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

PubMed

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

2014-01-01

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

Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study.

PubMed

Reis, Jared P; Loria, Catherine M; Steffen, Lyn M; Zhou, Xia; van Horn, Linda; Siscovick, David S; Jacobs, David R; Carr, J Jeffrey

2010-10-01

To determine the association of coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood with the presence and progression of coronary artery calcified (CAC) plaque and carotid intima-media thickness later in life. The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a cohort of 5115 white and black adults who were aged 18 to 30 years when they completed a baseline clinic examination from 1985 to 1986. Subsequent examinations were conducted 2, 5, 7, 10, 15, and 20 years later. After multivariable adjustment, no association was observed between average coffee, decaffeinated coffee, or caffeine consumption (years 0 and 7) and presence of CAC (score, >0 Agatston units at year 15 or 20), CAC progression (incident CAC at year 20 or increase in CAC score by ≥20 Agatston units), or high carotid intima-media thickness (>80th percentile, year 20). However, tea consumption displayed a nonsignificant trend for an inverse association with CAC (P=0.08 for trend) and an inverse association with CAC progression (P=0.04 for trend) but no association with high carotid intima-media thickness (P>0.20 for trend). Stratification of the coffee analyses by sex, race, or smoking yielded similar nonsignificant patterns. We observed no substantial association between coffee or caffeine intake and coronary and carotid atherosclerosis. However, our results suggested an inverse association between tea and CAC but not carotid atherosclerosis.

Prognostic significance of day-by-day variability of home blood pressure on progression to macroalbuminuria in patients with diabetes.

PubMed

Ushigome, Emi; Matsumoto, Shinobu; Oyabu, Chikako; Kitagawa, Noriyuki; Tanaka, Toru; Hasegawa, Goji; Ohnishi, Masayoshi; Tsunoda, Sei; Ushigome, Hidetaka; Yokota, Isao; Nakamura, Naoto; Oda, Yohei; Asano, Mai; Tanaka, Muhei; Yamazaki, Masahiro; Fukui, Michiaki

2018-05-01

Previously, we have shown in cross-sectional analysis of patients with type 2 diabetes mellitus that the presence of diabetic nephropathy is associated with increased home blood pressure (HBP) variability. We now examine the prognostic significance of HBP variability in substantially the same cohort. We performed a prospective cohort study of type 2 diabetes patients. We analyzed 714 patients. Major exclusion criteria are missing data of urinary albumin excretion and newly prescribed or stopped renin-angiotensin system inhibitors during 2-year follow-up. Patients were instructed to perform triplicate morning and evening HBP measurements for 14 consecutive days. We computed day-by-day HBP variability as within-patient standard deviation (SD) and coefficient of variation (CV) of measurements. During the follow-up period of 2 years, 23 patients progressed to macroalbuminuria. The changing risk of progression to macroalbuminuria with increasing day-by-day variability of morning SBP was better depicted using smoothing spline analyses. Patients with greater SD of morning SBP tended to significantly progress to macroalbuminuria [odds ratio: 5.24 (95% confidence interval: 2.10-13.03; P > 0.001)]. Patients with greater CV of morning SBP also tended to significantly progress to macroalbuminuria [odds ratio: 3.36 (95% confidence interval: 1.39-8.12; P = 0.007)]. Day-by-day variability of morning SBP was proven as an independent predictor for progression to macroalbuminuria in patients with type 2 diabetes.

Mitigating the Erratic Behavior of the Transportation Working Capital Fund Through Accurate Forecasting

DTIC Science & Technology

2015-06-19

trigger a massive tsunami hitting the Fukushima Nuclear Power Plant creating the largest nuclear incident since the Chernobyl disaster in1986. The...progress. Though Kadena is several hundred miles closer to Osan than Misawa, once the pallet arrives at Kadena it will need to be processed and may...example is after rates are stabilized (fixed rate for the entire year of execution) there is a sudden spike in aviation fuel prices. A substantial

Influence of model assumptions about HIV disease progression after initiating or stopping treatment on estimates of infections and deaths averted by scaling up antiretroviral therapy

PubMed Central

Sucharitakul, Kanes; Boily, Marie-Claude; Dimitrov, Dobromir

2018-01-01

Background Many mathematical models have investigated the population-level impact of expanding antiretroviral therapy (ART), using different assumptions about HIV disease progression on ART and among ART dropouts. We evaluated the influence of these assumptions on model projections of the number of infections and deaths prevented by expanded ART. Methods A new dynamic model of HIV transmission among men who have sex with men (MSM) was developed, which incorporated each of four alternative assumptions about disease progression used in previous models: (A) ART slows disease progression; (B) ART halts disease progression; (C) ART reverses disease progression by increasing CD4 count; (D) ART reverses disease progression, but disease progresses rapidly once treatment is stopped. The model was independently calibrated to HIV prevalence and ART coverage data from the United States under each progression assumption in turn. New HIV infections and HIV-related deaths averted over 10 years were compared for fixed ART coverage increases. Results Little absolute difference (<7 percentage points (pp)) in HIV infections averted over 10 years was seen between progression assumptions for the same increases in ART coverage (varied between 33% and 90%) if ART dropouts reinitiated ART at the same rate as ART-naïve MSM. Larger differences in the predicted fraction of HIV-related deaths averted were observed (up to 15pp). However, if ART dropouts could only reinitiate ART at CD4<200 cells/μl, assumption C predicted substantially larger fractions of HIV infections and deaths averted than other assumptions (up to 20pp and 37pp larger, respectively). Conclusion Different disease progression assumptions on and post-ART interruption did not affect the fraction of HIV infections averted with expanded ART, unless ART dropouts only re-initiated ART at low CD4 counts. Different disease progression assumptions had a larger influence on the fraction of HIV-related deaths averted with expanded ART. PMID:29554136

Measurement of fetal head descent using the 'angle of progression' on transperineal ultrasound imaging is reliable regardless of fetal head station or ultrasound expertise.

PubMed

Dückelmann, A M; Bamberg, C; Michaelis, S A M; Lange, J; Nonnenmacher, A; Dudenhausen, J W; Kalache, K D

2010-02-01

To assess whether ultrasound experience or fetal head station affects the reliability of measurement of fetal head descent using the angle of progression on intrapartum ultrasound images obtained by a single experienced operator, and to determine reliability of measurements when images were acquired by different operators with variable ultrasound experience. One experienced obstetrician performed 44 transperineal ultrasound examinations of women at term and in prolonged second stage of labor with the fetus in the occipitoanterior position. Three midwives without ultrasound experience, three obstetricians with < 5 years' experience and three obstetricians with > 10 years' experience measured fetal head descent based on the angle of progression in the images obtained. The angle of progression was measured by two obstetricians in independent ultrasound examinations of 24 laboring women at term with the fetus in the cephalic position to allow assessment of the reliability of image acquisition. Intraclass correlation coefficients (ICCs) with 95% confidence interval (CI) were used to evaluate interobserver reliability and Bland-Altman analysis was used to assess interobserver agreement. In total, 444 measurements were performed and compared. Interobserver reliability with respect to offline image analysis was substantial (overall ICC, 0.72; 95% CI, 0.63-0.81). ICCs were 0.82 (95% CI, 0.70-0.89), 0.81 (95% CI, 0.71-0.88) and 0.61 (95% CI, 0.43-074) for observers with > 10 years', < 5 years' and no ultrasound experience, respectively. There were no significant differences between ICCs among observer groups according to ultrasound experience. Fetal head station did not affect reliability. Bland-Altman analysis indicated reasonable agreement between measurements obtained by two different operators with > 10 years' and < 5 years' ultrasound experience (bias, -1.09 degrees ; 95% limits of agreement, -8.76 to 6.58). The reliability of measurement of the angle of progression following separate image acquisition by two experienced operators was similar to the reliability of offline image analysis (ICC, 0.86; 95% CI, 0.70-0.93). Measurement of the angle of progression on transperineal ultrasound imaging is reliable regardless of fetal head station or the clinician's level of ultrasound experience.

Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts.

PubMed

Carpenter, Lewis; Norton, Sam; Nikiphorou, Elena; Jayakumar, Keeranur; McWilliams, Daniel F; Rennie, Kirsten L; Dixey, Josh; Kiely, Patrick; Walsh, David Andrew; Young, Adam

2017-12-01

To assess the 5-year progression of erosions and joint space narrowing (JSN) and their associations with rheumatoid factor (RF) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years. Radiographic joint damage was recorded using the Sharp/van der Heijde (SHS) method in the Early Rheumatoid Arthritis Study (ERAS), 1986-2001, and the Early Rheumatoid Arthritis Network (ERAN), 2002-2013. Mixed-effects negative binomial regression estimated changes in radiographic damage over 5 years, including erosions and JSN, separately. RF, along with age, sex, and baseline markers of disease activity were controlled for. A total of 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SHS score at baseline (ERAN 6.2 versus ERAS 10.5; P < 0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P < 0.001). Seventy-four percent of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS 3.9 versus ERAN 1.2; P < 0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P < 0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF-positive patients was substantially higher for ERAS (RF positive 8.6 versus RF negative 5.1; P < 0.001), relative to ERAN (RF positive 2.0 versus RF negative 1.9; P = 0.855). Radiographic progression was shown to be significantly reduced between the 2 cohorts, and was associated with lower baseline damage and other factors, including changes in early disease-modifying antirheumatic drug use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment. © 2017, American College of Rheumatology.

Frequency of Evidence-Based Screening for Retinopathy in Type 1 Diabetes.

PubMed

Nathan, David M; Bebu, Ionut; Hainsworth, Dean; Klein, Ronald; Tamborlane, William; Lorenzi, Gayle; Gubitosi-Klug, Rose; Lachin, John M

2017-04-20

In patients who have had type 1 diabetes for 5 years, current recommendations regarding screening for diabetic retinopathy include annual dilated retinal examinations to detect proliferative retinopathy or clinically significant macular edema, both of which require timely intervention to preserve vision. During 30 years of the Diabetes Control and Complications Trial (DCCT) and its longitudinal follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, retinal photography was performed at intervals of 6 months to 4 years. We used retinal photographs from the DCCT/EDIC study to develop a rational screening frequency for retinopathy. Markov modeling was used to determine the likelihood of progression to proliferative diabetic retinopathy or clinically significant macular edema in patients with various initial retinopathy levels (no retinopathy or mild, moderate, or severe nonproliferative diabetic retinopathy). The models included recognized risk factors for progression of retinopathy. Overall, the probability of progression to proliferative diabetic retinopathy or clinically significant macular edema was limited to approximately 5% between retinal screening examinations at 4 years among patients who had no retinopathy, 3 years among those with mild retinopathy, 6 months among those with moderate retinopathy, and 3 months among those with severe nonproliferative diabetic retinopathy. The risk of progression was also closely related to mean glycated hemoglobin levels. The risk of progression from no retinopathy to proliferative diabetic retinopathy or clinically significant macular edema was 1.0% over 5 years among patients with a glycated hemoglobin level of 6%, as compared with 4.3% over 3 years among patients with a glycated hemoglobin level of 10%. Over a 20-year period, the frequency of eye examinations was 58% lower with our practical, evidence-based schedule than with routine annual examinations, which resulted in substantial cost savings. Our model for establishing an individualized schedule for retinopathy screening on the basis of the patient's current state of retinopathy and glycated hemoglobin level reduced the frequency of eye examinations without delaying the diagnosis of clinically significant disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360893 and NCT00360815 .).

Impact of family planning programs in reducing high-risk births due to younger and older maternal age, short birth intervals, and high parity.

PubMed

Brown, Win; Ahmed, Saifuddin; Roche, Neil; Sonneveldt, Emily; Darmstadt, Gary L

2015-08-01

Several studies show that maternal and neonatal/infant mortality risks increase with younger and older maternal age (<18 and >34 years), high parity (birth order >3), and short birth intervals (<24 months). Family planning programs are widely viewed as having contributed to substantial maternal and neonatal mortality decline through contraceptive use--both by reducing unwanted births and by reducing the burden of these high-risk births. However, beyond averting births, the empirical evidence for the role of family planning in reducing high-risk births at population level is limited. We examined data from 205 Demographic and Health Surveys (DHS), conducted between 1985 and 2013, to describe the trends in high-risk births and their association with the pace of progress in modern contraceptive prevalence rate (yearly increase in rate of MCPR) in 57 developing countries. Using Blinder-Oaxaca decomposition technique, we then examine the contributions of family planning program, economic development (GDP per capita), and educational improvement (secondary school completion rate) on the progress of MCPR in order to link the net contribution of family planning program to the reduction of high-risk births mediated through contraceptive use. Countries that had the fastest progress in improving MCPR experienced the greatest declines in high-risk births due to short birth intervals (<24 months), high parity births (birth order >3), and older maternal age (>35 years). Births among younger women <18 years, however, did not decline significantly during this period. The decomposition analysis suggests that 63% of the increase in MCPR was due to family planning program efforts, 21% due to economic development, and 17% due to social advancement through women's education. Improvement in MCPR, predominately due to family planning programs, is a major driver of the decline in the burden of high-risk births due to high parity, shorter birth intervals, and older maternal age in developing countries. The lack of progress in the decline of births in younger women <18 years of age underscores the need for more attention to ensure that quality contraceptive methods are available to adolescent women in order to delay first births. This study substantiates the significance of family planning programming as a major health intervention for preventing high-risk births and associated maternal and child mortality, but it highlights the need for concerted efforts to strengthen service provision for adolescents. Copyright © 2015 Elsevier Inc. All rights reserved.

An Interactive, Physics-Based Unmanned Ground Vehicle Simulator Leveraging Open Source Gaming Technology: Progress in the Development and Application of the Virtual Autonomous Navigation Environment (VANE) Desktop

DTIC Science & Technology

2009-01-01

interface, mechatronics, video games 1. INTRODUCTION Engineering methods have substantially and continuously evolved over the past 40 years. In the past...1970s, video games have pioneered interactive simulation and laid the groundwork for inexpensive computing that individuals, corporations, and...purposes. This has not gone unnoticed, and software technology and techniques evolved for video games are beginning to have extraordinary impact in

Parent-Body Modification of Chondritic Meteorites

NASA Technical Reports Server (NTRS)

Rubin, Alan

2003-01-01

This proposal focused on the parent-body modification of chondritic materials and substantial progress was made in the last year. A summary of the work accomplished during this period is discussed. The topics include: 1) Chromite-Plagioclase Assemblages in Ordinary Chondrites; 2) The Gujba Bencubbin-like meteorite fall; 3) NWA428: A rock that Experienced Impact-induced Annealing; 4) Spade: An Annealed H-chondrite Impact-melt Breccia; and 5) Post-shock Annealing in Ordinary Chondrites. A list of the papers submitted or published during the period is also presented.

PROGNOSTIC VALUE OF SHAPE-DESCRIPTIVE FACTORS FOR THE PROGRESSION OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PubMed

Pfau, Maximilian; Lindner, Moritz; Goerdt, Lukas; Thiele, Sarah; Nadal, Jennifer; Schmid, Matthias; Schmitz-Valckenberg, Steffen; Sadda, SriniVas R; Holz, Frank G; Fleckenstein, Monika

2018-05-16

To systematically compare the prognostic value of multiple shape-descriptive factors in the natural course of the disease. A total of 296 eyes of 201 patients (female patients 130; mean age: 72.2 ± 13.08 years) with a median follow-up of 2.38 years from 2 prospective, noninterventional natural history studies (Fundus-Autofluorescence-in-Age-related-Macular-Degeneration [clinicaltrials.gov identifier NCT00393692], Directional-Spread-in-Geographic-Atrophy [NCT02051998]) were included in the analysis. Serial fundus autofluorescence images were annotated using semiautomated image analysis software to determine the lesion area, circularity, perimeter, and caliper diameters. These variables and the fundus autofluorescence phenotype were evaluated for prediction of the future square root progression rates using linear mixed-effects models. For the combined model, leave-one-out cross validation on patient level (Scenario 1: previously unknown patient) resulted in a goodness-to-fit (R value) of 0.244 and leave-one-out cross validation on visit level (Scenario 2: previous observation of the patient) in a R value of 0.391. This indicated that shape-descriptive factors could explain 24.4% of the variance in geographic atrophy progression in previously unknown patients and 39.1% in patients with previous observation. These findings confirm the relevance of shape-descriptive factors and previous progression as prognostic variables for geographic atrophy progression. However, a substantial part of the remaining variation in geographic atrophy progression seems to depend on other variables, some of which are visible in optical coherence tomography.

Ten years of Nature Reviews Neuroscience: insights from the highly cited

PubMed Central

Luo, Liqun; Rodriguez, Eugenio; Jerbi, Karim; Lachaux, Jean-Philippe; Martinerie, Jacques; Corbetta, Maurizio; Shulman, Gordon L.; Piomelli, Daniele; Turrigiano, Gina G.; Nelson, Sacha B.; Joëls, Marian; de Kloet, E. Ronald; Holsboer, Florian; Amodio, David M.; Frith, Chris D.; Block, Michelle L.; Zecca, Luigi; Hong, Jau-Shyong; Dantzer, Robert; Kelley, Keith W.; Craig, A. D. (Bud)

2012-01-01

To celebrate the first 10 years of Nature Reviews Neuroscience, we invited the authors of the most cited article of each year to look back on the state of their field of research at the time of publication and the impact their article has had, and to discuss the questions that might be answered in the next 10 years. This selection of highly cited articles provides interesting snapshots of the progress that has been made in diverse areas of neuroscience. They show the enormous influence of neuroimaging techniques and highlight concepts that have generated substantial interest in the past decade, such as neuroimmunology, social neuroscience and the `network approach' to brain function. These advancements will pave the way for further exciting discoveries that lie ahead. PMID:20852655

Demand Side Management: An approach to peak load smoothing

NASA Astrophysics Data System (ADS)

Gupta, Prachi

A preliminary national-level analysis was conducted to determine whether Demand Side Management (DSM) programs introduced by electric utilities since 1992 have made any progress towards their stated goal of reducing peak load demand. Estimates implied that DSM has a very small effect on peak load reduction and there is substantial regional and end-user variability. A limited scholarly literature on DSM also provides evidence in support of a positive effect of demand response programs. Yet, none of these studies examine the question of how DSM affects peak load at the micro-level by influencing end-users' response to prices. After nearly three decades of experience with DSM, controversy remains over how effective these programs have been. This dissertation considers regional analyses that explore both demand-side solutions and supply-side interventions. On the demand side, models are estimated to provide in-depth evidence of end-user consumption patterns for each North American Electric Reliability Corporation (NERC) region, helping to identify sectors in regions that have made a substantial contribution to peak load reduction. The empirical evidence supports the initial hypothesis that there is substantial regional and end-user variability of reductions in peak demand. These results are quite robust in rapidly-urbanizing regions, where air conditioning and lighting load is substantially higher, and regions where the summer peak is more pronounced than the winter peak. It is also evident from the regional experiences that active government involvement, as shaped by state regulations in the last few years, has been successful in promoting DSM programs, and perhaps for the same reason we witness an uptick in peak load reductions in the years 2008 and 2009. On the supply side, we estimate the effectiveness of DSM programs by analyzing the growth of capacity margin with the introduction of DSM programs. The results indicate that DSM has been successful in offsetting the need for additional production capacity by the means of demand response measures, but the success is limited to only a few regions. The rate of progress in the future will depend on a wide range of improved technologies and a continuous government monitoring for successful adoption of demand response programs to manage growing energy demand.

Lipid Droplets and Mycobacterium leprae Infection

PubMed Central

Elamin, Ayssar A.; Stehr, Matthias; Singh, Mahavir

2012-01-01

Leprosy is a chronic infectious disease and is a major source of morbidity in developing countries. Leprosy is caused by the obligate intracellular bacterium Mycobacterium leprae, which infects as primary target Schwann cells. Lepromatous leprosy exhibits multiple lesions of the skin, eyes, nerves, and lymph nodes. The sites of infection are characterized by the presence of foamy macrophages, fully packed with lipid droplets (LDs), which are induced by M. leprae. In the last years, it has become evident that M. tuberculosis imports lipids from foamy macrophages and is dependent on fatty acids for growth in infected macrophages. M. leprae seems to have similar mechanisms for scavenging lipids from the host. But due to the inability to culture M. leprae on laboratory media, research progresses only slowly. However, in the last years, substantial progress has been made in the field of lipid metabolism in M. leprae. Herein, we will present and summarize the lipid droplets formation and the metabolism of lipids during M. leprae infection. PMID:23209912

SP-100 - The national space reactor power system program in response to future needs

NASA Astrophysics Data System (ADS)

Armijo, J. S.; Josloff, A. T.; Bailey, H. S.; Matteo, D. N.

The SP-100 system has been designed to meet comprehensive and demanding NASA/DOD/DOE requirements. The key requirements include: nuclear safety for all mission phases, scalability from 10's to 100's of kWe, reliable performance at full power for seven years of partial power for ten years, survivability in civil or military threat environments, capability to operate autonomously for up to six months, capability to protect payloads from excessive radiation, and compatibility with shuttle and expendable launch vehicles. The authors address of major progress in terms of design, flexibility/scalability, survivability, and development. These areas, with the exception of survivability, are discussed in detail. There has been significant improvement in the generic flight system design with substantial mass savings and simplification that enhance performance and reliability. Design activity has confirmed the scalability and flexibility of the system and the ability to efficiently meet NASA, AF, and SDIO needs. SP-100 development continues to make significant progress in all key technology areas.

Hitler's parkinsonism.

PubMed

Boettcher, Lillian B; Bonney, Phillip A; Smitherman, Adam D; Sughrue, Michael E

2015-07-01

Of the multitude of medical and psychiatric conditions ascribed to Hitler both in his lifetime and since his suicide in April 1945, few are more substantiated than parkinsonism. While the timeline of the development of this condition, as well as its etiology, are debated, there is clear evidence for classic manifestations of the disease, most prominently a resting tremor but also stooped posture, bradykinesia, micrographia, and masked facial expressions, with progression steadily seen over his final years. Though ultimately speculation, some have suggested that Hitler suffered from progressive cognitive and mood disturbances, possibly due to parkinsonism, that affected the course of events in the war. Here, the authors discuss Hitler's parkinsonism in the context of the Third Reich and its eventual destruction, maintaining that ultimately his disease had little effect on the end result.

Dendritic integration: 60 years of progress.

PubMed

Stuart, Greg J; Spruston, Nelson

2015-12-01

Understanding how individual neurons integrate the thousands of synaptic inputs they receive is critical to understanding how the brain works. Modeling studies in silico and experimental work in vitro, dating back more than half a century, have revealed that neurons can perform a variety of different passive and active forms of synaptic integration on their inputs. But how are synaptic inputs integrated in the intact brain? With the development of new techniques, this question has recently received substantial attention, with new findings suggesting that many of the forms of synaptic integration observed in vitro also occur in vivo, including in awake animals. Here we review six decades of progress, which collectively highlights the complex ways that single neurons integrate their inputs, emphasizing the critical role of dendrites in information processing in the brain.

Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification

PubMed Central

Korolev, Igor O.; Symonds, Laura L.; Bozoki, Andrea C.

2016-01-01

Background Individuals with mild cognitive impairment (MCI) have a substantially increased risk of developing dementia due to Alzheimer's disease (AD). In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level. Methods Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139) and those who did not (n = 120) during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI) data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework. Results Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87). Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex). Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions. Conclusions We developed an accurate prognostic model for predicting MCI-to-dementia progression over a three-year period. The model utilizes widely available, cost-effective, non-invasive markers and can be used to improve patient selection in clinical trials and identify high-risk MCI patients for early treatment. PMID:26901338

Cardio-oncology: Concepts and practice

PubMed Central

Cubbon, Richard M.; Lyon, Alexander R.

2016-01-01

Substantial progress in cancer therapy increasingly allows higher cure rates, and even advanced disease can be stabilized, allowing improved survival with quality of life for months to years, meaning comorbid diseases are a growing determinant of outcome. Cardiovascular events substantially contribute to long-term morbidity and mortality in people living with or surviving cancer. In recognition of this, the subspecialty of cardio-oncology has emerged, and aims to promote cardiovascular heath, whilst facilitating the most effective cancer therapy. This review describes the concept of cardio-oncology, and illustrates the role played by a specialist team in improving outcomes, using heart failure secondary to breast cancer treatment as an example. We aim to highlight pivotal original research and comprehensive summaries of the most relevant topics, providing an overview for cardiologists and oncologists about this increasingly important medical problem. PMID:27056658

Intratumoral heterogeneity and TERT promoter mutations in progressive/higher-grade meningiomas

PubMed Central

Juratli, Tareq A.; Thiede, Christian; Koerner, Mara V.A.; Tummala, Shilpa S.; Daubner, Dirk; Shankar, Ganesh M.; Williams, Erik A.; Martinez-Lage, Maria; Soucek, Silke; Robel, Katja; Penson, Tristan; Krause, Mechthild; Appold, Steffen; Meinhardt, Matthias; Pinzer, Thomas; Miller, Julie J.; Krex, Dietmar; Ely, Heather A.; Silverman, Ian M.; Christiansen, Jason; Schackert, Gabriele; Wakimoto, Hiroaki; Kirsch, Matthias; Brastianos, Priscilla K.; Cahill, Daniel P.

2017-01-01

Background Recent studies have reported mutations in the telomerase reverse transcriptase promoter (TERTp) in meningiomas. We sought to determine the frequency, clonality and clinical significance of telomere gene alterations in a cohort of patients with progressive/higher-grade meningiomas. Methods We characterized 64 temporally- and regionally-distinct specimens from 26 WHO grade III meningioma patients. On initial diagnoses, the meningiomas spanned all WHO grades (3 grade I, 13 grade II and 10 grade III). The tumor samples were screened for TERTp and ATRX/DAXX mutations, and TERT rearrangements. Additionally, TERTp was sequenced in a separate cohort of 19 patients with radiation-associated meningiomas. We examined the impact of mutational status on patients’ progression and overall survival. Results Somatic TERTp mutations were detected in six patients (6/26 = 23%). Regional intratumoral heterogeneity in TERTp mutation status was noted. In 4 patients, TERTp mutations were detected in recurrent specimens but not in the available specimens of the first surgery. Additionally, a TERT gene fusion (LPCAT1-TERT) was found in one sample. In contrary, none of the investigated samples harbored an ATRX or DAXX mutation. In the cohort of radiation-induced meningiomas, TERTp mutation was detected in two patients (10.5%). Importantly, we found that patients with emergence of TERTp mutations had a substantially shorter OS than their TERTp wild-type counterparts (2.7 years, 95% CI 0.9 – 4.5 years versus 10.8 years, 95% CI 7.8 -12.8 years, p=0.003). Conclusions In progressive/higher-grade meningiomas,TERTp mutations are associated with poor survival, supporting a model in which selection of this alteration is a harbinger of aggressive tumor development. In addition, we observe spatial intratumoral heterogeneity of TERTp mutation status, consistent with this model of late emergence in tumor evolution. Thus, early detection of TERTp mutations may define patients with more aggressive meningiomas. Stratification for TERT alterations should be adopted in future clinical trials of progressive/higher-grade meningiomas. PMID:29312603

Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

PubMed Central

Colihueque, Nelson; Araneda, Cristian

2014-01-01

Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

Mapping local variation in educational attainment across Africa

NASA Astrophysics Data System (ADS)

Graetz, Nicholas; Friedman, Joseph; Osgood-Zimmerman, Aaron; Burstein, Roy; Biehl, Molly H.; Shields, Chloe; Mosser, Jonathan F.; Casey, Daniel C.; Deshpande, Aniruddha; Earl, Lucas; Reiner, Robert C.; Ray, Sarah E.; Fullman, Nancy; Levine, Aubrey J.; Stubbs, Rebecca W.; Mayala, Benjamin K.; Longbottom, Joshua; Browne, Annie J.; Bhatt, Samir; Weiss, Daniel J.; Gething, Peter W.; Mokdad, Ali H.; Lim, Stephen S.; Murray, Christopher J. L.; Gakidou, Emmanuela; Hay, Simon I.

2018-03-01

Educational attainment for women of reproductive age is linked to reduced child and maternal mortality, lower fertility and improved reproductive health. Comparable analyses of attainment exist only at the national level, potentially obscuring patterns in subnational inequality. Evidence suggests that wide disparities between urban and rural populations exist, raising questions about where the majority of progress towards the education targets of the Sustainable Development Goals is occurring in African countries. Here we explore within-country inequalities by predicting years of schooling across five by five kilometre grids, generating estimates of average educational attainment by age and sex at subnational levels. Despite marked progress in attainment from 2000 to 2015 across Africa, substantial differences persist between locations and sexes. These differences have widened in many countries, particularly across the Sahel. These high-resolution, comparable estimates improve the ability of decision-makers to plan the precisely targeted interventions that will be necessary to deliver progress during the era of the Sustainable Development Goals.

[Localized scleroderma (morphea) in childhood].

PubMed

Weibel, L

2012-02-01

Localized scleroderma or morphea is a sclerosing connective tissue disease of the skin, which may affect underlying tissues such as subcutis, muscle and bone. Many patients show extracutaneous symptoms and antinuclear antibodies, however, secondary transformation into systemic sclerosis does not occur. Localized scleroderma usually begins in childhood with a wide variation in its clinical spectrum. The linear variant is the most common subtype in children, associated with a progressive course and increased risk of complications. The disease may progress over years and result in severe functional and cosmetic disability. The etiology of localized scleroderma remains unknown. A genetic background is suspected, while triggers such as trauma, vaccinations and infections may lead to secondary immunologic phenomena. Localized scleroderma often remains unrecognized for a long time, resulting in substantial delay in treatment. The combination of systemic corticosteroids and methotrexate has been established as first-line therapy for progressive (usually linear) disease, whereas phototherapy (UVA-1 or UVB-narrow band) is suitable for adolescents with superficial circumscribed subtypes.

A model for the progressive failure of laminated composite structural components

NASA Technical Reports Server (NTRS)

Allen, D. H.; Lo, D. C.

1991-01-01

Laminated continuous fiber polymeric composites are capable of sustaining substantial load induced microstructural damage prior to component failure. Because this damage eventually leads to catastrophic failure, it is essential to capture the mechanics of progressive damage in any cogent life prediction model. For the past several years the authors have been developing one solution approach to this problem. In this approach the mechanics of matrix cracking and delamination are accounted for via locally averaged internal variables which account for the kinematics of microcracking. Damage progression is predicted by using phenomenologically based damage evolution laws which depend on the load history. The result is a nonlinear and path dependent constitutive model which has previously been implemented to a finite element computer code for analysis of structural components. Using an appropriate failure model, this algorithm can be used to predict component life. In this paper the model will be utilized to demonstrate the ability to predict the load path dependence of the damage and stresses in plates subjected to fatigue loading.

Effects of sources of variability on sample sizes required for RCTs, applied to trials of lipid-altering therapies on carotid artery intima-media thickness.

PubMed

Gould, A Lawrence; Koglin, Joerg; Bain, Raymond P; Pinto, Cathy-Anne; Mitchel, Yale B; Pasternak, Richard C; Sapre, Aditi

2009-08-01

Studies measuring progression of carotid artery intima-media thickness (cIMT) have been used to estimate the effect of lipid-modifying therapies cardiovascular event risk. The likelihood that future cIMT clinical trials will detect a true treatment effect is estimated by leveraging results from prior studies. The present analyses assess the impact of between- and within-study variability based on currently published data from prior clinical studies on the likelihood that ongoing or future cIMT trials will detect the true treatment effect of lipid-modifying therapies. Published data from six contemporary cIMT studies (ASAP, ARBITER 2, RADIANCE 1, RADIANCE 2, ENHANCE, and METEOR) including data from a total of 3563 patients were examined. Bayesian and frequentist methods were used to assess the impact of between study variability on the likelihood of detecting true treatment effects on 1-year cIMT progression/regression and to provide a sample size estimate that would specifically compensate for the effect of between-study variability. In addition to the well-described within-study variability, there is considerable between-study variability associated with the measurement of annualized change in cIMT. Accounting for the additional between-study variability decreases the power for existing study designs. In order to account for the added between-study variability, it is likely that future cIMT studies would require a large increase in sample size in order to provide substantial probability (> or =90%) to have 90% power of detecting a true treatment effect.Limitation Analyses are based on study level data. Future meta-analyses incorporating patient-level data would be useful for confirmation. Due to substantial within- and between-study variability in the measure of 1-year change of cIMT, as well as uncertainty about progression rates in contemporary populations, future study designs evaluating the effect of new lipid-modifying therapies on atherosclerotic disease progression are likely to be challenged by large sample sizes in order to demonstrate a true treatment effect.

Strengthening Māori participation in the New Zealand health and disability workforce.

PubMed

Ratima, Mihi M; Brown, Rachel M; Garrett, Nick K G; Wikaire, Erena I; Ngawati, Renei M; Aspin, Clive S; Potaka, Utiku K

2007-05-21

Substantial progress has been made in Māori health and disability workforce development in the past 15 years. Key factors in successful programs to increase Māori health workforce recruitment and retention include Māori leadership, mentorship and peer support; and comprehensive support within study programs and in the transitions between school, university and work. The interventions to date provide a strong basis for ongoing action to address inequities in Māori health workforce participation, and are likely to be relevant to health workforce development approaches for other indigenous peoples.

After Muskoka.

PubMed

Landrivon, G; Aboubaker, S; Nkurunziza, T; Habimana, P; Grimaldi, C

2016-11-01

Substantial progress has been accomplished in reducing maternal, neonatal, and infant mortality, but the work to meet the Millennium Development Goals, boosted by numerous initiatives, including Muskoka, is far from finished. Since 2016, the Sustainable Development Goals, as well as the International Strategy for Women's, Children's, and Adolescent Health 2016 - 2030, have provided to the countries and development partners a consistent framework for action enlarged to all of the dimensions of human development, while keeping women, children, and adolescents at its heart. In this context, the Muskoka program, after an initial 5-year cycle, will continue in 2017.

Subacute sclerosing panencephalitis: a case report.

PubMed

Praticò, A D; Saporito, M; Iacono, O; Castellano-Chiodo, D; Pavone, P

2011-02-01

Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence caused by persistent defective measles virus. Clinical manifestations appear many years after the acute measles infection. The incidence of SSPE has substantially declined after the introduction of an effective vaccine. We report a case of a child with SSPE that began with atonia, dysarthria, and intellectual deterioration without the presence of any particular EEG anomalies. We have reported this girl who was affected by this severe affliction in the hope that, because of the rarity of SSPE, it would not go undiagnosed.

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

Code of Federal Regulations, 2012 CFR

2012-07-01

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

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

Code of Federal Regulations, 2011 CFR

2011-07-01

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

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

Code of Federal Regulations, 2013 CFR

2013-07-01

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

Breeding progress, variation, and correlation of grain and quality traits in winter rye hybrid and population varieties and national on-farm progress in Germany over 26 years.

PubMed

Laidig, Friedrich; Piepho, Hans-Peter; Rentel, Dirk; Drobek, Thomas; Meyer, Uwe; Huesken, Alexandra

2017-05-01

Grain yield of hybrid varieties and population varieties in official German variety trials increased by 23.3 and 18.1%, respectively, over the last 26 years. On-farm gain in grain yield (18.9%) was comparable to that of population varieties in variety trials, yet at a level considerably lower than in variety trials. Rye quality is subject to large year-to-year fluctuation. Increase in grain yield and decline of protein concentration did not negatively influence quality traits. Performance progress of grain and quality traits of 78 winter rye varieties tested in official German trials to assess the value for cultivation and use (VCU) were evaluated during 1989 and 2014. We dissected progress into a genetic and a non-genetic component for hybrid and population varieties by applying mixed models, including regression components to model trends. VCU trial results were compared with grain yield and quality data from a national harvest survey (on-farm data). Yield gain for hybrid varieties was 23.3% (18.9 dt ha -1 ) and for population varieties 18.1% (13.0 dt ha -1 ) relative to 1989. On-farm yield progress of 18.9% (8.7 dt ha -1 ) was considerably lagging behind VCU trials, and mean yield levels were substantially lower than in field trials. Most of the yield progress was generated by genetic improvement. For hybrid varieties, ear density was the determining yield component, whereas for population varieties, it was thousand grain mass. Results for VCU trials showed no statistically significant gains or losses in rye quality traits. For on-farm data, we found a positive but non-significant gain in falling number and amylogram viscosity and temperature. Variation of grain and quality traits was strongly influenced by environments, whereas genotypic variation was less than 19% of total variation. Grain yield was strongly negatively associated with protein concentration, yet was weakly to moderately positively associated with quality traits. In general, our results from VCU trials and on-farm data indicated that increasing grain yield and decreasing protein concentration did not negatively affect rye quality traits.

[Impact of disease progression on health status, quality of life and costs in rheumatoid arthritis in Hungary].

PubMed

Péntek, Márta; Szekanecz, Zoltán; Czirják, László; Poór, Gyula; Rojkovich, Bernadette; Polgár, Anna; Genti, György; Kiss, Csaba György; Sándor, Zsuzsa; Májer, István; Brodszky, Valentin; Gulácsi, László

2008-04-20

Rheumatoid arthritis (RA) is a chronic, progressive polyarthritis leading to substantial disability. Standardised data on consequences of disease progression are needed for clinical assessments and also for cost-effectiveness models. To analyse the impact of disease progression on health status, disease specific quality of life and costs in Hungary. A cross-sectional survey was performed between April and August, 2004, involving consecutive RA patients of 6 hospital based rheumatology outpatient centres. Self-completed questionnaires were used to assess functional (HAQ) and health status (EQ-5D), quality of life (RAQoL). Disease activity (DAS) and costs were also surveyed, statistical analysis was performed. 255 patients were involved [mean age 55.5 +/- 12.3 years; disease duration 9.0 +/- 9.3 years; HAQ 1.38 +/- 0.76; EQ-5D 0.46 +/- 0.33; RAQoL 16.2 +/- 8.1; DAS 5.09 +/- 1.42; costs 1,043,163 (+/- 844,750) HUF/patient/year, conversion 1 Euro = 250 HUF]. Correlation was significant between the parameters ( p < 0.01): EQ-5D index = 1.014 - 0.25 x HAQ-0.041 x DAS; HAQ = 0.314 + 0.065 x RAQoL. Analysis by disease severity levels (HAQ groups 0.5 difference) revealed that health status worsens (mean EQ-5D: 0.784; 0.576; 0.504; 0.367; 0.211; 0.022) and costs increase (mean 628,280; 888,187; 953,759; 1,291,218; 1,346,112; 1,371,674 HUF/patient/year) with disease progression. Minimally important worsening of functional ability (0.25 HAQ increase) corresponds to -0.0705 EQ-5D and +1.884 RAQoL change. Lower health status difference (EQ-5D -0.05725) was calculated in patients with lower disease activity (DAS < 5.1). Correlation between disease progression, health status, quality of life and costs does not differ significantly from international results. The amount of costs is much lower in all disease severity levels than in developed European countries. Our study serves baseline data for health economic analysis in RA in Hungary.

Working towards TB elimination the WHO Regional Strategic Plan (2006-2015).

PubMed

Nair, Nani; Cooreman, Erwin

2006-03-01

DOTS has expanded rapidly in the South-East Asia Region over the period of the Partnership's first Global Plan (2001-2005), with almost 100% geographical coverage achieved in 2005. All countries have made impressive progress in improving coverage and quality. This progress has been made possible through strong political commitment and large investments in TB control for improved infrastructure, reliable drug supply, increased staffing, improved laboratory services, and intensified training and supervision. Accomplishing the objectives outlined in this document will require sustaining the progress in all countries and particularly in the five high burden countries for achieving major regional and global impact. National TB programmes will need to be supported to maintain or surpass the 70% case detection and 85% treatment success rates. The achievement of the TB-related targets linked to the MDGs will also depend on how effectively initiatives such as DOTS-Plus, PPM DOTS and interventions for TB/ HIV among others, are implemented. National governments and development partners must fulfill their commitments to mobilizing and sustaining adequate resources to support the full range of activities envisaged. The benefits of full and effective implementation of all the planned interventions would be substantial. These will result in 20 to 25 million TB cases being treated in DOTS program mes and more than 150 000 drug-resistant cases receiving treatment through DOTS-Plus during the period 2006-2015. In addition, at least 250 000 HIV-infected TB patients may also receive anti-retroviral therapy. As a consequence, the prevalence of TB is expected to fall below 175/100 000 and the number of TB deaths is expected to fall to between 100 000 and 150 000 per year. There would also be substantial economic benefits given that TB disproportionately affects adults in their most productive years. Considering these aspects, it is expected that the TB incidence will decline significantly during this period so that the Millennium Development Goals would be met by or ahead of 2015.

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

From Scribbles to Scrabble: Preschool Children’s Developing Knowledge of Written Language

PubMed Central

Puranik, Cynthia S.; Lonigan, Christopher J.

2011-01-01

The purpose of this study was to concurrently examine the development of written language across several writing tasks and to investigate how writing features develop in preschool children. Emergent written language knowledge of 372 preschoolers was assessed using numerous writing tasks. The findings from this study indicate that children possess a great deal of writing knowledge before beginning school. Children appear to progress along a continuum from scribbling to conventional spelling, and this progression is linear and task dependent. There was clear evidence to support the claim that universal writing features develop before language-specific features. Children as young as 3 years possess knowledge regarding universal and language-specific writing features. There is substantial developmental continuity in literacy skills from the preschool period into early elementary grades. Implications of these findings on writing development are discussed. PMID:22448101

Dementia Pugilistica Revisited

PubMed Central

Castellani, Rudy J.; Perry, George

2017-01-01

 Extensive exposure of boxers to neurotrauma in the early 20th century led to the so-called punch drunk syndrome, which was formally recognized in the medical literature in 1928. “Punch drunk” terminology was replaced by the less derisive ‘dementia pugilistica’ in 1937. In the early case material, the diagnosis of dementia pugilistica required neurological deficits, including slurring dysarthria, ataxia, pyramidal signs, extrapyramidal signs, memory impairment, and personality changes, although the specific clinical substrate has assumed lesser importance in recent years with a shift in focus on molecular pathogenesis. The postmortem neuropathology of dementia pugilistica has also evolved substantially over the past 90 years, from suspected concussion-related hemorrhages to diverse structural and neurofibrillary changes to geographic tauopathy. Progressive neurodegenerative tauopathy is among the prevailing theories for disease pathogenesis currently, although this may be overly simplistic. Careful examination of historical cases reveals both misdiagnoses and a likelihood that dementia pugilistica at that time was caused by cumulative structural brain injury. More recent neuropathological studies indicate subclinical and possibly static tauopathy in some athletes and non-athletes. Indeed, it is unclear from the literature whether retired boxers reach the inflection point that tends toward progressive neurodegeneration in the manner of Alzheimer’s disease due to boxing. Even among historical cases with extreme levels of exposure, progressive disease was exceptional. PMID:29036831

An alternate pathophysiologic paradigm of sepsis and septic shock

PubMed Central

Kumar, Anand

2014-01-01

The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. PMID:24184742

Effects of Electromagnetic Fields on Fish and Invertebrates Task 2.1.3: Effects on Aquatic Organisms Fiscal Year 2012 Progress Report Environmental Effects of Marine and Hydrokinetic Energy

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

Woodruff, Dana L.; Cullinan, Valerie I.; Copping, Andrea E.

2013-05-20

Energy generated by the world’s oceans and rivers offers the potential to make substantial contributions to the domestic and global renewable energy supply. However, the marine and hydrokinetic (MHK) energy industry faces challenges related to siting, permitting, construction, and operation of pilotand commercial-scale facilities. One of the challenges is to understand the potential effects to marine organisms from electromagnetic fields, which are produced as a by-product of transmitting power from offshore to onshore locations through underwater transmission cables. This report documents the progress of the third year of research (fiscal year 2012) to investigate environmental issues associated with marine andmore » hydrokinetic energy (MHK) generation. This work was conducted by Pacific Northwest National Laboratory (PNNL) for the U.S. Department of Energy’s (DOE’s) Office of Energy Efficiency and Renewable Energy (EERE) Wind and Water Technologies Office. The report addresses the effects of electromagnetic fields (EMFs) on selected marine species where significant knowledge gaps exist. The species studied this fiscal year included one fish and two crustacean species: the Atlantic halibut (Hippoglossus hippoglossus), Dungeness crab (Metacarcinus magister), and American lobster (Homarus americanus).« less

Nuclear Receptors in Neurodegenerative Diseases

PubMed Central

Skerrett, Rebecca; Malm, Tarja; Landreth, Gary

2014-01-01

Nuclear receptors have generated substantial interest in the past decade as potential therapeutic targets for the treatment of neurodegenerative disorders. Despite years of effort, effective treatments for progressive neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and ALS remain elusive, making non-classical drug targets such as nuclear receptors an attractive alternative. A substantial literature in mouse models of disease and several clinical trials have investigated the role of nuclear receptors in various neurodegenerative disorders, most prominently AD. These studies have met with mixed results, yet the majority of studies in mouse models report positive outcomes. The mechanisms by which nuclear receptor agonists affect disease pathology remain unclear. Deciphering the complex signaling underlying nuclear receptor action in neurodegenerative diseases is essential for understanding this variability in preclinical studies, and for the successful translation of nuclear receptor agonists into clinical therapies. PMID:24874548

Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy

PubMed Central

Barroso, Fabio; González‐Duarte, Alejandra; Conceição, Isabel; Obici, Laura; Keohane, Denis; Amass, Leslie

2016-01-01

ABSTRACT Transthyretin familial amyloid polyneuropathy (TTR‐FAP) is a rare, severe, and irreversible, adult‐onset, hereditary disorder caused by autosomal‐dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR‐FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease‐modifying treatment options for a wider spectrum of patients with TTR‐FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation‐specific predictive genetic testing in first‐degree relatives of index patients diagnosed with TTR‐FAP and the structured clinical follow‐up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353–360, 2016 PMID:27273296

[Current Status of Targeted Treatment in Breast Cancer].

PubMed

Seiffert, Katharina; Schmalfeldt, Barbara; Müller, Volkmar

2017-11-01

Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival. For patients with HER2-positive disease the addition of Pertuzumab to Trastuzumab in combination with chemotherapy has been a significant improvement in anti-HER2 therapy in early as well as metastatic breast cancer. Evidence-based further line therapy options in the metastatic setting include T-DM1 and in later lines Lapatinib. For triple negative disease the angiogenesis inhibitor Bevacizumab is approved, which increases progression free survival. Immune checkpoint inhibitors, PARP-inhibitors or anti-androgens represent promising strategies, all of which are currently being evaluated in clinical trials. The development of predictive biomarkers to guide targeted therapies is still the subject of research. © Georg Thieme Verlag KG Stuttgart · New York.

Examining the progression and consistency of thermal concepts: a cross-age study

NASA Astrophysics Data System (ADS)

Adadan, Emine; Yavuzkaya, Merve Nur

2018-03-01

This cross-sectional study examined how the progression and consistency of students' understanding of thermal concepts in everyday contexts changes across the grade levels. A total of 656 Turkish students from Grade 8 (age 13-14), Grade 10 (age 15-16), and the first year of college (age 19-20) participated in the study. The data were analysed using statistical procedures (descriptive and inferential). Findings indicated a substantial progression in the students' scientific understanding of thermal concepts across grade levels. In addition, the students' alternative conceptions about thermal concepts generally decreased in frequency across grade levels, but certain alternative conceptions were observed in every grade level to a similar extent. Even though the number of students who consistently used scientific ideas increased across grade levels, the number of students who consistently used non-scientific ideas decreased across grade levels. However, the number of students who used scientific and non-scientific ideas inconsistently generally increased as they progressed in the science curriculum. These findings can be associated with either fragmentation or alternative conceptions that result from the gradual enrichment processes students experience when they try to integrate scientific concepts into their conceptual frameworks.

Measles mortality reduction contributes substantially to reduction of all cause mortality among children less than five years of age, 1990-2008.

PubMed

van den Ent, Maya M V X; Brown, David W; Hoekstra, Edward J; Christie, Athalia; Cochi, Stephen L

2011-07-01

The Millennium Development Goal 4 (MDG4) to reduce mortality in children aged <5 years by two-thirds from 1990 to 2015 has made substantial progress. We describe the contribution of measles mortality reduction efforts, including those spearheaded by the Measles Initiative (launched in 2001, the Measles Initiative is an international partnership committed to reducing measles deaths worldwide and is led by the American Red Cross, the Centers for Disease Control and Prevention, UNICEF, the United Nations Foundation, and the World Health Organization). We used published data to assess the effect of measles mortality reduction on overall and disease-specific global mortality rates among children aged <5 years by reviewing the results from studies with the best estimates on causes of deaths in children aged 0-59 months. The estimated measles-related mortality among children aged <5 years worldwide decreased from 872,000 deaths in 1990 to 556,000 in 2001 (36% reduction) and to 118,000 in 2008 (86% reduction). All-cause mortality in this age group decreased from >12 million in 1990 to 10.6 million in 2001 (13% reduction) and to 8.8 million in 2008 (28% reduction). Measles accounted for about 7% of deaths in this age group in 1990 and 1% in 2008, equal to 23% of the global reduction in all-cause mortality in this age group from 1990 to 2008. Aggressive efforts to prevent measles have led to this remarkable reduction in measles deaths. The current funding gap and insufficient political commitment for measles control jeopardizes these achievements and presents a substantial risk to achieving MDG4. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

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

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

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

2011-09-13

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

Potential Use of γ-Secretase Modulators in the Treatment of Alzheimer Disease

PubMed Central

Wagner, Steven L.; Tanzi, Rudolph E.; Mobley, William C.; Galasko, Douglas

2013-01-01

Although significant progress has occurred in the past 20 years regarding our understanding of Alzheimer disease pathogenesis, we have yet to identify disease-modifying therapeutics capable of substantially altering the clinical course of this prevalent neurodegenerative disease. In this short review, we discuss 2 approaches that are currently being tested clinically (γ-secretase inhibition and γ-secretase modulation) and emphasize the significant differences between these 2 therapeutic approaches. We also discuss certain genetic- and biomarker-based translational and clinical trial paradigms that may assist in developing a useful therapeutic agent. PMID:22801784

C++ software quality in the ATLAS experiment: tools and experience

NASA Astrophysics Data System (ADS)

Martin-Haugh, S.; Kluth, S.; Seuster, R.; Snyder, S.; Obreshkov, E.; Roe, S.; Sherwood, P.; Stewart, G. A.

2017-10-01

In this paper we explain how the C++ code quality is managed in ATLAS using a range of tools from compile-time through to run time testing and reflect on the substantial progress made in the last two years largely through the use of static analysis tools such as Coverity®, an industry-standard tool which enables quality comparison with general open source C++ code. Other available code analysis tools are also discussed, as is the role of unit testing with an example of how the GoogleTest framework can be applied to our codebase.

Multicanonical hybrid Monte Carlo algorithm: Boosting simulations of compact QED

NASA Astrophysics Data System (ADS)

Arnold, G.; Schilling, K.; Lippert, Th.

1999-03-01

We demonstrate that substantial progress can be achieved in the study of the phase structure of four-dimensional compact QED by a joint use of hybrid Monte Carlo and multicanonical algorithms through an efficient parallel implementation. This is borne out by the observation of considerable speedup of tunnelling between the metastable states, close to the phase transition, on the Wilson line. We estimate that the creation of adequate samples (with order 100 flip-flops) becomes a matter of half a year's run time at 2 Gflops sustained performance for lattices of size up to 244.

Update on diagnosis and treatment of idiopathic pulmonary fibrosis

PubMed Central

Baddini-Martinez, José; Baldi, Bruno Guedes; da Costa, Cláudia Henrique; Jezler, Sérgio; Lima, Mariana Silva; Rufino, Rogério

2015-01-01

Idiopathic pulmonary fibrosis is a type of chronic fibrosing interstitial pneumonia, of unknown etiology, which is associated with a progressive decrease in pulmonary function and with high mortality rates. Interest in and knowledge of this disorder have grown substantially in recent years. In this review article, we broadly discuss distinct aspects related to the diagnosis and treatment of idiopathic pulmonary fibrosis. We list the current diagnostic criteria and describe the therapeutic approaches currently available, symptomatic treatments, the action of new drugs that are effective in slowing the decline in pulmonary function, and indications for lung transplantation. PMID:26578138

Preventing HIV infection in women.

PubMed

Adimora, Adaora A; Ramirez, Catalina; Auerbach, Judith D; Aral, Sevgi O; Hodder, Sally; Wingood, Gina; El-Sadr, Wafaa; Bukusi, Elizabeth A

2013-07-01

Although the number of new infections has declined recently, women still constitute almost half of the world's 34 million people with HIV infection, and HIV remains the leading cause of death among women of reproductive age. Prevention research has made considerable progress during the past few years in addressing the biological, behavioral, and social factors that influence women's vulnerability to HIV infection. Nevertheless, substantial work still must be performed to implement scientific advancements and to resolve many questions that remain. This article highlights some of the recent advances and persistent gaps in HIV prevention research for women and outlines key research and policy priorities.

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

24 CFR 1006.430 - Corrective and remedial action.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

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.

From the Earth Summit to Rio+20: integration of health and sustainable development.

PubMed

Haines, Andy; Alleyne, George; Kickbusch, Ilona; Dora, Carlos

2012-06-09

In 2012, world leaders will meet at the Rio+20 conference to advance sustainable development--20 years after the Earth Summit that resulted in agreement on important principles but insufficient action. Many of the development goals have not been achieved partly because social (including health), economic, and environmental priorities have not been addressed in an integrated manner. Adverse trends have been reported in many key environmental indicators that have worsened since the Earth Summit. Substantial economic growth has occurred in many regions but nevertheless has not benefited many populations of low income and those that have been marginalised, and has resulted in growing inequities. Variable progress in health has been made, and inequities are persistent. Improved health contributes to development and is underpinned by ecosystem stability and equitable economic progress. Implementation of policies that both improve health and promote sustainable development is urgently needed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Scholarly productivity for nursing clinical track faculty.

PubMed

Tschannen, Dana; Anderson, Christine; Strobbe, Stephen; Bay, Esther; Bigelow, April; Dahlem, Chin Hwa Gina Y; Gosselin, Ann K; Pollard, Jennifer; Seng, Julia S

2014-01-01

Recent years have yielded substantial advancement by clinical track faculty in cohort expansion and collective contributions to the discipline of nursing. As a result, standards for progression and promotion for clinical faculty need to be more fully developed, articulated, and disseminated. Our school formed a task force to examine benchmarks for the progression and promotion of clinical faculty across schools of nursing, with the goal of guiding faculty, reviewers, and decision makers about what constitutes excellence in scholarly productivity. Results from analyses of curriculum vitae of clinical professors or associate professors at six universities with high research activity revealed a variety of productivity among clinical track members, which included notable diversity in the types of scholarly products. Findings from this project help quantify types of scholarship for clinical faculty at the time of promotion. This work provides a springboard for greater understanding of the contributions of clinical track faculty to nursing practice. Copyright © 2014 Elsevier Inc. All rights reserved.

Rapidly progressing facial leishmaniasis: effective treatment with liposomal amphotericin B and a review of the management of Old World cutaneous leishmaniasis.

PubMed

Islam, Shamim

2018-05-01

Cutaneous leishmaniasis (CL), a common condition in many parts of the world, is being increasingly encountered in non-endemic countries secondary to immigration. The clinical manifestations and course can vary substantially, with appropriate management ranging from observation for self-healing lesions to urgent treatment to prevent damaging anatomical and cosmetic sequelae. While there are now several effective medications, optimal therapy is not well defined, and decision-making can be challenged by the location of lesions and various drug issues, including availability, mode of delivery and adverse effects. A 7-year-old Afghani boy who presented shortly after arriving in the United States with a rapidly progressing crusting and ulcerative facial rash caused by Leishmania tropica is described. The various drugs currently available for CL and experience of using liposomal amphotericin B specifically are reviewed.

Current perspective of neuroprotection and glaucoma

PubMed Central

Tian, Kailin; Shibata-Germanos, Shannon; Pahlitzsch, Milena; Cordeiro, M Francesca

2015-01-01

Glaucoma is the second leading cause of blindness worldwide and is most notably characterized by progressive optic nerve atrophy and advancing loss of retinal ganglion cells (RGCs). The main concomitant factor is the elevated intraocular pressure (IOP). Existing treatments are focused generally on lowering IOP. However, both RGC loss and optic nerve atrophy can independently occur with IOP at normal levels. In recent years, there has been substantial progress in the development of neuroprotective therapies for glaucoma in order to restore vital visual function. The present review intends to offer a brief insight into conventional glaucoma treatments and discuss exciting current developments of mostly preclinical data in novel neuroprotective strategies for glaucoma that include recent advances in noninvasive diagnostics going beyond IOP maintenance for an enhanced global view. Such strategies now target RGC loss and optic nerve damage, opening a critical therapeutic window for preventative monitoring and treatment. PMID:26635467

Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.

PubMed

Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; van der Kop, Mia L; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen

2012-07-18

Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.

The Health IT Regional Extension Center Program: evolution and lessons for health care transformation.

PubMed

Lynch, Kimberly; Kendall, Mat; Shanks, Katherine; Haque, Ahmed; Jones, Emily; Wanis, Maggie G; Furukawa, Michael; Mostashari, Farzad

2014-02-01

Assess the Regional Extension Center (REC) program's progress toward its goal of supporting over 100,000 providers in small, rural, and underserved practices to achieve meaningful use (MU) of an electronic health record (EHR). Data collected January 2010 through June 2013 via monitoring and evaluation of the 4-year REC program. Descriptive study of 62 REC programs. Primary data collected from RECs were merged with nine other datasets, and descriptive statistics of progress by practice setting and penetration of targeted providers were calculated. RECs recruited almost 134,000 primary care providers (PCPs), or 44 percent of the nation's PCPs; 86 percent of these were using an EHR with advanced functionality and almost half (48 percent) have demonstrated MU. Eighty-three percent of Federally Qualified Health Centers and 78 percent of the nation's Critical Access Hospitals were participating with an REC. RECs have made substantial progress in assisting PCPs with adoption and MU of EHRs. This infrastructure supports small practices, community health centers, and rural and public hospitals to use technology for care delivery transformation and improvement. © Health Research and Educational Trust.

Cost-Effectiveness of Pembrolizumab Versus Ipilimumab in Ipilimumab-Naïve Patients with Advanced Melanoma in the United States.

PubMed

Wang, Jingshu; Chmielowski, Bartosz; Pellissier, James; Xu, Ruifeng; Stevinson, Kendall; Liu, Frank Xiaoqing

2017-02-01

Recent clinical trials have shown that pembrolizumab significantly prolonged progression-free survival and overall survival compared with ipilimumab in ipilimumab-naïve patients with unresectable or metastatic melanoma. However, there has been no published evidence on the cost-effectiveness of pembrolizumab for this indication. To assess the long-term cost-effectiveness of pembrolizumab versus ipilimumab in ipilimumab-naïve patients with unresectable or meta-static melanoma from a U.S. integrated health system perspective. A partitioned-survival model was developed, which divided overall survival time into progression-free survival and postprogression survival. The model used Kaplan-Meier estimates of progression-free survival and overall survival from a recent randomized phase 3 study (KEYNOTE-006) that compared pembrolizumab and ipilimumab. Extrapolation of progression-free survival and overall survival beyond the clinical trial was based on parametric functions and literature data. The base-case time horizon was 20 years, and costs and health outcomes were discounted at a rate of 3% per year. Clinical data-including progression-free survival and overall survival data spanning a median follow-up time of 15 months, as well as quality of life and adverse event data from the ongoing KEYNOTE-006 trial-and cost data from public sources were used to populate the model. Costs included those of drug acquisition, treatment administration, adverse event management, and disease management of advanced melanoma. The incremental cost-effectiveness ratio (ICER) expressed as cost difference per quality-adjusted life-year (QALY) gained was the main outcome, and a series of sensitivity analyses were performed to test the robustness of the results. In the base case, pembrolizumab was projected to increase the life expectancy of U.S. patients with advanced melanoma by 1.14 years, corresponding to a gain of 0.79 discounted QALYs over ipilimumab. The model also projected an average increase of $63,680 in discounted perpatient costs of treatment with pembrolizumab versus ipilimumab. The corresponding ICER was $81,091 per QALY ($68,712 per life-year) over a 20-year time horizon. With $100,000 per QALY as the threshold, when input parameters were varied in deterministic one-way sensitivity analyses, the use of pembrolizumab was cost-effective relative to ipilimumab in most ranges. Further, in a comprehensive probabilistic sensitivity analysis, the ICER was cost-effective in 83% of the simulations. Compared with ipilimumab, pembrolizumab had higher expected QALYs and was cost-effective for the treatment of patients with unresectable or metastatic melanoma from a U.S. integrated health system perspective. This study was supported by funding from Merck & Co., which reviewed and approved the manuscript before journal submission. Wang, Pellissier, Xu, Stevinson, and Liu are employees of, and own stock in, Merck & Co. Chmielowski has served as a paid consultant for Merck & Co. and received a consultant fee for clinical input in connection with this study. Chmielowski also reports receiving advisory board and speaker bureau fees from multiple major pharmaceutical companies. Wang led the modeling and writing of the manuscript. Chmielowski, Xu, Stevinson, and Pellissier contributed substantially to the modeling design and methodology. Liu led the data collection work and contributed substantially to writing the manuscript. In conducting the analysis and writing the manuscript, the authors followed Merck publication polices and the "cost-effectiveness analysis alongside clinical trials-good research practices and the CHEERS reporting format as recommended by the International Society for Pharmacoeconomics and Outcomes Research.

Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

PubMed

de Bono, Johann S; Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; Small, Eric J; Shore, Neal D; Fizazi, Karim; De Porre, Peter; Kheoh, Thian; Li, Jinhui; Todd, Mary B; Ryan, Charles J; Flaig, Thomas W

2017-04-01

Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P). This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (≥75 yr) and younger (<75 yr) patient subgroups. Data were collected at the final OS analysis (96% of expected death events). Subsequent therapy data were prospectively collected, while response and discontinuation data were collected retrospectively following discontinuation of the study drug. At the discretion of the investigator, 67% (365/546) of patients from the AA arm received subsequent treatment with one or more agents approved for mCRPC. Efficacy analysis was performed for patients for whom baseline and at least one post-baseline prostate-specific antigen (PSA) values were available. Baseline and at least one post-baseline PSA values were available for 100 AA patients who received docetaxel as FST. While acknowledging the limitations of post hoc analyses, 40% (40/100) of these patients had an unconfirmed ≥50% PSA decline with first subsequent docetaxel therapy, and 27% (27/100) had a confirmed ≥50% PSA decline. The median docetaxel treatment duration among these 100 patients was 4.2 mo. Docetaxel was the most common FST among older and younger patients from each treatment arm. However, 43% (79/185) of older patients who progressed on AA received no subsequent therapy for mCRPC, compared with 17% (60/361) of younger patients. Patients with mCRPC who progress with AA treatment may still derive benefit from subsequent docetaxel therapy. These data support further assessment of treatment patterns following AA treatment for mCRPC, particularly among older patients. ClinicalTrials.gov NCT00887198. Treatment patterns for advanced prostate cancer have changed substantially in the last few years. This additional analysis provides evidence of clinical benefit for subsequent chemotherapy in men with advanced prostate cancer whose disease progressed after treatment with abiraterone acetate. Older patients were less likely to be treated with subsequent therapy. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Rosuvastatin Slows Progression of Subclinical Atherosclerosis in Patients with Treated HIV Infection

PubMed Central

Longenecker, Chris T.; Sattar, Abdus; Gilkeson, Robert; Mccomsey, Grace A.

2016-01-01

Objective To determine the effect of statins on the progression of subclinical atherosclerosis in a population of HIV-infected adults on antiretroviral therapy. Design Double-blind, randomized clinical trial Methods SATURN-HIV was a 96-week double-blind, randomized clinical trial of 10 mg daily rosuvastatin (n=72) versus placebo (n=75) in a population of HIV-infected subjects on stable antiretroviral therapy with LDL-cholesterol ≤130mg/dL (≤3.36mmol/L) and evidence of heightened T-cell activation (CD8+CD38+HLA-DR+ ≥19%) or increased inflammation (high sensitivity C-reactive protein ≥2mg/L (≥19mmol/L)). Change in common carotid artery IMT (CCA-IMT) was the primary outcome. Secondary outcomes were changes in LDL and coronary artery calcium (CAC). Results Median (Q1, Q3) age was 46 (40, 53) years; 78% were male and 68% African American; 49% were on a protease inhibitor. Mean (95% CI) change in LDL was −21 (−27 to −15) mg/dL [−0.54 (−0.70 to −0.39) mmol/L] in the rosuvastatin arm. In a multivariable linear mixed-effects model, assignment to statin was associated with 0.019mm (95% CI: 0.002–0.037mm) less progression of CCA-IMT over 96 weeks. We did not find substantial effect modification by level of inflammation or immune activation biomarkers, except for a borderline statistically significant interaction for soluble vascular cell adhesion molecule (p=0.065). There was no difference in CAC change (p=0.61). Conclusions Rosuvastatin effectively lowers LDL and appears to substantially slow progression of CCA-IMT in patients with treated HIV infection. Future study is needed to determine whether subjects with higher levels of inflammation or immune activation derive greater cardiovascular benefit from statin therapy. PMID:27203715

Aligning incentives in orthopaedics: opportunities and challenges -- the Case Medical Center experience.

PubMed

Marcus, Randall E; Zenty, Thomas F; Adelman, Harlin G

2009-10-01

For 30 years, the orthopaedic faculty at Case Western Reserve University worked as an independent private corporation within University Hospitals Case Medical Center (Hospital). However, by 2002, it became progressively obvious to our orthopaedic practice that we needed to modify our business model to better manage the healthcare regulatory changes and decreased reimbursement if we were to continue to attract and retain the best and brightest orthopaedic surgeons to our practice. In 2002, our surgeons created a new entity wholly owned by the parent corporation at the Hospital. As part of this transaction, the parties negotiated a balanced employment model designed to fully integrate the orthopaedic surgeons into the integrated delivery system that included the Hospital. This new faculty practice plan adopted a RVU-based compensation model for the physicians, with components that created incentives both for clinical practice and for academic and administrative service contributions. Over the past 5 years, aligning incentives with the Hospital has substantially increased the clinical productivity of the surgeons and has also benefited the Hospital and our patients. Furthermore, aligned incentives between surgeons and hospitals could be of substantial financial benefit to both, as Medicare moves forward with its bundled project initiative.

Mild cognitive impairment, amnestic type: an epidemiologic study.

PubMed

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

2004-07-13

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

The Mixed Economic Progress of Immigrants.

ERIC Educational Resources Information Center

Schoeni, Robert F.; And Others

This report examines whether the economic well-being of male immigrants to the United States improves substantially over time, details differences in economic progress of immigrants from different countries of origin, and assesses the impact of educational attainment on immigrants' earnings. Analyses are based on Public Use Micro Samples of the…

Transforming Performance Measurement for the 21st Century

ERIC Educational Resources Information Center

Hatry, Harry P.

2014-01-01

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

THE DISADVANTAGED CHILDREN AND YOUTH OF AMERICA.

ERIC Educational Resources Information Center

OETTINGER, KATHERINE B.

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

Evaluating Test Validity: Reprise and Progress

ERIC Educational Resources Information Center

Shepard, Lorrie A.

2016-01-01

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

Histological effects of givinostat in boys with Duchenne muscular dystrophy.

PubMed

Bettica, Paolo; Petrini, Stefania; D'Oria, Valentina; D'Amico, Adele; Catteruccia, Michela; Pane, Marika; Sivo, Serena; Magri, Francesca; Brajkovic, Simona; Messina, Sonia; Vita, Gian Luca; Gatti, Barbara; Moggio, Maurizio; Puri, Pier Lorenzo; Rocchetti, Maurizio; De Nicolao, Giuseppe; Vita, Giuseppe; Comi, Giacomo P; Bertini, Enrico; Mercuri, Eugenio

2016-10-01

Duchenne Muscular Dystrophy (DMD) is caused by mutations in the dystrophin gene leading to dystrophin deficiency, muscle fiber degeneration and progressive fibrotic replacement of muscles. Givinostat, a histone deacetylase (HDAC) inhibitor, significantly reduced fibrosis and promoted compensatory muscle regeneration in mdx mice. This study was conducted to evaluate whether the beneficial histological effects of Givinostat could be extended to DMD boys. Twenty ambulant DMD boys aged 7 to <11 years on stable corticosteroid treatment were enrolled in the study and treated for ≥12 months with Givinostat. A muscle biopsy was collected at the beginning and at the end of treatment to evaluate the amount of muscle and fibrotic tissue. Histological effects were the primary objectives of the study. Treatment with Givinostat significantly increased the fraction of muscle tissue in the biopsies and reduced the amount of fibrotic tissue. It also substantially reduced tissue necrosis and fatty replacement. Overall the drug was safe and tolerated. Improvement in functional tests was not observed in this study, but the sample size of the study was not sufficient to draw definitive conclusions. This study showed that treatment with Givinostat for more than 1 year significantly counteracted histological disease progression in ambulant DMD boys aged 7 to 10 years. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Interrupting the transmission of wild polioviruses with vaccines: immunological considerations.

PubMed Central

Ghendon, Y.; Robertson, S. E.

1994-01-01

In 1988 the World Health Assembly set the goal of global poliomyelitis eradication by the year 2000. Substantial progress has been made, and 143 countries reported no poliomyelitis cases associated with the wild virus in 1993. This article reviews the immunological considerations relevant to interrupting the transmission of wild polioviruses with vaccines. Although serum immunity prevents poliomyelitis in the individual, it is local immunity that is important in preventing the transmission of polioviruses in the community. Natural infection and vaccination with oral polioviruses vaccine (OPV) produce local immunity in the intestine and the nasopharynx in about 70-80% of individuals. In contrast, inactivated poliovirus vaccine (IPV) produces local intestinal immunity in only 20-30% of the individuals. With either vaccine, however, a substantial proportion of the immunized population can transmit the wild virus. Moreover, although serum immunity is long-lasting, limited data suggest that local immunity may not be as persistent. To interrupt the transmission of wild polioviruses efforts should be made to achieve and sustain high levels of poliovirus vaccine coverage. Recent outbreaks show that wild poliovirus poses a risk for unimmunized individuals, even when overall coverage levels are high. Delivery of poliovirus vaccine to hard-to-reach populations will be of increasing importance as countries progress toward the final stages of poliomyelitis eradication. The immunization status of persons from poliomyelitis-free countries should be updated prior to travel to poliomyelitis-endemic areas. PMID:7867144

Comparative effectiveness of incorporating a hypothetical DCIS prognostic marker into breast cancer screening.

PubMed

Trentham-Dietz, Amy; Ergun, Mehmet Ali; Alagoz, Oguzhan; Stout, Natasha K; Gangnon, Ronald E; Hampton, John M; Dittus, Kim; James, Ted A; Vacek, Pamela M; Herschorn, Sally D; Burnside, Elizabeth S; Tosteson, Anna N A; Weaver, Donald L; Sprague, Brian L

2018-02-01

Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Kaolinosis in a cotton mill worker.

PubMed

Levin, J L; Frank, A L; Williams, M G; McConnell, W; Suzuki, Y; Dodson, R F

1996-02-01

A 62-year-old white male employed for 43 years in the polishing room of a cotton textile mill was admitted to a tertiary care center with progressive dyspnea and productive cough that had not responded to therapy for tuberculosis. In spite of aggressive antibiotic therapy and respiratory support, the patient died as a consequence of respiratory failure. Small rounded and irregular opacities had been noted on the chest radiograph. Review of job-site spirometry demonstrated a worsening restrictive pattern over a 4-year period prior to his death. Additional occupational history revealed long-term exposure to kaolin in the polishing room, and pathologic examination of lung tissue confirmed extensive fibrosis and substantial quantities of kaolin. Kaolinosis is a disease typically found among individuals involved in mining or processing this material rather than in user industries. This case illustrates the importance of obtaining a complete occupational history in reaching a diagnosis. The clinicopathologic aspects of kaolinosis are also reviewed.

Closing the gaps in child health in the Pacific: An achievable goal in the next 20 years

PubMed Central

Duke, Trevor; Kado, Joseph H; Auto, James; Amini, James; Gilbert, Katherine

2015-01-01

It is not inconceivable that by 2035 the substantial gaps in child health across the Pacific can close significantly. Currently, Australia and New Zealand have child mortality rates of 5 and 6 per 1000 live births, respectively, while Pacific island developing nations have under 5 mortality rates ranging from 13 to 16 (Vanuatu, Fiji and Tonga) to 47 and 58 per 1000 live births (Kiribati and Papua New Guinea, respectively). However, these Pacific child mortality rates are falling, by an average of 1.4% per year since 1990, and more rapidly (1.9% per year) since 2000. Based on progress elsewhere, there is a need to (i) define the specific things needed to close the gaps in child health; (ii) be far more ambitious and hopeful than ever before; and (iii) form a new regional compact based on solidarity and interdependence. PMID:25586845

Self-report measures of executive functioning are a determinant of academic performance in first-year students at a university of applied sciences

PubMed Central

Baars, Maria A. E.; Nije Bijvank, Marije; Tonnaer, Geertje H.; Jolles, Jelle

2015-01-01

Recent studies in late adolescents (age 17+) show that brain development may proceed till around the 25th year of age. This implies that study performance in higher education could be dependent upon the stage of brain maturation and neuropsychological development. Individual differences in development of neuropsychological skills may thus have a substantial influence on the outcome of the educational process. This hypothesis was evaluated in a large survey of 1760 first-year students at a University of Applied Sciences, of which 1332 are included in the current analyses. This was because of their fit within the age range we pre-set (17–20 years' old at start of studies). Student characteristics and three behavioral ratings of executive functioning (EF) were evaluated with regard to their influence on academic performance. Self-report measures were used: self-reported attention, planning, and self-control and self-monitoring. Results showed that students with better self-reported EF at the start of the first year of their studies obtained more study credits at the end of that year than students with a lower EF self-rating. The correlation between self-control and self-monitoring on the one hand, and study progress on the other, appeared to differ for male and female students and to be influenced by the level of prior education. The results of this large-scale study could have practical relevance. The profound individual differences between students may at least partly be a consequence of their stage of development as an adolescent. Students who show lower levels of attention control, planning, and self-control/self-monitoring can be expected to have a problem in study planning and study progress monitoring and hence study progress. The findings imply that interventions directed at the training of these (executive) functions should be developed and used in higher education in order to improve academic achievement, learning attitude, and motivation. PMID:26300823

Self-report measures of executive functioning are a determinant of academic performance in first-year students at a university of applied sciences.

PubMed

Baars, Maria A E; Nije Bijvank, Marije; Tonnaer, Geertje H; Jolles, Jelle

2015-01-01

Recent studies in late adolescents (age 17+) show that brain development may proceed till around the 25th year of age. This implies that study performance in higher education could be dependent upon the stage of brain maturation and neuropsychological development. Individual differences in development of neuropsychological skills may thus have a substantial influence on the outcome of the educational process. This hypothesis was evaluated in a large survey of 1760 first-year students at a University of Applied Sciences, of which 1332 are included in the current analyses. This was because of their fit within the age range we pre-set (17-20 years' old at start of studies). Student characteristics and three behavioral ratings of executive functioning (EF) were evaluated with regard to their influence on academic performance. Self-report measures were used: self-reported attention, planning, and self-control and self-monitoring. Results showed that students with better self-reported EF at the start of the first year of their studies obtained more study credits at the end of that year than students with a lower EF self-rating. The correlation between self-control and self-monitoring on the one hand, and study progress on the other, appeared to differ for male and female students and to be influenced by the level of prior education. The results of this large-scale study could have practical relevance. The profound individual differences between students may at least partly be a consequence of their stage of development as an adolescent. Students who show lower levels of attention control, planning, and self-control/self-monitoring can be expected to have a problem in study planning and study progress monitoring and hence study progress. The findings imply that interventions directed at the training of these (executive) functions should be developed and used in higher education in order to improve academic achievement, learning attitude, and motivation.

49 CFR 213.113 - Defective rails.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

49 CFR 213.113 - Defective rails.

Code of Federal Regulations, 2011 CFR

2011-10-01

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

49 CFR 213.113 - Defective rails.

Code of Federal Regulations, 2012 CFR

2012-10-01

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

49 CFR 213.113 - Defective rails.

Code of Federal Regulations, 2013 CFR

2013-10-01

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

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

ERIC Educational Resources Information Center

Baker, Laura

2017-01-01

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

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

ERIC Educational Resources Information Center

Glover, Jacob I.

2012-01-01

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

Recent Advances and Future Opportunities to Address Challenges in Offloading Diabetic Feet: A Mini-Review.

PubMed

Crews, Ryan T; King, Abagayle L; Yalla, Sai V; Rosenblatt, Noah J

2018-01-16

Diabetic foot ulcers (DFU) are a substantial dilemma for geriatric individuals with diabetes. The breakdown in tissue associated with DFU is typically a result of repetitive cycles of physical stress placed on the feet during weight-bearing activity. Accordingly, a key tenet in healing as well as preventing DFU is the use of offloading footwear to redistribute physical stress away from high stress locations such as bony prominences. Over the last several years there has been a substantial amount of effort directed at better understanding and implementing the practice of offloading. A review of this work as well as relevant technological advances is presented in this paper. Specifically, we will discuss the following topics in association with offloading diabetic feet: achieving optimal offloading, dosing activity/physical stress, thermal monitoring to detect preulcerative tissue damage, adherence with offloading devices, and optimizing the user experience. In addition to presenting progress to date, potential directions for further advancement are discussed. © 2018 S. Karger AG, Basel.

Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy.

PubMed

Schmidt, Hartmut H-J; Barroso, Fabio; González-Duarte, Alejandra; Conceição, Isabel; Obici, Laura; Keohane, Denis; Amass, Leslie

2016-09-01

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, severe, and irreversible, adult-onset, hereditary disorder caused by autosomal-dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR-FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease-modifying treatment options for a wider spectrum of patients with TTR-FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation-specific predictive genetic testing in first-degree relatives of index patients diagnosed with TTR-FAP and the structured clinical follow-up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353-360, 2016. © 2016 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.

Carbon chemistry of circumstellar envelopes

NASA Technical Reports Server (NTRS)

Bieging, John H.

1990-01-01

The chemical composition of envelopes surrounding cool evolved stars, as determined from microwave spectroscopic observations, is reviewed. Emphasis is placed on recent observations with the new large mm-wavelength telescopes and interferometer arrays, and on new theoretical work, especially concerning ion-molecule chemistry of carbon-bearing in these envelopes. Thermal (as opposed to maser) emission lines are discussed. Much progress has been made in the past few years in the theoretical understanding of these objects. It is already clear, however, that observations with the new generation of mm-telescopes will require substantial improvements in the theoretical models to achieve a thorough understanding of the data now becoming available.

[The dermatological indications of laser: beyond cosmetic target.

PubMed

Abosaleh, Marem; Boehncke, Wolf-Henning; Laubach, Hans

2017-01-11

During the last 30 years, the use of lasers in dermatology has gone far beyond the spectrum of aesthetic and cosmetic applications. Techniques are more than simple removal by CO2 Laser. Increasing knowledge, understanding, and experience have helped to effectively treat numerous important skin diseaes by the use of lasers. However, high-quality clinical trials are sparse in this domain. Consequently, so far only the treatment of hemangiomas and warts is a laser indication reimbursed by insurance companies. This article discusses three types of skin diseases where substantial progress has been reported in the scientific literature in 2016, namely pigmentary disorders, vascular diseases, and inflammatory dermatoses.

It's more than dollars and cents: the impact of childhood cancer on parents' occupational and financial health.

PubMed

Wakefield, Claire E; McLoone, Jordana K; Evans, Nadia T; Ellis, Sarah J; Cohn, Richard J

2014-01-01

Few studies have evaluated the impact of childhood cancer on parents' occupational/financial status. This study explored parents' occupational/financial experiences posttreatment. Semistructured interviews were administered to 78 parents (44 mothers) of childhood cancer survivors diagnosed in the preceding 5 years. Transcripts were organized into themes using QSR NVivo8. Parents reported familial, psychological, and practical factors affecting their ability to return to work. Prioritizing family, reinstigating career progression, and negative workplace attitudes were particularly challenging. Parents of children with cancer experience substantial work-family conflict after their child's physical recovery from cancer. Family friendly policies and further research are recommended.

The time-dependent density matrix renormalisation group method

NASA Astrophysics Data System (ADS)

Ma, Haibo; Luo, Zhen; Yao, Yao

2018-04-01

Substantial progress of the time-dependent density matrix renormalisation group (t-DMRG) method in the recent 15 years is reviewed in this paper. By integrating the time evolution with the sweep procedures in density matrix renormalisation group (DMRG), t-DMRG provides an efficient tool for real-time simulations of the quantum dynamics for one-dimensional (1D) or quasi-1D strongly correlated systems with a large number of degrees of freedom. In the illustrative applications, the t-DMRG approach is applied to investigate the nonadiabatic processes in realistic chemical systems, including exciton dissociation and triplet fission in polymers and molecular aggregates as well as internal conversion in pyrazine molecule.

Preventing HIV Infection in Women

PubMed Central

Adimora, Adaora A.; Ramirez, Catalina; Auerbach, Judith D.; Aral, Sevgi O.; Hodder, Sally; Wingood, Gina; El-Sadr, Wafaa; Bukusi, Elizabeth Anne

2014-01-01

Although the number of new infections has declined recently, women still constitute almost half of the world's 34 million people with HIV infection, and HIV remains the leading cause of death among women of reproductive age. Prevention research has made considerable progress during the past few years in addressing the biological, behavioral and social factors that influence women's vulnerability to HIV infection. Nevertheless, substantial work still must be done in order to implement scientific advancements and to resolve the many questions that remain. This article highlights some of the recent advances and persistent gaps in HIV prevention research for women and outlines key research and policy priorities. PMID:23764631

Guillain-Barré syndrome: What have we learnt during one century? A personal historical perspective.

PubMed

Uncini, A

2016-10-01

We are approaching the centenary of the first description of Guillain-Barré syndrome. The past 30 years had witnessed an amazing progress in the understanding of the immunological and pathological mechanisms of this disorder. We now recognize that Guillain-Barré syndrome is remarkably heterogeneous and under this umbrella term are several variants and subtypes with distinct clinical, electrophysiological and immunopathological features. This review is a historical journey, through a personal perspective, following the milestones that led to the current substantial knowledge of Guillain-Barré syndrome. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Radiographic progression in children with polyarticular juvenile rheumatoid arthritis: a pilot study

PubMed Central

Mason, T; Reed, A; Nelson, A; Thomas, K

2005-01-01

Methods: Initial and subsequent films of 13 white children (10 girls) were read blind by a paediatric radiologist for the presence of joint space narrowing (JSN), erosions, and relative carpal length (RCL). Results: One child had subcutaneous nodules; one (of 11) was rheumatoid factor positive; six were ANA positive. Median age at diagnosis was 10.7 years (2.5 to 15.9). Median number of involved joints (swelling, pain, or decreased range of motion) at diagnosis was 16 (6 to 33). Four initial x rays had either erosions or JSN. Subsequent x rays were done at (median) 13.3 (8.3 to 24.9) months after initial x rays. One of 10 subsequent x rays had shortened RCL, and six of 13 were worse than the initial ones. Four of these developed new erosions, one had increased number of erosions, and one developed new JSN. Conclusions: About half the children with polyarticular juvenile rheumatoid arthritis will have evidence of radiographic progression within two years after diagnosis. Thus newly diagnosed children are at high risk of substantial joint destruction and potential disability, emphasising the need for prompt treatment. PMID:15708901

SHINING A LIGHT ON XERODERMA PIGMENTOSUM

PubMed Central

DiGiovanna, John J.; Kraemer, Kenneth H.

2012-01-01

Xeroderma pigmentosum (XP) is a rare, autosomal recessive disorder of DNA repair characterized by sun sensitivity and ultraviolet (UV) induced skin and mucous membrane cancers. Described in 1874 by Moriz Kaposi in Vienna, nearly 100 years later James Cleaver in San Francisco reported defective DNA repair in XP cells. This eventually provided the basis for a mechanistic link between sun exposure, DNA damage, somatic mutations and skin cancer. XP cells were found to have defects in 7 of the proteins of the nucleotide excision repair pathway and in DNA polymerase eta. XP cells are hypersensitive to killing by UV and XP cancers have characteristic “UV signature” mutations. Clinical studies at NIH found a nearly 10,000-fold increase in skin cancer in XP patients under age 20 years demonstrating the substantial importance of DNA repair in cancer prevention in the general population. About 25 % of XP patients have progressive neurological degeneration with progressive loss of neurons, probably from DNA damage induced by oxidative metabolism which kills non-dividing cells in the nervous system. Interestingly, patients with another disorder, trichothiodystrophy have defects in some of the same genes as XP but they have primary developmental abnormalities without an increase in skin cancer. PMID:22217736

Animal Welfare in Studies on Murine Tuberculosis: Assessing Progress over a 12-Year Period and the Need for Further Improvement

PubMed Central

Franco, Nuno Henrique; Correia-Neves, Margarida; Olsson, I. Anna S.

2012-01-01

There is growing concern over the welfare of animals used in research, in particular when these animals develop pathology. The present study aims to identify the main sources of animal distress and to assess the possible implementation of refinement measures in experimental infection research, using mouse models of tuberculosis (TB) as a case study. This choice is based on the historical relevance of mouse studies in understanding the disease and the present and long-standing impact of TB on a global scale. Literature published between 1997 and 2009 was analysed, focusing on the welfare impact on the animals used and the implementation of refinement measures to reduce this impact. In this 12-year period, we observed a rise in reports of ethical approval of experiments. The proportion of studies classified into the most severe category did however not change significantly over the studied period. Information on important research parameters, such as method for euthanasia or sex of the animals, were absent in a substantial number of papers. Overall, this study shows that progress has been made in the application of humane endpoints in TB research, but that a considerable potential for improvement remains. PMID:23110093

Progressing batch hydrolysis process

DOEpatents

Wright, J.D.

1985-01-10

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

Progressing batch hydrolysis process

DOEpatents

Wright, John D.

1986-01-01

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

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

NASA Astrophysics Data System (ADS)

MacDougall, A. H.; Knutti, R.

2015-12-01

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

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

NASA Astrophysics Data System (ADS)

MacDougall, Andrew; Knutti, Reto

2016-04-01

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

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

PubMed Central

1996-01-01

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

The Contribution of Health Care and Other Interventions to Black–White Disparities in Life Expectancy, 1980–2007

PubMed Central

Beltrán-Sánchez, Hiram; Macinko, James

2014-01-01

Black–white mortality disparities remain sizable in the United States. In this study, we use the concept of avoidable/amenable mortality to estimate cause-of-death contributions to the difference in life expectancy between whites and blacks by gender in the United States in 1980, 1993, and 2007. We begin with a review of the concept of “avoidable mortality” and results of prior studies using this cause-of-death classification. We then present the results of our empirical analyses. We classified causes of death as amenable to medical care, sensitive to public health policies and health behaviors, ischemic heart disease, suicide, HIV/AIDS, and all other causes combined. We used vital statistics data on deaths and Census Bureau population estimates and standard demographic decomposition techniques. In 2007, causes of death amenable to medical care continued to account for close to 2 years of the racial difference in life expectancy among men (2.08) and women (1.85). Causes amenable to public health interventions made a larger contribution to the racial difference in life expectancy among men (1.17 years) than women (0.08 years). The contribution of HIV/AIDS substantially widened the racial difference among both men (1.08 years) and women (0.42 years) in 1993, but its contribution declined over time. Despite progress observed over the time period studied, a substantial portion of black–white disparities in mortality could be reduced given more equitable access to medical care and health interventions. PMID:24554793

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

PubMed

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

2016-10-01

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

Industry progress to market a healthful diet to American children and adolescents.

PubMed

Kraak, Vivica I; Story, Mary; Wartella, Ellen A; Ginter, Jaya

2011-09-01

The IOM released an expert committee report in 2005 that assessed the nature, extent, and influence of food and beverage marketing practices on the diets and health of American children and adolescents. The report concluded that prevailing marketing practices did not support a healthful diet and offered recommendations for diverse stakeholders to promote a healthful diet. The investigators evaluated progress made by food, beverage, and restaurant companies; trade associations; entertainment companies; and the media to achieve the IOM report recommendations over 5 years. A literature review was conducted of electronic databases and relevant government, industry, and media websites between December 1, 2005, and January 31, 2011. Evidence selection was guided by the IOM LEAD principles (i.e., locate, evaluate, and assemble evidence to inform decisions) and five qualitative-research criteria, and it was validated by data and investigator triangulation. The investigators selected and categorized 117 data sources into two evidence tables used to evaluate industry progress (i.e., no, limited, moderate, and extensive). Food and beverage companies made moderate progress; however, limited progress was made by other industry subsectors. Industry stakeholders used integrated marketing communications (IMC) to promote primarily unhealthy products, which threaten children's and adolescents' health and miss opportunities to promote a healthy eating environment. Diverse industry stakeholders have several untapped opportunities to advance progress by promoting IMC to support a healthful diet; substantially strengthening self-regulatory programs; supporting truthful and non-misleading product labeling and health claims; engaging in partnerships; and funding independent evaluations of collective efforts. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Renal transplant immunology in the last 20 years: A revolution towards graft and patient survival improvement.

PubMed

Sá, Helena; Leal, Rita; Rosa, Manuel Santos

2017-05-04

To deride the hope of progress is the ultimate fatuity, the last word in poverty of spirit and meanness of mind. There is no need to be dismayed by the fact that we cannot yet envisage a definitive solution of our problems, a resting-place beyond which we need not try to go. -P.B. Medawar, 1969 * Thomas E. Starlz, also known as the Father of Clinical Transplantation, once said that organ transplantation was the supreme exception to the rule that most major advances in medicine spring from discoveries in basic science [Starzl T. The mystique of organ transplantation. J Am Coll Surg 2005 Aug;201(2):160-170]. In fact, the first successful identical-twin kidney transplantation performed by Murray's team in December 1954 (Murray J et al. Renal homotransplantations in identical twins. Surg Forum 1955;6:432-436) was the example of an upside down translation medicine: Human clinical transplantation began and researchers tried to understand the underlying immune response and how to control the powerful rejection pathways through experimental models. In the last 20 years, we have witnessed an amazing progress in the knowledge of immunological mechanisms regarding alloimmune response and an outstanding evolution on the identification and characterization of major and minor histocompatibility antigens. This review presents an historical and clinical perspective of those important advances in kidney transplantation immunology in the last 20 years, which contributed to the improvement in patients' quality of life and the survival of end-stage renal patients. In spite of these significant progresses, some areas still need substantial progress, such as the definition of non-invasive biomarkers for acute rejection; the continuous reduction of immunosuppression; the extension of graft survival, and finally the achievement of real graft tolerance extended to HLA mismatch donor: recipient pairs.

Development of a 'toolkit' to identify medical students at risk of failure to thrive on the course: an exploratory retrospective case study

PubMed Central

2011-01-01

Background An earlier study at Nottingham suggested that 10-15% of the medical student intake was likely to fail completely or have substantial problems on the course. This is a problem for the students, the Faculty, and society as a whole. If struggling students could be identified early in the course and additional pastoral resources offered, some of this wastage might be avoided. An exploratory case study was conducted to determine whether there were common indicators in the early years, over and above academic failure, that might aid the identification of students potentially at risk. Methods The study group was drawn from five successive cohorts. Students who had experienced difficulties were identified in any of four ways: from Minutes of the Academic Progress Committee; by scanning examination lists at key stages (end of the first two years, and finals at the end of the clinical course); from lists of students flagged to the Postgraduate Deanery as in need of extra monitoring or support; and from progress files of those who had left the course prematurely. Relevant data were extracted from each student's course progress file into a customised database. Results 1188 students were admitted over the five years. 162 (14%) were identified for the study, 75 of whom had failed to complete the course by October 2010. In the 87 who did graduate, a combination of markers in Years 1 and 2 identified over half of those who would subsequently have the most severe problems throughout the course. This 'toolkit' comprised failure of 3 or more examinations per year, an overall average of <50%, health or social difficulties, failure to complete Hepatitis B vaccination on time, and remarks noted about poor attitude or behaviour. Conclusions A simple toolkit of academic and non-academic markers could be used routinely to help identify potential strugglers at an early stage, enabling additional support and guidance to be given to these students. PMID:22098629

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

ERIC Educational Resources Information Center

Jackson, Gregory A.

2007-01-01

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

ROLE OF THE RENAL MICROCIRCULATION IN PROGRESSION OF CHRONIC KIDNEY INJURY IN OBESITY

PubMed Central

Chade, Alejandro R.; Hall, John E.

2016-01-01

Background Obesity is largely responsible for the growing incidence and prevalence of diabetes, cardiovascular, and renal disease. Current strategies to prevent and treat obesity and its consequences have been insufficient to reverse the ongoing trends. Lifestyle modification or pharmacological therapies often produce modest weight loss which is not sustained and recurrence of obesity is frequently observed, leading to progression of target organ damage in many obese subjects. Therefore, research efforts have focused not only on the factors that regulate energy balance, but also on understanding mechanisms of target organ injury in obesity. Summary and Key message Microvascular disease plays a pivotal role in progressive kidney injury from different etiologies such as hypertension, diabetes, and atherosclerosis, which are all important consequences of chronic obesity. The microvascular networks are anatomical units that are closely adapted to specific functions of nutrition and removal of waste in every organ. Damage of the small vessels in several tissues and organs has been reported in obesity and may increase cardio-renal risk. However, the mechanisms by which obesity and its attendant cardiovascular and metabolic consequences interact to cause renal microvascular injury and chronic kidney disease are still unclear, although substantial progress has been made in recent years. This review addresses potential mechanisms and consequences of obesity-induced renal microvascular injury as well as current treatments that may provide protection of the renal microcirculation and slow progressive kidney injury in obesity. PMID:27771702

Treatment of malignant phaeochromocytoma with a combination of cyclophosphamide, vincristine and dacarbazine: own experience and overview of the contemporary literature.

PubMed

Deutschbein, Timo; Fassnacht, Martin; Weismann, Dirk; Reincke, Martin; Mann, Klaus; Petersenn, Stephan

2015-01-01

Malignant phaeochromocytomas are rare and highly aggressive tumours. This retrospective study evaluated the outcome of combined chemotherapy with cyclophosphamide, vincristine and dacarbazine (also known as CVD regimen). Patients with histologically and radiologically confirmed malignant phaeochromocytoma who were treated with the CVD regimen for progressive disease were retrospectively identified from chart review. Treatment cycles were usually repeated at 21-day intervals, with cyclophosphamide (750 mg/m(2) ), vincristine (1·4 mg/m(2) ) and dacarbazine (600 mg/m(2) ) on day 1, and dacarbazine only (600 mg/m(2) ) on day 2. The main outcome measures were best response during treatment and progression-free survival. Eight patients (4 males; median age 55·5 (range 31-77) years) with progressive disease underwent a median of 6 (range 3-11) cycles. Best treatment responses were as follows: partial response, n = 2 (25%); stable disease, n = 3 (38%); and progressive disease, n = 3 (38%). The median progression-free survival was 5·4 (range 2·5-26·8) months. After the initial administration of 6 cycles, two patients received a second course of chemotherapy with another 6 cycles after new progressive disease had been detected. Subsequently, these patients were progression-free for another 6·0 and 6·4 months. Mild gastrointestinal symptoms and fatigue were the most common adverse events. Although objective tumour response rates were lower than previously reported in small series, the CVD regimen allowed disease stabilization for a substantial period of time and may therefore be considered as a treatment option in advanced stages. To improve disease outcome, however, new therapeutic approaches and larger multicentre studies are needed. © 2014 John Wiley & Sons Ltd.

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

PubMed Central

Romiti, M. L.; Colognesi, C.; Cancrini, C.; Mas, A.; Berrino, M.; Salvatori, F.; Orlandi, P.; Jansson, M.; Palomba, E.; Plebani, A.; Bertran, J. M.; Hernandez, M.; de Martino, M.; Amoroso, A.; Tovo, P. A.; Rossi, P.; Espanol, T.; Scarlatti, G.

2000-01-01

BACKGROUND: A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. MATERIALS AND METHODS: To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. RESULTS: No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). CONCLUSIONS: Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment. PMID:10803406

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

PubMed

Romiti, M L; Colognesi, C; Cancrini, C; Mas, A; Berrino, M; Salvatori, F; Orlandi, P; Jansson, M; Palomba, E; Plebani, A; Bertran, J M; Hernandez, M; de Martino, M; Amoroso, A; Tovo, P A; Rossi, P; Espanol, T; Scarlatti, G

2000-01-01

A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.

Time to change the blind men and the elephant approach to Parkinson disease?

PubMed

Racette, Brad A; Willis, Allison W

2015-07-14

Parkinson disease (PD) is a progressive neurodegenerative disease that is associated with substantial morbidity and early mortality. Disease-related costs exceed $10 billion, not including medications, out-of-pocket expenses, or societal costs. Symptomatic treatment with levodopa, which has been available for over 30 years, and advanced therapies such as deep brain stimulation improve outcomes. Yet most new medications for PD provide a therapeutic benefit that is relatively modest compared to the benefits from levodopa. Despite dozens of neuroprotective clinical trials, there are no medications proven to slow the progression of the disease. Given these limitations, we provide evidence of the potential public health impact of a research agenda that emphasizes identification of risk factors to reduce disease burden through exposure mitigation. In addition, we emphasize health care policy that focuses on increasing health care expenditures for neurologic evaluation and management services to increase access to specialists to improve disease outcomes and reduce costs through better disease management. © 2015 American Academy of Neurology.

Time to change the blind men and the elephant approach to Parkinson disease?

PubMed Central

Willis, Allison W.

2015-01-01

Parkinson disease (PD) is a progressive neurodegenerative disease that is associated with substantial morbidity and early mortality. Disease-related costs exceed $10 billion, not including medications, out-of-pocket expenses, or societal costs. Symptomatic treatment with levodopa, which has been available for over 30 years, and advanced therapies such as deep brain stimulation improve outcomes. Yet most new medications for PD provide a therapeutic benefit that is relatively modest compared to the benefits from levodopa. Despite dozens of neuroprotective clinical trials, there are no medications proven to slow the progression of the disease. Given these limitations, we provide evidence of the potential public health impact of a research agenda that emphasizes identification of risk factors to reduce disease burden through exposure mitigation. In addition, we emphasize health care policy that focuses on increasing health care expenditures for neurologic evaluation and management services to increase access to specialists to improve disease outcomes and reduce costs through better disease management. PMID:26070339

We Can Change the Natural History of Type 2 Diabetes

PubMed Central

Ratner, Robert E.; Buse, John B.; Kahn, Steven E.

2014-01-01

As diabetes develops, we currently waste the first ∼10 years of the natural history. If we found prediabetes and early diabetes when they first presented and treated them more effectively, we could prevent or delay the progression of hyperglycemia and the development of complications. Evidence for this comes from trials where lifestyle change and/or glucose-lowering medications decreased progression from prediabetes to diabetes. After withdrawal of these interventions, there was no “catch-up”—cumulative development of diabetes in the previously treated groups remained less than in control subjects. Moreover, achieving normal glucose levels even transiently during the trials was associated with a substantial reduction in subsequent development of diabetes. These findings indicate that we can change the natural history through routine screening to find prediabetes and early diabetes, combined with management aimed to keep glucose levels as close to normal as possible, without hypoglycemia. We should also test the hypothesis with a randomized controlled trial. PMID:25249668

Pancreatic cancer

PubMed Central

Vincent, Audrey; Herman, Joseph; Schulick, Rich; Hruban, Ralph H; Goggins, Michael

2011-01-01

Substantial progress has been made in our understanding of the biology of pancreatic cancer, and advances in patients’ management have also taken place. Evidence is beginning to show that screening first-degree relatives of individuals with several family members affected by pancreatic cancer can identify non-invasive precursors of this malignant disease. The incidence of and number of deaths caused by pancreatic tumours have been gradually rising, even as incidence and mortality of other common cancers have been declining. Despite developments in detection and management of pancreatic cancer, only about 4% of patients will live 5 years after diagnosis. Survival is better for those with malignant disease localised to the pancreas, because surgical resection at present offers the only chance of cure. Unfortunately, 80–85% of patients present with advanced unresectable disease. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. Hence, we need to understand the biological mechanisms that contribute to development and progression of pancreatic tumours. In this Seminar we will discuss the most common and deadly form of pancreatic cancer, pancreatic ductal adenocarcinoma. PMID:21620466

The Twin Epidemics of Tuberculosis and HIV.

PubMed

Varghese, George M; Janardhanan, Jeshina; Ralph, Ravikar; Abraham, Ooriapadickal C

2013-02-01

The deadly combination of tuberculosis (TB) and human immunodeficiency virus (HIV) currently ravaging the world, taking a toll of about 0.35 million people every year, is one of the major public health crises of the decade. Throughout the course of HIV infection, the risk of acquisition, reactivation, and reinfection of TB keeps increasing substantially as the immune deficiency progresses. TB coinfected patients inadvertently facilitate HIV infection by release of the proinflammatory cytokines and overexpression of coreceptors CXCR4 and CCR5; thereby, the progression of each is facilitated. The difficulties in diagnosing active tuberculosis in HIV-infected individuals poses a great challenge that is further complicated by the challenges in identification of latent TB infection, creating a setback to preventive therapy. Furthermore, prescribing antituberculous therapy and antiretroviral therapy together poses several management challenges, including drug interactions, added toxicities, and TB immune reconstitution inflammatory syndrome. The current approach to diagnosis, prevention, and treatment strategies in TB and HIV coinfected individuals, along with epidemiology and overview of pathogenetic interplay of both microbes, is reviewed here.

Poverty and mortality among the elderly: measurement of performance in 33 countries 1960-92.

PubMed

Wang, J; Jamison, D T; Bos, E; Vu, M T

1997-10-01

This paper analyses the effect of income and education on life expectancy and mortality rates among the elderly in 33 countries for the period 1960-92 and assesses how that relationship has changed over time as a result of technical progress. Our outcome variables are life expectancy at age 60 and the probability of dying between age 60 and age 80 for both males and females. The data are from vital-registration based life tables published by national statistical offices for several years during this period. We estimate regressions with determinants that include GDP per capita (adjusted for purchasing power), education and time (as a proxy for technical progress). As the available measure of education failed to account for variation in life expectancy or mortality at age 60, our reported analyses focus on a simplified model with only income and time as predictors. The results indicate that, controlling for income, mortality rates among the elderly have declined considerably over the past three decades. We also find that poverty (as measured by low average income levels) explains some of the variation in both life expectancy at age 60 and mortality rates among the elderly across the countries in the sample. The explained amount of variation is more substantial for females than for males. While poverty does adversely affect mortality rates among the elderly (and the strength of this effect is estimated to be increasing over time), technical progress appears far more important in the period following 1960. Predicted female life expectancy (at age 60) in 1960 at the mean income level in 1960 was, for example 18.8 years; income growth to 1992 increased this by an estimated 0.7 years, whereas technical progress increased it by 2.0 years. We then use the estimated regression results to compare country performance on life expectancy of the elderly, controlling for levels of poverty (or income), and to assess how performance has varied over time. High performing countries, on female life expectancy at age 60, for the period around 1990, included Chile (1.0 years longer life expectancy), China (1.7 years longer), France (2.0 years longer), Japan (1.9 years longer), and Switzerland (1.3 years longer). Poorly performing countries included Denmark (1.1 years shorter life expectancy than predicted from income), Hungary (1.4 years shorter), Iceland (1.2 years shorter), Malaysia (1.6 years shorter), and Trinidad and Tobago (3.9 years shorter). Chile and Switzerland registered major improvements in relative performance over this period; Norway, Taiwan and the USA, in contrast showed major declines in performance between 1980 and the early 1990s.

Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes: a prospective cohort study.

PubMed

Ligthart, Symen; van Herpt, Thijs T W; Leening, Maarten J G; Kavousi, Maryam; Hofman, Albert; Stricker, Bruno H C; van Hoek, Mandy; Sijbrands, Eric J G; Franco, Oscar H; Dehghan, Abbas

2016-01-01

Data are scarce for the lifetime risk of developing impaired glucose metabolism, including prediabetes, as are data for the risk of eventual progression from prediabetes to diabetes and for initiation of insulin treatment in previously untreated patients with diabetes. We aimed to calculate the lifetime risk of the full range of glucose impairments, from normoglycaemia to prediabetes, type 2 diabetes, and eventual insulin use. In this prospective population-based cohort analysis, we used data from the population-based Rotterdam Study. We identified diagnostic events by use of general practitioners' records, hospital discharge letters, pharmacy dispensing data, and serum fasting glucose measurements taken at the study centre (Rotterdam, Netherlands) visits. Normoglycaemia, prediabetes, and diabetes were defined on the basis of WHO criteria for fasting glucose (normoglycaemia: ≤6·0 mmol/L; prediabetes: >6·0 mmol/L and <7·0 mmol/L; and diabetes ≥7·0 mmol/L or use of glucose-lowering drug). We calculated lifetime risk using a modified version of survival analysis adjusted for the competing risk of death. We also estimated the lifetime risk of progression from prediabetes to overt diabetes and from diabetes free of insulin treatment to insulin use. Additionally, we calculated years lived with healthy glucose metabolism. We used data from 10 050 participants from the Rotterdam Study. During a follow-up of up to 14·7 years (between April 1, 1997, and Jan 1, 2012), 1148 participants developed prediabetes, 828 developed diabetes, and 237 started insulin treatment. At age 45 years, the remaining lifetime risk was 48·7% (95% CI 46·2-51·3) for prediabetes, 31·3% (29·3-33·3) for diabetes, and 9·1% (7·8-10·3) for insulin use. In individuals aged 45 years, the lifetime risk to progress from prediabetes to diabetes was 74·0% (95% CI 67·6-80·5), and 49·1% (38·2-60·0) of the individuals with overt diabetes at this age started insulin treatment. The lifetime risks attenuated with advancing age, but increased with increasing BMI and waist circumference. On average, individuals with severe obesity lived 10 fewer years without glucose impairment compared with normal-weight individuals. Impaired glucose metabolism is a substantial burden on population health, and our findings emphasise the need for more effective prevention strategies, which should be implemented as soon in a person's life as possible. The substantial lifetime risk of prediabetes and diabetes in lean individuals also supports risk factor control in non-obese individuals. Erasmus MC and Erasmus University Rotterdam; Netherlands Organisation for Scientific Research; Netherlands Organisation for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomics Initiative; Netherlands Ministry of Education, Culture and Science; Netherlands Ministry of Health, Welfare and Sports; European Commission; and Municipality of Rotterdam. Copyright © 2016 Elsevier Ltd. All rights reserved.

Financing universal health coverage—effects of alternative tax structures on public health systems: cross-national modelling in 89 low-income and middle-income countries

PubMed Central

Reeves, Aaron; Gourtsoyannis, Yannis; Basu, Sanjay; McCoy, David; McKee, Martin; Stuckler, David

2015-01-01

Summary Background How to finance progress towards universal health coverage in low-income and middle-income countries is a subject of intense debate. We investigated how alternative tax systems affect the breadth, depth, and height of health system coverage. Methods We used cross-national longitudinal fixed effects models to assess the relationships between total and different types of tax revenue, health system coverage, and associated child and maternal health outcomes in 89 low-income and middle-income countries from 1995–2011. Findings Tax revenue was a major statistical determinant of progress towards universal health coverage. Each US$100 per capita per year of additional tax revenues corresponded to a yearly increase in government health spending of $9·86 (95% CI 3·92–15·8), adjusted for GDP per capita. This association was strong for taxes on capital gains, profits, and income ($16·7, 9·16 to 24·3), but not for consumption taxes on goods and services (−$4·37, −12·9 to 4·11). In countries with low tax revenues (<$1000 per capita per year), an additional $100 tax revenue per year substantially increased the proportion of births with a skilled attendant present by 6·74 percentage points (95% CI 0·87–12·6) and the extent of financial coverage by 11·4 percentage points (5·51–17·2). Consumption taxes, a more regressive form of taxation that might reduce the ability of the poor to afford essential goods, were associated with increased rates of post-neonatal mortality, infant mortality, and under-5 mortality rates. We did not detect these adverse associations with taxes on capital gains, profits, and income, which tend to be more progressive. Interpretation Increasing domestic tax revenues is integral to achieving universal health coverage, particularly in countries with low tax bases. Pro-poor taxes on profits and capital gains seem to support expanding health coverage without the adverse associations with health outcomes observed for higher consumption taxes. Progressive tax policies within a pro-poor framework might accelerate progress toward achieving major international health goals. Funding Commission of the European Communities (FP7–DEMETRIQ), the European Union's HRES grants, and the Wellcome Trust. PMID:25982041

Financing universal health coverage--effects of alternative tax structures on public health systems: cross-national modelling in 89 low-income and middle-income countries.

PubMed

Reeves, Aaron; Gourtsoyannis, Yannis; Basu, Sanjay; McCoy, David; McKee, Martin; Stuckler, David

2015-07-18

How to finance progress towards universal health coverage in low-income and middle-income countries is a subject of intense debate. We investigated how alternative tax systems affect the breadth, depth, and height of health system coverage. We used cross-national longitudinal fixed effects models to assess the relationships between total and different types of tax revenue, health system coverage, and associated child and maternal health outcomes in 89 low-income and middle-income countries from 1995-2011. Tax revenue was a major statistical determinant of progress towards universal health coverage. Each US$100 per capita per year of additional tax revenues corresponded to a yearly increase in government health spending of $9.86 (95% CI 3.92-15.8), adjusted for GDP per capita. This association was strong for taxes on capital gains, profits, and income ($16.7, 9.16 to 24.3), but not for consumption taxes on goods and services (-$4.37, -12.9 to 4.11). In countries with low tax revenues (<$1000 per capita per year), an additional $100 tax revenue per year substantially increased the proportion of births with a skilled attendant present by 6.74 percentage points (95% CI 0.87-12.6) and the extent of financial coverage by 11.4 percentage points (5.51-17.2). Consumption taxes, a more regressive form of taxation that might reduce the ability of the poor to afford essential goods, were associated with increased rates of post-neonatal mortality, infant mortality, and under-5 mortality rates. We did not detect these adverse associations with taxes on capital gains, profits, and income, which tend to be more progressive. Increasing domestic tax revenues is integral to achieving universal health coverage, particularly in countries with low tax bases. Pro-poor taxes on profits and capital gains seem to support expanding health coverage without the adverse associations with health outcomes observed for higher consumption taxes. Progressive tax policies within a pro-poor framework might accelerate progress toward achieving major international health goals. Commission of the European Communities (FP7-DEMETRIQ), the European Union's HRES grants, and the Wellcome Trust. Copyright © 2015 Reeves et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

The end of measles and congenital rubella: an achievable dream?

PubMed

Adamo, G; Sturabotti, G; D'Andrea, E; Baccolini, V; Romano, F; Iannazzo, S; Marzuillo, C; Villari, P

2017-01-01

Despite substantial progress towards measles and rubella control, outbreaks continue to threaten elimination goals worldwide. This paper aims to document progress towards the global eradication of measles and rubella. In particular, it investigates the major challenges faced by Italy in reaching the elimination goals. A review of the most important literature was carried out. Furthermore, a systematic review of the scientific literature on measles and rubella in the Italian setting was performed for the period 2000-2016. In the National Plan 2010-2015, Italy renewed its commitment to eliminate measles and rubella by 2015. However, Italy recently experienced a high measles burden (2,205 cases in 2013, 1,694 in 2014). Between June 2015 and May 2016, 515 cases were reported, accounting for 28% all cases in Europe. Immunization coverage decreased in recent years, with no Region reaching the 95% target. The systematic review included a total of 175 papers, with an upward trend in the number of published articles, which demonstrates an increasing interest in the field of measles and rubella. The review highlights the need to improve the commitment of the Italian Regions to the elimination goals; to promote Supplementary Immunization Activities (SIAs); to improve the communication skills of health care workers; to improve the health literacy of citizens; and to enhance integrated measles and rubella surveillance. Elimination of measles and rubella in Italy will require a substantial improvement in both commitment of the 21 Regions and activity of the whole country towards the WHO goals.

Progress and challenges of the rural cooperative medical scheme in China

PubMed Central

Xu, Ke

2014-01-01

Abstract Problem During China’s transition to a market economy in the 1980s and 1990s, the rural population faced substantial barriers to accessing health care and encountered heavier financial burdens than urban residents in paying for necessary health services. Approach In 2003, China started to implement a rural cooperative medical scheme (RCMS), mainly through government subsidies. The scheme operates at the county level and offers a modest benefit package. Local setting In spite of rapid economic growth since the early 1980s, income disparities in China have increased, particularly between rural and urban populations. In response, the government has put greater emphasis on social development, including health system development. Examples are the prioritization of improved access to health services and the reduction of the burden of payment for necessary services. Relevant changes After 10 years of implementation, the RCMS now provides coverage to the entire rural population and has substantially improved access to health care. Yet despite a drop in out-of-pocket payments as a proportion of total health expenditure, paying for necessary services continues to cause financial hardship for many rural residents. Lessons learnt In its first decade, the RCMS made progress through political mobilization, government subsidies, the readiness of the health-care delivery system, and the availability of a monitoring and evaluation system. Further improving the RCMS will require a focus on cost containment, quality improvement and making the scheme portable. PMID:24940019

Regulating Availability: How Access to Alcohol Affects Drinking and Problems in Youth and Adults

PubMed Central

Gruenewald, Paul J.

2011-01-01

Regulations on the availability of alcohol have been used to moderate alcohol problems in communities throughout the world for thousands of years. In the latter half of the 20th century, quantitative studies of the effects of these regulations on drinking and related problems began in earnest as public health practitioners began to recognize the full extent of the harmful consequences related to drinking. This article briefly outlines the history of this work over four areas, focusing on the minimum legal drinking age, the privatization of alcohol control systems, outlet densities, and hours and days of sale. Some historical background is provided to emphasize the theoretical and empirical roots of this work and to highlight the substantial progress that has been made in each area. In general, this assessment suggests that higher minimum legal drinking ages, greater monopoly controls over alcohol sales, lower outlet numbers and reduced outlet densities, and limited hours and days of sale can effectively reduce alcohol sales, use, and problems. There are, however, substantial gaps in the research literature and a near absence of the quantitative theoretical work needed to direct alcohol-control efforts. Local community responses to alcohol policies are complex and heterogeneous, sometimes reinforcing and sometimes mitigating the effects of availability regulations. Quantitative models of policy effects are essential to accelerate progress toward the formulation and testing of optimal control strategies for the reduction of alcohol problems. PMID:22330225

Measles and rubella elimination in the WHO Region for Europe: progress and challenges.

PubMed

O'Connor, P; Jankovic, D; Muscat, M; Ben-Mamou, M; Reef, S; Papania, M; Singh, S; Kaloumenos, T; Butler, R; Datta, S

2017-08-01

Globally measles remains one of the leading causes of death among young children even though a safe and cost-effective vaccine is available. The World Health Organization (WHO) European Region has seen a decline in measles and rubella cases in recent years. The recent outbreaks have primarily affected adolescents and young adults with no vaccination or an incomplete vaccination history. Eliminating measles and rubella is one of the top immunization priorities of the European Region as outlined in the European Vaccine Action Plan 2015-2020. Following the 2010 decision by the Member States in the Region to initiate the process of verifying elimination, the European Regional Verification Commission for Measles and Rubella Elimination (RVC) was established in 2011. The RVC meets every year to evaluate the status of measles and rubella elimination in the Region based on documentation submitted by each country's National Verification Committees. The verification process was however modified in late 2014 to assess the elimination status at the individual country level instead of at regional level. The WHO European Region has made substantial progress towards measles and rubella elimination over the past 5 years. The RVC's conclusion in 2016 that 70% and 66% of the 53 Member States in the Region had interrupted the endemic transmission of measles and rubella, respectively, by 2015 is a testament to this progress. Nevertheless, where measles and rubella remain endemic, challenges in vaccination service delivery and disease surveillance will need to be addressed through focused technical assistance from WHO and development partners. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Fifteen years of sector-wide approach (SWAp) in Bangladesh health sector: an assessment of progress

PubMed Central

Ahsan, Karar Zunaid; Streatfield, Peter Kim; Ijdi, Rashida -E-; Escudero, Gabriela Maria; Khan, Abdul Waheed; Reza, M M

2016-01-01

The Ministry of Health and Family Welfare (MOHFW) of the Government of Bangladesh embarked on a sector-wide approach (SWAp) modality for the health, nutrition and population (HNP) sector in 1998. This programmatic shift initiated a different set of planning disciplines and practices along with institutional changes in the MOHFW. Over the years, the SWAp modality has evolved in Bangladesh as the MOHFW has learnt from its implementation and refined the program design. This article explores the progress made, both in terms of achievement of health outcomes and systems strengthening results, since the implementation of the SWAp for Bangladesh’s health sector. Secondary analyses of survey data from 1993 to 2011 as well as a literature review of published and grey literature on health SWAp in Bangladesh was conducted for this assessment. Results of the assessment indicate that the MOHFW made substantial progress in health outcomes and health systems strengthening. SWAps facilitated the alignment of funding and technical support around national priorities, and improved the government’s role in program design as well as in implementation and development partner coordination. Notable systemic improvements have taken place in the country systems with regards to monitoring and evaluation, procurement and service provision, which have improved functionality of health facilities to provide essential care. Implementation of the SWAp has, therefore, contributed to an accelerated improvement in key health outcomes in Bangladesh over the last 15 years. The health SWAp in Bangladesh offers an example of a successful adaptation of such an approach in a complex administrative structure. Based on the lessons learned from SWAp implementation in Bangladesh, the MOHFW needs to play a stronger stewardship and regulatory role to reap the full benefits of a SWAp in its subsequent programming. PMID:26582744

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

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

REDUCE CHILD MORTALITY AS A MILLENNIUM DEVELOPMENI GOAL IN ROMANIA.

PubMed

Duma, Olga-Odetta; Roşu, Solange Tamara; Petrariu, F D; Manole, M; Constantin, Brânduşa

2016-01-01

To assess the efforts made in Romania towards achieving the Goal 4 from MDGs--Reduce Child Mortality. A descriptive study about the deaths among Romanian children under five, between 2002 and 2015, from the perspective of the MDGs. To help track progress toward this commitment, following specific targets and indicators were developed: Target 1-Halve the mortality rate in children aged 1-4 years between 2002-2015; Target 2--Reduce infant mortality by 40% between 2002 and 2015; Target 3--Eliminate measles by 2007. The comparison allows establish the status (achieved or not) for each target. From 2002, the under-five mortality rate recorded a continuous descendent trend till now (20.8 to 10.3 under five deaths per 1000 inhabitants in 2013). The infant mortality rates declined from 17.3 to 8.5 deaths per 1,000 live births (2002-2013). Eliminating measles by 2007--was achieved one year later, because of the measles epidemic in 2005 and 2006. High vaccination rates have been maintained, with the proportion of children 1 year old vaccinated against measles reaching and being maintained at between 94-98%. Substantial progress has been made in Romania, in achieving the Millennium Development Goal no. 4. All the three targets were achieved. However, infant mortality still remains above the average of European Union (4 infant deaths per 1,000 live-births).

Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes.

PubMed

Cheah, C Y; Chihara, D; Romaguera, J E; Fowler, N H; Seymour, J F; Hagemeister, F B; Champlin, R E; Wang, M L

2015-06-01

Although ibrutinib is highly effective in patients with relapsed/refractory mantle cell lymphoma (MCL), a substantial proportion of patients have resistant disease. The subsequent outcomes of such patients are unknown. We carried out a retrospective review of all patients with MCL treated with ibrutinib at MD Anderson Cancer Center between January 2011 and January 2014 using pharmacy and clinical databases. Patients who had discontinued ibrutinib for any reason were included in the study. We identified 42 patients with MCL who discontinued therapy due to disease progression on treatment (n = 28), toxicity (n = 6), elective stem-cell transplant in remission (n = 4) or withdrawn consent (n = 4). The median age was 69 years, 35 (83%) were male; the median number of prior treatments was 2 (range 1-8) and the median time from initial diagnosis of MCL to commencing ibrutinib was 3.0 (range 0.5-15.5) years. Patients had received a median of 6.5 (range 1-43) cycles of ibrutinib. Among 31 patients who experienced disease progression following ibrutinib and underwent salvage therapy, the overall and complete response rates were 32% and 19%, respectively. After a median follow-up of 10.7 (range 2.4-38.9) months from discontinuation of ibrutinib, the median overall survival (OS) among patients with disease progression was 8.4 months. By univariate analysis, elevated serum lactate dehydrogenase at progression was associated with inferior OS. The outcome of patients with MCL who experience disease progression following ibrutinib therapy is poor, with both low response rates to salvage therapy and short duration of responses. Further studies to better understand and overcome ibrutinib resistance are urgently needed. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Maternal and child health in Brazil: progress and challenges.

PubMed

Victora, Cesar G; Aquino, Estela M L; do Carmo Leal, Maria; Monteiro, Carlos Augusto; Barros, Fernando C; Szwarcwald, Celia L

2011-05-28

In the past three decades, Brazil has undergone rapid changes in major social determinants of health and in the organisation of health services. In this report, we examine how these changes have affected indicators of maternal health, child health, and child nutrition. We use data from vital statistics, population censuses, demographic and health surveys, and published reports. In the past three decades, infant mortality rates have reduced substantially, decreasing by 5·5% a year in the 1980s and 1990s, and by 4·4% a year since 2000 to reach 20 deaths per 1000 livebirths in 2008. Neonatal deaths account for 68% of infant deaths. Stunting prevalence among children younger than 5 years decreased from 37% in 1974-75 to 7% in 2006-07. Regional differences in stunting and child mortality also decreased. Access to most maternal-health and child-health interventions increased sharply to almost universal coverage, and regional and socioeconomic inequalities in access to such interventions were notably reduced. The median duration of breastfeeding increased from 2·5 months in the 1970s to 14 months by 2006-07. Official statistics show stable maternal mortality ratios during the past 10 years, but modelled data indicate a yearly decrease of 4%, a trend which might not have been noticeable in official reports because of improvements in death registration and the increased number of investigations into deaths of women of reproductive age. The reasons behind Brazil's progress include: socioeconomic and demographic changes (economic growth, reduction in income disparities between the poorest and wealthiest populations, urbanisation, improved education of women, and decreased fertility rates), interventions outside the health sector (a conditional cash transfer programme and improvements in water and sanitation), vertical health programmes in the 1980s (promotion of breastfeeding, oral rehydration, and immunisations), creation of a tax-funded national health service in 1988 (coverage of which expanded to reach the poorest areas of the country through the Family Health Program in the mid-1990s); and implementation of many national and state-wide programmes to improve child health and child nutrition and, to a lesser extent, to promote women's health. Nevertheless, substantial challenges remain, including overmedicalisation of childbirth (nearly 50% of babies are delivered by caesarean section), maternal deaths caused by illegal abortions, and a high frequency of preterm deliveries. Copyright © 2011 Elsevier Ltd. All rights reserved.

The impact of the worldwide Millennium Development Goals campaign on maternal and under-five child mortality reduction: 'Where did the worldwide campaign work most effectively?'

PubMed

Cha, Seungman

2017-01-01

As the Millennium Development Goals campaign (MDGs) came to a close, clear evidence was needed on the contribution of the worldwide MDG campaign. We seek to determine the degree of difference in the reduction rate between the pre-MDG and MDG campaign periods and its statistical significance by region. Unlike the prevailing studies that measured progress in 1990-2010, this study explores by percentage how much MDG progress has been achieved during the MDG campaign period and quantifies the impact of the MDG campaign on the maternal and under-five child mortality reduction during the MDG era by comparing observed values with counterfactual values estimated on the basis of the historical trend. The low accomplishment of sub-Saharan Africa toward the MDG target mainly resulted from the debilitated progress of mortality reduction during 1990-2000, which was not related to the worldwide MDG campaign. In contrast, the other regions had already achieved substantial progress before the Millennium Declaration was proclaimed. Sub-Saharan African countries have seen the most remarkable impact of the worldwide MDG campaign on maternal and child mortality reduction across all different measurements. In sub-Saharan Africa, the MDG campaign has advanced the progress of the declining maternal mortality ratio and under-five mortality rate, respectively, by 4.29 and 4.37 years. Sub-Saharan African countries were frequently labeled as 'off-track', 'insufficient progress', or 'no progress' even though the greatest progress was achieved here during the worldwide MDG campaign period and the impact of the worldwide MDG campaign was most pronounced in this region in all respects. It is time to learn from the success stories of the sub-Saharan African countries. Erroneous and biased measurement should be avoided for the sustainable development goals to progress.

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

ERIC Educational Resources Information Center

Anderson, O. Roger

2014-01-01

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

Progress and Challenges in Subseasonal Prediction

NASA Technical Reports Server (NTRS)

Schubert, Siegfried

2003-01-01

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

CHOD/BVAM Chemotherapy and Whole-Brain Radiotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma

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

Laack, Nadia N.; O'Neill, Brian Patrick, E-mail: boneill@mayo.edu; Ballman, Karla V.

Purpose: To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients 70 years old and younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint wasmore » 1-year survival. Results: Thirty-six patients (19 men, 17 women) enrolled between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty (83%) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1. All 36 patients were eligible for survival and response evaluations. Median time to progression was 12.3 months, and median survival was 18.5 months. The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%, respectively. The best response was complete response in 10 patients and immediate progression in 7 patients. Ten (28%) patients had at least one grade 3 or higher neurologic toxicity. Conclusions: This regimen did improve the survival of PCNSL patients but also caused substantial toxicity. The improvement in survival is less than that reported with high-dose methotrexate-based therapies.« less

High cancer-related mortality in an urban, predominantly African-American, HIV-infected population.

PubMed

Riedel, David J; Mwangi, Evelyn Ivy W; Fantry, Lori E; Alexander, Carla; Hossain, Mian B; Pauza, C David; Redfield, Robert R; Gilliam, Bruce L

2013-04-24

To determine mortality associated with a new cancer diagnosis in an urban, predominantly African-American, HIV-infected population. Retrospective cohort study. All HIV-infected patients diagnosed with cancer between 1 January 2000 and 30 June 2010 were reviewed. Mortality was examined using Kaplan-Meier estimates and Cox proportional hazards models. There were 470 cases of cancer among 447 patients. Patients were predominantly African-American (85%) and male (79%). Non-AIDS-defining cancers (NADCs, 69%) were more common than AIDS-defining cancers (ADCs, 31%). Cumulative cancer incidence increased significantly over the study period. The majority (55.9%) was taking antiretroviral therapy (ART) at cancer diagnosis or started afterward (26.9%); 17.2% never received ART. Stage 3 or 4 cancer was diagnosed in 67%. There were 226 deaths during 1096 person years of follow-up, yielding an overall mortality rate of 206 per 1000 person years. The cumulative mortality rate at 30 days, 1 year, and 2 years was 6.5, 32.2, and 41.4%, respectively. Mortality was similar between patients on ART whether they started before or after the cancer diagnosis but was higher in patients who never received ART. In patients with a known cause of death, 68% were related to progression of the underlying cancer. In a large cohort of urban, predominantly African-American patients with HIV and cancer, many patients presented with late-stage cancer. There was substantial 30-day and 2-year mortality, although ART had a significant mortality benefit. Deaths were most often caused by progression of cancer and not from another HIV-related or AIDS-related event.

[Drug delivery systems using nano-sized drug carriers].

PubMed

Nakayama, Masamichi; Okano, Teruo

2005-07-01

Nanotechnology has attracted great attention all over the world in recent several years and has led to the establishment of the novel technical field of "nanomedicine" through collaboration with advanced medical technology. Particularly, site-specific drug targeting using particle drug carrier systems has made substantial progress and been actively developed. This review explains the essential factors (size and chemical character) of drug carriers to allow long circulation in the bloodstream avoiding the reticuloendothelial system, and shows the present status and future perspective of several types of nano-carrier systems (water-soluble polymer, liposome and polymeric micelle). We also introduce the novel concept of multi-targeting system (combination of two or more targeting methodologies) for ideal drug therapies.

Bridging the two cultures of risk analysis

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

Jasanoff, S.

1993-04-01

During the past 15 years, risk analysis has come of age as an interdisciplinary field of remarkable breadth, nurturing connections among fields as diverse as mathematics, biostatistics, toxicology, and engineering on one hand, and law, psychology, sociology, and economics on the other hand. In this editorial, the author addresses the question: What has the presence of social scientists in the network meant to the substantive development of the field of risk analysis The answers offered here discuss the substantial progress in bridging the two cultures of risk analysis. Emphasis is made of the continual need for monitoring risk analysis. Topicsmore » include: the micro-worlds of risk assessment; constraining assumptions; and exchange programs. 14 refs.« less

Buckling of Carbon Nanotubes: A State of the Art Review

PubMed Central

Shima, Hiroyuki

2011-01-01

The nonlinear mechanical response of carbon nanotubes, referred to as their “buckling" behavior, is a major topic in the nanotube research community. Buckling means a deformation process in which a large strain beyond a threshold causes an abrupt change in the strain energy vs. deformation profile. Thus far, much effort has been devoted to analysis of the buckling of nanotubes under various loading conditions: compression, bending, torsion, and their certain combinations. Such extensive studies have been motivated by (i) the structural resilience of nanotubes against buckling and (ii) the substantial influence of buckling on their physical properties. In this contribution, I review the dramatic progress in nanotube buckling research during the past few years. PMID:28817032

Blood banking in China.

PubMed

Shan, Hua; Wang, Jing-Xing; Ren, Fu-Rong; Zhang, Yuan-Zhi; Zhao, Hai-Yan; Gao, Guo-Jing; Ji, Yang; Ness, Paul M

2002-11-30

While transfusion-transmissible diseases, including AIDS and viral hepatitis, continue to spread especially in developing countries, the issue of safeguarding the world's blood supply is of paramount importance. China houses more than 20% of the earth's population, and thus its blood supply has the potential to affect the global community. In recent years, Chinese blood centres have tried to improve the nation's blood safety. Although substantial progress has already been made, many daunting difficulties remain. Traditional cultural barriers need to be overcome to successfully mobilise volunteer blood donors. Gaps in information and technology still need to be closed. Insufficiency of economic resources also restrict the blood bank industry. Other developing countries face many of the same challenges as China.

New genes as drivers of phenotypic evolution

PubMed Central

Chen, Sidi; Krinsky, Benjamin H.; Long, Manyuan

2014-01-01

During the course of evolution, genomes acquire novel genetic elements as sources of functional and phenotypic diversity, including new genes that originated in recent evolution. In the past few years, substantial progress has been made in understanding the evolution and phenotypic effects of new genes. In particular, an emerging picture is that new genes, despite being present in the genomes of only a subset of species, can rapidly evolve indispensable roles in fundamental biological processes, including development, reproduction, brain function and behaviour. The molecular underpinnings of how new genes can develop these roles are starting to be characterized. These recent discoveries yield fresh insights into our broad understanding of biological diversity at refined resolution. PMID:23949544

New genes as drivers of phenotypic evolution.

PubMed

Chen, Sidi; Krinsky, Benjamin H; Long, Manyuan

2013-09-01

During the course of evolution, genomes acquire novel genetic elements as sources of functional and phenotypic diversity, including new genes that originated in recent evolution. In the past few years, substantial progress has been made in understanding the evolution and phenotypic effects of new genes. In particular, an emerging picture is that new genes, despite being present in the genomes of only a subset of species, can rapidly evolve indispensable roles in fundamental biological processes, including development, reproduction, brain function and behaviour. The molecular underpinnings of how new genes can develop these roles are starting to be characterized. These recent discoveries yield fresh insights into our broad understanding of biological diversity at refined resolution.

DUV light source sustainability achievements and next steps

NASA Astrophysics Data System (ADS)

Roman, Yzzer; Cacouris, Ted; Raju, Kumar Raja Guvindan; Kanawade, Dinesh; Gillespie, Walt; Luo, Siqi; Mason, Eric; Manley, David; Das, Saptaparna

2018-03-01

Key sustainability opportunities have been executed in support of corporate initiatives to reduce the environmental footprint and decrease the running cost of DUV light sources. Previously, substantial neon savings were demonstrated over several years through optimized gas management technologies. Beyond this work, Cymer is developing the XLGR 100, a self-contained neon recycling system, to enable minimal gas consumption. The high efficiency results of the XLGR 100 in a production factory are validated in this paper. Cymer has also developed new light source modules with 33% longer life in an effort to reduce raw and associated resource consumption. In addition, a progress report is included regarding the improvements developed to reduce light source energy consumption.

Evolution of endovascular stroke therapies and devices.

PubMed

Wallace, Adam N; Kansagra, Akash P; McEachern, James; Moran, Christopher J; Cross, Dewitte T; Derdeyn, Colin P

2016-01-01

Acute ischemic stroke is caused by occlusion of a cerebral artery, resulting in loss of brain tissue and neurologic deficits. However, a portion of the ischemic brain can be salvaged if blood flow is restored within an appropriate time frame. The past year has seen the publication of five positive randomized controlled trials demonstrating substantial benefit of mechanical thrombectomy in select patients with large vessel cerebrovascular occlusion. This progress is related to several factors, but most importantly, dramatic improvements in speed and rates of recanalization with the latest generation devices. In this article, we review the evolution of endovascular acute ischemic stroke therapies and key design features of the most widely used devices.

Experimental approaches for the treatment of malignant gliomas

PubMed Central

Arko, Leopold; Katsyv, Igor; Park, Grace E.; Luan, William Patrick; Park, John K.

2010-01-01

Malignant gliomas, which include glioblastomas and anaplastic astrocytomas, are the most common primary tumors of the brain. Over the past 30 years, the standard treatment for these tumors has evolved to include maximal safe surgical resection, radiation therapy and temozolomide chemotherapy. While the median survival of patients with glioblastomas has improved from 6 months to 14.6 months, these tumors continue to be lethal for the vast majority of patients. There has, however, been recent substantial progress in our mechanistic understanding of tumor development and growth. The translation of these genetic, epigenetic and biochemical findings into therapies that have been tested in clinical trials is the subject of this review. PMID:20546782

Survival Gains from First‐Line Systemic Therapy in Metastatic Non‐Small Cell Lung Cancer in the U.S., 1990–2015: Progress and Opportunities

PubMed Central

Goulart, Bernardo H. L.; Ravelo, Arliene; Kolkey, Holli; Ramsey, Scott D.

2017-01-01

Abstract Background. Approximately 190,000 Americans are diagnosed with non‐small cell lung cancer (NSCLC) annually, and about half have metastatic (Stage IV) disease. These patients have historically had poor survival prognosis, but several new therapies introduced since 2000 provide options for improved outcomes. The objectives of this study were to quantify survival gains from 1990, when best supportive care (BSC) only was standard, to 2015 and to estimate the impact of expanded use of systemic therapies in clinically appropriate patients. Materials and Methods. We developed a simulation model to estimate survival gains for patients with metastatic NSCLC from 1990–2015. Survival estimates were derived from major clinical trials and extrapolated to a lifetime horizon. Proportions of patients receiving available therapies were derived from the Surveillance, Epidemiology, and End Results database and a commercial treatment registry. We also estimated gains in overall survival (OS) in scenarios in which systemic therapy use increased by 10% and 30% relative to current use. Results. From 1990–2015, one‐year survival proportion increased by 14.1% and mean per‐patient survival improved by 4.2 months (32,700 population life years). Increasing treated patients by 10% or 30% increased OS by 5.1 months (39,700 population life years) and 6.9 months (53,800 population life years), respectively. Conclusion. Although survival remains poor in metastatic NSCLC relative to other common cancers, meaningful progress in per‐patient and population‐level outcomes has been realized over the past 25 years. These advances can be improved even further by increasing use of systemic therapies in the substantial proportion of patients who are suitable for treatment yet who currently receive BSC only. Implications for Practice. Approximately 93,500 Americans are diagnosed with metastatic non‐small cell lung cancer (NSCLC) annually. Historically, these patients have had poor survival prognosis, but newer therapies provide options for improved outcomes. This simulation modeling study quantified metastatic NSCLC survival gains from 1990–2015. Over this period, the one‐year survival proportion and mean per‐patient survival increased by 14.1% and 4.2 months, respectively. Though metastatic NSCLC survival remains poor, the past 25 years have brought meaningful gains. Additional gains could be realized by increasing systemic therapy use in the substantial proportion of patients who are suitable for treatment, yet currently receive only supportive care. PMID:28242792

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

NASA Astrophysics Data System (ADS)

MacDougall, Andrew H.; Knutti, Reto

2016-04-01

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

[Towards a new vaccine economy?].

PubMed

Poirot, P; Martin, J F

1994-01-01

When Jonas Salk announced in the mid-50s the availability of a new vaccine against poliomyelitis, the world had the impression that it was now controlling infectious diseases. In fact, the success of this vaccine has been considerable and although some innovations lead to the launch of vaccines against flu, measles, rubella or mumps, the world vaccine market remained remarkably stable till the mid-80s. However, since 1984 (launch of the hepatitis B vaccine) there have been very substantial changes and further change is expected in the next ten years in the world market. Today, big companies are making a concentrated supply: Pasteur Mérieux with its subsidiary Connaught, SmithKline Beecham who acquired the Belgian company RIT, and Merck & Co. who is joining its forces with Pasteur Mérieux. Medium sized and small companies remain and reflect the situation of the past, but must work hard to secure their long term existence eventhough the world demand is going to double before the year 2000. Very substantial technological innovations explain to a large extent the development of the supply: progress in molecular biology, and particularly genetic engineering, lead to recombinant vaccines of which hepatitis B is the best example with worldwide sales in the range of $600 million a year. Similarly, conjugation technologies have allowed the development of new vaccines against meningitis, particularly Haemophilus influenzae type b. More recently, an efficacious vaccine against hepatitis A has been launched and many new products will be marketed in the next years against herpes, Lyme disease, and agents of other meningitis, etc.(ABSTRACT TRUNCATED AT 250 WORDS)

Report of the Defense Science Board Task Force on National Aero-Space Plane (NASP) Program

NASA Technical Reports Server (NTRS)

1992-01-01

Six years ago, the Defense Science Board (DSB) initiated a review of the concept, technical basis, program content, and missions of the National Aerospace Plane (NASP) program. The report was completed in Sep. 1988, and the recommendations contributed to strengthening the technical efforts in the NASP program. Since then, substantial technological progress has been made in the technology development phase (Phase 2) of the program. Phase 2 of the program is currently scheduled to end in late Fiscal Year 1993, with a decision whether to proceed to the experimental flight vehicle phase (Phase 3) to be made at that time. This decision will be a very significant one for the Department of Defense (DoD) and the National Aeronautics and Space Administration (NASA). In February of this year, the DSB was chartered to revisit the NASP program to assess the degree to which the many technical challenges of the program have been resolved, or are likely to be resolved by the end of Phase 2.

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.

Career Choices and Career Progression of Junior Doctors in Dermatology: Surveys of UK Medical Graduates.

PubMed

Barat, Atena; Goldacre, Michael J; Lambert, Trevor W

2018-01-01

To report UK-trained doctors' career choices for dermatology, career destinations, and factors influencing career pathways. Multicohort multipurpose longitudinal surveys of UK-trained doctors who graduated between 1974 and 2015. In all, 40,412 doctors (58% of graduates) responded in year 1, 31,466 (64%) in year 3, and 24,970 (67%) in year 5. One year after graduation, 1.7% of women and 0.6% of men made dermatology their first choice but by five years after graduation the respective figures were 1.0% and 0.7%. Compared to their predecessors, its popularity fell more substantially from years 1 to 5 among recent graduates (2005-15), particularly for women (from 2.1% in year 1 to 0.8% in year 5) compared with a fall from 0.8% to 0.5% among men. The most important factor influencing dermatology choice was "hours/working conditions": in year one, 69% regarded this as important compared with 31% of those choosing other hospital physician specialties. Only 18% of respondents who chose dermatology at year 1 eventually worked in it; however, almost all practising dermatologists (94%), 10 years after qualifying, had made their future career decision by year 5. Dermatology is popular among female UK graduates. Most dermatologists made their career decision late but decisively.

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

PubMed

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

2006-07-01

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

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

PubMed Central

Hummelen, Ruben; Hemsworth, Jaimie; Reid, Gregor

2010-01-01

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

Reliability of kinetic visual field testing in children with mutation-proven retinal dystrophies: Implications for therapeutic clinical trials.

PubMed

Dedania, Vaidehi S; Liu, Jerry Y; Schlegel, Dana; Andrews, Chris A; Branham, Kari; Khan, Naheed W; Musch, David C; Heckenlively, John R; Jayasundera, K Thiran

2018-01-01

Kinetic visual field testing is used to monitor disease course in retinal dystrophy clinical care and treatment response in treatment trials, which are increasingly recruiting children. This study investigates Goldmann visual field (GVF) changes in young children with mutation-proven retinal dystrophies as they age and with progression of the retinal degeneration. Retrospective review of children ≤ 17 years old with a mutation-proven retinal dystrophy. Objective clinical disease activity was assessed by a retinal degeneration specialist masked to GVF results. Digital quantification of GVF area was performed. Twenty-nine children (58 eyes), ages 5-16, were identified. GVF area increased with age despite progression in 20 children and clinical stability in nine children. Mean ± standard error increase in GVF area/year was 333 ± 130 mm 2 (I4e, p = 0.012), 720 ± 155 mm 2 (III4e, p < 0.001), and 759 ± 167 mm 2 (IV4e, p < 0.001), with greater increases at earlier ages. Repeatability coefficients were 7381 mm 2 (I4e), 9379 mm 2 (III4e), and 10346 mm 2 (IV4e), indicating a large variability. At 2.5 years after the baseline GVF the area increased ≥ 20%, the criterion for positive treatment outcome defined in recent published therapeutic trials, in 38% (I4e), 34% (III4e), and 33% (IV4e) of eyes. In a substantial proportion of children with mutation-proven retinal dystrophies, there is a significant increase in GVF area with age, particularly those < 12 years, despite progression or stability of disease. These findings suggest that change in GVF area in children with retinal dystrophies can be an unreliable measure of response to treatment and on which to base appropriate counseling about visual impairment.

Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2.

PubMed

Pritchard, Kathleen I; Burris, Howard A; Ito, Yoshinori; Rugo, Hope S; Dakhil, Shaker; Hortobagyi, Gabriel N; Campone, Mario; Csöszi, Tibor; Baselga, José; Puttawibul, Puttisak; Piccart, Martine; Heng, Daniel; Noguchi, Shinzaburo; Srimuninnimit, Vichien; Bourgeois, Hugues; Gonzalez Martin, Antonio; Osborne, Karen; Panneerselvam, Ashok; Taran, Tetiana; Sahmoud, Tarek; Gnant, Michael

2013-12-01

Postmenopausal women with hormone receptor-positive (HR(+)) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR(+) advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest. BOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR(+) advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up. Baseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths. Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR(+) advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Progress and challenges in TB vaccine development

PubMed Central

Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H.E.; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

2018-01-01

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our “failed” trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development. PMID:29568497

Tracking progress towards global drinking water and sanitation targets: A within and among country analysis.

PubMed

Fuller, James A; Goldstick, Jason; Bartram, Jamie; Eisenberg, Joseph N S

2016-01-15

Global access to safe drinking water and sanitation has improved dramatically during the Millennium Development Goal (MDG) period. However, there is substantial heterogeneity in progress between countries and inequality within countries. We assessed countries' temporal patterns in access to drinking water and sanitation using publicly available data. We then classified countries using non-linear modeling techniques as having one of the following trajectories: 100% coverage, linear growth, linear decline, no change, saturation, acceleration, deceleration, negative acceleration, or negative deceleration. We further assessed the degree to which temporal profiles follow a sigmoidal pattern and how these patterns might vary within a given country between rural and urban settings. Among countries with more than 10 data points, between 15% and 38% showed a non-linear trajectory, depending on the indicator. Overall, countries' progress followed a sigmoidal trend, but some countries are making better progress and some worse progress than would be expected. We highlight several countries that are not on track to meet the MDG for water or sanitation, but whose access is accelerating, suggesting better performance during the coming years. Conversely, we also highlight several countries that have made sufficient progress to meet the MDG target, but in which access is decelerating. Patterns were heterogeneous and non-linearity was common. Characterization of these heterogeneous patterns will help policy makers allocate resources more effectively. For example, policy makers can identify countries that could make use of additional resources or might be in need of additional institutional capacity development to properly manage resources; this will be essential to meet the forthcoming Sustainable Development Goals. Copyright © 2015 Elsevier B.V. All rights reserved.

Progress and challenges in TB vaccine development.

PubMed

Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H E; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

2018-01-01

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our "failed" trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

Early Rockets

NASA Image and Video Library

2004-04-15

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

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

DTIC Science & Technology

2014-01-01

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

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

ERIC Educational Resources Information Center

Schiefelbusch, Richard L.; Lent, James R.

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

Developments in early intervention for psychosis in Hong Kong.

PubMed

Wong, G H Y; Hui, C L M; Wong, D Y; Tang, J Y M; Chang, W C; Chan, S K W; Lee, E H M; Xu, J Q; Lin, J J X; Lai, D C; Tam, W; Kok, J; Chung, D W S; Hung, S F; Chen, E Y H

2012-09-01

The year 2011 marked the 10-year milestone of early intervention for psychosis in Hong Kong. Since 2001, the landscape of early psychosis services has changed markedly in Hong Kong. Substantial progress has been made in the areas of early intervention service implementation, knowledge generation, and public awareness promotion. Favourable outcomes attributable to the early intervention service are supported by solid evidence from local clinical research studies; early intervention service users showed improved functioning, ameliorated symptoms, and decreased hospitalisation and suicide rates. Continued development of early intervention in Hong Kong over the decade includes the introduction and maturation of several key platforms, such as the Hospital Authority Early Assessment Service for Young People with Psychosis programme, the Psychosis Studies and Intervention Unit by the University of Hong Kong, the Hong Kong Early Psychosis Intervention Society, the Jockey Club Early Psychosis Project, and the postgraduate Psychological Medicine (Psychosis Studies) programme. In this paper, we reviewed some of the major milestones in local service development with reference to features of the Hong Kong mental health system. We describe chronologically the implementation and consolidation of public early intervention services as well as recent progresses in public awareness work that are tied in with knowledge generation and transfer, and outline the prospects for early intervention in the next decade and those that follow.

MPNs as Inflammatory Diseases: The Evidence, Consequences, and Perspectives

PubMed Central

Hasselbalch, Hans Carl; Bjørn, Mads Emil

2015-01-01

In recent years the evidence is increasing that chronic inflammation may be an important driving force for clonal evolution and disease progression in the Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Abnormal expression and activity of a number of proinflammatory cytokines are associated with MPNs, in particular MF, in which immune dysregulation is pronounced as evidenced by dysregulation of several immune and inflammation genes. In addition, chronic inflammation has been suggested to contribute to the development of premature atherosclerosis and may drive the development of other cancers in MPNs, both nonhematologic and hematologic. The MPN population has a substantial inflammation-mediated comorbidity burden. This review describes the evidence for considering the MPNs as inflammatory diseases, A Human Inflammation Model of Cancer Development, and the role of cytokines in disease initiation and progression. The consequences of this model are discussed, including the increased risk of second cancers and other inflammation-mediated diseases, emphasizing the urgent need for rethinking our therapeutic approach. Early intervention with interferon-alpha2, which as monotherapy has been shown to be able to induce minimal residual disease, in combination with potent anti-inflammatory agents such as JAK-inhibitors is foreseen as the most promising new treatment modality in the years to come. PMID:26604428

Brain injury and health policy: twenty-five years of progress.

PubMed

Reid-Arndt, Stephanie A; Frank, Robert G; Hagglund, Kristofer J

2010-01-01

Legislative advocacy is a prerequisite for the development of research and community services benefiting individuals with traumatic brain injury (TBI). Dr Mitchell Rosenthal and other leaders in rehabilitation began the process of advocating for TBI services more than 25 years ago, before many in the field fully appreciated the necessity of these efforts. Since that time, substantial gains have been made through advocacy efforts on behalf of individuals with TBI and their families. This article provides an overview of the TBI advocacy movement, highlighting federal legislation resulting in appropriations for TBI services and protecting the rights of individuals with TBI. Key government entities engaged in developing states' TBI infrastructure and providing services to individuals with TBI and their families are also discussed. In addition to celebrating some of the successes that were initiated by the efforts of Dr Rosenthal and other visionaries, select shortcoming of current legislation is noted to provide insights regarding future advocacy needs.

Plan for Living on a Restless Planet Sets NASA's Solid Earth Agenda

NASA Astrophysics Data System (ADS)

Solomon, Sean C.; Baker, Victor R.; Bloxham, Jeremy; Booth, Jeffrey; Donnellan, Andrea; Elachi, Charles; Evans, Diane; Rignot, Eric; Burbank, Douglas; Chao, Benjamin F.; Chave, Alan; Gillespie, Alan; Herring, Thomas; Jeanloz, Raymond; LaBrecque, John; Minster, Bernard; Pittman, Walter C., III; Simons, Mark; Turcotte, Donald L.; Zoback, Mary Lou C.

What are the most important challenges facing solid Earth science today and over the next two decades? And what is the best approach for NASA, in partnership with other agencies, to address those challenges? A new report, Living on a Restless Planet, provides a blueprint for answering these questions. The top priority for a new spacecraft mission in the area of solid Earth science over the next 5 years, according to this report, is a satellite dedicated to Interferometric Synthetic Aperture Radar (InSAR). At the request of NASA, the Solid Earth Science Working Group (SESWG) developed a strategy for the highest priority objectives in solid Earth science for the space agency over the next 25 years. The strategy addresses six challenges that are of fundamental scientific importance, have strong implications for society, and are amenable to substantial progress through a concerted series of scientific observations from space.

Nanophotonic label-free biosensors for environmental monitoring.

PubMed

Chocarro-Ruiz, Blanca; Fernández-Gavela, Adrián; Herranz, Sonia; Lechuga, Laura M

2017-06-01

The field of environmental monitoring has experienced a substantial progress in the last years but still the on-site control of contaminants is an elusive problem. In addition, the growing number of pollutant sources is accompanied by an increasing need of having efficient early warning systems. Several years ago biosensor devices emerged as promising environmental monitoring tools, but their level of miniaturization and their fully operation outside the laboratory prevented their use on-site. In the last period, nanophotonic biosensors based on evanescent sensing have emerged as an outstanding choice for portable point-of-care diagnosis thanks to their capability, among others, of miniaturization, multiplexing, label-free detection and integration in lab-on-chip platforms. This review covers the most relevant nanophotonic biosensors which have been proposed (including interferometric waveguides, grating-couplers, microcavity resonators, photonic crystals and localized surface plasmon resonance sensors) and their recent application for environmental surveillance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Extended-range tiltable micromirror

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

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

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

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

PubMed

Mayo, Ray Cody; Leung, Jessica

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

Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy.

PubMed

Freise, Kevin J; Jones, Aksana K; Menon, Rajeev M; Verdugo, Maria E; Humerickhouse, Rod A; Awni, Walid M; Salem, Ahmed Hamed

2017-12-01

Venetoclax is indicated at a dosage of 400 mg daily (QD) for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least 1 prior therapy. Ongoing trials are evaluating venetoclax in combination with CD20 targeting monoclonal antibodies, such as rituximab. The objective of this research was to characterize the relationship between venetoclax exposures and progression-free survival (PFS) and to evaluate the effect of rituximab coadministration on PFS in patients with relapsed or refractory (R/R) CLL/small lymphocytic lymphoma (SLL). A total of 323 patients from 3 clinical studies of venetoclax, with and without rituximab coadministration, were pooled for the analyses. A time-variant relative risk survival model was used to relate plasma venetoclax concentrations and rituximab administration to PFS. Demographics and baseline disease characteristics were evaluated for their effect on PFS. A concentration-dependent effect of venetoclax on PFS and a prolonged synergistic effect of 6 cycles of concomitant rituximab were identified. The 17p deletion chromosomal aberration was not identified to affect the PFS of patients treated with venetoclax. A venetoclax dose of 400 mg daily QD was estimated to result in a substantial median PFS of 1.8 years (95% confidence interval [CI], 1.7-2.1), whereas the addition of 6 cycles of rituximab was estimated to increase the median PFS to 3.9 years (95% CI, 2.8-5.6). The analysis demonstrates a concentration-dependent effect of venetoclax on PFS and also a synergistic effect with rituximab. Combining venetoclax with the CD20 targeting monoclonal antibody rituximab in R/R CLL/SLL patients provides substantial synergistic benefit compared with increasing the venetoclax monotherapy dose. Copyright © 2016 John Wiley & Sons, Ltd.

The roles of physical habitat in reproduction and survival of pallid sturgeon and shovelnose sturgeon in the Lower Missouri River, progress 2005–06: Chapter D in Factors affecting the reproduction, recruitment, habitat, and population dynamics of pallid sturgeon and shovelnose sturgeon in the Missouri River

USGS Publications Warehouse

Jacobson, Robert B.; Johnson, Harold E.; Reuter, Joanna M.; Elliott, Caroline M.

2007-01-01

This report documents progress on three related components of habitat assessments in the Lower Missouri River during 2005–06. The habitat-use component links this research directly to sturgeon ecology research described in other chapters. The habitat availability and habitat dynamics assessments provide physical context for the ecological research. Results from 2005 to 2006 indicate that the methods developed to assess habitat use, quality, quantity, and dynamics are appropriate and sufficiently accurate to address critical questions about sturgeon habitat on the Lower Missouri River. Preliminary analysis of habitats occupied by adult female shovelnose sturgeon indicates that migrating sturgeon do not select for depth but seem to select for lower than reach-averaged velocities and higher than reach-averaged velocity gradients. Data collected to compile, calibrate, and validate multidimensional hydraulic models in probable spawning reaches appear to be sufficient to support the modeling objectives. Monitoring of selected channel cross sections and long profiles multiple times during the year showed little change at the upstreammost reach over the range of flows measured during 2006, likely because of channel stability associated with an armored bed. Geomorphic changes documented at monitoring cross sections increased with distance downstream. Hydroacoustic substrate-class parameters documented systematic changes with discharge and with hydraulic environment across the channel. Similarly, bed velocity varied predictably with discharge and hydraulic environment, indicating its potential as an indicator of bedload sediment transport. Longitudinal profiles showed substantial downstream movement of dunes over the monitored discharges, as well as substantial within-year variability in dune size. Observations of geomorphic change during the moderate flow range of 2006 support the hypothesis that the magnitude of flow modifications under consideration on the Lower Missouri River will be sufficient to transport sediment and potentially modify spawning habitats.

From Fancy to Reason: Scaling Deaf and Hearing Children’s Understanding of Theory of Mind and Pretence

PubMed Central

Peterson, Candida C.; Wellman, Henry M.

2011-01-01

We examined deaf and hearing children’s progression of steps in theory-of-mind (ToM) development including their understanding of social pretending. Ninety-three children (33 deaf; 60 hearing) aged 3 to 13 years were tested on a set of six closely-matched ToM tasks. Results showed that deaf children were delayed substantially behind hearing children in understanding pretending, false belief and other ToM concepts, in line with their delayed uptake of social pretend play. By using a scaling methodology, we confirmed previous evidence of a consistent five-step developmental progression for both groups. Moreover, by including social pretence understanding, both deaf and hearing children’s ToM sequences were shown to extend reliably to six sequential developmental steps. Finally and focally, even though both groups’ sequences were six steps long, the placement of pretence relative to other ToM milestones varied with hearing status. Deaf children understood social pretending at an earlier step in the ToM sequence than hearing children, albeit at a later chronological age. Theoretically, the findings are relevant to questions about how universal developmental progressions come together along with culturally-distinctive inputs and biological factors (such as hearing loss) to set the pace for ToM development. PMID:19998533

Molecular biology of anal squamous cell carcinoma: implications for future research and clinical intervention.

PubMed

Bernardi, Maria-Pia; Ngan, Samuel Y; Michael, Michael; Lynch, A Craig; Heriot, Alexander G; Ramsay, Robert G; Phillips, Wayne A

2015-12-01

Anal squamous cell carcinoma is a human papillomavirus-related disease, in which no substantial advances in treatment have been made in over 40 years, especially for those patients who develop disease relapse and for whom no surgical options exist. HPV can evade the immune system and its role in disease progression can be exploited in novel immunotherapy platforms. Although several studies have investigated the expression and inactivation (through loss of heterozygosity) of tumour suppressor genes in the pathways to cancer, no clinically valuable biomarkers have emerged. Regulators of apoptosis, including survivin, and agents targeting the PI3K/AKT pathway, offer opportunities for targeted therapy, although robust data are scarce. Additionally, antibody therapy targeting EGFR may prove effective, although its safety profile in combination with standard chemoradiotherapy has proven to be suboptimal. Finally, progress in the treatment of anal cancer has remained stagnant due to a lack of preclinical models, including cell lines and mouse models. In this Review, we discuss the molecular biology of anal squamous cell carcinoma, clinical trials in progress, and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a resource for investigation of new molecular pathways and for testing novel targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

From fancy to reason: scaling deaf and hearing children's understanding of theory of mind and pretence.

PubMed

Peterson, Candida C; Wellman, Henry M

2009-06-01

We examined deaf and hearing children's progression of steps in theory of mind (ToM) development including their understanding of social pretending. Ninety-three children (33 deaf; 60 hearing) aged 3-13 years were tested on a set of six closely matched ToM tasks. Results showed that deaf children were delayed substantially behind hearing children in understanding pretending, false belief (FB) and other ToM concepts, in line with their delayed uptake of social pretend (SP) play. By using a scaling methodology, we confirmed previous evidence of a consistent five-step developmental progression for both groups. Moreover, by including social pretence understanding, both deaf and hearing children's ToM sequences were shown to extend reliably to six sequential developmental steps. Finally and focally, even though both groups' sequences were six steps long, the placement of pretence relative to other ToM milestones varied with hearing status. Deaf children understood social pretending at an earlier step in the ToM sequence than hearing children, albeit at a later chronological age. Theoretically, the findings are relevant to questions about how universal developmental progressions come together along with culturally distinctive inputs and biological factors (such as hearing loss) to set the pace for ToM development.

Improving comparability of international migration statistics: contributions by the Conference of European Statisticians from 1971 to date.

PubMed

Kelly, J J

1987-01-01

This article summarizes the 3 main types of interrelated activities which the Conference of European Statisticians has worked on to improve the measurement and international comparability of international migration flows. The work has encompassed collaborating with the UN Statistical Commission on the preparation and implementation of the revised international recommendations on statistics of international migration, organizing a regular exchange of data on immigration and emigration flows among the UN Economic Commission for Europe countries and selected countries in other regions, and conducting bilateral studies on international migration within the framework of the Conference's program of work in this field of statistics. The bulk of the work which has been carried out to date by the conference has been conducted rather anonymously and even unobtrusively by the staff of national statistical offices in Economic Commission for Europe countries; they have achieved a modest but important amount of progress during the past 15 years. There is reason to expect that further progress will be made over the next decade, particularly if national statistical offices in the region continue to undertake bilateral studies and endeavor to improve their migration statistics. However, more substantial progress could be achieved if additional countries and organizations established projects aimed at achieving these ends (author's modified).

Dr. Goddard and a 1918 version of 'Bazooka'

NASA Technical Reports Server (NTRS)

2004-01-01

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

Posttransplantation lymphoproliferative disorder in lung transplant recipients: a 15-year single institution experience.

PubMed

Muchtar, Eli; Kramer, Mordechai R; Vidal, Liat; Ram, Ron; Gurion, Ronit; Rosenblat, Yivgenia; Bakal, Ilana; Shpilberg, Ofer

2013-10-15

Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication after solid-organ transplantation. Historically, most cases of PTLD among lung transplant recipients occurred within the first year from transplantation and were associated with Epstein-Barr virus (EBV) infection. However, there are increasing reports on a late-onset form of PTLD. We reviewed all charts of patients undergoing either lung or heart-lung transplantation in a tertiary transplantation center between the years 1997 and 2012 and compared clinical and pathologic parameters between early- and late-onset PTLD. Ten patients with PTLD were identified. Median (range) time from transplantation to PTLD diagnosis was 41 (4-128) months. Three patients developed early PTLD. All were pretransplantation EBV seronegative and asymptomatic when diagnosed during surveillance chest imaging. In contrast, the seven patients with late-onset PTLD were all EBV seropositive before transplantation and were symptomatic at diagnosis. Although early-onset PTLD uniformly involved the transplanted lung, this was relatively rare in late-onset PTLD (3 of 3 vs. 1 of 7). All patients were initially treated with reduction of immunosuppression, with at least one additional treatment modality used, mainly chemoimmunotherapy. Eight patients attained complete remission. With a median follow-up of 17 months, 8 patients died, mainly from treatment-related causes rather than disease progression. Our cohort of lung transplant recipients demonstrates a trend of late-onset PTLD with the majority of patients who died of treatment-related causes rather than disease progression. Therefore, substantial efforts should be focused on treatment-related mortality reduction.

Plasma Equilibrium Control in Nuclear Fusion Devices 2. Plasma Control in Magnetic Confinement Devices 2.1 Plasma Control in Tokamaks

NASA Astrophysics Data System (ADS)

Fukuda, Takeshi

The plasma control technique for use in large tokamak devices has made great developmental strides in the last decade, concomitantly with progress in the understanding of tokamak physics and in part facilitated by the substantial advancement in the computing environment. Equilibrium control procedures have thereby been established, and it has been pervasively recognized in recent years that the real-time feedback control of physical quantities is indispensable for the improvement and sustainment of plasma performance in a quasi-steady-state. Further development is presently undertaken to realize the “advanced plasma control” concept, where integrated fusion performance is achieved by the simultaneous feedback control of multiple physical quantities, combined with equilibrium control.

Nuclear medicine and imaging research: Quantitative studies in radiopharmaceutical science

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

Copper, M.; Beck, R.N.

1991-06-01

During the past three years the program has undergone a substantial revitalization. There has been no significant change in the scientific direction of this grant, in which emphasis continues to be placed on developing new or improved methods of obtaining quantitative data from radiotracer imaging studies. However, considerable scientific progress has been made in the three areas of interest: Radiochemistry, Quantitative Methodologies, and Experimental Methods and Feasibility Studies, resulting in a sharper focus of perspective and improved integration of the overall scientific effort. Changes in Faculty and staff, including development of new collaborations, have contributed to this, as has acquisitionmore » of additional and new equipment and renovations and expansion of the core facilities. 121 refs., 30 figs., 2 tabs.« less

Nonlinear Dynamics of High-Brightness Electron Beams and Beam-Plasma Interactions: Theories, Simulations, and Experiments

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

C. L. Bohn

2008-05-31

According to its original Statement of Work (SOW), the overarching objective of this project is: 'To enhance substantially the understanding of the fundamental dynamics of nonequilibrium high-brightness beams with space charge.' Our work and results over the past three and half years have been both intense and fruitful. Inasmuch as this project is inextricably linked to a larger, growing research program - that of the Beam Physics and Astrophysics Group (BPAG) - the progress that it has made possible cannot easily be separated from the global picture. Thus, this summary report includes major sections on 'global' developments and on thosemore » that can be regarded as specific to this project.« less

Targeted therapies in the treatment of urothelial cancers.

PubMed

Aragon-Ching, Jeanny B; Trump, Donald L

2017-07-01

Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

[Pathophysiology of hypertension : What are our current concepts?].

PubMed

Jordan, J

2015-03-01

In the year 2015, many questions regarding the pathophysiology of essential arterial hypertension remain unresolved. Substantial scientific progress has been made in various medical areas aided by novel molecular"omics" techniques. The findings could then be implemented in diagnostic and therapeutic procedures. In the field of hypertension research such methods have been applied in very large cohorts but have contributed less to pathophysiological understanding and clinical management than expected. The findings on the pathophysiological importance of baroreflex mechanisms, natriuretic peptides and osmotically inactive sodium storage discussed in this article all have something in common: all are based on small, carefully conducted human physiological investigations and often challenge current textbook knowledge. Nevertheless, these findings have opened up new research fields and are likely to affect clinical care.

Molecular genetics of alopecias.

PubMed

Ramot, Yuval; Zlotogorski, Abraham

2015-01-01

Recent developments in research methods and techniques, such as whole-exome and -genome sequencing, have substantially improved our understanding of genetic conditions. Special progress has been made in the field of genotrichoses, or hereditary hair diseases, a field that has been obscure for many years. The underlying genes for many of the monogenic hair diseases are now known. Additionally, complex analyses of large cohorts of patients have given us the first clues to the genes associated with polygenic hair disorders, such as androgenetic alopecia and alopecia areata. Thanks to these major findings, the sophisticated regulation of the morphogenesis, development and growth of hair follicles has begun to be revealed, and new players in this delicate molecular interplay have been exposed. © 2015 S. Karger AG, Basel.

Identification and Analysis of Antiviral Compounds Against Poliovirus.

PubMed

Leyssen, Pieter; Franco, David; Tijsma, Aloys; Lacroix, Céline; De Palma, Armando; Neyts, Johan

2016-01-01

The Global Polio Eradication Initiative, launched in 1988, had as its goal the eradication of polio worldwide by the year 2000 through large-scale vaccinations campaigns with the live attenuated oral PV vaccine (OPV) (Griffiths et al., Biologicals 34:73-74, 2006). Despite substantial progress, polio remains endemic in several countries and new imported cases are reported on a regular basis ( http://www.polioeradication.org/casecount.asp ).It was recognized by the poliovirus research community that developing antivirals against poliovirus would be invaluable in the post-OPV era. Here, we describe three methods essential for the identification of selective inhibitors of poliovirus replication and for determining their mode of action by time-of-drug-addition studies as well as by the isolation of compound-resistant poliovirus variants.

Managing interoperability and complexity in health systems.

PubMed

Bouamrane, M-M; Tao, C; Sarkar, I N

2015-01-01

In recent years, we have witnessed substantial progress in the use of clinical informatics systems to support clinicians during episodes of care, manage specialised domain knowledge, perform complex clinical data analysis and improve the management of health organisations' resources. However, the vision of fully integrated health information eco-systems, which provide relevant information and useful knowledge at the point-of-care, remains elusive. This journal Focus Theme reviews some of the enduring challenges of interoperability and complexity in clinical informatics systems. Furthermore, a range of approaches are proposed in order to address, harness and resolve some of the many remaining issues towards a greater integration of health information systems and extraction of useful or new knowledge from heterogeneous electronic data repositories.

Increasing the Impact of Materials in and beyond Bio-Nano Science.

PubMed

Björnmalm, Mattias; Faria, Matthew; Caruso, Frank

2016-10-19

This is an exciting time for the field of bio-nano science: enormous progress has been made in recent years, especially in academic research, and materials developed and studied in this area are poised to make a substantial impact in real-world applications. Herein, we discuss ways to leverage the strengths of the field, current limitations, and valuable lessons learned from neighboring fields that can be adopted to accelerate scientific discovery and translational research in bio-nano science. We identify and discuss five interconnected topics: (i) the advantages of cumulative research; (ii) the necessity of aligning projects with research priorities; (iii) the value of transparent science; (iv) the opportunities presented by "dark data"; and (v) the importance of establishing bio-nano standards.

Biotechnological applications of transglutaminases.

PubMed

Rachel, Natalie M; Pelletier, Joelle N

2013-10-22

In nature, transglutaminases catalyze the formation of amide bonds between proteins to form insoluble protein aggregates. This specific function has long been exploited in the food and textile industries as a protein cross-linking agent to alter the texture of meat, wool, and leather. In recent years, biotechnological applications of transglutaminases have come to light in areas ranging from material sciences to medicine. There has also been a substantial effort to further investigate the fundamentals of transglutaminases, as many of their characteristics that remain poorly understood. Those studies also work towards the goal of developing transglutaminases as more efficient catalysts. Progress in this area includes structural information and novel chemical and biological assays. Here, we review recent achievements in this area in order to illustrate the versatility of transglutaminases.

Guillain-Barre syndrome caused by hepatitis E infection: case report and literature review.

PubMed

Zheng, Xiaoqin; Yu, Liang; Xu, Qiaomai; Gu, Silan; Tang, Lingling

2018-01-23

Hepatitis E infection is a global disorder that causes substantial morbidity. Numerous neurologic illnesses, including Guillain-Barre syndrome (GBS), have occurred in patients with hepatitis E virus (HEV) infection. We report a 58 year-old non-immunocompromised man who presented with progressive muscle weakness in all extremities during an episode of acute HEV infection, which was confirmed by measuring the anti-HEV IgM antibodies in the serum. Both cerebrospinal fluid examination and electrophysiological study were in agreement with the diagnosis of HEV-associated GBS. Following the treatment with intravenous immunoglobulin, the patient's neurological condition improved rapidly. HEV infection should be strongly considered in patients with neurological symptoms, especially those with elevated levels of liver enzymes.

Evolving Views on a Dynamic Greenhouse Earth

NASA Astrophysics Data System (ADS)

Hollis, Chris; Huber, Matthew

2009-06-01

Climatic and Biotic Events of the Paleogene (CBEP 2009) Conference; Wellington, New Zealand, 12-15 January 2009; The Paleogene (65-24 million years ago) was a dynamic period in Earth's history in which major mammal groups became established and diversified, rapid and repeated extreme global warming events occurred, and climate began its stuttering progression from a greenhouse to an icehouse climate state. With atmospheric carbon dioxide concentrations in the range projected to occur over the next several centuries (>1000 parts per million), the Paleogene is also a window into our future (see J. C. Zachos et al., Nature, 451, 279-283, 2008). Long-standing interest in understanding the causes and consequences of global change in the Paleogene and the current timeliness of greenhouse climate research explain why conferences are periodically devoted to the climatic and biotic events of the Paleogene. The 2009 conference, held in New Zealand, attracted 130 participants from 20 countries. Presentations demonstrated substantial progress in new climate proxy development, new multiproxy approaches, and closer integration of paleoclimate records with climate models, consolidating around three main issues.

Unilateral lung transplantation for pulmonary fibrosis.

PubMed

1986-05-01

Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

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

PubMed

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

2003-10-01

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

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

PubMed Central

Liu, Ya-Ling; Nascimento, Marcelle; Burne, Robert A

2012-01-01

Alkali production by oral bacteria is believed to have a major impact on oral microbial ecology and to be inibitory to the initiation and progression of dental caries. A substantial body of evidence is beginning to accumulate that indicates the modulation of the alkalinogenic potential of dental biofilms may be a promising strategy for caries control. This brief review highlights recent progress toward understanding molecular genetic and physiologic aspects of important alkali-generating pathways in oral bacteria, and the role of alkali production in the ecology of dental biofilms in health and disease. PMID:22996271

Imaging Cellular Architecture with X-rays

PubMed Central

Larabell, Carolyn A.; Nugent, Keith A.

2012-01-01

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

The impact of the worldwide Millennium Development Goals campaign on maternal and under-five child mortality reduction: ‘Where did the worldwide campaign work most effectively?’

PubMed Central

Cha, Seungman

2017-01-01

ABSTRACT Background: As the Millennium Development Goals campaign (MDGs) came to a close, clear evidence was needed on the contribution of the worldwide MDG campaign. Objective: We seek to determine the degree of difference in the reduction rate between the pre-MDG and MDG campaign periods and its statistical significance by region. Design: Unlike the prevailing studies that measured progress in 1990–2010, this study explores by percentage how much MDG progress has been achieved during the MDG campaign period and quantifies the impact of the MDG campaign on the maternal and under-five child mortality reduction during the MDG era by comparing observed values with counterfactual values estimated on the basis of the historical trend. Results: The low accomplishment of sub-Saharan Africa toward the MDG target mainly resulted from the debilitated progress of mortality reduction during 1990–2000, which was not related to the worldwide MDG campaign. In contrast, the other regions had already achieved substantial progress before the Millennium Declaration was proclaimed. Sub-Saharan African countries have seen the most remarkable impact of the worldwide MDG campaign on maternal and child mortality reduction across all different measurements. In sub-Saharan Africa, the MDG campaign has advanced the progress of the declining maternal mortality ratio and under-five mortality rate, respectively, by 4.29 and 4.37 years. Conclusions: Sub-Saharan African countries were frequently labeled as ‘off-track’, ‘insufficient progress’, or ‘no progress’ even though the greatest progress was achieved here during the worldwide MDG campaign period and the impact of the worldwide MDG campaign was most pronounced in this region in all respects. It is time to learn from the success stories of the sub-Saharan African countries. Erroneous and biased measurement should be avoided for the sustainable development goals to progress. PMID:28168932

Provision of bednets and water filters to delay HIV-1 progression: cost-effectiveness analysis of a Kenyan multisite study.

PubMed

Kern, Eli; Verguet, Stéphane; Yuhas, Krista; Odhiambo, Frederick H; Kahn, James G; Walson, Judd

2013-08-01

To estimate the effectiveness, costs and cost-effectiveness of providing long-lasting insecticide-treated nets (LLINs) and point-of-use water filters to antiretroviral therapy (ART)-naïve HIV-infected adults and their family members, in the context of a multisite study in Kenya of 589 HIV-positive adults followed on average for 1.7 years. The effectiveness, costs and cost-effectiveness of the intervention were estimated using an epidemiologic-cost model. Model epidemiologic inputs were derived from the Kenya multisite study data, local epidemiological data and from the published literature. Model cost inputs were derived from published literature specific to Kenya. Uncertainty in the model estimates was assessed through univariate and multivariate sensitivity analyses. We estimated net cost savings of about US$ 26 000 for the intervention, over 1.7 years. Even when ignoring net cost savings, the intervention was found to be very cost-effective at a cost of US$ 3100 per death averted or US$ 99 per disability-adjusted life year (DALY) averted. The findings were robust to the sensitivity analysis and remained most sensitive to both the duration of ART use and the cost of ART per person-year. The provision of LLINs and water filters to ART-naïve HIV-infected adults in the Kenyan study resulted in substantial net cost savings, due to the delay in the initiation of ART. The addition of an LLIN and a point-of-use water filter to the existing package of care provided to ART-naïve HIV-infected adults could bring substantial cost savings to resource-constrained health systems in low- and middle-income countries. © 2013 Blackwell Publishing Ltd.

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

DTIC Science & Technology

2013-12-01

carcinoma (CRC) in IBD patients and experimental models. Nonetheless, the pathogenic link, interrelationship, and practical clinical application of these...and are continuing final data analysis and latest imaging studies. This project has potentially high impact because of the substantial incidence of...pathogenic link, interrelationship, and practical clinical application of these various theories of progression have remained elusive. We proposed that

Early Rockets

NASA Image and Video Library

1940-03-21

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

Early Rockets

NASA Image and Video Library

2004-04-15

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

Stage IV-S neuroblastoma. Results with definitive therapy

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

Stokes, S.H.; Thomas, P.R.; Perez, C.A.

1984-05-15

The results of management of 14 patients with Stage IV-S neuroblastoma are reported. The treatment policy, although not consistent over this time span, in general used a combination of radiotherapy and chemotherapy or infrequently one modality alone. Twelve of 14 (86%) survived more than 6 years. One patient, with a solitary mediastinal primary tumor, died of rapidly progressive disease at three months. The other death occurred in a 4.5-year-old presenting with hepatomegaly at diagnosis followed by skeletal dissemination 2.5 years later. Thirteen of the patients were younger than 1 year of age. Of the 11 patients that received radiotherapy, 4more » experienced mild asymptomatic scoliosis or kyphoscoliosis at 3 to 12 years after initial therapy. A review of the literature indicates that spontaneous regression in this tumor is very frequent; therefore, it is recommended that for the common presentation of massive hepatomegaly in an infant, close observation is warranted, unless life threatening complications occur. However, initial therapeutic intervention may be indicated in those patients with life threatening presentations. This data did not substantiate the necessity for complete surgical excision of the primary tumor, as has been suggested by others.« less

The safety net medical home initiative: transforming care for vulnerable populations.

PubMed

Sugarman, Jonathan R; Phillips, Kathryn E; Wagner, Edward H; Coleman, Katie; Abrams, Melinda K

2014-11-01

Despite findings that medical homes may reduce or eliminate health care disparities among underserved and minority populations, most previous medical home pilot and demonstration projects have focused on health care delivery systems serving commercially insured patients and Medicare beneficiaries. To develop a replicable approach to support medical home transformation among diverse practices serving vulnerable and underserved populations. Facilitated by a national program team, convening organizations in 5 states provided coaching and learning community support to safety net practices over a 4-year period. To guide transformation, we developed a framework of change concepts aligned with supporting tools including implementation guides, activity checklists, and measurement instruments. Sixty-five health centers, homeless clinics, private practices, residency training centers, and other safety net practices in Colorado, Idaho, Massachusetts, Oregon, and Pennsylvania. We evaluated implementation of the change concepts using the Patient-Centered Medical Home-Assessment, and conducted a survey of participating practices to assess perceptions of the impact of the technical assistance. All practices implemented key features of the medical home model, and nearly half (47.6%) implemented the 33 identified key changes to a substantial degree as evidenced by level A Patient-Centered Medical Home-Assessment scores. Two thirds of practices that achieved substantial implementation did so only after participating in the initiative for >2 years. By the end of the initiative, 83.1% of sites achieved external recognition as medical homes. Despite resource constraints and high-need populations, safety net clinics made considerable progress toward medical home implementation when provided robust, multimodal support over a 4-year period.

Career Choices and Career Progression of Junior Doctors in Dermatology: Surveys of UK Medical Graduates

PubMed Central

Barat, Atena; Goldacre, Michael J.

2018-01-01

Objective To report UK-trained doctors' career choices for dermatology, career destinations, and factors influencing career pathways. Methods Multicohort multipurpose longitudinal surveys of UK-trained doctors who graduated between 1974 and 2015. Results In all, 40,412 doctors (58% of graduates) responded in year 1, 31,466 (64%) in year 3, and 24,970 (67%) in year 5. One year after graduation, 1.7% of women and 0.6% of men made dermatology their first choice but by five years after graduation the respective figures were 1.0% and 0.7%. Compared to their predecessors, its popularity fell more substantially from years 1 to 5 among recent graduates (2005–15), particularly for women (from 2.1% in year 1 to 0.8% in year 5) compared with a fall from 0.8% to 0.5% among men. The most important factor influencing dermatology choice was “hours/working conditions”: in year one, 69% regarded this as important compared with 31% of those choosing other hospital physician specialties. Only 18% of respondents who chose dermatology at year 1 eventually worked in it; however, almost all practising dermatologists (94%), 10 years after qualifying, had made their future career decision by year 5. Conclusion Dermatology is popular among female UK graduates. Most dermatologists made their career decision late but decisively. PMID:29785180

Clinical and Cost Implications of Universal Versus Locally Advanced-Stage and Advanced-Stage-Only Molecular Testing for Epidermal Growth Factor Receptor Mutations and Anaplastic Lymphoma Kinase Rearrangements in Non-Small Cell Lung Carcinoma: A Tertiary Academic Institution Experience.

PubMed

Sauter, Jennifer L; Butnor, Kelly J

2016-04-01

Although epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-directed therapies are not approved for patients with early-stage non-small cell lung carcinoma (NSCLC), many institutions perform EGFR and ALK testing for all patients with NSCLC at the time of initial diagnosis. Current consensus guidelines recommend EGFR testing and suggest ALK testing at the time of initial diagnosis for patients with advanced disease. To examine the cost and clinical impact of EGFR and ALK testing of patients with early-stage NSCLC. Records from all patients with a diagnosis of NSCLC made on a nonresection specimen at our institution during a single calendar year (2012) were reviewed, and a cost analysis was performed. Of 133 total patients, 47 (35%) had early-stage (stage I or II) disease and 86 (65%) had locally advanced (stage III) or advanced (stage IV) disease at presentation. Eight of 47 patients with early-stage disease (17%) had progression/recurrence during 18 to 30 months of follow-up, 6 of 8 (75%) of whom had pathologic confirmation of progression/recurrence. The estimated additional cost of EGFR and ALK testing for all newly diagnosed patients with NSCLC at our institution is $75,200 per year, compared to testing only patients with locally advanced and advanced-stage disease. The cost of universal molecular testing of NSCLC is substantial. EGFR and ALK testing of patients with early-stage disease appears to have negligible clinical impact, as most patients do not have disease recurrence/progression. Those whose disease recurs/progresses typically undergo rebiopsy. Our findings do not support the practice of universal EGFR and ALK testing in NSCLC at the time of initial diagnosis.

Counting the cost of negligence in neurosurgery: Lessons to be learned from 10 years of claims in the NHS.

PubMed

Hamdan, Alhafidz; Strachan, Roger D; Nath, Fredrick; Coulter, Ian C

2015-04-01

Despite substantial progress in modernising neurosurgery, the specialty still tops the list of medico-legal claims. Understanding the factors associated with negligence claims is vital if we are to identify areas of underperformance and subsequently improve patient safety. Here we provide data on trends in neurosurgical negligence claims over a 10-year period in England. We used data provided by the National Health Service Litigation Authority to analyse negligence claims related to neurosurgery from the financial years 2002/2003 to 2011/2012. Using the abstracts provided, we extracted information pertaining to the underlying pathology, injury severity, nature of misadventure and claim value. Over the 10-year period, the annual number of claims increased significantly. In total, there were 794 negligence claims (range 50-117/year); of the 613 closed cases, 405 (66.1%) were successful. The total cost related to claims during the 10 years was £65.7 million, with a mean claim per successful case of £0.16 million (total damages, defence and claimant costs of £45.1, £6.36 and £14.3 million, respectively). Claims related to emergency cases were more costly compared to those of elective cases (£209,327 vs. £112,627; P=0.002). Spinal cases represented the most frequently litigated procedures (350; 44.1% of total), inadequate surgical performance the most common misadventure (231; 29.1%) and fatality the commonest injury implicated in claims (102; 12.8%). Negligence claims related to wrong-site surgery and cauda equina syndrome were frequently successful (26/26; 100% and 14/16; 87.5% of closed cases, respectively). In England, the number of neurosurgical negligence claims is increasing, the financial cost substantial, and the burden significant. Lessons to be learned from the study are of paramount importance to reduce future cases of negligence and improve patient care.

Open Questions on the Global Contraction of Mercury

NASA Astrophysics Data System (ADS)

Klimczak, C.; Byrne, P. K.

2018-05-01

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

Effects of a classroom intervention with spatial play materials on children's object and viewer transformation abilities.

PubMed

Vander Heyden, Karin M; Huizinga, Mariette; Jolles, Jelle

2017-02-01

Children practice their spatial skills when playing with spatial toys, such as construction materials, board games, and puzzles. Sex and SES differences are observed in the engagement in such spatial play activities at home, which relate to individual differences in spatial performance. The current study investigated the effects of explicitly providing spatial play activities in the school setting on different types of spatial ability. We presented 8- to 10-year-old children with a short and easy-to-adopt classroom intervention comprising a set of different spatial play materials. The design involved a pretest-posttest comparison between the intervention group (n = 70) and a control group without intervention (n = 70). Effects were examined on object transformation ability (i.e., a paper-and-pencil mental rotation and paper folding task) and viewer transformation ability (i.e., a hands-on 3D spatial perspective-taking task). Results showed specific effects: there were no differences between the intervention and control group in progress on the two object transformation tasks. Substantial improvements were found for the intervention group compared to the control group on the viewer transformation task. Training progress was not related to sex and socioeconomic background of the child. These findings support the value of spatial play in the classroom for the spatial development of children between 8 and 10 years of age. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

NASA Astrophysics Data System (ADS)

Egbert, Gary D.; Ray, Richard D.

2013-09-01

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

Fifteen years of sector-wide approach (SWAp) in Bangladesh health sector: an assessment of progress.

PubMed

Ahsan, Karar Zunaid; Streatfield, Peter Kim; Ijdi, Rashida-E-; Escudero, Gabriela Maria; Khan, Abdul Waheed; Reza, M M

2016-06-01

The Ministry of Health and Family Welfare (MOHFW) of the Government of Bangladesh embarked on a sector-wide approach (SWAp) modality for the health, nutrition and population (HNP) sector in 1998. This programmatic shift initiated a different set of planning disciplines and practices along with institutional changes in the MOHFW. Over the years, the SWAp modality has evolved in Bangladesh as the MOHFW has learnt from its implementation and refined the program design. This article explores the progress made, both in terms of achievement of health outcomes and systems strengthening results, since the implementation of the SWAp for Bangladesh's health sector. Secondary analyses of survey data from 1993 to 2011 as well as a literature review of published and grey literature on health SWAp in Bangladesh was conducted for this assessment. Results of the assessment indicate that the MOHFW made substantial progress in health outcomes and health systems strengthening. SWAps facilitated the alignment of funding and technical support around national priorities, and improved the government's role in program design as well as in implementation and development partner coordination. Notable systemic improvements have taken place in the country systems with regards to monitoring and evaluation, procurement and service provision, which have improved functionality of health facilities to provide essential care. Implementation of the SWAp has, therefore, contributed to an accelerated improvement in key health outcomes in Bangladesh over the last 15 years. The health SWAp in Bangladesh offers an example of a successful adaptation of such an approach in a complex administrative structure. Based on the lessons learned from SWAp implementation in Bangladesh, the MOHFW needs to play a stronger stewardship and regulatory role to reap the full benefits of a SWAp in its subsequent programming. © The Author 2015. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

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

NASA Technical Reports Server (NTRS)

Egbert, Gary; Ray, Richard

2012-01-01

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

Presence of acute and chronic renal failure in patients with paroxysmal nocturnal hemoglobinuria: results of a retrospective analysis from the Spanish PNH Registry.

PubMed

Villegas, Ana; Núñez, Ramiro; Gaya, Anna; Cuevas-Ruiz, María Victoria; Bosch, José Miguel; Carral, Anna; Arrizabalaga, Beatriz; Gómez-Roncero, María Isabel; Mora, Asunción; Bravo, Pilar; Lavilla, Esperanza; Monteserín, Carmen; Hernández, Belén; Martínez-Barranco, Pilar; Jarque, Isidro; Urquía, María Anunciación; García-Donas, Gloria; Brunet, Salut; González, Fernando Ataulfo; Urbano, Álvaro

2017-10-01

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening blood disease. With the advent of eculizumab treatment, renal function has substantially improved, although no data from real-world clinical practice are available. An observational, retrospective, multicenter study was conducted in Spain on clinical data obtained from outpatient visits of patients with PNH (Spanish PNH Registry) who had experienced acute (ARF) or chronic (CRF) renal failure. Of the 128 patients registered (April 2014), 60 were diagnosed with classic PNH. Twenty-seven (45.0%) patients with a mean age of 48.5 (±16.2) years had renal failure, ARF or CRF, and were included in this study. Near half of the patients (n = 13; 48.1%) presented with ARF alone, 33.3% (n = 9) had CRF with episodes of ARF, while 18.5% (n = 5) were diagnosed with CRF alone. For patients with diagnosis of PNH and renal failure (n = 27), the median time to the first ARF episode was 6.5 (CI 95%; 2.2, 14.9) years, whereas the median to the diagnosis of CRF was 14.5 (CI 95%; 3.8, 19.2) years after the diagnosis of PNH. Patients with ARF (n = 22) were treated with eculizumab and did not experience new episodes of ARF, except for one patient with sepsis. Of the patients with CRF, two received treatment without experiencing further episodes of ARF. Sixteen patients who completed treatment (11 with ARF and 5 with ARF + CRF) recovered from the episode of ARF or from CRF. Of the remaining patients treated with eculizumab, one patient improved from stages III to II, three patients stabilized without showing disease progression, and one patient progressed from stages III to IV. Treatment with eculizumab in PNH patients has beneficial effects on renal function, preventing ARF and progression to CRF.

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

PubMed

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

2014-12-13

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

Dr. Robert H. Goddard and His Rocket

NASA Technical Reports Server (NTRS)

2004-01-01

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

Dr. Robert H. Goddard and His Rocket

NASA Technical Reports Server (NTRS)

1940-01-01

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

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

PubMed

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

2015-06-20

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

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

PubMed Central

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

2014-01-01

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

Stagnant neonatal mortality and persistent health inequality in middle-income countries: a case study of the Philippines.

PubMed

Kraft, Aleli D; Nguyen, Kim-Huong; Jimenez-Soto, Eliana; Hodge, Andrew

2013-01-01

The probability of survival through childhood continues to be unequal in middle-income countries. This study uses data from the Philippines to assess trends in the prevalence and distribution of child mortality and to evaluate the country's socioeconomic-related child health inequality. Using data from four Demographic and Health Surveys we estimated levels and trends of neonatal, infant, and under-five mortality from 1990 to 2007. Mortality estimates at national and subnational levels were produced using both direct and indirect methods. Concentration indices were computed to measure child health inequality by wealth status. Multivariate regression analyses were used to assess the contribution of interventions and socioeconomic factors to wealth-related inequality. Despite substantial reductions in national under-five and infant mortality rates in the early 1990s, the rates of declines have slowed in recent years and neonatal mortality rates remain stubbornly high. Substantial variations across urban-rural, regional, and wealth equity-markers are evident, and suggest that the gaps between the best and worst performing sub-populations will either be maintained or widen in the future. Of the variables tested, recent wealth-related inequalities are found to be strongly associated with social factors (e.g. maternal education), regional location, and access to health services, such as facility-based delivery. The Philippines has achieved substantial progress towards Millennium Development Goal 4, but this success masks substantial inequalities and stagnating neonatal mortality trends. This analysis supports a focus on health interventions of high quality--that is, not just facility-based delivery, but delivery by trained staff at well-functioning facilities and supported by a strong referral system--to re-start the long term decline in neonatal mortality and to reduce persistent within-country inequalities in child health.

[A comparison of characteristics of pathologic hobbies in schizophrenic patients of different age].

PubMed

Sergeev, I I; Deych, R V; Malinochka, S A

2016-01-01

To analyze age-related pathologic hobbies in patients with schizophrenia spectrum disorders. Forty-three inpatients, aged from 4 to 16 years, and 31 patients, aged from 18 to 65 years, were studied. Clinical/psychopathological analysis, psychological experiment and clinical statistics were used. Pathological hobbies substantially differed depending on the age (3-6, 7-15 and 18-65 years). In preschool age, hobbies were immature and infantile, arose autochthonously, their course was relatively stable and they had limited maladaptive effects. In junior school/teenager age, hobbies were more distinct and were associated with more diverse and mature realization patterns. Their origin was more depended on environmental factors, the course was persistent or attack-like with more pronounced and steady maladaptive effects. In some cases, there was a trend to pathological hobby progression. Abnormal hobbies in patients of mature age were the most diverse in their subjects and forms of realization as well as in their clinical variants and dynamic types. In the group of mature patients with schizophrenic spectrum disorders, there was a significantly higher percentage of psychotic forms of pathological hobbies.

Lung Transplantation for Cystic Fibrosis: Results, Indications, Complications, and Controversies

PubMed Central

Lynch, Joseph P.; Sayah, David M.; Belperio, John A.; Weigt, S. Sam

2016-01-01

Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (~50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. PMID:25826595

Cost of chronic hepatitis B infection in South Korea.

PubMed

Yang, Bong-Min; Kim, Cheol-Hwan; Kim, Ji-Yun

2004-01-01

To estimate the direct medical costs of chronic hepatitis B (CHB) infection and its liver disease sequelae in South Korea. Korea is a hepatitis B-endemic area with 5.79% to 10.87% of males and 1.51% to 4.44% of females over 20 years of age carrying the virus. It is estimated that 25% of carriers will develop serious hepatitis B virus (HBV)-related complications. While vaccination programs have reduced the prevalence of hepatitis B in people younger than 20 years, significant CHB-related morbidity will continue to occur for the next 15 to 30 years until the benefits of the vaccination programs take effect. Direct medical costs for six CHB-related disease states, including hepatocellular carcinoma and liver transplant, were estimated for the year 2001. Four data sources were used to gather information: the National Health Insurance Corporation database, patients' medical charts, expert opinion, and patient survey data. In 2001, the total medical costs of six CHB-related diseases were 250 million Korean Won (KRW) (equivalent to U.S. 208.6 million dollars), based on an exchange rate of KRW 1200 = US 1 dollar. Annual treatment costs per patient ranged from KRW297,392 (US 248 dollars) for chronic hepatitis B to KRW 80.6 million (U.S. 67,156 dollars) for liver transplant. The cost of treatment rose continuously with liver disease progression. The main cost driver was inpatient hospitalizations (including surgical costs). CHB-related diseases are a significant cost burden to the South Korean healthcare system. In addition to the obvious clinical benefits, the prevention or delay of chronic hepatitis B liver disease progression in South Korea could result in substantial economic benefits to the whole society.

3D Maps from Multiple MRI Illustrate Changing Atrophy Patterns as Subjects Progress from MCI to AD

PubMed Central

Whitwell, Jennifer L; Przybelski, Scott; Weigand, Stephen D; Knopman, David S; Boeve, Bradley F; Petersen, Ronald C; Jack, Clifford R

2009-01-01

Summary Mild cognitive impairment (MCI), particularly the amnestic subtype (aMCI), is considered as a transitional stage between normal aging and a diagnosis of clinically probable Alzheimer's disease (AD). The aMCI construct is particularly useful as it provides an opportunity to assess a clinical stage which in most subjects represents prodromal AD. The aim of this study was to assess the progression of cerebral atrophy over multiple serial MRI during the period from aMCI to conversion to AD. Thirty-three subjects were selected that fulfilled clinical criteria for aMCI and had three serial MRI scans: the first scan approximately three years before conversion to AD, the second scan approximately one year before conversion, and the third scan at the time of conversion from aMCI to AD. A group of 33 healthy controls were age and gender-matched to the study cohort. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aMCI subjects at each time-point compared to the control group. Customized templates and prior probability maps were used to avoid normalization and segmentation bias. The pattern of grey matter loss in the aMCI subject scans that were three years before conversion was focused primarily on the medial temporal lobes, including the amygdala, anterior hippocampus and entorhinal cortex, with some additional involvement of the fusiform gyrus, compared to controls. The extent and magnitude of the cerebral atrophy further progressed by the time the subjects were one year before conversion. At this point atrophy in the temporal lobes spread to include the middle temporal gyrus, and extended into more posterior regions of the temporal lobe to include the entire extent of the hippocampus. The parietal lobe also started to become involved. By the time the subjects had converted to a clinical diagnosis of AD the pattern of grey matter atrophy had become still more widespread with more severe involvement of the medial temporal lobes and the temporoparietal association cortices and, for the first time, substantial involvement of the frontal lobes. This pattern of progression fits well with the Braak and Braak neurofibrillary pathological staging scheme in AD. It suggests that the earliest changes occur in the anterior medial temporal lobe and fusiform gyrus, and that these changes occur at least three years before conversion to AD. These results also suggest that 3-dimensional patterns of grey matter atrophy may help to predict the time to conversion in subjects with aMCI. PMID:17533169

Progress Toward Polio Eradication - Worldwide, January 2016-March 2018.

PubMed

Khan, Farrah; Datta, S Deblina; Quddus, Arshad; Vertefeuille, John F; Burns, Cara C; Jorba, Jaume; Wassilak, Steven G F

2018-05-11

In 1988, when an estimated 350,000 cases of poliomyelitis occurred in 125 countries, the World Health Assembly resolved to eradicate polio globally. Transmission of wild poliovirus (WPV) continues uninterrupted in only three countries (Afghanistan, Nigeria, and Pakistan) (1), and among the three serotypes, WPV type 1 (WPV1) remains the only confirmed circulating type. This report describes global progress toward polio eradication during January 2016-March 2018, and updates previous reports (2). In 2017, 22 WPV1 cases were reported, a 41% decrease from the 37 WPV1 cases reported in 2016. As of April 24, 2018, eight WPV1 cases have been reported (seven in Afghanistan and one in Pakistan), compared with five cases during the same period in 2017. In Pakistan, continuing WPV1 transmission has been confirmed in multiple areas in 2018 by isolation from wastewater samples. In Nigeria, ongoing endemic WPV1 transmission was confirmed in 2016 (3); although WPV was not detected in 2017 or in 2018 to date, limitations in access for vaccination and surveillance in insurgent-held areas in northeastern Nigeria might permit continued undetected poliovirus transmission. Substantial progress toward polio eradication has continued in recent years; however, interruption of WPV transmission will require overcoming remaining challenges to reaching and vaccinating every missed child. Until poliovirus eradication is achieved, all countries must remain vigilant by maintaining high population immunity and sensitive poliovirus surveillance.

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

PubMed Central

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

2016-01-01

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

Sequential Progressions in a Theory of Mind Scale: Longitudinal Perspectives

PubMed Central

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

2011-01-01

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

A new look at the decomposition of agricultural productivity growth incorporating weather effects.

PubMed

Njuki, Eric; Bravo-Ureta, Boris E; O'Donnell, Christopher J

2018-01-01

Random fluctuations in temperature and precipitation have substantial impacts on agricultural output. However, the contribution of these changing configurations in weather to total factor productivity (TFP) growth has not been addressed explicitly in econometric analyses. Thus, the key objective of this study is to quantify and to investigate the role of changing weather patterns in explaining yearly fluctuations in TFP. For this purpose, we define TFP to be a measure of total output divided by a measure of total input. We estimate a stochastic production frontier model using U.S. state-level agricultural data incorporating growing season temperature and precipitation, and intra-annual standard deviations of temperature and precipitation for the period 1960-2004. We use the estimated parameters of the model to compute a TFP index that has good axiomatic properties. We then decompose TFP growth in each state into weather effects, technological progress, technical efficiency, and scale-mix efficiency changes. This approach improves our understanding of the role of different components of TFP in agricultural productivity growth. We find that annual TFP growth averaged 1.56% between 1960 and 2004. Moreover, we observe substantial heterogeneity in weather effects across states and over time.

A new look at the decomposition of agricultural productivity growth incorporating weather effects

PubMed Central

Bravo-Ureta, Boris E.; O’Donnell, Christopher J.

2018-01-01

Random fluctuations in temperature and precipitation have substantial impacts on agricultural output. However, the contribution of these changing configurations in weather to total factor productivity (TFP) growth has not been addressed explicitly in econometric analyses. Thus, the key objective of this study is to quantify and to investigate the role of changing weather patterns in explaining yearly fluctuations in TFP. For this purpose, we define TFP to be a measure of total output divided by a measure of total input. We estimate a stochastic production frontier model using U.S. state-level agricultural data incorporating growing season temperature and precipitation, and intra-annual standard deviations of temperature and precipitation for the period 1960–2004. We use the estimated parameters of the model to compute a TFP index that has good axiomatic properties. We then decompose TFP growth in each state into weather effects, technological progress, technical efficiency, and scale-mix efficiency changes. This approach improves our understanding of the role of different components of TFP in agricultural productivity growth. We find that annual TFP growth averaged 1.56% between 1960 and 2004. Moreover, we observe substantial heterogeneity in weather effects across states and over time. PMID:29466461

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

EPA Pesticide Factsheets

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

Career intentions and choices of paediatricians entering training in the UK.

PubMed

Shortland, David; Roland, Damian; Lumsden, Daniel Edward; Ewing, Carol; L'Esperance, Veline; McColgan, Martin; Winch, Rachel; Mahmood, Shazia

2015-06-01

The paediatric workforce has grown substantially in recent years. Roles have changed considerably with the introduction of working time legislation and a move towards a trained doctor solution. By gaining a better understanding of paediatric trainees' career intentions, this study aims to assess whether the right workforce is being trained to meet the future demand for paediatric services in the UK. A survey was sent to paediatric specialist trainees, when they were expected to have completed their 1st year of Specialty Training or Fixed Term Specialty Training Appointments, in 2009 (part 1). A second survey was sent to the same cohort when they were expected to have completed their 3rd year in 2011 (part 2). In part 1 of the survey, the response rate was 79.1%. In part 2 the response rate was 80.5%. Of those who had responded to part 1, 87.4% also responded to part 2. The attrition rate of trainees leaving the paediatric training scheme between the 1st year and 3rd year of training was 15%. Of those still training in paediatrics after the 3rd year, 38.7% intended to be subspecialty paediatricians, 25.7% general paediatricians, 5.4% community paediatricians and 3.5% academic paediatricians. 26% were undecided and 0.6% did not intend to follow a career in paediatrics at all. The proportion of trainees who were undecided about their career intentions had risen substantially from 7.7% after the 1st year. There was a decrease in trainees' confidence in obtaining a consultant post between the 1st year and the 3rd year. Workforce planning is a complex task and this study shows that trainees will change their career plans while progressing through their run-through programmes. A better understanding of these factors will enable the Royal College of Paediatrics and Chld Health to deliver the right workforce for the UK. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Predicting long-term carbon sequestration in response to CO 2 enrichment: How and why do current ecosystem models differ?

DOE PAGES

Walker, Anthony P.; Zaehle, Sönke; Medlyn, Belinda E.; ...

2015-04-27

Large uncertainty exists in model projections of the land carbon (C) sink response to increasing atmospheric CO 2. Free-Air CO 2 Enrichment (FACE) experiments lasting a decade or more have investigated ecosystem responses to a step change in atmospheric CO 2 concentration. To interpret FACE results in the context of gradual increases in atmospheric CO 2 over decades to centuries, we used a suite of seven models to simulate the Duke and Oak Ridge FACE experiments extended for 300 years of CO 2 enrichment. We also determine key modeling assumptions that drive divergent projections of terrestrial C uptake and evaluatemore » whether these assumptions can be constrained by experimental evidence. All models simulated increased terrestrial C pools resulting from CO 2 enrichment, though there was substantial variability in quasi-equilibrium C sequestration and rates of change. In two of two models that assume that plant nitrogen (N) uptake is solely a function of soil N supply, the net primary production response to elevated CO 2 became progressively N limited. In four of five models that assume that N uptake is a function of both soil N supply and plant N demand, elevated CO 2 led to reduced ecosystem N losses and thus progressively relaxed nitrogen limitation. Many allocation assumptions resulted in increased wood allocation relative to leaves and roots which reduced the vegetation turnover rate and increased C sequestration. Additionally, self-thinning assumptions had a substantial impact on C sequestration in two models. As a result, accurate representation of N process dynamics (in particular N uptake), allocation, and forest self-thinning is key to minimizing uncertainty in projections of future C sequestration in response to elevated atmospheric CO 2.« less

Progressing beyond SLMTA: Are internal audits and corrective action the key drivers of quality improvement?

PubMed

Maina, Robert N; Mengo, Doris M; Mohamud, Abdikher D; Ochieng, Susan M; Milgo, Sammy K; Sexton, Connie J; Moyo, Sikhulile; Luman, Elizabeth T

2014-01-01

Kenya has implemented the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme to facilitate quality improvement in medical laboratories and to support national accreditation goals. Continuous quality improvement after SLMTA completion is needed to ensure sustainability and continue progress toward accreditation. Audits were conducted by qualified, independent auditors to assess the performance of five enrolled laboratories using the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist. End-of-programme (exit) and one year post-programme (surveillance) audits were compared for overall score, star level (from zero to five, based on scores) and scores for each of the 12 Quality System Essential (QSE) areas that make up the SLIPTA checklist. All laboratories improved from exit to surveillance audit (median improvement 38 percentage points, range 5-45 percentage points). Two laboratories improved from zero to one star, two improved from zero to three stars and one laboratory improved from three to four stars. The lowest median QSE scores at exit were: internal audit; corrective action; and occurrence management and process improvement (< 20%). Each of the 12 QSEs improved substantially at surveillance audit, with the greatest improvement in client management and customer service, internal audit and information management (≥ 50 percentage points). The two laboratories with the greatest overall improvement focused heavily on the internal audit and corrective action QSEs. Whilst all laboratories improved from exit to surveillance audit, those that focused on the internal audit and corrective action QSEs improved substantially more than those that did not; internal audits and corrective actions may have acted as catalysts, leading to improvements in other QSEs. Systematic identification of core areas and best practices to address them is a critical step toward strengthening public medical laboratories.

The burden of migraine in the United States: current and emerging perspectives on disease management and economic analysis.

PubMed

Hazard, Elisabeth; Munakata, Julie; Bigal, Marcelo E; Rupnow, Marcia F T; Lipton, Richard B

2009-01-01

Migraine is often perceived as a low-impact condition that imposes a limited burden to society and the health-care system. This study reviews the current understanding of the burden of migraine in the U.S., the history of economic understanding of migraine treatment and identifies emergent trends for future studies evaluating clinical and economic outcomes of migraine treatment. This study traced the history of economic articles published on migraine by performing a literature search using PubMed MEDLINE database and ancestral searches of relevant articles. The intention was not to provide an exhaustive review of every article or adjudicate between studies with different findings. Migraine affects millions of individuals worldwide, generally during the most productive years of a person's life. Studies show that migraineurs are underdiagnosed, undertreated, and experience substantial decreases in functioning and productivity, which in turn translates into diminished quality of life for individuals, and financial burdens to both health-care systems and employers. Economic evaluations of migraine therapies have evolved with new clinical developments beginning with cognitive-behavioral therapy, introduction of triptans, concern over medication overuse, and emergence of migraine prophylaxis. Now recent clinical studies suggest that migraine may be a progressive disease with cardiovascular, cerebrovascular, and long-term neurologic effects. Migraine imposes a substantial burden on patients, families, employers and societies. The economic standards by which migraine and treatment are evaluated have evolved in response to clinical developments. Emerging evidence suggests that migraine is a chronic and progressive disease. If confirmed, approaches to acute and prophylactic treatments and economic evaluations of migraine treatment may require major reconsideration.

Progressing beyond SLMTA: Are internal audits and corrective action the key drivers of quality improvement?

PubMed Central

Mengo, Doris M.; Mohamud, Abdikher D.; Ochieng, Susan M.; Milgo, Sammy K.; Sexton, Connie J.; Moyo, Sikhulile; Luman, Elizabeth T.

2014-01-01

Background Kenya has implemented the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme to facilitate quality improvement in medical laboratories and to support national accreditation goals. Continuous quality improvement after SLMTA completion is needed to ensure sustainability and continue progress toward accreditation. Methods Audits were conducted by qualified, independent auditors to assess the performance of five enrolled laboratories using the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist. End-of-programme (exit) and one year post-programme (surveillance) audits were compared for overall score, star level (from zero to five, based on scores) and scores for each of the 12 Quality System Essential (QSE) areas that make up the SLIPTA checklist. Results All laboratories improved from exit to surveillance audit (median improvement 38 percentage points, range 5–45 percentage points). Two laboratories improved from zero to one star, two improved from zero to three stars and one laboratory improved from three to four stars. The lowest median QSE scores at exit were: internal audit; corrective action; and occurrence management and process improvement (< 20%). Each of the 12 QSEs improved substantially at surveillance audit, with the greatest improvement in client management and customer service, internal audit and information management (≥ 50 percentage points). The two laboratories with the greatest overall improvement focused heavily on the internal audit and corrective action QSEs. Conclusion Whilst all laboratories improved from exit to surveillance audit, those that focused on the internal audit and corrective action QSEs improved substantially more than those that did not; internal audits and corrective actions may have acted as catalysts, leading to improvements in other QSEs. Systematic identification of core areas and best practices to address them is a critical step toward strengthening public medical laboratories. PMID:29043193

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

PubMed

Schluger, Neil W; Koppaka, Ram

2014-03-01

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

Microbiomes of Site-Specific Dental Plaques from Children with Different Caries Status.

PubMed

Richards, Vincent P; Alvarez, Andres J; Luce, Amy R; Bedenbaugh, Molly; Mitchell, Mary Lyn; Burne, Robert A; Nascimento, Marcelle M

2017-08-01

The oral microbiota associated with the initiation and progression of dental caries has yet to be fully characterized. The Human Oral Microbe Identification Using Next-Generation Sequencing (HOMI NGS ) approach was used to analyze the microbiomes of site-specific supragingival dental plaques from children with different caries status. Fifty-five children (2 to 7 years of age) were assessed at baseline and at 12 months and grouped as caries free (CF), caries active with enamel lesions (CAE), and caries active with dentin carious lesions (CA). Plaque samples from caries-free tooth surfaces (PF) and from enamel carious lesions (PE) and dentin carious lesions (PD) were collected. 16S community profiles were obtained by HOMI NGS , and 408 bacterial species and 84 genus probes were assigned. Plaque bacterial communities showed temporal stability, as there was no significant difference in beta diversity values between the baseline and 12-month samples. Irrespective of collection time points, the microbiomes of healthy tooth surfaces differed substantially from those found during caries activity. All pairwise comparisons of beta diversity values between groups were significantly different ( P < 0.05), except for comparisons between the CA-PF, CAE-PE, and CA-PE groups. Streptococcus genus probe 4 and Neisseria genus probe 2 were the most frequently detected taxa across the plaque groups, followed by Streptococcus sanguinis , which was highly abundant in CF-PF. Well-known acidogenic/aciduric species such as Streptococcus mutans , Scardovia wiggsiae , Parascardovia denticolens , and Lactobacillus salivarius were found almost exclusively in CA-PD. The microbiomes of supragingival dental plaque differ substantially among tooth surfaces and children of different caries activities. In support of the ecological nature of caries etiology, a steady transition in community species composition was observed with disease progression. Copyright © 2017 American Society for Microbiology.

Microbiomes of Site-Specific Dental Plaques from Children with Different Caries Status

PubMed Central

Alvarez, Andres J.; Luce, Amy R.; Bedenbaugh, Molly; Mitchell, Mary Lyn

2017-01-01

ABSTRACT The oral microbiota associated with the initiation and progression of dental caries has yet to be fully characterized. The Human Oral Microbe Identification Using Next-Generation Sequencing (HOMINGS) approach was used to analyze the microbiomes of site-specific supragingival dental plaques from children with different caries status. Fifty-five children (2 to 7 years of age) were assessed at baseline and at 12 months and grouped as caries free (CF), caries active with enamel lesions (CAE), and caries active with dentin carious lesions (CA). Plaque samples from caries-free tooth surfaces (PF) and from enamel carious lesions (PE) and dentin carious lesions (PD) were collected. 16S community profiles were obtained by HOMINGS, and 408 bacterial species and 84 genus probes were assigned. Plaque bacterial communities showed temporal stability, as there was no significant difference in beta diversity values between the baseline and 12-month samples. Irrespective of collection time points, the microbiomes of healthy tooth surfaces differed substantially from those found during caries activity. All pairwise comparisons of beta diversity values between groups were significantly different (P < 0.05), except for comparisons between the CA-PF, CAE-PE, and CA-PE groups. Streptococcus genus probe 4 and Neisseria genus probe 2 were the most frequently detected taxa across the plaque groups, followed by Streptococcus sanguinis, which was highly abundant in CF-PF. Well-known acidogenic/aciduric species such as Streptococcus mutans, Scardovia wiggsiae, Parascardovia denticolens, and Lactobacillus salivarius were found almost exclusively in CA-PD. The microbiomes of supragingival dental plaque differ substantially among tooth surfaces and children of different caries activities. In support of the ecological nature of caries etiology, a steady transition in community species composition was observed with disease progression. PMID:28507066

Nematicons and Their Electro-Optic Control: Light Localization and Signal Readdressing via Reorientation in Liquid Crystals

PubMed Central

Piccardi, Armando; Alberucci, Alessandro; Assanto, Gaetano

2013-01-01

Liquid crystals in the nematic phase exhibit substantial reorientation when the molecules are driven by electric fields of any frequencies. Exploiting such a response at optical frequencies, self-focusing supports transverse localization of light and the propagation of self-confined beams and waveguides, namely “nematicons”. Nematicons can guide other light signals and interact with inhomogeneities and other beams. Moreover, they can be effectively deviated by using the electro-optic response of the medium, leading to several strategies for voltage-controlled reconfiguration of light-induced guided-wave circuits and signal readdressing. Hereby, we outline the main features of nematicons and review the outstanding progress achieved in the last twelve years on beam self-trapping and electro-optic readdressing. PMID:24108367

Rocky coast processes: with special reference to the recession of soft rock cliffs.

PubMed

Sunamura, Tsuguo

2015-01-01

Substantial progress in research on the recession of coastal cliffs composed of soft materials has been made in recent years and data with higher accuracy have been accumulated. This paper provides the state of the art review in the recession studies and highlights two new findings obtained from the reanalysis of existing data. The review topics are: episodic and localized nature of cliff recession; the development of cliffline; the relationship between cliff height and recession rate; mechanisms of cliff toe erosion by waves; a fundamental equation for wave-induced toe erosion; factors controlling toe erosion; and slope instabilities and mass movements. The findings are presented on (1) the temporal change in cliffline recession mode and (2) the effect of beach sediment at the cliff base on the cliff erosion.

Observations of Pronounced Greenland Ice Sheet Firn Warming and Implications for Runoff Production

NASA Technical Reports Server (NTRS)

Polashenski, Chris; Courville, Zoe; Benson, Carl; Wagner, Anna; Chen, Justin; Wong, Gifford; Hawley, Robert; Hall, Dorothy

2014-01-01

Field measurements of shallow borehole temperatures in firn across the northern Greenland ice sheet are collected during May 2013. Sites first measured in 19521955 are revisited, showing long-term trends in firn temperature. Results indicate a pattern of substantial firn warming (up to +5.7C) at midlevel elevations (1400-2500 m) and little temperature change at high elevations (2500 m). We find that latent heat transport into the firn due to meltwater percolation drives the observed warming. Modeling shows that heat is stored at depth for several years, and energy delivered from consecutive melt events accumulates in the firn. The observed warming is likely not yet in equilibrium with recent melt production rates but captures the progression of sites in the percolation facies toward net runoff production.

MOTIVATING ACTION AND MAINTAINING CHANGE: THE TIME-VARYING ROLE OF HOMEWORK FOLLOWING A BRIEF COUPLES INTERVENTION

PubMed Central

Hawrilenko, Matt; Fleming, CJ Eubanks; Goldstein, Alana; Cordova, James V.

2015-01-01

Studies regarding the effectiveness of homework assignments in cognitive-behavioral treatments have demonstrated mixed results. This study investigated predictors of compliance with homework recommendations and the time-varying relationship of recommendation completion with treatment response in a brief couples intervention (N=108). More satisfied couples and couples with more motivation to change completed more recommendations, whereas couples with children completed fewer. The association between recommendation completion and treatment response varied with the passage of time, with the strongest effect observed six-months after the intervention, but no discernible differences at one year post-intervention. Couples that completed more recommendations experienced more rapid treatment gains, but even those couples doing substantially fewer recommendations ultimately realized equivalent treatment effects, although they progressed more slowly. Implications are discussed. PMID:26456167

Peroxisome-mitochondria interplay and disease.

PubMed

Schrader, Michael; Costello, Joseph; Godinho, Luis F; Islinger, Markus

2015-07-01

Peroxisomes and mitochondria are ubiquitous, highly dynamic organelles with an oxidative type of metabolism in eukaryotic cells. Over the years, substantial evidence has been provided that peroxisomes and mitochondria exhibit a close functional interplay which impacts on human health and development. The so-called "peroxisome-mitochondria connection" includes metabolic cooperation in the degradation of fatty acids, a redox-sensitive relationship, an overlap in key components of the membrane fission machineries and cooperation in anti-viral signalling and defence. Furthermore, combined peroxisome-mitochondria disorders with defects in organelle division have been revealed. In this review, we present the latest progress in the emerging field of peroxisomal and mitochondrial interplay in mammals with a particular emphasis on cooperative fatty acid β-oxidation, redox interplay, organelle dynamics, cooperation in anti-viral signalling and the resulting implications for disease.

Recent advances in kidney transplantation: a viewpoint from the Descartes advisory board.

PubMed

Abramowicz, Daniel; Oberbauer, Rainer; Heemann, Uwe; Viklicky, Ondrej; Peruzzi, Licia; Mariat, Christophe; Crespo, Marta; Budde, Klemens; Oniscu, Gabriel C

2018-01-12

Transplantation medicine is a rapidly evolving field. Keeping afloat of the published literature to offer the best clinical care to our patients is a daunting task. As part of its educational mission, the Descartes advisory board identified seven topics in kidney transplantation where there has been substantial progresses over the last years: kidney allocation within Eurotransplant; kidney exchange strategies; kidney machine perfusion strategies; the changing landscape of anti-human leukocyte antigen (HLA) antibodies; the new immunosuppressive drugs in the pipeline; strategies for immunosuppression minimization; and the continuous enigma of focal segmental glomerular sclerosis recurrence after transplantation. Here, we have summarized the main knowledge and the main challenges of these seven topics with the aim to provide transplant professionals at large with key bullet points to successfully understand these new concepts.

Genome Editing and Its Applications in Model Organisms.

PubMed

Ma, Dongyuan; Liu, Feng

2015-12-01

Technological advances are important for innovative biological research. Development of molecular tools for DNA manipulation, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly-interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas), has revolutionized genome editing. These approaches can be used to develop potential therapeutic strategies to effectively treat heritable diseases. In the last few years, substantial progress has been made in CRISPR/Cas technology, including technical improvements and wide application in many model systems. This review describes recent advancements in genome editing with a particular focus on CRISPR/Cas, covering the underlying principles, technological optimization, and its application in zebrafish and other model organisms, disease modeling, and gene therapy used for personalized medicine. Copyright © 2016 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

Paradoxical topiramate-induced hyperphagia successfully treated with phentermine in a woman with migraine.

PubMed

Johnson, Jacinta L; Rolan, Paul E

2015-08-01

We report a 49-year-old female migraineur who experienced paradoxical hyperphagia and concurrent intrusive food thoughts leading to rapid weight gain and a substantial increase in waist circumference. A significant reduction in migraine frequency was also observed during topiramate treatment, a widely used migraine prophylactic agent which is generally associated with weight loss. Withdrawal of topiramate saw appetite return to baseline levels, however, migraine frequency was again increased. Topiramate was reinitiated in combination with phentermine, a drug indicated for weight management, without reoccurrence of adverse effects. Migraine control was maintained and progressive weight loss ensued. Combination treatment with phentermine may be a useful strategy should other patients experience this adverse reaction while gaining therapeutic anti-migraine benefit from topiramate. Copyright © 2015 Elsevier Ltd. All rights reserved.

A semiconductor photon-sorter

NASA Astrophysics Data System (ADS)

Bennett, A. J.; Lee, J. P.; Ellis, D. J. P.; Farrer, I.; Ritchie, D. A.; Shields, A. J.

2016-10-01

Obtaining substantial nonlinear effects at the single-photon level is a considerable challenge that holds great potential for quantum optical measurements and information processing. Of the progress that has been made in recent years one of the most promising methods is to scatter coherent light from quantum emitters, imprinting quantum correlations onto the photons. We report effective interactions between photons, controlled by a single semiconductor quantum dot that is weakly coupled to a monolithic cavity. We show that the nonlinearity of a transition modifies the counting statistics of a Poissonian beam, sorting the photons in number. This is used to create strong correlations between detection events and to create polarization-correlated photons from an uncorrelated stream using a single spin. These results pave the way for semiconductor optical switches operated by single quanta of light.

[Management of localized, locally advanced and metastatic pancreatic adenocarcinoma].

PubMed

Delpero, Jean-Robert; Turrini, Olivier; Raoul, Jean-Luc

2015-03-01

Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy. The prognosis is extremely poor because PDAC is usually a systemic disease at diagnosis. All stages, the survival does not exceed 5% at 5 years. However 15% of PDAC can be resected and today a margin-negative resection followed by adjuvant chemotherapy remains the only potential for a prolonged survival. Postoperative mortality had significantly decreased and the benefit of postoperative adjuvant chemotherapy has been clearly shown. Substantial progress has been made in the field of palliative chemotherapy by introducing new chemotherapy regimens (FOLFIRINOX [folinic acid, 5-fluorouracil, irinotecan and oxaliplatin] and gemcitabine/nab-paclitaxel), when the patient's performance status allows the use of these drugs. The role of radiation therapy remains controversial.

Intraoperative neural monitoring in thyroid surgery: lessons learned from animal studies

PubMed Central

Randolph, Gregory W.; Lu, I-Cheng; Chang, Pi-Ying; Chen, Yi-Ting; Hun, Pao-Chu; Lin, Yi-Chu; Dionigi, Gianlorenzo; Chiang, Feng-Yu

2016-01-01

Recurrent laryngeal nerve (RLN) injury remains a significant morbidity associated with thyroid and parathyroid surgery. In the past decade, surgeons have increasingly used intraoperative neural monitoring (IONM) as an adjunct technique for localizing and identifying the RLN, detecting RLN injury, and predicting the outcome of vocal cord function. In recent years, many animal studies have investigated common pitfalls and new applications of IONM. For example, the use of IONM technology in animal models has proven valuable in studies of the electrophysiology of RLN injury. The advent of animal studies has substantially improved understanding of IONM technology. Lessons learned from animal studies have immediate clinical applications in establishing reliable strategies for preventing intraoperative RLN injury. This article gives an overview of the research progress on IONM-relevant animal models. PMID:27867861

Generalized social anxiety disorder: A still-neglected anxiety disorder 3 decades since Liebowitz's review.

PubMed

Nagata, Toshihiko; Suzuki, Futoshi; Teo, Alan R

2015-12-01

In the 3 decades since Liebowitz's review of 'a neglected anxiety disorder,' controversy and challenges have remained in the study of social anxiety disorder (SAD). This review examines evidence around the classification and subtyping of SAD, focusing on generalized SAD. Substantial discrepancies and variation in definition, epidemiology, assessment, and treatment of generalized SAD exist as the international literature on it has grown. In East Asian cultures in particular, study of taijin kyofusho has been important to a broadened conceptualization of SAD into generalized SAD. Despite important progress with biological and other studies, many challenges in the understanding of generalized SAD will remain in the years to come. © 2015 The Authors. Psychiatry and Clinical Neurosciences © 2015 Japanese Society of Psychiatry and Neurology.

Antibody engineering and therapeutics conference. The annual meeting of the antibody society, Huntington Beach, CA, December 7-11, 2014.

PubMed

Larrick, James W; Parren, Paul W H I; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A; Burton, Dennis R; Adams, Gregory P; Weiner, Louis M; Scott, Jamie K; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M

2014-01-01

The 25th anniversary of the Antibody Engineering & Therapeutics Conference, the Annual Meeting of The Antibody Society, will be held in Huntington Beach, CA, December 7-11, 2014. Organized by IBC Life Sciences, the event will celebrate past successes, educate participants on current activities and offer a vision of future progress in the field. Keynote addresses will be given by academic and industry experts Douglas Lauffenburger (Massachusetts Institute of Technology), Ira Pastan (National Cancer Institute), James Wells (University of California, San Francisco), Ian Tomlinson (GlaxoSmithKline) and Anthony Rees (Rees Consulting AB and Emeritus Professor, University of Bath). These speakers will provide updates of their work, placed in the context of the substantial growth of the industry over the past 25 years.

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

PubMed

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

1999-01-01

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

Economic burden of osteoporosis in women: data from the 2008 French hospital database (PMSI).

PubMed

Maravic, Milka; Jouaneton, Baptiste; Vainchtock, Alexandre; Tochon, Valerie

2012-01-01

To estimate the number and costs of hospitalisations associated with osteoporosis in France. Data for women aged 50 years and over were extracted from the 2008 French Hospital National Database. Criteria for acute care were established according to ICD-10 codes related to osteoporosis. As coding rules are not systematically used, an additional extraction which included surgical stays for hip fractures was performed in order to be more exhaustive. The two datasets were merged and duplicate stays excluded. Among women hospitalised in acute care during 2008, we selected those progressing to rehabilitation care within the year. We assessed the numbers of hospitalisations and women, proportion of surgical management, length of stay in acute care and numbers of rehabilitation days and costs. Hospital costs were calculated according to the National Hospital Tariff and National Scale of Costs, respectively, for acute and rehabilitation care based on 2009 tariffs. There were 67.807 hospitalisations (64.793 patients) associated with osteoporosis; 83% of total hospitalisations were in patients aged ≥75 years. A total of 80% of hospitalisations were associated with surgical management of fractures and 31.458 patients (49%) progressed from hospitalisation to rehabilitation. The mean ±SD length of stay was 12±8 days for hospitalisation and 43±31 days for rehabilitation care. The overall cost of hospitalisations was €415.4 million, of which 4.2% was related to medical devices. The overall cost of rehabilitation was €331.8 million. In 2008, postmenopausal osteoporosis was associated with a substantial economic burden at hospital in France.

Student and faculty perceptions of problem-based learning on a family medicine clerkship.

PubMed

McGrew, M C; Skipper, B; Palley, T; Kaufman, A

1999-03-01

The value of problem-based learning (PBL) in the preclinical years of medical school has been described widely in the literature. This study evaluates student and faculty perceptions of PBL during the clinical years of medical school, on a family medicine clerkship. Students used a 4-point scale to rate clerkship educational components on how well learning was facilitated. Faculty narratives of their perceptions of PBL were reviewed. Educational components that involved active learning by students--clinical activity, independent learning, and PBL tutorials--were ranked highest by students. Faculty perceived that PBL on the clerkship simulated "real-life" learning, included more behavioral and population issues, and provided substantial blocks of student contact time for improved student evaluation. Students and faculty in a family medicine clerkship ranked PBL sessions higher than any other nonclinical component of the clerkship. In addition to providing students with opportunities for self-directed learning, the PBL sessions provide faculty with more contact time with students, thereby enhancing the assessment of students' learning and progress.

Progress and plans of a remote sensing program for the International Field Year for the Great Lakes (IFYGL)

NASA Technical Reports Server (NTRS)

Polcyn, F. C.; Wagner, T. W. (Principal Investigator)

1972-01-01

The author has identified the following significant results. ERTS-1 coverage of the 32,000 square mile Lake Ontario Basin is being used to study short term and seasonal changes which affect many aspects of water problems in the Great Lakes. As part of the International Field Year for the Great Lakes (IFYGL), a coordinated, synoptic study of the Lake Ontario Basin, processed ERTS-1 imagery will contribute to the data base of synchronized observations being made by investigators from many U.S. and Canadian government agencies and universities. The first set of ERTS data has been received and will be processed shortly for parameters of hydrological and limnological significance such as land use, terrain features, and water quality. When complete, nine ERTS-1 frames recorded during a substantially clear period will provide coverage of the entire Basin. Seven frames show all but a small portion of the southern and eastern end of the Basin. Many drainage basin characteristics are clearly identifiable on the imagery.

Accounting for the Process of Disablement and Longitudinal Outcomes Among the Near Elderly and Elderly.

PubMed

Rupp, Kalman; Dushi, Irena

2017-01-01

Using a new disability measure applicable to both the near elderly and elderly population, we track respondents aged 51-61 in 1992 from the Health and Retirement Study and account for their status over 20 years. We demonstrate that to screen in as disabled and to screen out as nondisabled require different analytic strategies and use multiple indicators to establish three groups: disabled, nondisabled, and a residual category with ambiguous status. We use work-disability and Supplemental Security Income/Disability Insurance (SSI/DI) receipt for testing distributional outcomes and assessing face validity of our disability measure. Selective attrition due to death and institutionalization is substantial over 20 years. Persistent disability is the dominant adverse outcome of initial disability shock. Overtime exits due to death become progressively more important; 44% disabled at baseline are dead by Wave 11 compared to 21% for nondisabled. Disability status at baseline is associated with financial insecurity persisting to Wave 11 among survivors.

The history of MF59(®) adjuvant: a phoenix that arose from the ashes.

PubMed

O'Hagan, Derek T; Ott, Gary S; Nest, Gary Van; Rappuoli, Rino; Giudice, Giuseppe Del

2013-01-01

The first clinical trial of an MF59(®)-adjuvanted influenza vaccine (Novartis) was conducted 20 years ago in 1992. The product that emerged (Fluad(®), Novartis) was licensed first in Italy in 1997 and is now licensed worldwide in 30 countries. US licensure is expected in the coming years. By contrast, many alternative adjuvanted vaccines have failed to progress. The key decisions that allowed MF59 to succeed in such a challenging environment are highlighted here and the lessons that were learned along the way are discussed. MF59 was connected to vaccines that did not succeed and was perceived as a 'failure' before it was a success. Importantly, it never failed for safety reasons and was always well tolerated. Even when safety issues have emerged for alternative adjuvants, careful analysis of the substantial safety database for MF59 have shown that there are no significant concerns with widespread use, even in more 'sensitive' populations.

Advancing Early Childhood Development: from Science to Scale 1

PubMed Central

Black, Maureen M; Walker, Susan P; Fernald, Lia C H; Andersen, Christopher T; DiGirolamo, Ann M; Lu, Chunling; McCoy, Dana C; Fink, Günther; Shawar, Yusra R; Shiffman, Prof Jeremy; Devercelli, Amanda E; Wodon, Quentin T; Vargas-Barón, Emily; Grantham-McGregor, Sally

2018-01-01

Early childhood development programmes vary in coordination and quality, with inadequate and inequitable access, especially for children younger than 3 years. New estimates, based on proxy measures of stunting and poverty, indicate that 250 million children (43%) younger than 5 years in low-income and middle-income countries are at risk of not reaching their developmental potential. There is therefore an urgent need to increase multisectoral coverage of quality programming that incorporates health, nutrition, security and safety, responsive caregiving, and early learning. Equitable early childhood policies and programmes are crucial for meeting Sustainable Development Goals, and for children to develop the intellectual skills, creativity, and wellbeing required to become healthy and productive adults. In this paper, the first in a three part Series on early childhood development, we examine recent scientific progress and global commitments to early childhood development. Research, programmes, and policies have advanced substantially since 2000, with new neuroscientific evidence linking early adversity and nurturing care with brain development and function throughout the life course. PMID:27717614

Characterization of fluid physics effects on cardiovascular response to microgravity (G-572)

NASA Technical Reports Server (NTRS)

Pantalos, George M.; Bennett, Thomas E.; Sharp, M. Keith; Woodruff, Stewart; Oleary, Sean; Gillars, Kevin; Lemon, Mark; Sojka, Jan

1995-01-01

The investigation of cardiovascular adaptation to space flight has seen substantial advancement in the last several years. In-flight echocardiographic measurements of astronaut cardiac function on the Space Shuttle have documented an initial increase, followed by a progressive reduction in both left ventricular volume index and stroke volume with a compensatory increase in heart rate to maintain cardiac output. To date, the reduced cardiac size and stroke volume have been presumed to be the consequence of the reduction in circulating fluid volume within a few days after orbital insertion. However, no specific mechanism for the reduced stroke volume has been identified. The following investigation proposes the use of a hydraulic model of the cardiovascular system to examine the possibility that the observed reduction in stroke volume may, in part, be related to fluid physics effects on heart function. The automated model is being prepared to fly as a Get Away Special (GAS) payload within the next year.

Verrucous form of chilblain lupus erythematosus.

PubMed

Pock, L; Petrovská, P; Becvár, R; Mandys, V; Hercogová, J

2001-09-01

A 45-year-old woman had symmetrical livid plaques with yellowish hyperkeratoses for 5 years, which progressed on to the fingers and toes and on the soles of the feet. Two years later creamy, whitish areas and maceration appeared on the buccal mucosa and the lips. A skin biopsy revealed massive collagen hyaline degeneration in the perivascular area, hyperkeratosis and hypergranulosis, small lymphocyte infiltrates with several melanophages and extravasates of erythrocytes in the upper corium in perivascular areas and hydropic degeneration of basal keratinocytes. The findings using direct immunofluorescence were compatible with lupus erythematosus (LE). Laboratory investigation showed a slight leucopenia and thrombopenia, a slightly elevated erythrocyte sedimentation rate, hypocomplementaemia C3 and C4, a high titre of rheumatoid factor and antinuclear antibodies positivity of extractable nuclear antigen. The results reflected probably the development of a systemic form of the disease. The patient was successfully managed by methylprednisolone and hydroxychloroquine. After 1 year of therapy, a new skin biopsy revealed a substantial reduction of hyperkeratosis and hyaline degeneration of collagen tissue in the perivascular areas. The combination of the extensive hyperkeratosis and hyalinization thus seems to be features of the long-lasting, untreated lesions in chilblain LE.

Can Non-HLA Single Nucleotide Polymorphisms Help Stratify Risk in TrialNet Relatives at Risk for Type 1 Diabetes?

PubMed

Steck, Andrea K; Xu, Ping; Geyer, Susan; Redondo, Maria J; Antinozzi, Peter; Wentworth, John M; Sosenko, Jay; Onengut-Gumuscu, Suna; Chen, Wei-Min; Rich, Stephen S; Pugliese, Alberto

2017-08-01

Genome-wide association studies identified >50 type 1 diabetes (T1D) associated non-human leukocyte antigens (non-HLA) loci. The purpose of this study was to assess the contribution of non-HLA single nucleotide polymorphisms (SNPs) to risk of disease progression. The TrialNet Pathway to Prevention Study follows relatives of T1D patients for development of autoantibodies (Abs) and T1D. Using the Immunochip, we analyzed 53 diabetes-associated, non-HLA SNPs in 1016 Ab-positive, at-risk non-Hispanic white relatives. Effect of SNPs on the development of multiple Abs and T1D. Cox proportional analyses included all substantial non-HLA SNPs, HLA genotypes, relationship to proband, sex, age at initial screening, initial Ab type, and number. Factors involved in progression from single to multiple Abs included age at screening, relationship to proband, HLA genotypes, and rs3087243 (cytotoxic T lymphocyte antigen-4). Significant factors for diabetes progression included age at screening, Ab number, HLA genotypes, rs6476839 [GLIS family zinc finger 3 (GLIS3)], and rs3184504 [SH2B adaptor protein 3 (SH2B3)]. When glucose area under the curve (AUC) was included, factors involved in disease progression included glucose AUC, age at screening, Ab number, relationship to proband, HLA genotypes, rs6476839 (GLIS3), and rs7221109 (CCR7). In stratified analyses by age, glucose AUC, age at screening, sibling, HLA genotypes, rs6476839 (GLIS3), and rs4900384 (C14orf64) were significantly associated with progression to diabetes in participants <12 years old, whereas glucose AUC, sibling, rs3184504 (SH2B3), and rs4900384 (C14orf64) were significant in those ≥12. In conclusion, we identified five non-HLA SNPs associated with increased risk of progression from Ab positivity to disease that may improve risk stratification for prevention trials. Copyright © 2017 by the Endocrine Society

Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice: results from the ESPOIR early arthritis cohort.

PubMed

Gaujoux-Viala, Cécile; Rincheval, Nathalie; Dougados, Maxime; Combe, Bernard; Fautrel, Bruno

2017-12-01

Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and dosage, which are often not optimal. To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years. Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables. Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year. Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Longitudinal analysis of endurance and respiratory function from a natural history study of Morquio A syndrome.

PubMed

Harmatz, Paul R; Mengel, Karl Eugen; Giugliani, Roberto; Valayannopoulos, Vassili; Lin, Shuan-Pei; Parini, Rossella; Guffon, Nathalie; Burton, Barbara K; Hendriksz, Christian J; Mitchell, John J; Martins, Ana Maria; Jones, Simon A; Guelbert, Norberto; Vellodi, Ashok; Wijburg, Frits A; Yang, Ke; Slasor, Peter; Decker, Celeste

2015-02-01

Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that individuals with Morquio A syndrome show substantial impairment in multiple domains including endurance and respiratory function (Harmatz et al., Mol Genet Metab, 2013). Here, 1- and 2-year longitudinal endurance and respiratory function data are presented. Endurance was assessed using the 6-minute walk test (6MWT) and the 3-minute stair climb test (3MSCT). Respiratory function was evaluated by measuring forced vital capacity (FVC) and maximum voluntary ventilation (MVV). Data were analyzed using repeated measures ANCOVA models. Annualized estimates of change were determined using model estimates and interpolation. 353, 184, and 78 subjects were assessed at Year 0 (baseline), Year 1, and Year 2, respectively. The overall annualized estimate of change (SE) in 6MWT distance was -4.86±3.25m; a larger decline of -6.84±5.38m was observed in the subset of subjects meeting the inclusion/exclusion criteria of the Phase 3 clinical trial of elosulfase alfa (≥5years of age with baseline 6MWT distance ≥30 and ≤325m). In contrast, little change (-0.14±0.60stairs/min) was observed in 3MSCT. Annualized changes (SE) in FVC and MVV were 2.44±0.68% and 1.01±2.38%, respectively. FVC and MVV increased in patients aged ≤14years, but decreased in older patients. The natural history of Morquio A syndrome is characterized by progressive impairment of endurance as measured by the 6MWT. Longitudinal trends in FVC and MVV showing increase in younger patients, but decrease in older patients, are likely to be influenced by growth. Changes in 6MWT may represent a sensitive measure of disease progression in ambulatory Morquio A patients. Copyright © 2014. Published by Elsevier Inc.

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

EPA Pesticide Factsheets

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

Providing Clinicians and Patients With Actual Prognosis: Cancer in the Context of Competing Causes of Death

PubMed Central

Mariotto, Angela B.; Woloshin, Steven; Schwartz, Lisa M.

2014-01-01

Background To isolate progress against cancer from changes in competing causes of death, population cancer registries have traditionally reported cancer prognosis (net measures). But clinicians and cancer patients generally want to understand actual prognosis (crude measures): the chance of surviving, dying from the specific cancer and from competing causes of death in a given time period. Objective To compare cancer and actual prognosis in the United States for four leading cancers—lung, breast, prostate, and colon—by age, comorbidity, and cancer stage and to provide templates to help patients, clinicians, and researchers understand actual prognosis. Method Using population-based registry data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated cancer prognosis (relative survival) and actual prognosis (five-year overall survival and the “crude” probability of dying from cancer and competing causes) for three important prognostic determinants (age, comorbidity [Charlson-score from 2012 SEER-Medicare linkage dataset] and cancer stage at diagnosis). Result For younger, healthier, and earlier stage cancer patients, cancer and actual prognosis estimates were quite similar. For older and sicker patients, these prognosis estimates differed substantially. For example, the five-year overall survival for an 85-year-old patient with colorectal cancer is 54% (cancer prognosis) versus 22% (actual prognosis)—the difference reflecting the patient’s substantial chance of dying from competing causes. The corresponding five-year chances of dying from the patient’s cancer are 46% versus 37%. Although age and comorbidity lowered actual prognosis, stage at diagnosis was the most powerful factor: The five-year chance of colon cancer death was 10% for localized stage and 83% for distant stage. Conclusion Both cancer and actual prognosis measures are important. Cancer registries should routinely report both cancer and actual prognosis to help clinicians and researchers understand the difference between these measures and what question they can and cannot answer. We encourage them to use formats like the ones presented in this paper to communicate them clearly. PMID:25417239

Providing clinicians and patients with actual prognosis: cancer in the context of competing causes of death.

PubMed

Howlader, Nadia; Mariotto, Angela B; Woloshin, Steven; Schwartz, Lisa M

2014-11-01

To isolate progress against cancer from changes in competing causes of death, population cancer registries have traditionally reported cancer prognosis (net measures). But clinicians and cancer patients generally want to understand actual prognosis (crude measures): the chance of surviving, dying from the specific cancer and from competing causes of death in a given time period. To compare cancer and actual prognosis in the United States for four leading cancers-lung, breast, prostate, and colon-by age, comorbidity, and cancer stage and to provide templates to help patients, clinicians, and researchers understand actual prognosis. Using population-based registry data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated cancer prognosis (relative survival) and actual prognosis (five-year overall survival and the "crude" probability of dying from cancer and competing causes) for three important prognostic determinants (age, comorbidity [Charlson-score from 2012 SEER-Medicare linkage dataset] and cancer stage at diagnosis). For younger, healthier, and earlier stage cancer patients, cancer and actual prognosis estimates were quite similar. For older and sicker patients, these prognosis estimates differed substantially. For example, the five-year overall survival for an 85-year-old patient with colorectal cancer is 54% (cancer prognosis) versus 22% (actual prognosis)-the difference reflecting the patient's substantial chance of dying from competing causes. The corresponding five-year chances of dying from the patient's cancer are 46% versus 37%. Although age and comorbidity lowered actual prognosis, stage at diagnosis was the most powerful factor: The five-year chance of colon cancer death was 10% for localized stage and 83% for distant stage. Both cancer and actual prognosis measures are important. Cancer registries should routinely report both cancer and actual prognosis to help clinicians and researchers understand the difference between these measures and what question they can and cannot answer. We encourage them to use formats like the ones presented in this paper to communicate them clearly. Published by Oxford University Press 2014.

Accelerated hand bone mineral density loss is associated with progressive joint damage in hands and feet in recent-onset rheumatoid arthritis.

PubMed

Güler-Yüksel, Melek; Klarenbeek, Naomi B; Goekoop-Ruiterman, Yvonne P M; de Vries-Bouwstra, Jeska K; van der Kooij, Sjoerd M; Gerards, Andreas H; Ronday, H Karel; Huizinga, Tom W J; Dijkmans, Ben A C; Allaart, Cornelia F; Lems, Willem F

2010-01-01

To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years. In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years. 68% of the patients had accelerated hand BMD loss (>-0.003 g/cm2) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage. In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year.

The Healthy People 2020 Objectives for Kidney Disease: How Far Have We Come, and Where Do We Need to Go?

PubMed

Wetmore, James B; Liu, Jiannong; Li, Suying; Hu, Yan; Peng, Yi; Gilbertson, David T; Collins, Allan J

2017-01-06

The Healthy People 2020 initiative established goals for patients with CKD and ESRD. We assessed United States progress toward some of these key goals. Using data from the Centers for Medicare and Medicaid Services ESRD database, we created yearly cohorts of patients on incident and prevalent dialysis from 2000 to 2013. Change in event rate or proportion change over the study years was modeled using Poisson regression with adjustment for age, race, sex, and primary cause of ESRD. For all-cause mortality in prevalent patients, Healthy People 2020 sought approximately 0.8% relative annual improvement; actual improvement was 2.7%. Improvement was greatest for patients ages 18-44 years old (3.8%; P<0.01 versus 2.8% for ages 65-74 years old) and 2.3% even for patients ages ≥75 years old. For mortality in incident patients, the relative annual decrease was 2.1% overall, a twofold improvement over the goal; mortality decreased nearly twice as much in black as in white patients (3.2% versus 1.8%; P<0.001). Geographic variation was substantial; the relative annual decrease was 0.6% in the Midwest and more than fourfold greater (2.7%) in the South. Cardiovascular mortality in prevalent patients decreased dramatically at 5.0% per year, far exceeding the annual goal of approximately 0.8%; the decrease was greatest in patients ages ≥75 years old (5.5%; P<0.001 versus ages 65-74 years old; 5.1%). The relative annual increase in percentages of patients with a fistula at dialysis initiation was 2.4%, roughly three times the goal; the increase was greater for black than white patients (3.2% versus 2.3%; P<0.01). Adjusted regional differences varied greater than twofold: 2.0% for the South versus 4.1% for the Midwest. Thus, although gains have been substantial, not all groups have benefitted equally. Goal development for Healthy People 2030 should consider changes in goal paradigms, such as tailoring by geographic region and incorporating patient-centered goals. Copyright © 2016 by the American Society of Nephrology.

The Healthy People 2020 Objectives for Kidney Disease: How Far Have We Come, and Where Do We Need to Go?

PubMed Central

Wetmore, James B.; Liu, Jiannong; Li, Suying; Hu, Yan; Peng, Yi; Gilbertson, David T.

2017-01-01

The Healthy People 2020 initiative established goals for patients with CKD and ESRD. We assessed United States progress toward some of these key goals. Using data from the Centers for Medicare and Medicaid Services ESRD database, we created yearly cohorts of patients on incident and prevalent dialysis from 2000 to 2013. Change in event rate or proportion change over the study years was modeled using Poisson regression with adjustment for age, race, sex, and primary cause of ESRD. For all-cause mortality in prevalent patients, Healthy People 2020 sought approximately 0.8% relative annual improvement; actual improvement was 2.7%. Improvement was greatest for patients ages 18–44 years old (3.8%; P<0.01 versus 2.8% for ages 65–74 years old) and 2.3% even for patients ages ≥75 years old. For mortality in incident patients, the relative annual decrease was 2.1% overall, a twofold improvement over the goal; mortality decreased nearly twice as much in black as in white patients (3.2% versus 1.8%; P<0.001). Geographic variation was substantial; the relative annual decrease was 0.6% in the Midwest and more than fourfold greater (2.7%) in the South. Cardiovascular mortality in prevalent patients decreased dramatically at 5.0% per year, far exceeding the annual goal of approximately 0.8%; the decrease was greatest in patients ages ≥75 years old (5.5%; P<0.001 versus ages 65–74 years old; 5.1%). The relative annual increase in percentages of patients with a fistula at dialysis initiation was 2.4%, roughly three times the goal; the increase was greater for black than white patients (3.2% versus 2.3%; P<0.01). Adjusted regional differences varied greater than twofold: 2.0% for the South versus 4.1% for the Midwest. Thus, although gains have been substantial, not all groups have benefitted equally. Goal development for Healthy People 2030 should consider changes in goal paradigms, such as tailoring by geographic region and incorporating patient-centered goals. PMID:27577245

The case for the relativistic hot big bang cosmology

NASA Technical Reports Server (NTRS)

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

1991-01-01

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

Porcine models of muscular dystrophy

USDA-ARS?s Scientific Manuscript database

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

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

Code of Federal Regulations, 2011 CFR

2011-07-01

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

78 FR 16908 - Determinations Under the African Growth and Opportunity Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-19

... STATES TRADE REPRESENTATIVE Determinations Under the African Growth and Opportunity Act AGENCY... substantial progress toward implementing and following, the customs procedures required by the African Growth... lesser developed beneficiary sub-Saharan African country. In Proclamation 7350 (October 2, 2000), the...

A systematic review of US rangeland social science

USDA-ARS?s Scientific Manuscript database

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-04

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

Controversies in the Diagnosis and Management of NAFLD and NASH.

PubMed

Rinella, Mary E; Loomba, Rohit; Caldwell, Stephen H; Kowdley, Kris; Charlton, Michael; Tetri, Brent; Harrison, Stephen A

2014-04-01

Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of chronic liver disease in the United States. Nonalcoholic steatohepatitis (NASH) occurs in a subset of patients with NAFLD and is characterized by the presence of hepa-tocellular injury, which is progressive in a substantial proportion of cases and can lead to cirrhosis and all of its complications. Although the diagnosis of NAFLD can be made through imaging studies or liver biopsy, the diagnosis of NASH still requires histologic confirmation. Liver biopsy should be performed in the presence of risk factors for advanced disease. Measures aimed at promoting weight loss, a healthier lifestyle, and optimization of metabolic risk factors remain the cornerstone of management of NAFLD. Therapeutic agents that are presently considered the most promising in NAFLD are effective in less than 50% of patients. Among patients with biopsy-proven NASH, treatment with pharmacologic agents should be considered; however, the role of specific agents in NASH still needs further study. Despite a wealth of research over the past 15 years, many controversies remain with respect to the diagnosis and management of NAFLD and NASH as well as the influence of alcohol on liver disease progression in these patients.

Optimization of genetics to create therapies for metastatic (stage IV) non-small-cell lung cancer.

PubMed

Rosell, Rafael; Moran, Teresa; Viteri, Santiago; Carcereny, Enric; Gasco, Amaya; Quiroga, Vanessa; Wei, Jia; Camps, Carlos; Massuti, Bartomeu

2010-07-01

Non-small-cell lung cancer (NSCLC) is a disseminated disease in 50% of cases, with a gloomy prognosis and median survivals of < 1 year. Based on substantial advances, cancer biology insights and novel biotechnology tools, customized treatment provides hints that cisplatin-based treatment can be optimized in favorable subgroups of patients according to gene expression DNA repair profiles. In 2004, it was discovered that 10-15% of NSCLC can harbor a new class of EGFR mutation conferring specific sensitivity to EGFR tyrosine kinase inhibitors. The homologous recombination pathway provides information for customizing cisplatin-based chemotherapy. BRCA1 plays a central role in this pathway that can be used in tailoring chemotherapy. Patient subgroups can obtain significant increases in progression-free survival. For EGFR lung-addicted cancers, treatment with EGFR tyrosine kinase inhibitors like erlotinib provide impressive improvement in progression-free survival--up to 14 months with significant enhanced survival. Customized chemotherapy based on BRCA1 models can contribute to demonstrating this approach's clinical relevance, and the implementation of EGFR mutation assessment is warranted to identify EGFR-addicted lung cancers with a different prognosis that could benefit from a specifically targeted therapy approach.

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

Gorelenkov, Nikolai N

The area of energetic particle (EP) physics of fusion research has been actively and extensively researched in recent decades. The progress achieved in advancing and understanding EP physics has been substantial since the last comprehensive review on this topic by W.W. Heidbrink and G.J. Sadler [1]. That review coincided with the start of deuterium-tritium (DT) experiments on Tokamak Fusion Test reactor (TFTR) and full scale fusion alphas physics studies. Fusion research in recent years has been influenced by EP physics in many ways including the limitations imposed by the "sea" of Alfven eigenmodes (AE) in particular by the toroidicityinduced AEsmore » (TAE) modes and reversed shear Alfven (RSAE). In present paper we attempt a broad review of EP physics progress in tokamaks and spherical tori since the first DT experiments on TFTR and JET (Joint European Torus) including helical/stellarator devices. Introductory discussions on basic ingredients of EP physics, i.e. particle orbits in STs, fundamental diagnostic techniques of EPs and instabilities, wave particle resonances and others are given to help understanding the advanced topics of EP physics. At the end we cover important and interesting physics issues toward the burning plasma experiments such as ITER (International Thermonuclear Experimental Reactor).« less

Extracellular matrix components in breast cancer progression and metastasis.

PubMed

Oskarsson, Thordur

2013-08-01

The extracellular matrix (ECM) is composed of highly variable and dynamic components that regulate cell behavior. The protein composition and physical properties of the ECM govern cell fate through biochemical and biomechanical mechanisms. This requires a carefully orchestrated and thorough regulation considering that a disturbed ECM can have serious consequences and lead to pathological conditions like cancer. In breast cancer, many ECM proteins are significantly deregulated and specific matrix components promote tumor progression and metastatic spread. Intriguingly, several ECM proteins that are associated with breast cancer development, overlap substantially with a group of ECM proteins induced during the state of tissue remodeling such as mammary gland involution. Fibrillar collagens, fibronectin, hyaluronan and matricellular proteins are matrix components that are common to both involution and cancer. Moreover, some of these proteins have in recent years been identified as important constituents of metastatic niches in breast cancer. In addition, specific ECM molecules, their receptors or enzymatic modifiers are significantly involved in resistance to therapeutic intervention. Further analysis of these ECM proteins and the downstream ECM mediated signaling pathways may provide a range of possibilities to identify druggable targets against advanced breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chinese Herbal Medicine as a Potential Treatment of Abdominal Aortic Aneurysm

PubMed Central

Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Wang, Ning; Bensoussan, Alan

2018-01-01

Abdominal aortic aneurysm (AAA) is an irreversible condition where the abdominal aorta is dilated leading to potentially fatal consequence of aortic rupture. Multiple mechanisms are involved in the development and progression of AAA, including chronic inflammation, oxidative stress, vascular smooth muscle (VSMC) apoptosis, immune cell infiltration and extracellular matrix (ECM) degradation. Currently surgical therapies, including minimally invasive endovascular aneurysm repair (EVAR), are the only viable interventions for AAAs. However, these treatments are not appropriate for the majority of AAAs, which measure <50 mm. Substantial effort has been invested to identify and develop pharmaceutical treatments such as statins and doxycycline for this potentially lethal condition but these interventions failed to offer a cure or to retard the progression of AAA. Chinese herbal medicine (CHM) has been used for the management of cardiovascular diseases for thousands of years in China and other Asian countries. The unique multi-component and multi-target property of CHMs makes it a potentially ideal therapy for multifactorial diseases such as AAA. In this review, we review the current scientific evidence to support the use of CHMs for the treatment of AAA. Mechanisms of action underlying the effects of CHMs on AAA are also discussed. PMID:29732374

Progress in neutron-, X-ray- and VIS spectroscopic diagnostics of large-scale plasma focus experiments at ICDMP

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

Schmidt, Hellmut

Substantial progress has been made in various diagnostics for investigating results of experiments during the last years performed with the PF1000 device at IPPLM, Warsaw, Poland. In addition to standard diagnostics of the electrical characteristics of up to 1 MJ discharges in a Mather type plasma focus geometry, such as high speed photography, X-ray, fast electron beam and time-integrated neutron measurements, there have been made among others at least three quite successful efforts recently: 1) Setting up of a neutron time-of-flight line with up to five scintillation detectors including optical fibre based data collection equipment, 2) Use of a Mechellemore » spectrometer with CCD registration and possibility to take time-resolved spectra with resolutions down to 100 ns and 3) Setting up and using pinhole cameras equipped with solid state nuclear track detectors for the detection of fusion generated protons. Correlations of emission events as well as plasma and electrical current dynamics are investigated. Neutron emission characteristics and fusion products production mechanisms are discussed considering a generalized beam target model, called Gyrating Particle Model.« less

Chinese Herbal Medicine as a Potential Treatment of Abdominal Aortic Aneurysm.

PubMed

Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Wang, Ning; Bensoussan, Alan

2018-01-01

Abdominal aortic aneurysm (AAA) is an irreversible condition where the abdominal aorta is dilated leading to potentially fatal consequence of aortic rupture. Multiple mechanisms are involved in the development and progression of AAA, including chronic inflammation, oxidative stress, vascular smooth muscle (VSMC) apoptosis, immune cell infiltration and extracellular matrix (ECM) degradation. Currently surgical therapies, including minimally invasive endovascular aneurysm repair (EVAR), are the only viable interventions for AAAs. However, these treatments are not appropriate for the majority of AAAs, which measure <50 mm. Substantial effort has been invested to identify and develop pharmaceutical treatments such as statins and doxycycline for this potentially lethal condition but these interventions failed to offer a cure or to retard the progression of AAA. Chinese herbal medicine (CHM) has been used for the management of cardiovascular diseases for thousands of years in China and other Asian countries. The unique multi-component and multi-target property of CHMs makes it a potentially ideal therapy for multifactorial diseases such as AAA. In this review, we review the current scientific evidence to support the use of CHMs for the treatment of AAA. Mechanisms of action underlying the effects of CHMs on AAA are also discussed.

Postpneumonectomy syndrome in children: advantages and long-term follow-up of expandable prosthesis.

PubMed

Podevin, G; Larroquet, M; Camby, C; Audry, G; Plattner, V; Heloury, Y

2001-09-01

Pneumonectomy in children can be complicated by a severe mediastinal shift, which leads to bronchial stretching resulting in severe respiratory failure. This postpneumonectomy syndrome can be corrected by inserting a prosthesis in the empty side of the chest. Forty-two children, from 6 months to 15 years old, underwent a pneumonectomy. Seven of these patients were treated surgically for severe manifestations of postpneumonectomy syndrome. First insertion of an expandable prosthesis was followed up in 5 cases by its replacement with a breast prosthesis in adolescence. The expandable prosthesis was injected periodically with saline solution to maintain the mediastinum in a midline position as the children grew. The mean delay between pneumonectomy and first prosthesis implantation was 5 years (range, 11 months to 8 years). Pulmonary function tests showed a substantial improvement in the obstructive syndrome in all patients except one, in whom the functional improvement was moderate. The mean follow-up after the expandable prosthesis implantation was 6 years (range, 6 months to 10 years) and all patients are doing well. The insertion of an intrathoracic prosthesis can dramatically improve the clinical symptoms and reduce the functional obstructive syndrome. The expandable prosthesis allowed for progressive, well-tolerated recentering of the mediastinum and adjustment for growth. Copyright 2001 by W.B. Saunders Company.

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

PubMed

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

2016-10-18

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

Vital Signs: Human Immunodeficiency Virus Testing and Diagnosis Delays — United States

PubMed Central

Dailey, Andre F.; Hoots, Brooke E.; Song, Ruiguang; Hayes, Demorah; Fulton, Paul; Prejean, Joseph; Hernandez, Angela L.; Koenig, Linda J.; Valleroy, Linda A.

2017-01-01

Background Persons unaware of their human immunodeficiency virus (HIV) infection account for approximately 40% of ongoing transmissions in the United States. Persons are unaware of their infection because of delayed HIV diagnoses that represent substantial missed opportunities to improve health outcomes and prevent HIV transmission. Methods Data from CDC’s National HIV Surveillance System were used to estimate, among persons with HIV infection diagnosed in 2015, the median interval (and range) from infection to diagnosis (diagnosis delay), based on the first CD4 test after HIV diagnosis and a CD4 depletion model indicating disease progression and, among persons living with HIV in 2015, the percentage with undiagnosed infection. Data from CDC’s National HIV Behavioral Surveillance were analyzed to determine the percentage of persons at increased risk for HIV infection who had tested in the past 12 months and who had missed opportunities for testing. Results An estimated 15% of persons living with HIV in 2015 were unaware of their infection. Among the 39,720 persons with HIV infection diagnosed in 2015, the estimated median diagnosis delay was 3.0 years (interquartile range = 0.7–7.8 years); diagnosis delay varied by race/ethnicity (from 2.2 years among whites to 4.2 years among Asians) and transmission category (from 2.0 years among females who inject drugs to 4.9 years among heterosexual males). Among persons interviewed through National HIV Behavioral Surveillance, 71% of men who have sex with men, 58% of persons who inject drugs, and 41% of heterosexual persons at increased risk for HIV infection reported testing in the past 12 months. In each risk group, at least two thirds of persons who did not have an HIV test had seen a health care provider in the past year. Conclusions Delayed HIV diagnoses continue to be substantial for some population groups and prevent early entry to care to improve health outcomes and reduce HIV transmission to others. Implications for Public Health Practice Health care providers and others providing HIV testing can reduce HIV-related adverse health outcomes and risk for HIV transmission by implementing routine and targeted HIV testing to decrease diagnosis delays. PMID:29190267

Vital Signs: Human Immunodeficiency Virus Testing and Diagnosis Delays - United States.

PubMed

Dailey, Andre F; Hoots, Brooke E; Hall, H Irene; Song, Ruiguang; Hayes, Demorah; Fulton, Paul; Prejean, Joseph; Hernandez, Angela L; Koenig, Linda J; Valleroy, Linda A

2017-12-01

Persons unaware of their human immunodeficiency virus (HIV) infection account for approximately 40% of ongoing transmissions in the United States. Persons are unaware of their infection because of delayed HIV diagnoses that represent substantial missed opportunities to improve health outcomes and prevent HIV transmission. Data from CDC's National HIV Surveillance System were used to estimate, among persons with HIV infection diagnosed in 2015, the median interval (and range) from infection to diagnosis (diagnosis delay), based on the first CD4 test after HIV diagnosis and a CD4 depletion model indicating disease progression and, among persons living with HIV in 2015, the percentage with undiagnosed infection. Data from CDC's National HIV Behavioral Surveillance were analyzed to determine the percentage of persons at increased risk for HIV infection who had tested in the past 12 months and who had missed opportunities for testing. An estimated 15% of persons living with HIV in 2015 were unaware of their infection. Among the 39,720 persons with HIV infection diagnosed in 2015, the estimated median diagnosis delay was 3.0 years (interquartile range = 0.7-7.8 years); diagnosis delay varied by race/ethnicity (from 2.2 years among whites to 4.2 years among Asians) and transmission category (from 2.0 years among females who inject drugs to 4.9 years among heterosexual males). Among persons interviewed through National HIV Behavioral Surveillance, 71% of men who have sex with men, 58% of persons who inject drugs, and 41% of heterosexual persons at increased risk for HIV infection reported testing in the past 12 months. In each risk group, at least two thirds of persons who did not have an HIV test had seen a health care provider in the past year. Delayed HIV diagnoses continue to be substantial for some population groups and prevent early entry to care to improve health outcomes and reduce HIV transmission to others. Health care providers and others providing HIV testing can reduce HIV-related adverse health outcomes and risk for HIV transmission by implementing routine and targeted HIV testing to decrease diagnosis delays.

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

PubMed

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

2017-05-01

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

CANCER RISK ASSESSMENT AND PREVENTION: WHERE DO WE STAND?

EPA Science Inventory

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

An Innovative Approach to Integrated Training for Smallholder Dairying

ERIC Educational Resources Information Center

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

2014-01-01

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

Trajectories of Change in Youth Anxiety during Cognitive Behavior Therapy

PubMed Central

Peris, Tara S.; Compton, Scott N.; Kendall, Philip C.; Birmaher, Boris; Sherill, Joel; March, John; Gosch, Elizabeth; Ginsburg, Golda; Rynn, Moira; McCracken, James T.; Keeton, Courtney P.; Sakolsky, Dara; Suveg, Cynthia; Aschenbrand, Sasha; Almirall, Daniel; Iyengar, Satish; Walkup, John T.; Albano, Anne Marie; Piacentini, John

2015-01-01

Objective To evaluate changes in the trajectory of youth anxiety following the introduction of specific cognitive behavior therapy (CBT) components: relaxation training, cognitive restructuring, and exposure tasks. Methods 488 youths ages 7–17 years (50% female; 74% ≤ 12 years) were randomly assigned to receive either CBT, sertraline (SRT), their combination (COMB), or pill placebo (PBO) as part of their participation in the Child/Adolescent Anxiety Multimodal Study (CAMS). Youths in the CBT conditions were evaluated weekly by therapists using the Clinical Global Impression Scale-Severity (CGI-S; Guy, 1976) and the Children’s Global Assessment Scale (CGAS; Schaffer et al., 1983) and every four weeks by blind independent evaluators (IEs) using the Pediatric Anxiety Ratings Scale (PARS; Rupp Study Group, 2002). Youths in SRT and PBO were included as controls. Results Longitudinal discontinuity analyses indicated that the introduction of both cognitive restructuring (e.g., changing self-talk) and exposure tasks significantly accelerated the rate of progress on measures of symptom severity and global functioning moving forward in treatment; the introduction of relaxation training had limited impact. Counter to expectations, no strategy altered the rate of progress in the specific domain of anxiety that it was intended to target (i.e., somatic symptoms, anxious self-talk, avoidance behavior). Conclusions Findings support CBT theory and suggest that cognitive restructuring and exposure tasks each make substantial contributions to improvement in youth anxiety. Implications for future research are discussed. PMID:25486372

The social and economic burden of frontotemporal degeneration

PubMed Central

Howard, David H.; Denny, Sharon S.; Dickinson, Susan; Tatton, Nadine

2017-01-01

Objective: To quantify the socioeconomic burden of frontotemporal degeneration (FTD) compared to previously published data for Alzheimer disease (AD). Methods: A 250-item internet survey was administered to primary caregivers of patients with behavioral-variant FTD (bvFTD), primary progressive aphasia, FTD with motor neuron disease, corticobasal syndrome, or progressive supranuclear palsy. The survey included validated scales for disease staging, behavior, activities of daily living, caregiver burden, and health economics, as well as investigator-designed questions to capture patient and caregiver experience with FTD. Results: The entire survey was completed by 674 of 956 respondents (70.5%). Direct costs (2016 US dollars) equaled $47,916 and indirect costs $71,737, for a total annual per-patient cost of $119,654, nearly 2 times higher than reported costs for AD. Patients ≥65 years of age, with later stages of disease, and with bvFTD correlated with higher direct costs, while patients <65 years of age and men were associated with higher indirect costs. An FTD diagnosis produced a mean decrease in household income from $75,000 to $99,000 12 months before diagnosis to $50,000 to $59,999 12 months after diagnosis, resulting from lost days of work and early departure from the workforce. Conclusions: The economic burden of FTD is substantial. Counting productivity-related costs, per-patient costs for FTD appear to be greater than per-patient costs reported for AD. There is a need for biomarkers for accurate and timely diagnosis, effective treatments, and services to reduce this socioeconomic burden. PMID:28978658

The South African Experience of Conservation and Social Forestry Outreach Nurseries

NASA Astrophysics Data System (ADS)

Botha, Jenny; Witkowski, Ed T. F.; Cock, Jacklyn

2006-11-01

Outreach nurseries are favored conservation and social forestry tools globally, but, as with many integrated conservation and development programs (ICDPs), they do not always produce anticipated results. A synopsis of the experience of South African practitioners is provided in this study of 65 outreach nurseries. South African outreach nurseries frequently include financial objectives, creating additional challenges in simultaneously attaining conservation and socioeconomic goals. Progress was hindered by biophysical problems (e.g., lack of water, poor soils, etc.) as well as the harsh socioeconomic conditions facing most communities in which nurseries had been established. Attaining financial viability was challenging. Business management skills were often restricted, and few viability studies included adequate market research. Costs to community participants were usually high, and benefits were limited. Conservation objectives were frequently lost in the struggle to attain financial viability. The management of social processes also proved challenging. Although small scale and relatively straightforward compared with many ICDPs, nurseries usually require substantial institutional support, including a range of technical, business, and development services. Project time frames need to be reconsidered, as practitioners estimate that it takes 5-10 years for nurseries to start meeting objectives, and donors and implementing agencies often operate on 2-3-year project cycles. Detailed viability studies are essential, incorporating a social probe and an assessment of potential impacts of projects on community participants. Progress needs to be continuously evaluated to enable institutions and community participants to adapt to changing conditions as well as ensure that the spectrum of objectives are being achieved.

The South African experience of conservation and social forestry outreach nurseries.

PubMed

Botha, Jenny; Witkowski, Ed T F; Cock, Jacklyn

2006-11-01

Outreach nurseries are favored conservation and social forestry tools globally, but, as with many integrated conservation and development programs (ICDPs), they do not always produce anticipated results. A synopsis of the experience of South African practitioners is provided in this study of 65 outreach nurseries. South African outreach nurseries frequently include financial objectives, creating additional challenges in simultaneously attaining conservation and socioeconomic goals. Progress was hindered by biophysical problems (e.g., lack of water, poor soils, etc.) as well as the harsh socioeconomic conditions facing most communities in which nurseries had been established. Attaining financial viability was challenging. Business management skills were often restricted, and few viability studies included adequate market research. Costs to community participants were usually high, and benefits were limited. Conservation objectives were frequently lost in the struggle to attain financial viability. The management of social processes also proved challenging. Although small scale and relatively straightforward compared with many ICDPs, nurseries usually require substantial institutional support, including a range of technical, business, and development services. Project time frames need to be reconsidered, as practitioners estimate that it takes 5-10 years for nurseries to start meeting objectives, and donors and implementing agencies often operate on 2-3-year project cycles. Detailed viability studies are essential, incorporating a social probe and an assessment of potential impacts of projects on community participants. Progress needs to be continuously evaluated to enable institutions and community participants to adapt to changing conditions as well as ensure that the spectrum of objectives are being achieved.

Care Partners and Multiple Sclerosis

PubMed Central

Quig, Mary Elizabeth; Tyry, Tuula; Marrie, Ruth Ann; Cutter, Gary; Shearin, Edward; Johnson, Kamau; Simsarian, James

2015-01-01

Background: Caring for someone with multiple sclerosis (MS) can be a stressful experience that requires clinical attention. We investigated the impact of caregiver stress on the emotional well-being and physical health of the MS care partner using the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. Methods: Care partners of NARCOMS participants were invited to complete an online questionnaire that captured demographic characteristics, health status, caregiver burden as measured by the Zarit Caregiver Burden Interview, and impact of caregiving on employment. Results: Of 1446 care partners who agreed to participate, 1333 had complete data. Most were men (n = 825, 61.9%), with a mean (SD) age of 51.1 (11.2) years. The mean (SD) Zarit total score was 24.6 (15.1), placing the overall group in the mild caregiver burden range. Compared with male care partners, female care partners reported higher levels of burden and stress and more medication use for stress/anxiety and mood disorders. Male care partners were more likely to report physical concerns. Care partners of people with primary progressive MS reported greater perceived burden than did partners of people with secondary progressive MS and relapsing-remitting MS. More than 40% of care partners (559 of 1288) had missed work during the past year owing to caregiving responsibilities. Conclusions: Care partners of people with MS have substantial physical and psychological health concerns and experience an adverse impact on employment. Future research should evaluate how to mitigate the adverse effects of caregiving and evaluate positive aspects of the role. PMID:26664330

Drivers and implications of change in global ocean health over the past five years

PubMed Central

Frazier, Melanie; Afflerbach, Jamie; O’Hara, Casey; Katona, Steven; Stewart Lowndes, Julia S.; Jiang, Ning; Pacheco, Erich; Scarborough, Courtney; Polsenberg, Johanna

2017-01-01

Growing international and national focus on quantitatively measuring and improving ocean health has increased the need for comprehensive, scientific, and repeated indicators to track progress towards achieving policy and societal goals. The Ocean Health Index (OHI) is one of the few indicators available for this purpose. Here we present results from five years of annual global assessment for 220 countries and territories, evaluating potential drivers and consequences of changes and presenting lessons learned about the challenges of using composite indicators to measure sustainability goals. Globally scores have shown little change, as would be expected. However, individual countries have seen notable increases or declines due in particular to improvements in the harvest and management of wild-caught fisheries, the creation of marine protected areas (MPAs), and decreases in natural product harvest. Rapid loss of sea ice and the consequent reduction of coastal protection from that sea ice was also responsible for declines in overall ocean health in many Arctic and sub-Arctic countries. The OHI performed reasonably well at predicting near-term future scores for many of the ten goals measured, but data gaps and limitations hindered these predictions for many other goals. Ultimately, all indicators face the substantial challenge of informing policy for progress toward broad goals and objectives with insufficient monitoring and assessment data. If countries and the global community hope to achieve and maintain healthy oceans, we will need to dedicate significant resources to measuring what we are trying to manage. PMID:28678881

Climatology of Urban-regional Systems

NASA Technical Reports Server (NTRS)

Pease, R. W.

1971-01-01

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

Rocky coast processes: with special reference to the recession of soft rock cliffs

PubMed Central

SUNAMURA, Tsuguo

2015-01-01

Substantial progress in research on the recession of coastal cliffs composed of soft materials has been made in recent years and data with higher accuracy have been accumulated. This paper provides the state of the art review in the recession studies and highlights two new findings obtained from the reanalysis of existing data. The review topics are: episodic and localized nature of cliff recession; the development of cliffline; the relationship between cliff height and recession rate; mechanisms of cliff toe erosion by waves; a fundamental equation for wave-induced toe erosion; factors controlling toe erosion; and slope instabilities and mass movements. The findings are presented on (1) the temporal change in cliffline recession mode and (2) the effect of beach sediment at the cliff base on the cliff erosion. PMID:26568322

Advances in mechanisms of asthma, allergy, and immunology in 2011.

PubMed

Boyce, Joshua A; Bochner, Bruce; Finkelman, Fred D; Rothenberg, Marc E

2012-02-01

2011 was marked by rapid progress in the identification of basic mechanisms of allergic disease and the translation of these mechanisms into human cell systems. Studies published in the Journal of Allergy and Clinical Immunology this year provided new insights into the molecular determinants of allergenicity, as well as the environmental, cellular, and genetic factors involved in sensitization to allergens. Several articles focused on mechanisms of allergen immunotherapy and the development of novel strategies to achieve tolerance to allergens. Additional studies identified substantial contributions from T(H)17-type cells and cytokines to human disease pathogenesis. Finally, new therapeutic applications of anti-IgE were identified. The highlights of these studies and their potential clinical implications are summarized in this review. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

50 years of the International Committee on Taxonomy of Viruses: progress and prospects.

PubMed

Adams, Michael J; Lefkowitz, Elliot J; King, Andrew M Q; Harrach, Balázs; Harrison, Robert L; Knowles, Nick J; Kropinski, Andrew M; Krupovic, Mart; Kuhn, Jens H; Mushegian, Arcady R; Nibert, Max L; Sabanadzovic, Sead; Sanfaçon, Hélène; Siddell, Stuart G; Simmonds, Peter; Varsani, Arvind; Zerbini, Francisco Murilo; Orton, Richard J; Smith, Donald B; Gorbalenya, Alexander E; Davison, Andrew J

2017-05-01

We mark the 50th anniversary of the International Committee on Taxonomy of Viruses (ICTV) by presenting a brief history of the organization since its foundation, showing how it has adapted to advancements in our knowledge of virus diversity and the methods used to characterize it. We also outline recent developments, supported by a grant from the Wellcome Trust (UK), that are facilitating substantial changes in the operations of the ICTV and promoting dialogue with the virology community. These developments will generate improved online resources, including a freely available and regularly updated ICTV Virus Taxonomy Report. They also include a series of meetings between the ICTV and the broader community focused on some of the major challenges facing virus taxonomy, with the outcomes helping to inform the future policy and practice of the ICTV.

Complications in implant dentistry

PubMed Central

Hanif, Ayesha; Qureshi, Saima; Sheikh, Zeeshan; Rashid, Haroon

2017-01-01

After tooth loss, an individual may seek tooth replacement so that his/her function and esthetics could be restored. Clinical prosthodontics, during the past decade, has significantly improved and developed according to the advancements in the science and patient's demands and needs. Conventional options in prosthodontics for substituting a missing single tooth include the removable partial denture, partial and full coverage bridgework, and resin-bonded bridgework. Dental implants have gained increasing popularity over the years as they are capable of restoring the function to near normal in both partial and completely edentulous arches. With substantial evidence available, fixed implant-supported prosthesis are fully acknowledged as a reliable treatment option for the replacement of single or multiple missing teeth nowadays. While dental implants are increasingly becoming the choice of replacement for missing teeth, the impediments associated with them are progressively emerging too. PMID:28435381

[Attention and aging].

PubMed

Siéroff, Eric; Piquard, Ambre

2004-12-01

Due to progress in the cognitive theories in the last twenty years, the description of attentional deficits associated with normal or pathological aging has substantially improved. In this article, attentional deficits are presented according to Posner theory, which describes three sub-systems in a global network of attention: vigilance, selective attention, command. This theory not only characterizes the functions of these subsystems, but gives precise indications about their anatomical and neurochemical substrates. Several clinical tests can be described for each of these different subsystems. The main attentional deficits are presented in the second part of this paper: if some decline of the attentional command occurs in normal aging, a real deficit in this subsystem is found in most degenerative processes (frontotemporal dementia, Alzheimer and Parkinson diseases). Alzheimer disease is also frequently associated with a deficit of selective spatial attention, early in the evolution of the disease.

Regional chloride distribution in the Northern Atlantic Coastal Plain aquifer system from Long Island, New York, to North Carolina

USGS Publications Warehouse

Charles, Emmanuel

2016-08-31

Although additional offshore chloride data are available compared to 27 years ago (1989), the offshore information remains sparse, resulting in less confidence in the offshore interpretations than in the onshore interpretations. Regionally, the 250- and 10,000-mg/L isochlors tend to map progressively eastward from the deepest to the shallowest aquifers across the Northern Atlantic Coastal Plain aquifer system but with some exceptions. The additional data, conceptual understanding, and interpretations in the vicinity of the buried Chesapeake Bay impact structure in eastern Virginia resulted in substantial refinement of isochlors in that area. Overall, the interpretations in this study are updates of the previous regional study from 1989 but do not comprise major differences in interpretation and do not indicate regional movement of the freshwater-saltwater interface since then.

Computer modeling of Epilepsy

PubMed Central

Lytton, William W.

2009-01-01

Preface Epilepsy is a complex set of disorders that can involve many areas of cortex as well as underlying deep brain systems. The myriad manifestations of seizures, as varied as déjà vu and olfactory hallucination, can thereby give researchers insights into regional functions and relations. Epilepsy is also complex genetically and pathophysiologically, involving microscopic (ion channels, synaptic proteins), macroscopic (brain trauma and rewiring) and intermediate changes in a complex interplay of causality. It has long been recognized that computer modeling will be required to disentangle causality, to better understand seizure spread and to understand and eventually predict treatment efficacy. Over the past few years, substantial progress has been made modeling epilepsy at levels ranging from the molecular to the socioeconomic. We review these efforts and connect them to the medical goals of understanding and treating this disorder. PMID:18594562

Emotion comprehension: the impact of nonverbal intelligence.

PubMed

Albanese, Ottavia; De Stasio, Simona; Di Chiacchio, Carlo; Fiorilli, Caterina; Pons, Francisco

2010-01-01

A substantial body of research has established that emotion understanding develops throughout early childhood and has identified three hierarchical developmental phases: external, mental, and reflexive. The authors analyzed nonverbal intelligence and its effect on children's improvement of emotion understanding and hypothesized that cognitive level is a consistent predictor of emotion comprehension. In all, 366 children (182 girls, 184 boys) between the ages of 3 and 10 years were tested using the Test of Emotion Comprehension and the Coloured Progressive Matrices. The data obtained by using the path analysis model revealed that nonverbal intelligence was statistically associated with the ability to recognize emotions in the 3 developmental phases. The use of this model showed the significant effect that cognitive aspect plays on the reflexive phase. The authors aim to contribute to the debate about the influence of cognitive factors on emotion understanding.

The Impact of Smoking Bans on Smoking and Consumer Behavior: Quasi-Experimental Evidence from Switzerland.

PubMed

Boes, Stefan; Marti, Joachim; Maclean, Johanna Catherine

2015-11-01

In this paper, we exploit the progressive implementation of smoking bans in public venues at the state level in Switzerland to evaluate both the direct effects on smoking and the potential unintended consequences of these legislations on consumer behaviors as measured by visiting restaurants/bars and discos ('going out'). Our results indicate that public venue smoking bans in Switzerland reduce smoking rates, but the findings do not emerge until 1 year following the ban. This pattern of results is consistent with delays in ban enforcement on the part of business owners, difficulties in changing addictive behaviors such as smoking, and/or learning on the part of smokers. We find evidence that smoking bans influence going-out behavior and there is substantial heterogeneity across venue and consumer characteristics. Copyright © 2014 John Wiley & Sons, Ltd.

Patterns and Predictors of Language and Literacy Abilities 4-10 Years in the Longitudinal Study of Australian Children.

PubMed

Zubrick, Stephen R; Taylor, Catherine L; Christensen, Daniel

2015-01-01

Oral language is the foundation of literacy. Naturally, policies and practices to promote children's literacy begin in early childhood and have a strong focus on developing children's oral language, especially for children with known risk factors for low language ability. The underlying assumption is that children's progress along the oral to literate continuum is stable and predictable, such that low language ability foretells low literacy ability. This study investigated patterns and predictors of children's oral language and literacy abilities at 4, 6, 8 and 10 years. The study sample comprised 2,316 to 2,792 children from the first nationally representative Longitudinal Study of Australian Children (LSAC). Six developmental patterns were observed, a stable middle-high pattern, a stable low pattern, an improving pattern, a declining pattern, a fluctuating low pattern, and a fluctuating middle-high pattern. Most children (69%) fit a stable middle-high pattern. By contrast, less than 1% of children fit a stable low pattern. These results challenged the view that children's progress along the oral to literate continuum is stable and predictable. Multivariate logistic regression was used to investigate risks for low literacy ability at 10 years and sensitivity-specificity analysis was used to examine the predictive utility of the multivariate model. Predictors were modelled as risk variables with the lowest level of risk as the reference category. In the multivariate model, substantial risks for low literacy ability at 10 years, in order of descending magnitude, were: low school readiness, Aboriginal and/or Torres Strait Islander status and low language ability at 8 years. Moderate risks were high temperamental reactivity, low language ability at 4 years, and low language ability at 6 years. The following risk factors were not statistically significant in the multivariate model: Low maternal consistency, low family income, health care card, child not read to at home, maternal smoking, maternal education, family structure, temperamental persistence, and socio-economic area disadvantage. The results of the sensitivity-specificity analysis showed that a well-fitted multivariate model featuring risks of substantive magnitude did not do particularly well in predicting low literacy ability at 10 years.

Progression of visual field in patients with primary open-angle glaucoma - ProgF study 1.

PubMed

Aptel, Florent; Aryal-Charles, Nishal; Giraud, Jean-Marie; El Chehab, Hussam; Delbarre, Maxime; Chiquet, Christophe; Romanet, Jean-Paul; Renard, Jean-Paul

2015-12-01

To evaluate the visual field rate of progression of patients with treated ocular hypertension (OHT) and primary open-angle glaucoma (POAG) in clinical practice, using the mean deviation (MD) and the visual field index (VFI). Non-interventional cohort study. From a large multicentre database representative of the French population, 441 eyes of 228 patients with treated OHT or POAG followed up at least 6 years with Humphrey 24.2 Sita-Standard visual field examination at least twice a year were identified. From initial data, eyes were classified in five groups: 121 with OHT, 188 with early glaucoma (MD greater than -6 dB), 45 with moderate glaucoma (MD -6 to -12 dB), 41 with advanced glaucoma (MD -12 to -18 dB) and 46 with severe glaucoma (MD less than -18 dB). Rate of progression during the follow-up period was calculated using the trend analysis of the Guided Progression Analysis software. The mean duration of follow-up was 8.4 ± 2.7 years and the mean number of visual field, 18.4 ± 3.5. In eyes with OHT, rate of progression was -0.09 dB/year (-0.17%VFI/year). In eyes with POAG, rate of progression was -0.32 dB/year (-0.83%VFI/year) in eyes with early glaucoma, -0.52 dB/year (-1.81%VFI/year) in moderate glaucoma, -0.54 dB/year (-2.35%VFI/year) in advanced glaucoma and -0.45 dB/year (-1.97%VFI/year) in severe glaucoma. In eyes with POAG, a significant progression (p < 0.05) was detected in 159 of 320 eyes (49.7%) with trend analysis and 117 of 320 eyes (36.6%, likely progression) or 183 of 320 eyes (57.2%, possible and likely progression) with event analysis. Primary open-angle glaucoma is a progressive disease in the majority of patients despite cautioned treatment and follow-up. The rate of progression varies greatly among subjects. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

PubMed

Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

2018-01-01

The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

Robert H. Goddard and His Liquid-Gasoline Rocket

NASA Technical Reports Server (NTRS)

1926-01-01

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

Early Rockets

NASA Image and Video Library

1926-03-16

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

Early Rockets

NASA Image and Video Library

1926-03-16

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

Can Progress in Reducing Alcohol-Impaired Driving Fatalities Be Resumed?

PubMed Central

Fell, James C.; Beirness, Douglas J.; Voas, Robert B.; Smith, Gordon S; Jonah, Brian; Maxwell, Jane Carlisle; Price, Jana; Hedlund, James

2016-01-01

Objective Despite successes in the 1980s and early 1990s, progress in reducing impaired driving fatalities in the United States has stagnated in recent years. Since 1997, the percentage of drivers involved in fatal crashes with illegal blood alcohol concentration (BAC) levels has remained at approximately 20% to 22%. Many experts believe that public complacency, competing social and public health issues, and the lack of political fortitude have all contributed to this stagnation. The number of alcohol-related crashes, injuries, and fatalities is still unacceptable, and most are preventable. The public needs to be aware that the problem presented by drinking drivers has not been solved. Political leaders need guidance on which measures will affect the problem, and stakeholders need to be motivated once again to implement effective strategies. Methods The National Academy of Sciences (NAS) Transportation Research Board (TRB) Alcohol, Other Drugs, and Transportation Committee (ANB50) sponsored a workshop held at the NAS facility in Woods Hole, MA, on August 24–25, 2015, to discuss the lack of progress in reducing impaired driving and to make recommendations for future progress. A total of 26 experts in research and policy related to alcohol-impaired driving participated in the workshop. The workshop began by examining the static situation in the rate of alcohol-impaired driving fatal crashes to determine what factors may be inhibiting further progress. The workshop then discussed eight effective strategies that have not been fully implemented in the United States. Workshop participants (16 of the 26) rated their top three strategies. Results Three strategies received the most support: Impose administrative sanctions for drivers with BACs = .05 to .08 g/dL.Require alcohol ignition interlocks for all alcohol-impaired driving offenders.Increase the frequency of sobriety checkpoints, including enacting legislation to allow them in the 11 states that currently prohibit them. Five other important strategies included the following: (a) increase alcohol taxes to raise the price and reduce alcohol consumption; (b) re-engage the public and raise the priority of impaired driving; (c) lower the illegal per se BAC limit to .05 for a criminal offense; (d) develop and implement in-vehicle alcohol detection systems; and (e) expand the use of screening and brief interventions in medical facilities. Conclusions Each of these strategies is proven to be effective, yet all are substantially underutilized. Each is used in some jurisdictions in the United States or Canada, but none is used extensively. Any one of the three strategies implemented on a widespread basis would decrease impaired driving crashes, injuries, and fatalities. Based on the research, all three together would have a substantial impact on the problem. PMID:26980557

Can progress in reducing alcohol-impaired driving fatalities be resumed? Results of a workshop sponsored by the Transportation Research Board, Alcohol, Other Drugs, and Transportation Committee (ANB50).

PubMed

Fell, James C; Beirness, Douglas J; Voas, Robert B; Smith, Gordon S; Jonah, Brian; Maxwell, Jane Carlisle; Price, Jana; Hedlund, James

2016-11-16

Despite successes in the 1980s and early 1990s, progress in reducing impaired driving fatalities in the United States has stagnated in recent years. Since 1997, the percentage of drivers involved in fatal crashes with illegal blood alcohol concentration (BAC) levels has remained at approximately 20 to 22%. Many experts believe that public complacency, competing social and public health issues, and the lack of political fortitude have all contributed to this stagnation. The number of alcohol-related crashes, injuries, and fatalities is still unacceptable, and most are preventable. The public needs to be aware that the problem presented by drinking drivers has not been solved. Political leaders need guidance on which measures will affect the problem, and stakeholders need to be motivated once again to implement effective strategies. The National Academy of Sciences (NAS) Transportation Research Board (TRB), Alcohol, Other Drugs, and Transportation Committee (ANB50) sponsored a workshop held at the NAS facility in Woods Hole, Massachusetts, on August 24-25, 2015, to discuss the lack of progress in reducing impaired driving and to make recommendations for future progress. A total of 26 experts in research and policy related to alcohol-impaired driving participated in the workshop. The workshop began by examining the static situation in the rate of alcohol-impaired driving fatal crashes to determine what factors may be inhibiting further progress. The workshop then discussed 8 effective strategies that have not been fully implemented in the United States. Workshop participants (16 of the 26) rated their top 3 strategies. 3 strategies received the most support: 1. Impose administrative sanctions for drivers with BACs = 0.05 to 0.08 g/dL. 2. Require alcohol ignition interlocks for all alcohol-impaired driving offenders. 3. Increase the frequency of sobriety checkpoints, including enacting legislation to allow them in the 11 states that currently prohibit them. 5 other important strategies included the following: (1) increase alcohol taxes to raise the price and reduce alcohol consumption; (2) reengage the public and raise the priority of impaired driving; (3) lower the illegal per se BAC limit to 0.05 for a criminal offense; (4) develop and implement in-vehicle alcohol detection systems; and (5) expand the use of screening and brief interventions in medical facilities. Each of these strategies is proven to be effective, yet all are substantially underutilized. Each is used in some jurisdictions in the United States or Canada, but none is used extensively. Any one of the 3 strategies implemented on a widespread basis would decrease impaired driving crashes, injuries, and fatalities. Based on the research, all 3 together would have a substantial impact on the problem.

Exploring the experiences and coping strategies of international medical students

PubMed Central

2011-01-01

Background Few studies have addressed the challenges that international medical students face and there is a dearth of information on the behavioural strategies these students adopt to successfully progress through their academic program in the face of substantial difficulties of language barrier, curriculum overload, financial constraints and assessment tasks that require high proficiency in communication skills. Methods This study was designed primarily with the aim of enhancing understanding of the coping strategies, skill perceptions and knowledge of assessment expectations of international students as they progress through the third and fourth years of their medical degree at the School of Medicine, University of Tasmania, Australia. Results Survey, focus group discussion and individual interviews revealed that language barriers, communication skills, cultural differences, financial burdens, heavy workloads and discriminatory bottlenecks were key factors that hindered their adaptation to the Australian culture. Quantitative analyses of their examination results showed that there were highly significant (p < 0.001) variations between student performances in multiple choice questions, short answer questions and objective structured clinical examinations (70.3%, 49.7% & 61.7% respectively), indicating existence of communication issues. Conclusions Despite the challenges, these students have adopted commendable coping strategies and progressed through the course largely due to their high sense of responsibility towards their family, their focus on the goal of graduating as medical doctors and their support networks. It was concluded that faculty needs to provide both academic and moral support to their international medical students at three major intervention points, namely point of entry, mid way through the course and at the end of the course to enhance their coping skills and academic progression. Finally, appropriate recommendations were made. PMID:21702988

Single neuropsychological test scores associated with rate of cognitive decline in early Alzheimer disease.

PubMed

Parikh, Mili; Hynan, Linda S; Weiner, Myron F; Lacritz, Laura; Ringe, Wendy; Cullum, C Munro

2014-01-01

Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in the rate of cognitive decline. For research and clinical purposes it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate. Our objective was to use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in participants with mild AD. We reviewed the records of a series of 96 consecutive participants with mild AD from 1995 to 2011 who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over 2 years, participants were classified as Faster (n = 45) or Slower (n = 51) Progressors. Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed. Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups. Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression.

Classroom interactions: exploring the practices of high- and low-expectation teachers.

PubMed

Rubie-Davies, Christine M

2007-06-01

Early research exploring teacher expectations concentrated on the dyadic classroom interactions of teachers with individual students. More recent studies have shown whole class factors to have more significance in portraying teachers' expectations. Recently teachers having high or low expectations for all their students have been identified. The aim of the current investigation was to explore whether the classroom exchanges of high- and low-expectation teachers differed substantially and might be considered a mechanism for teachers' expectations. The participants were 12 primary school teachers from eight schools who had been identified as having expectations for their students' learning that were either significantly above or below the children's achievement level. The teachers formed three groups called high-expectation, low-expectation and average-progress teachers. The participants were observed twice in the academic year during half-hour reading lessons. Two people observed each lesson, one completing a structured observation protocol and the other a running record and audiotape. In contrast to the average progress and low expectation teachers, the high-expectation teachers spent more time providing a framework for students' learning, provided their students with more feedback, questioned their students using more higher-order questions, and managed their students' behaviour more positively. There appear to be important differences in the classroom environments for the students of high-expectation, average-progress and low-expectation teachers. The differences apply to both the instructional and socioemotional environments of the classroom. Such disparities may act as mechanisms for teacher expectation effects.

Accelerating Progress in Eating Disorders Prevention: A Call for Policy Translation Research and Training.

PubMed

Austin, S Bryn

2016-01-01

The public health burden of eating disorders is well documented, and over the past several decades, researchers have made important advances in the prevention of eating disorders and related problems with body image. Despite these advances, however, several critical limitations to the approaches developed to date leave the field far from achieving the large-scale impact that is needed. This commentary provides a brief review of what achievements in prevention have been made and identifies the gaps that limit the potential for greater impact on population health. A plan is then offered with specific action steps to accelerate progress in high-impact prevention, most compellingly by promoting a shift in priorities to policy translation research and training for scholars through the adoption of a triggers-to-action framework. Finally, the commentary provides an example of the application of the triggers-to-action framework as practiced at the Strategic Training Initiative for the Prevention of Eating Disorders, a program based at the Harvard T. H. Chan School of Public Health and Boston Children's Hospital. Much has been achieved in the nearly 30 years of research carried out for the prevention of eating disorders and body image problems, but several critical limitations undermine the field's potential for meaningful impact. Through a shift in the field's priorities to policy translation research and training with an emphasis on macro-environmental influences, the pace of progress in prevention can be accelerated and the potential for large-scale impact substantially improved.

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

ERIC Educational Resources Information Center

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

2016-01-01

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

76 FR 68617 - National Diabetes Month, 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-04

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

37 CFR 11.306 - Trial publicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

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

37 CFR 11.306 - Trial publicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

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

24 CFR 597.403 - Revocation of designation.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium.

PubMed

Klein, Ronald; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T V M; Sivakumaran, Theru A; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K; Lee, Kristine E; Stricker, Bruno H; Vingerling, Johannes R; Mitchell, Paul; Klein, Barbara E K; Klaver, Caroline C W; Wang, Jie Jin

2014-09-01

To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Meta-analysis. setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES), and Rotterdam Study (RS). observation procedures: Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. main outcome measures: Incidence of AMD. The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the 3 studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. Copyright © 2014 Elsevier Inc. All rights reserved.

High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia

PubMed Central

Cao, Chuanhai; Loewenstein, David A.; Lin, Xiaoyang; Zhang, Chi; Wang, Li; Duara, Ranjan; Wu, Yougui; Giannini, Alessandra; Bai, Ge; Cai, Jianfeng; Greig, Maria; Schofield, Elizabeth; Ashok, Raj; Small, Brent; Potter, Huntington; Arendash, Gary W.

2017-01-01

Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer’s disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65–88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2–4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (−51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 µM) in MCI subjects were associated with no conversion to dementia during the ensuing 2–4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI. PMID:22430531

The future of breast cancer systemic therapy: the next 10 years.

PubMed

Telli, Melinda L; Sledge, George W

2015-02-01

Over the past 50 years, substantial progress has been made in the systemic treatment of early-stage and advanced breast cancer. The use of chemotherapy in the adjuvant and metastatic settings has demonstrated proven efficacy and it has been clearly demonstrated that targeting the estrogen receptor and human growth factor receptor 2 (HER2) is efficacious in early and advanced disease. Despite these advances, vexing clinical challenges remain particularly related to the treatment of triple-negative breast cancer (TNBC; estrogen receptor [ER]-negative, progesterone receptor [PR]-negative, and HER2-negative) where little progress has been made therapeutically in more than a decade. While recurrences of hormone-responsive breast cancer are overall less common, late relapses after cessation of endocrine therapy are a more frequent occurrence in modern times and reflect the problem of underlying tumor dormancy that as yet has not been overcome. Multiple molecular tools are now available to interrogate the biology of breast cancer, though exactly how to make this information meaningful in the clinic has proven challenging, and molecularly driven clinical trials have faced feasibility challenges. In parallel, focus has expanded from tumor to host with the ability to ascertain underlying germline alterations, such as inherited BRCA1 and BRCA2 mutations, which may be responsible for breast cancer carcinogenesis and, importantly, may have implications for treatment. These clinical advances in germline genetics, made possible by both scientific investigation as well as the courts, still face challenges related to increasing encounters with variants of unknown significance and difficulty in predicting risks associated with less well-characterized inherited cancer predisposition syndromes. In this paper, we attempt to predict the next 10 years of breast cancer, in particular focusing on how the past serves as prologue to the future in this disease.

CDC National Health Report: leading causes of morbidity and mortality and associated behavioral risk and protective factors--United States, 2005-2013.

PubMed

Johnson, Nicole Blair; Hayes, Locola D; Brown, Kathryn; Hoo, Elizabeth C; Ethier, Kathleen A

2014-10-31

Although substantial progress has been made in improving the health of persons in the United States, serious problems remain to be solved. Life expectancy is increasing, and the rates of the leading causes of death are improving in many cases; however, numerous indicators (i.e., measures of observed or calculated data on the status of a condition) of the health and safety of the U.S. population remain poor. This report reviews population health in the United States and provides an assessment of recent progress in meeting high-priority health objectives. The health status indicators described in this report were selected because of their direct relation to the leading causes of death and other substantial sources of morbidity and mortality and should be the focus of prevention efforts. Data are reported starting in 2005 (or the earliest available year since 2005) through the current data year. Because data sources and specific indicators vary regarding when data are available, the most recent year for which data are available might range from 2010 to 2013. Data were obtained from 17 CDC surveys or surveillance systems and three non-CDC sources to provide a view of this particular point of time in the nation's health and trends in recent years. Data from the following CDC surveillance systems and surveys were used: Behavioral Risk Factor Surveillance System (BRFSS); Emerging Infections Program/Active Bacterial Core surveillance (EIP/ABCs); Foodborne Diseases Active Surveillance Network (FoodNet); Internet Panel Surveys: Influenza Vaccination Coverage Among Health-Care Personnel and Influenza Vaccination Coverage Among Pregnant Women; National Ambulatory Medical Care Survey (NAMCS); National Health and Nutrition Examination Survey (NHANES); National Health Interview Survey (NHIS); National Healthcare Safety Network (NHSN); National HIV Surveillance System; National Hospital Discharge Survey (NHDS); National Immunization Survey (NIS); National Immunization Survey-Teen (NIS-Teen); National Notifiable Disease Surveillance System (NNDSS); Nationally Notifiable STD Surveillance; National Vital Statistics System (NVSS); and Youth Risk Behavior Surveillance System (YRBSS). Three non-CDC sources were used: the Alcohol and Tobacco Tax and Trade Bureau Monthly Statistical Releases; the National Highway Traffic Safety Administration Fatality Analysis Reporting System (FARS); and the Substance Abuse and Mental Health Services Administration's National Survey on Drug Use and Health (NSDUH). Since 2005, life expectancy at birth in the U.S. has increased by 1 year; however, the number of persons who died prematurely was relatively constant. The years of potential life lost declined for eight of the 10 leading causes of death. Age-adjusted rates declined among all leading causes except deaths attributable to Alzheimer's disease and suicide, although the numbers of deaths increased for most causes. Heart disease, stroke, and deaths attributed to motor-vehicle injuries demonstrated notable declines since 2005. Numbers and rates increased for both Alzheimer's disease and suicide. The number of deaths from drug poisoning increased by approximately 11,000, and the number of deaths among older adults caused by falls increased by approximately 7,000. Risk and protective factors for these leading causes of death also showed mixed progress. Current smoking among adults remained stable at approximately 25% while smoking among youths declined to a record low of 15.7%. Obesity rates remained level at approximately 35% for adults and approximately 17% for youths. Approximately 21% of adults met recommended levels of physical activity, consistent with results recorded in the 3 previous years. Control of blood pressure and cholesterol increased to 46.3% and 29.5%, respectively. During the 2012-13 influenza season, vaccination rates reached highs of 72.0% for health-care personnel, 56.6% for children aged <17 years, 50.5% for pregnant women, and 41.5% for persons aged >18 years. Other important measures of the health of the U.S. population also varied. Rates of foodborne illness varied from year to year, with average annual increases for Salmonella and Salmonella serotype Enteritidis. Listeria rates were stable in recent years at 0.26 cases per 100,000 population. Shiga toxin-producing E. coli (STEC) O157 increased during the past 3 years to a rate of 1.15 cases per 100,000 population, even though the annual change for the study period noted an average decline overall. Health-care-associated infections declined, on average, for central-line associated bloodstream infections (CLABSI), surgical site infections (SSI), and Methicillin-resistant Staphylococcus aureus (MRSA) infection. The percentage of persons living with HIV who know their serostatus increased to 84.2%, but trends fluctuated for the number of new HIV infections and the rate of HIV transmission among adolescents and adults. Chlamydia rates increased by an average of 3.3% per year for persons aged 15-19 years and by 4.9% per year for women aged 20-24 years. The number of new cases of hepatitis C and hepatitis C-associated deaths increased by an average of 6.4% and 6.0% per year. Indictors of maternal and child health all improved, including historically low rates of infant mortality (6.1 per 1,000 live births) and teen births (26.6 per 1,000 female population). The percentage of infants breastfed at 6 months increased to 49.4%. Among children aged 19-35 months, 70.4% received the set of universally recommended vaccines, an increase of 2.9% from the previous year. The findings in this report indicate that progress has been steady but slow for many of the priority health issues in the United States. The age-adjusted rates for most of the leading causes of death are declining, but in some cases, the number of deaths is increasing, in part reflecting the growing U.S. population. Several protective factors that have registered substantial average increases (e.g., physical activity among adults, high blood pressure control, and human papillomavirus vaccination among adolescent females) have stalled in recent years. Many protective factors, even those with impressive relative gains, still represent only a minority of the U.S. population (e.g., control of high cholesterol at 29.5%). More data are needed to properly interpret fluctuating trends, such as those observed with the number of HIV infections and HIV transmission rates. Finally, some indicators of disease that appear to be increasing, such as chlamydia and hepatitis C, reflect increased efforts to engage in targeted screening but also suggest that the actual burden of infection is much greater than the reported data alone indicate. Although not all-inclusive, this compilation highlights important health concerns, points to areas in which important success has been achieved, and highlights areas in which more effort is needed. By tracking progress, public health officials, program managers, and decision makers can better identify areas for improvement and institute policies and programs to improve health and the quality of life.

Early vegetation development after grassland restoration by sowing low-diversity seed mixtures in former sunflower and cereal fields.

PubMed

Vida, Enikö; Valkó, Orsolya; Kelemen, A; Török, P; Deák, B; Miglécz, T; Lengyel, Sz; Tóthmérész, B

2010-01-01

We studied the early vegetation dynamics in former croplands (sunflower and cereal fields) sown with a low-diversity seed mixture (composed of 2 native grass species) in Egyek-Pusztakócs, Hortobágy National Park, East-Hungary. The percentage cover of vascular plants was recorded in 4 permanent plots per field on 7 restored fields between 2006 and 2009. Ten aboveground biomass samples per field were also collected in June in each year. We addressed two questions: (i) How do seed sowing and annual mowing affect the species richness, biomass and cover of weeds? (ii) How fast does the cover of sown grasses develop after seed sowing? Weedy species were characteristic in the first year after sowing. In the second and third year their cover and species richness decreased. From the second year onwards the cover of perennial grasses increased. Spontaneously immigrating species characteristic to the reference grasslands were also detected with low cover scores. Short-lived weeds were suppressed as their cover and biomass significantly decreased during the study. The amount of litter and sown grass biomass increased progressively. However, perennial weed cover, especially the cover of Cirsium arvense increased substantially. Our results suggest that grassland vegetation can be recovered by sowing low diversity mixtures followed up by yearly mowing. Suppression of perennial weed cover needs more frequent mowing (multiple times a year) or grazing.

Cognitive activity limitations one year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury.

PubMed

Sommer, Jens Bak; Norup, Anne; Poulsen, Ingrid; Morgensen, Jesper

2013-09-01

To examine cognitive activity limitations and predictors of outcome 1 year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury. The study included 119 patients with severe traumatic brain injury admitted to centralized sub-acute rehabilitation in the Eastern part of Denmark during a 5-year period from 2005 to 2009. Level of consciousness was assessed consecutively during rehabilitation and at 1 year post-trauma. Severity of traumatic brain injury was classified according to duration of post-traumatic amnesia. The cognitive subscale of Functional Independence MeasureTM (Cog-FIM) was used to assess cognitive activity limitations. Multivariate logistic regression analyses were performed to identify predictors of an independent level of functioning. The majority of patients progressed to a post-confusional level of consciousness during the first year post-trauma. At follow-up 33-58% of patients had achieved functional independence within the cognitive domains on the Cog-FIM. Socio-economic status, duration of acute care and post-traumatic amnesia were significant predictors of outcome. Substantial recovery was documented among patients with severe traumatic brain injury during the first year post-trauma. The results of the current study suggest that absence of consciousness at discharge from acute care should not preclude patients from being referred to specialized sub-acute rehabilitation.

26 CFR 1.274-6T - Substantiation with respect to certain types of listed property for taxable years beginning after...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 3 2013-04-01 2013-04-01 false Substantiation with respect to certain types of listed property for taxable years beginning after 1985 (temporary). 1.274-6T Section 1.274-6T Internal... TAXES (CONTINUED) Items Not Deductible § 1.274-6T Substantiation with respect to certain types of listed...

26 CFR 1.274-6T - Substantiation with respect to certain types of listed property for taxable years beginning after...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 3 2014-04-01 2014-04-01 false Substantiation with respect to certain types of listed property for taxable years beginning after 1985 (temporary). 1.274-6T Section 1.274-6T Internal... TAXES (CONTINUED) Items Not Deductible § 1.274-6T Substantiation with respect to certain types of listed...

26 CFR 1.274-6T - Substantiation with respect to certain types of listed property for taxable years beginning after...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 3 2011-04-01 2011-04-01 false Substantiation with respect to certain types of listed property for taxable years beginning after 1985 (temporary). 1.274-6T Section 1.274-6T Internal... TAXES (CONTINUED) Items Not Deductible § 1.274-6T Substantiation with respect to certain types of listed...

26 CFR 1.274-6T - Substantiation with respect to certain types of listed property for taxable years beginning after...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 3 2012-04-01 2012-04-01 false Substantiation with respect to certain types of listed property for taxable years beginning after 1985 (temporary). 1.274-6T Section 1.274-6T Internal... TAXES (CONTINUED) Items Not Deductible § 1.274-6T Substantiation with respect to certain types of listed...

Disrupted progression of the intestinal microbiota with age in children with cystic fibrosis.

PubMed

Nielsen, Shaun; Needham, Bronwen; Leach, Steven T; Day, Andrew S; Jaffe, Adam; Thomas, Torsten; Ooi, Chee Y

2016-05-04

Cystic fibrosis (CF) is a genetic disorder that leads to formation of thick epithelial secretions in affected organs. Chronic microbial infections associated with thick mucus secretions are the hallmarks of lung disease in CF. Despite similar conditions existing in the gastrointestinal tract, it is much less studied. We therefore examined the microbial communities within the gastrointestinal tract of children with and without CF (either pancreatic sufficient or insufficient) across a range of childhood ages (0.87-17 years). We observed a substantial reduction in the richness and diversity of gut bacteria associated with CF from early childhood (2 years) until late adolescence (17 years). A number of bacteria that establish themselves in the gut of healthy children were unable to do so in children with CF. In contrast, a few bacteria dominated the gut microbiota in children with CF and are unlikely to be beneficial for the metabolic function of the gut. A functioning pancreas (pancreatic sufficient) under a CF lifestyle showed little effect on microbial communities. Our results argue that any attempts to rectify the loss of bacterial diversity and provide normal bacterial function in the gut of CF patients should be conducted no later than early childhood.

Impact of cancer therapy-related exposures on late mortality in childhood cancer survivors

PubMed Central

Gibson, Todd M.; Robison, Leslie L.

2015-01-01

Survival of children and adolescents diagnosed with cancer has improved dramatically in recent decades, but the substantial burden of late morbidity and mortality (i.e. more than five years after cancer diagnosis) associated with pediatric cancer treatments is increasingly being recognized. Progression or recurrence of the initial cancer is a primary cause of death in the initial post-diagnosis period, but as survivors age there is a dramatic shift in the cause-specific mortality profile. By 15 years post-diagnosis, the death rate attributable to health-related causes other than recurrence or external causes (e.g. accidents, suicide, assault) exceeds that due to primary disease, and by 30 years these causes account for the largest proportion of cumulative mortality. The two most prominent causes of treatment-related mortality in childhood cancer survivors are subsequent malignant neoplasms and cardiovascular problems, incidence of which can be largely attributed to the long-term toxicities of radiation and chemotherapy exposures. These late effects of treatment are likely to increase in importance as survivors continue to age, inspiring continued research to better understand their etiology and to inform early detection or prevention efforts. PMID:25474125

Lung transplantation for cystic fibrosis: results, indications, complications, and controversies.

PubMed

Lynch, Joseph P; Sayah, David M; Belperio, John A; Weigt, S Sam

2015-04-01

Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (∼50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Acoustic Holography of the Solar Convection Zone with SOHO-MDI Observations

NASA Technical Reports Server (NTRS)

Lindsey, Charles

2005-01-01

The original grant with the title stated above was NAG5-10984, awarded to the Solar Physics Research Corporation (SPRC) in July, 2001, and was to be a three-year project. The basic theme of the project was the development and application of computational seismic holography for imaging, diagnostics, and monitoring of magnetic anomalies beneath active regions, in the deep solar interior, and on the Sun's far surface. The project was roughly separated into the following five tasks: (1) A holographic survey of active regions. (2) p-Mode absorption diagnostics of magnetic regions. (3) Acoustic modeling of the shallow subphotospheres of active regions and the quiet-Sun supergranulation based on phase-correlation seismic holography. (4) Seismic holography of the deep convection zone. (5) Improvements in holographic imaging of the far surface of the Sun. Following the death of Karen Harvey, President of SPRC, during the first year, the grant was transferred to Northwest Research Associates as NAG5-12901. Substantial but progress had been made on most of the above tasks in the first year under NAG5-10984, but none were completed. This work was continued under NAG5-12901.

Optical Coherence Tomography Angiography Reveals Mature, Tangled Vascular Networks in Eyes With Neovascular Age-Related Macular Degeneration Showing Resistance to Geographic Atrophy.

PubMed

Dansingani, Kunal K; Freund, K Bailey

2015-10-01

To demonstrate a vascular pattern seen on optical coherence tomography angiography (OCTA) that appears to correlate with reduced rates of geographic atrophy (GA) in eyes receiving long-term anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). Non-consecutive, retrospective cohort study. Patients were included if they had received more than 50 anti-VEGF injections during a period of at least 4 years for neovascular AMD in at least one eye, with absence or minimal progression of GA. Clinical charts and imaging were reviewed retrospectively; study eyes underwent OCTA. Nine eyes of eight patients were included. Mean age was 82 years, and mean follow-up of study eyes 9.1 years; study eyes received a mean of 65.8 injections. OCTA revealed tangled networks of neovessels associated with type 1 lesions. With prolonged anti-VEGF treatment, GA appears to occur less commonly in eyes with type 1 neovascularization. OCTA shows mature tangled vessels with substantial flow within type 1 lesions. Mature, tangled networks may be associated with a decreased likelihood of developing GA despite the presence of choriocapillaris atrophy. Copyright 2015, SLACK Incorporated.

Regional Carbon Dioxide and Water Vapor Exchange Over Heterogeneous Terrain

NASA Technical Reports Server (NTRS)

Mahrt, Larry J.

2005-01-01

In spite of setbacks due to forest fires, eviction after a change of landowners and unanticipated need to upgrade and replace much of the instrumentation, substantial progress has been made during the past three years, resulting in major new findings. Although most of the results are in manuscript form, three papers have been published and a fourth was recently submitted. The data has been subjected to extensive quality control. Extra attention has been devoted to the influence of tilt rotation and flux-calculation method, particularly with respect to nocturnal fluxes. Previous/standard methods for calculating nocturnal fluxes with moderate and strong stability are inadequate and lead to large random fluxes errors for individual records, due partly to inadvertent inclusion of mesoscale motions that strongly contaminant the estimation of fluxes by weak turbulence. Such large errors are serious for process studies requiring carbon dioxide fluxes for individual records, but are substantially reduced when averaging fluxes over longer periods as in calculation of annual NEE budgets. We have employed a superior method for estimating fluxes in stable conditions with a variable averaging width . Mesoscale fluxes are generally unimportant except for events and are generally not systematic or predictable. Mesoscale or regional models of our region are not able to reproduce important aspects of the diurnally varying wind field

The World Spatiotemporal Analytics and Mapping Project (WSTAMP): Further Progress in Discovering, Exploring, and Mapping Spatiotemporal Patterns Across the World's Largest Open Source Data Sets

NASA Astrophysics Data System (ADS)

Piburn, J.; Stewart, R.; Myers, A.; Sorokine, A.; Axley, E.; Anderson, D.; Burdette, J.; Biddle, C.; Hohl, A.; Eberle, R.; Kaufman, J.; Morton, A.

2017-10-01

Spatiotemporal (ST) analytics applied to major data sources such as the World Bank and World Health Organization has shown tremendous value in shedding light on the evolution of cultural, health, economic, and geopolitical landscapes on a global level. WSTAMP engages this opportunity by situating analysts, data, and analytics together within a visually rich and computationally rigorous online analysis environment. Since introducing WSTAMP at the First International Workshop on Spatiotemporal Computing, several transformative advances have occurred. Collaboration with human computer interaction experts led to a complete interface redesign that deeply immerses the analyst within a ST context, significantly increases visual and textual content, provides navigational crosswalks for attribute discovery, substantially reduce mouse and keyboard actions, and supports user data uploads. Secondly, the database has been expanded to include over 16,000 attributes, 50 years of time, and 200+ nation states and redesigned to support non-annual, non-national, city, and interaction data. Finally, two new analytics are implemented for analyzing large portfolios of multi-attribute data and measuring the behavioral stability of regions along different dimensions. These advances required substantial new approaches in design, algorithmic innovations, and increased computational efficiency. We report on these advances and inform how others may freely access the tool.

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

PubMed

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

2015-01-01

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

Cytolethal distending toxin in isolates of Aggregatibacter actinomycetemcomitans from Ghanaian adolescents and association with serotype and disease progression.

PubMed

Höglund Åberg, Carola; Antonoglou, Georgios; Haubek, Dorte; Kwamin, Francis; Claesson, Rolf; Johansson, Anders

2013-01-01

The cytolethal distending toxin (Cdt) is a highly conserved exotoxin that are produced by a number of Gram negative bacteria, including Aggregatibacter actinomycetemcomitans, and affects mammalian cells by inhibiting cell division and causing apoptosis. A complete cdt-operon is present in the majority of A. actinomycetemcomitans, but the proportion of isolates that lack cdt-encoding genes (A, B and C) varies according to the population studied. The objectives of this study were to examine serotype, Cdt-genotype, and Cdt-activity in isolates of A. actinomycetemcomitans collected from an adolescent West African population and to examine the association between the carrier status of A. actinomycetemcomitans and the progression of attachment loss (AL). A total of 249 A. actinomycetemcomitans isolates from 200 Ghanaian adolescents were examined for serotype and cdt-genotype by PCR. The activity of the Cdt-toxin was examined by DNA-staining of exposed cultured cells and documented with flow cytometry. The periodontal status of the participants was examined at baseline and at a two-year follow-up. Presence of all three cdt-encoding genes was detected in 79% of the examined A. actinomycetemcomitans isolates. All these isolates showed a substantial Cdt-activity. The two different cdt-genotypes (with and without presence of all three cdt-encoding genes) showed a serotype-dependent distribution pattern. Presence of A. actinomycetemcomitans was significantly associated with progression of AL (OR = 5.126; 95% CI = [2.994-8.779], p<0.001). A. actinomycetemcomitans isolated from the Ghanaian adolescents showed a distribution of serotype and cdt-genotype in line with results based on other previously studied populations. Presence of A. actinomycetemcomitans was significantly associated with disease progression, in particular the b serotype, whereas the association with disease progression was not particularly related to cdt-genotype, and Cdt-activity.

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

PubMed

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

2015-09-01

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

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

PubMed

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

2015-03-01

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

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.

In search of average growth: describing within-year oral reading fluency growth across Grades 1-8.

PubMed

Nese, Joseph F T; Biancarosa, Gina; Cummings, Kelli; Kennedy, Patrick; Alonzo, Julie; Tindal, Gerald

2013-10-01

Measures of oral reading fluency (ORF) are perhaps the most often used assessment to monitor student progress as part of a response to intervention (RTI) model. Rates of growth in research and aim lines in practice are used to characterize student growth; in either case, growth is generally defined as linear, increasing at a constant rate. Recent research suggests ORF growth follows a nonlinear trajectory, but limitations related to the datasets used in such studies, composed of only three testing occasions, curtails their ability to examine the true functional form of ORF growth. The purpose of this study was to model within-year ORF growth using up to eight testing occasions for 1448 students in Grades 1 to 8 to assess (a) the average growth trajectory for within-year ORF growth, (b) whether students vary significantly in within-year ORF growth, and (c) the extent to which findings are consistent across grades. Results demonstrated that for Grades 1 to 7, a quadratic growth model fit better than either linear or cubic growth models, and for Grade 8, there was no substantial, stable growth. Findings suggest that the expectation for linear growth currently used in practice may be unrealistic. Copyright © 2013 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Changes in tobacco use among youths aged 13-15 years - Panama, 2002 and 2008.

PubMed

2009-01-09

Tobacco use is the single most preventable cause of death in the world today, and the majority of smokers begin using tobacco products before age 18 years. However, before the late 1990s, few countries had reliable data on youth tobacco use. In 1999, the World Health Organization (WHO), CDC, and the Canadian Public Health Association developed the Global Youth Tobacco Survey (GYTS) to help countries monitor youth tobacco use. At the same time, WHO initiated the Framework Convention on Tobacco Control (WHO FCTC), the first international public health treaty on tobacco control. Panama ratified WHO FCTC in 2004 and enacted two key antitobacco regulations in 2005 and 2008. To evaluate progress toward attaining tobacco control goals in Panama, Panama's Ministry of Health, CDC, and WHO compared results from GYTS surveys conducted in Panama in 2002 and 2008. This report summarizes the results of that comparison, which revealed substantial decreases from 2002 to 2008 in youth current cigarette smoking (13.2% versus 4.3%), current use of tobacco products other than cigarettes (9.8% versus 5.8%), and likely initiation of smoking by never smokers (13.8% versus 10.0%). In addition, factors influencing tobacco use showed substantial decreases, including 1) exposure to secondhand smoke (SHS) at home and in public places, 2) best friends smoking, 3) protobacco advertising in newspapers and magazines, and 4) having an object with a tobacco company logo on it. These results suggest that comprehensive regulations in Panama helped reduce tobacco use among adolescents and further gains are possible.

How Reliable is the Temperature Forecast?

ERIC Educational Resources Information Center

Christmann, Edwin P.

2005-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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

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

EPA Pesticide Factsheets

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

Attachment in Middle Childhood: Progress and Prospects

ERIC Educational Resources Information Center

Bosmans, Guy; Kerns, Kathryn A.

2015-01-01

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

Genome editing: progress and challenges for medical applications.

PubMed

Carroll, Dana

2016-11-15

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

12 CFR 213.4 - Content of disclosures.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

ERIC Educational Resources Information Center

Jensen, Peter S.

2005-01-01

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

Why Do Teachers Leave? CenterView

ERIC Educational Resources Information Center

Center for the Future of Teaching and Learning, 2007

2007-01-01

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

Monitoring clinical progression with mitochondrial disease biomarkers

PubMed Central

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

2017-01-01

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

Mathematical Models of Breast and Ovarian Cancers

PubMed Central

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

2016-01-01

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

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

PubMed

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

2006-02-01

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

[The role of subclinical inflammation in progression of multifocal atherosclerosis during one year after myocardial infarction].

PubMed

Barbarash, O L; Usol'tseva, E N; Kashtalap, V V; Kolomytseva, I S; Sizova, I N; Volykova, M A; Shibanova, I A

2014-01-01

To elucidate role of subclinical inflammation in progression of atherosclerotic process in magistral noncoronary arteries in patients during one year after ST-elevation myocardial infarction (MI). We examined 168 men with MI (mean age 59.5 years). All patients during hospitalization underwent coronary angiography and color duplex scanning of brachiocephalic arteries. In a year ultrasound study of noncoronary vessels was repeated and progression of atherosclerosis assessed. Parameters of inflammation in blood serum were measured on days 10-14 of MI and after one year. At repeat study most patients demonstrated progression of noncoronary atherosclerosis. Some biomarkers measured during inhospital phase of MI (low concentration of anti-inflammatory interleukin 10 - IL-10, elevated N-terminal pro brain natriuretic peptide) allowed to distinguish group of patients with subsequent progression of noncoronary atherosclerosis. Elevated concentrations of C-reactive protein and 11-10 registered in a year after MI were also associated with more severe progression of atherosclerosis. Serum levels of neopterin and IL-12 remained stable in patients with and decreased in patients without pronounced progression of atherosclerosis.

Glucocorticoid treatment for the prevention of scoliosis in children with Duchenne muscular dystrophy: long-term follow-up.

PubMed

Lebel, David E; Corston, John A; McAdam, Laura C; Biggar, W Douglas; Alman, Benjamin A

2013-06-19

Duchenne muscular dystrophy, a progressive muscle disorder that occurs in males, causes a gradual decline in muscle strength. This progressive decline is associated with the development of scoliosis. Previous studies have shown that the use of glucocorticoids slows the progression of scoliosis, but it is unknown if the spine remains straight in the long term. We examined if glucocorticoid treatment has a long-term effect on the prevalence of scoliosis. Fifty-four boys who had been diagnosed with Duchenne muscular dystrophy while they were still walking were enrolled in a non-randomized comparative study of the glucocorticoid deflazacort. The families of thirty boys elected for them to use glucocorticoid treatment and the families of twenty-four boys elected for them not to have this treatment. The boys were matched for important baseline characteristics including age and pulmonary function. Every four to six months, they were examined for the development of scoliosis, and the duration of follow-up for surviving patients was fifteen years. Because surgery was recommended for spinal curves measuring >20° on sitting posteroanterior radiographs, a curve of this magnitude was used as the definition for a patient developing scoliosis. Five boys (21%) in the non-treatment group and one boy (3%) in the glucocorticoid treatment group died. At the most recent follow-up, of the boys who survived, six (20%) in the glucocorticoid treatment group and twenty-two (92%) in the non-treatment group developed scoliosis and underwent spinal surgery. After fifteen years of follow-up, the survivorship analysis (avoiding surgery) was 78% (95% confidence interval, 57% to 89%) in the treatment group and 8.3% (95% confidence interval, 0.8% to 28%) in the non-treatment group. Significance (p = 5.8 × 10(-7)) was calculated with log-rank and chi-square tests. None of the patients in the glucocorticoid group developed scoliosis after ten years of deflazacort treatment. The long-term use of the glucocorticoid results in a substantial decreased need for spinal surgery to treat scoliosis.

A review of soft-tissue sarcomas: translation of biological advances into treatment measures

PubMed Central

Mann, Michael J; Tolani, Bhairavi

2018-01-01

Soft-tissue sarcomas are rare malignant tumors arising from connective tissues and have an overall incidence of about five per 100,000 per year. While this diverse family of malignancies comprises over 100 histological subtypes and many molecular aberrations are prevalent within specific sarcomas, very few are therapeutically targeted. Instead of utilizing molecular signatures, first-line sarcoma treatment options are still limited to traditional surgery and chemotherapy, and many of the latter remain largely ineffective and are plagued by disease resistance. Currently, the mechanism of sarcoma oncogenesis remains largely unknown, thus necessitating a better understanding of pathogenesis. Although substantial progress has not occurred with molecularly targeted therapies over the past 30 years, increased knowledge about sarcoma biology could lead to new and more effective treatment strategies to move the field forward. Here, we discuss biological advances in the core molecular determinants in some of the most common soft-tissue sarcomas – liposarcoma, angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, Ewing’s sarcoma, and synovial sarcoma – with an emphasis on emerging genomic and molecular pathway targets and immunotherapeutic treatment strategies to combat this confounding disease. PMID:29785138

'Full dose' reirradiation of human cervical spinal cord.

PubMed

Ryu, S; Gorty, S; Kazee, A M; Bogart, J; Hahn, S S; Dalal, P S; Chung, C T; Sagerman, R H

2000-02-01

With the progress of modern multimodality cancer treatment, retreatment of late recurrences or second tumors became more commonly encountered in management of patients with cancer. Spinal cord retreatment with radiation is a common problem in this regard. Because radiation myelopathy may result in functional deficits, many oncologists are concerned about radiation-induced myelopathy when retreating tumors located within or immediately adjacent to the previous radiation portal. The treatment decision is complicated because it requires a pertinent assessment of prognostic factors with and without reirradiation, radiobiologic estimation of recovery of occult spinal cord damage from the previous treatment, as well as interactions because of multimodality treatment. Recent studies regarding reirradiation of spinal cord in animals using limb paralysis as an endpoint have shown substantial and almost complete recovery of spinal cord injury after a sufficient time after the initial radiotherapy. We report a case of "full" dose reirradiation of the entire cervical spinal cord in a patient who has not developed clinically detectable radiation-induced myelopathy on long-term follow-up of 17 years after the first radiotherapy and 5 years after the second radiotherapy.

Genetic Engineering Strategies for Enhanced Biodiesel Production.

PubMed

Hegde, Krishnamoorthy; Chandra, Niharika; Sarma, Saurabh Jyoti; Brar, Satinder Kaur; Veeranki, Venkata Dasu

2015-07-01

The focus on biodiesel research has shown a tremendous growth over the last few years. Several microbial and plant sources are being explored for the sustainable biodiesel production to replace the petroleum diesel. Conventional methods of biodiesel production have several limitations related to yield and quality, which led to development of new engineering strategies to improve the biodiesel production in plants, and microorganisms. Substantial progress in utilizing algae, yeast, and Escherichia coli for the renewable production of biodiesel feedstock via genetic engineering of fatty acid metabolic pathways has been reported in the past few years. However, in most of the cases, the successful commercialization of such engineering strategies for sustainable biodiesel production is yet to be seen. This paper systematically presents the drawbacks in the conventional methods for biodiesel production and an exhaustive review on the present status of research in genetic engineering strategies for production of biodiesel in plants, and microorganisms. Further, we summarize the technical challenges need to be tackled to make genetic engineering technology economically sustainable. Finally, the need and prospects of genetic engineering technology for the sustainable biodiesel production and the recommendations for the future research are discussed.

Multiple Symmetrical Lipomatosis--a mitochondrial disorder of brown fat.

PubMed

Plummer, C; Spring, P J; Marotta, R; Chin, J; Taylor, G; Sharpe, D; Athanasou, N A; Thyagarajan, D; Berkovic, S F

2013-07-01

Multiple Symmetrical Lipomatosis (MSL) is an unusual disorder characterized by the development of axial lipomas in adulthood. The pathoetiology of lipoma tissue in MSL remains unresolved. Seven patients with MSL were followed for a mean period of 12 years (8-20 years). All patients had cervical lipomas ranging from subtle lesions to disfiguring masses; six patients had peripheral neuropathy and five had proximal myopathy. Myoclonus, cerebellar ataxia and additional lipomas were variably present. All patients showed clinical progression. Muscle histopathology was consistent with mitochondrial disease. Five patients were positive for mtDNA point mutation m.8344A>G, three of whom underwent lipoma resection--all samples were positive for uncoupling protein-1 mRNA (unique to brown fat). Lipoma from one case stained positive for adipocyte fatty-acid protein-2 (unique to brown fat and immature adipocytes). This long-term study hallmarks the phenotypic heterogeneity of MSL's associated clinical features. The clinical, genetic and molecular findings substantiate the hypothesis that lipomas in MSL are due to a mitochondrial disorder of brown fat. Copyright © 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Application of the MALDI Biotyper to clinical microbiology: progress and potential.

PubMed

Kostrzewa, Markus

2018-03-01

The introduction of the MALDI Biotyper in laboratories substantially changed microbiology practice, this has been called a revolution. The system accelerated diagnostic while costs were reduced and accuracy was increased. In just a few years MALDI-TOF MS became the first-line identification tool for microorganisms. Ten years after its introduction, more than 2000 MALDI Biotyper systems are installed in laboratories which are performing routine diagnostic, and the number is still increasing. Areas covered: This article summarises changes in clinical microbiology introduced by the MALDI Biotyper and its effects, as it has been published in peer reviewed articles found in PubMed. Further, the potential of novel developments to increase the value of the system is described. Expert commentary: The MALDI Biotyper has significantly improved clinical microbiology in the area of microorganism identification. Now new developments and applications, e.g. for typing and resistance testing, might further increase its value in clinical microbiology. The systems might get the central diagnostic analyser which is getting integrated into the widely automated microbiology laboratories of the future.

[Tobacco use among paramedical students in Tunis].

PubMed

Fakhfakh, Radhouane; Jendoubi, Wiem; Achour, Noureddine

2010-08-01

To assess smoking habits among Tunisian paramedical students, and their attitudes and knowledge about smoking. During the first quarter of the school year 2002-2003 we investigate 1288 paramedical students of the College of Sciences and Techniques of the Health in Tunis. The smoker was the student who declare to smoke daily or by occasionally at the time of the survey. About three quarters of the students (77,2 %) were female and half of them was less than 20 years old. Smokers were those who smoked daily or occasionally. The prevalence of smoking was weak but it was 10 fold higher in male than in female (35,5% vs 3,5%) The rate of the ex-smokers was 4,1 %. Progress in studies does not affect smoking behaviour. The knowledge of tobacco induced diseases was generally good. However, there was substantial underestimation of tobacco contribution to causing bladder cancer, coronary artery disease and peripheral vascular disease. The study evidences insufficient awareness of medical students about their responsibilities for heath education and prevention. It is recommended to improve tobacco control educational programs at the paramedical students with elaboration of practical smoking cessation trainings.

A 37-year-old Menkes disease patient-Residual ATP7A activity and early copper administration as key factors in beneficial treatment.

PubMed

Tümer, Z; Petris, M; Zhu, S; Mercer, J; Bukrinski, J; Bilz, S; Baerlocher, K; Horn, N; Møller, L B

2017-11-01

Menkes disease (MD) is a lethal disorder characterized by severe neurological symptoms and connective tissue abnormalities; and results from malfunctioning of cuproenzymes, which cannot receive copper due to a defective intracellular copper transporting protein, ATP7A. Early parenteral copper-histidine supplementation may modify disease progression substantially but beneficial effects of long-term treatment have been recorded in only a few patients. Here we report on the eldest surviving MD patient (37 years) receiving early-onset and long-term copper treatment. He has few neurological symptoms without connective tissue disturbances; and a missense ATP7A variant, p.(Pro852Leu), which results in impaired protein trafficking while the copper transport function is spared. These findings suggest that some cuproenzymes maintain their function when sufficient copper is provided to the cells; and underline the importance of early initiated copper treatment, efficiency of which is likely to be dependent on the mutant ATP7A function. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Radiological Examinations in Pediatric Age.

PubMed

Siciliano, R

2017-01-01

Diagnostic radiology imaging is an essential tool for adequate clinical investigation of pathological processes and the drafting of a personalized therapy plan. However, in recent years, there has been a substantial increase of requests, mainly due to technological advances but also to social and cultural reasons, not always based on the principle of the diagnostic justification. The progress of recent years in the field of diagnostic radiology has made available to the physician a variety of sophisticated radiological examinations, which are not always used rationally and appropriately. The theme is of paramount importance, particularly in childhood or adolescence, characterized by elevated radiosensitivity (high cell turnover) and longer life expectancy; therefore, children exposed to ionizing radiation are theoretically subject to a higher risk of carcinogenesis compared to the general population. For these reasons the young patients should have greater protection and examinations must respect stringent appropriateness criteria. Far from underestimating the important diagnostic and therapeutic benefits that these procedures provide, the use of ionizing radiations must minimize the radiation-related risk in accordance with the ALARA principle (As Low As Reasonably Achievable), key principle of modern radiation protection.

Clinical synovitis in a particular joint is associated with progression of erosions and joint space narrowing in that same joint, but not in patients initially treated with infliximab.

PubMed

Klarenbeek, N B; Güler-Yüksel, M; van der Heijde, D M F M; Hulsmans, H M J; Kerstens, P J S M; Molenaar, T H E; de Sonnaville, P B J; Huizinga, T W J; Dijkmans, B A C; Allaart, C F

2010-12-01

To assess the relationship between joint tenderness, swelling and joint damage progression in individual joints and to evaluate the influence of treatment on these relationships. First-year data of the Behandel Strategieën (BeSt) study were used, in which patients recently diagnosed as having rheumatoid arthritis (RA) were randomly assigned into four different treatment strategies. Baseline and 1-year x-rays of the hands and feet were assessed using the Sharp-van der Heijde score (SHS). With generalised estimating equations, 3-monthly assessments of tender and swollen joints of year 1 were related to erosion progression, joint space narrowing (JSN) progression and total SHS progression at the individual joint level (definition > 0.5 SHS units) in year 1, corrected for potential confounders and within-patient correlation for multiple joints per patient. During year 1, 59% of all 13 959 joints analysed were ever tender and 45% ever swollen, 2.1% showed erosion progression, 1.9% JSN progression and 3.6% SHS progression. Swelling and tenderness were both independently associated with erosion and JSN progression with comparable OR, although with higher OR in the hands than in the feet. Local swelling and tenderness were not associated with local damage progression in patients initially treated with infliximab. Clinical signs of synovitis are associated with erosion and JSN progression in individual joints after 1 year in RA. A disconnect between synovitis and joint damage progression was observed at joint level in patients who were treated with methotrexate and infliximab as initial treatment, confirming the disconnect between synovitis and the development of joint damage in tumour necrosis factor blockers seen at patient level.

Does substantiated childhood maltreatment lead to poor quality of life in young adulthood? Evidence from an Australian birth cohort study.

PubMed

Abajobir, Amanuel Alemu; Kisely, Steve; Williams, Gail; Strathearn, Lane; Clavarino, Alexandra; Najman, Jake Moses

2017-07-01

To examine the independent effect of single and multiple forms of substantiated childhood maltreatment (CM) on quality of life (QoL), controlling for selected potential confounders and/or covariates, and concurrent depressive symptoms. We used data from a prospective pre-birth cohort of 8556 mothers recruited consecutively during their first antenatal clinic visit at the Mater Hospital from 1981 to 1983 in Brisbane, Australia. The data were linked to substantiated cases of CM reported to the child protection government agency up to the age of 14 years. The sample consisted of 3730 (49.7% female) young adults for whom there were complete data on QoL at the 21-year follow-up. The mean age of participants was 20.6 years. Logistic regression models were used to assess the association between CM and QoL measured at the 21-year follow-up. There were statistically significant associations between exposure to substantiated CM and poorer QoL. This also applied to the subcategories of childhood physical abuse, childhood emotional abuse (CEA), and neglect. These associations were generally stable after adjusting for confounders/covariates and concurrent depressive symptoms, except physical abuse. CEA with or without neglect significantly and particularly predicted worse subsequent QoL. Exposure to any substantiated maltreatment substantially contributed to worse QoL in young adulthood, with a particular association with CEA and neglect. Prior experiences of CM may have a substantial association with subsequent poorer QoL.

Stagnant Neonatal Mortality and Persistent Health Inequality in Middle-Income Countries: A Case Study of the Philippines

PubMed Central

Kraft, Aleli D.; Nguyen, Kim-Huong; Jimenez-Soto, Eliana; Hodge, Andrew

2013-01-01

Background The probability of survival through childhood continues to be unequal in middle-income countries. This study uses data from the Philippines to assess trends in the prevalence and distribution of child mortality and to evaluate the country’s socioeconomic-related child health inequality. Methodology Using data from four Demographic and Health Surveys we estimated levels and trends of neonatal, infant, and under-five mortality from 1990 to 2007. Mortality estimates at national and subnational levels were produced using both direct and indirect methods. Concentration indices were computed to measure child health inequality by wealth status. Multivariate regression analyses were used to assess the contribution of interventions and socioeconomic factors to wealth-related inequality. Findings Despite substantial reductions in national under-five and infant mortality rates in the early 1990s, the rates of declines have slowed in recent years and neonatal mortality rates remain stubbornly high. Substantial variations across urban-rural, regional, and wealth equity-markers are evident, and suggest that the gaps between the best and worst performing sub-populations will either be maintained or widen in the future. Of the variables tested, recent wealth-related inequalities are found to be strongly associated with social factors (e.g. maternal education), regional location, and access to health services, such as facility-based delivery. Conclusion The Philippines has achieved substantial progress towards Millennium Development Goal 4, but this success masks substantial inequalities and stagnating neonatal mortality trends. This analysis supports a focus on health interventions of high quality – that is, not just facility-based delivery, but delivery by trained staff at well-functioning facilities and supported by a strong referral system – to re-start the long term decline in neonatal mortality and to reduce persistent within-country inequalities in child health. PMID:23308278

Modelling historical changes in the force-of-infection of Chagas disease to inform control and elimination programmes: application in Colombia

PubMed Central

Nouvellet, Pierre; Conteh, Lesong; Vera, Mauricio Javier; Angulo, Victor Manuel; Dib, Juan Carlos; Parra -Henao, Gabriel Jaime; Basáñez, María Gloria

2017-01-01

Background WHO's 2020 milestones for Chagas disease include having all endemic Latin American countries certified with no intradomiciliary Trypanosoma cruzi transmission, and infected patients under care. Evaluating the variation in historical exposure to infection is crucial for assessing progress and for understanding the priorities to achieve these milestones. Methods Focusing on Colombia, all the available age-structured serological surveys (undertaken between 1995 and 2014) were searched and compiled. A total of 109 serosurveys were found, comprising 83 742 individuals from rural (indigenous and non-indigenous) and urban settings in 14 (out of 32) administrative units (departments). Estimates of the force-of-infection (FoI) were obtained by fitting and comparing three catalytic models using Bayesian methods to reconstruct temporal and spatial patterns over the course of three decades (between 1984 and 2014). Results Significant downward changes in the FoI were identified over the course of the three decades, and in some specific locations the predicted current seroprevalence in children aged 0–5 years is <1%. However, pronounced heterogeneity exists within departments, especially between indigenous, rural and urban settings, with the former exhibiting the highest FoI (up to 66 new infections/1000 people susceptible/year). The FoI in most of the indigenous settings remain unchanged during the three decades investigated. Current prevalence in adults in these 15 departments varies between 10% and 90% depending on the dynamics of historical exposure. Conclusions Assessing progress towards the control of Chagas disease requires quantifying the impact of historical exposure on current age-specific prevalence at subnational level. In Colombia, despite the evident progress, there is a marked heterogeneity indicating that in some areas the vector control interventions have not been effective, hindering the possibility of achieving interruption by 2020. A substantial burden of chronic cases remains even in locations where serological criteria for transmission interruption may have been achieved, therefore still demanding diagnosis and treatment interventions. PMID:29147578

Cross-sectional analysis of the effects of age on the hormonal, metabolic, and ultrasonographic features and the prevalence of the different phenotypes of polycystic ovary syndrome.

PubMed

Panidis, Dimitrios; Tziomalos, Konstantinos; Macut, Djuro; Delkos, Dimitrios; Betsas, George; Misichronis, Georgios; Katsikis, Ilias

2012-02-01

To assess the effects of age on the hormonal, metabolic, and ultrasonographic features of polycystic ovary syndrome (PCOS). Observational study. University department of obstetrics and gynecology. Patients with PCOS (n = 1,212) and healthy women (n = 254). None. Differences in the hormonal, metabolic, and ultrasonographic features of PCOS between age groups. A progressive decline in circulating androgens was observed with advancing age. Patients 21-30 years old had lower plasma glucose and insulin levels, lower area under the oral glucose tolerance test curve and lower homeostasis model assessment of insulin resistance index, and higher glucose/insulin and quantitative insulin sensitivity check index than patients 31-39 years old. The prevalence of PCOS phenotypes changed with age. More specifically, the distribution of the phenotypes did not differ substantially between patients ≤ 20 years old and patients 21-30 years old. However, a decline in the prevalence of phenotype 1 (characterized by anovulation, hyperandrogenemia, and polycystic ovaries) and an increase in the prevalence of phenotype 4 (characterized by anovulation and polycystic ovaries without hyperandrogenemia) were observed in patients 31-39 years old. In women with PCOS, hyperandrogenemia appears to diminish during reproductive life whereas insulin resistance worsens. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The natural history of human immunodeficiency virus infection: a five year study in a London cohort of homosexual men.

PubMed Central

Kelly, G E; Stanley, B S; Weller, I V

1990-01-01

Progression rates from asymptomatic to symptomatic Human Immunodeficiency Virus (HIV) infection according to the CDC classification were prospectively studied in a cohort of 172 seropositive homosexual and bisexual men. The median follow-up time was 4 years. The progression from data of entry to the study to any group IV disease was 56% (SE 7%) at 5 years. However, the progression from an estimated date of seroconversion to any group IV disease was 36% (SE 4%) at 5 years. This was more than double the progression rate to AIDS-14% (SE 3%) at 5 years calculated in the same way. There were no differences in progression to AIDS from group IV A (systemic symptoms such as unexplained fever, weight loss or persistent diarrhoea) and group IV C-2 (oral candida or oral hairy leukoplakia). Progression rates to AIDS were significantly lower (p = 0.02) in patients who were under 25 years of age at entry than in those over 25. A review of progression rates to AIDS among homosexual cohorts shows that they tend to be higher than in cohorts of haemophiliac patients, in the early stage of infection. However, when Pneumocystis carinii pneumonia is the outcome measure, progression rates in all studies are remarkably similar. PMID:2133371

ORNL Neutron Sciences Annual Report for 2007

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

Anderson, Ian S; Horak, Charlie M; Counce, Deborah Melinda

2008-07-01

This is the first annual report of the Oak Ridge National Laboratory Neutron Sciences Directorate for calendar year 2007. It describes the neutron science facilities, current developments, and future plans; highlights of the year's activities and scientific research; and information on the user program. It also contains information about education and outreach activities and about the organization and staff. The Neutron Sciences Directorate is responsible for operation of the High Flux Isotope Reactor and the Spallation Neutron Source. The main highlights of 2007 were highly successful operation and instrument commissioning at both facilities. At HFIR, the year began with themore » reactor in shutdown mode and work on the new cold source progressing as planned. The restart on May 16, with the cold source operating, was a significant achievement. Furthermore, measurements of the cold source showed that the performance exceeded expectations, making it one of the world's most brilliant sources of cold neutrons. HFIR finished the year having completed five run cycles and 5,880 MWd of operation. At SNS, the year began with 20 kW of beam power on target; and thanks to a highly motivated staff, we reached a record-breaking power level of 183 kW by the end of the year. Integrated beam power delivered to the target was 160 MWh. Although this is a substantial accomplishment, the next year will bring the challenge of increasing the integrated beam power delivered to 887 MWh as we chart our path toward 5,350 MWh by 2011.« less

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

NASA Technical Reports Server (NTRS)

Jackman, Angie; Johnson, Les

2017-01-01

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

Emodin and Its Role in Chronic Diseases.

PubMed

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

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

Aeronautics Education, Research, and Industry Alliance (AERIAL) Progress Report and Proposal for Funding Continuation NASA Nebraska EPSCoR

NASA Technical Reports Server (NTRS)

Bowen, Brent; Fink, Mary; Gogos, George; Moussavi, Massoum; Nickerson, Jocelyn; Rundquist, Donald; Russell, Valerie; Tarry, Scott

2004-01-01

The Aeronautics Education, Research, and Industry Alliance (AERIAL), which began as a comprehensive, multi-faceted NASA EPSCoR 2000 initiative, has contributed substantially to the strategic research and technology priorities of NASA, while intensifying Nebraska's rapidly growing aeronautics research and development endeavors. AERIAL has enabled Nebraska researchers to: (a) continue strengthening their collaborative relationships with NASA Field Centers, Codes, and Enterprises; (b) increase the capacity of higher education throughout Nebraska to invigorate and expand aeronautics research; and (c) expedite the development of aeronautics-related research infrastructure and industry in the state. Nebraska has placed emphasis on successfully securing additional funds from non-EPSCoR and non-NASA sources. AERIAL researchers have aggressively pursued additional funding opportunities offered by NASA, industry, and other agencies. This report contains a summary of AERIAL's activities and accomplishments during its first three years of implementation.

Prebiotics, probiotics, synbiotics, and the immune system: experimental data and clinical evidence.

PubMed

Frei, Remo; Akdis, Mübeccel; O'Mahony, Liam

2015-03-01

The intestinal immune system is constantly exposed to foreign antigens, which for the most part should be tolerated. Certain probiotics, prebiotics, and synbiotics are able to influence immune responses. In this review, we highlight the recent publications (within the last 2 years) that have substantially progressed this field. The immunological mechanisms underpinning probiotics, prebiotics, and synbiotics effects continue to be better defined with novel mechanisms being described for dendritic cells, epithelial cells, T regulatory cells, effector lymphocytes, natural killer T cells, and B cells. Many of the mechanisms being described are bacterial strain or metabolite specific, and should not be extrapolated to other probiotics or prebiotics. In addition, the timing of intervention seems to be important, with potentially the greatest effects being observed early in life. In this review, we discuss the recent findings relating to probiotics, prebiotics, and synbiotics, specifically their effects on immunological functions.

Transition and protective agency of early childhood learning behaviors as portents of later school attendance and adjustment.

PubMed

McDermott, Paul A; Rikoon, Samuel H; Fantuzzo, John W

2016-02-01

This article reports on the study of differential change trajectories for early childhood learning behaviors as they relate to future classroom adjustment and school attendance. A large sample (N=2152) of Head Start children was followed through prekindergarten, kindergarten, and 1st grade. Classroom learning behaviors were assessed twice each year by teachers who observed gradual declines in Competence Motivation and Attentional Persistence as children transitioned through schooling. Cross-classified multilevel growth models revealed distinct transitional pathways for future adjustment versus maladjustment and sporadic versus chronic absenteeism. Generalized multilevel logistic modeling and receiver operating characteristic curve analyses showed that teachers' earliest assessments were substantially predictive of eventual good classroom adjustment and school attendance, with increasing accuracy for prediction of future sociobehavioral adjustment as time progressed. Copyright © 2015 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Scientific Performance of a Nano-satellite MeV Telescope

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

Lucchetta, Giulio; Berlato, Francesco; Rando, Riccardo

Over the past two decades, both X-ray and gamma-ray astronomy have experienced great progress. However, the region of the electromagnetic spectrum around ∼1 MeV is not so thoroughly explored. Future medium-sized gamma-ray telescopes will fill this gap in observations. As the timescale for the development and launch of a medium-class mission is ∼10 years, with substantial costs, we propose a different approach for the immediate future. In this paper, we evaluate the viability of a much smaller and cheaper detector: a nano-satellite Compton telescope, based on the CubeSat architecture. The scientific performance of this telescope would be well below thatmore » of the instrument expected for the future larger missions; however, via simulations, we estimate that such a compact telescope will achieve a performance similar to that of COMPTEL.« less

Shock wave treatment in medicine.

PubMed

Shrivastava, S K; Kailash

2005-03-01

Extracorporeal shock wave therapy in orthopedics and traumatology is still a young therapy method. Since the last few years the development of shock wave therapy has progressed rapidly. Shock waves have changed the treatment of urolithiasis substantially. Today shock waves are the first choice to treat kidney and urethral stones. Urology has long been the only medical field for shock waves in medicine. Meanwhile shock waves have been used in orthopedics and traumatology to treat insertion tendinitis, avascular necrosis of the head of femur and other necrotic bone alterations. Another field of shock wave application is the treatment of tendons, ligaments and bones on horses in veterinary medicine. In the present paper we discuss the basic theory and application of shock waves and its history in medicine. The idea behind using shock wave therapy for orthopedic diseases is the stimulation of healing in tendons, surrounding tissue and bones.

Using Science Data and Models for Space Weather Forecasting - Challenges and Opportunities

NASA Technical Reports Server (NTRS)

Hesse, Michael; Pulkkinen, Antti; Zheng, Yihua; Maddox, Marlo; Berrios, David; Taktakishvili, Sandro; Kuznetsova, Masha; Chulaki, Anna; Lee, Hyesook; Mullinix, Rick;

Computer modelling of epilepsy.

PubMed

Lytton, William W

2008-08-01

Epilepsy is a complex set of disorders that can involve many areas of the cortex, as well as underlying deep-brain systems. The myriad manifestations of seizures, which can be as varied as déjà vu and olfactory hallucination, can therefore give researchers insights into regional functions and relations. Epilepsy is also complex genetically and pathophysiologically: it involves microscopic (on the scale of ion channels and synaptic proteins), macroscopic (on the scale of brain trauma and rewiring) and intermediate changes in a complex interplay of causality. It has long been recognized that computer modelling will be required to disentangle causality, to better understand seizure spread and to understand and eventually predict treatment efficacy. Over the past few years, substantial progress has been made in modelling epilepsy at levels ranging from the molecular to the socioeconomic. We review these efforts and connect them to the medical goals of understanding and treating the disorder.

Motivating Action and Maintaining Change: The Time-Varying Role of Homework Following a Brief Couples' Intervention.

PubMed

Hawrilenko, Matt; Eubanks Fleming, C J; Goldstein, Alana S; Cordova, James V

2016-07-01

Studies regarding the effectiveness of homework assignments in cognitive-behavioral treatments have demonstrated mixed results. This study investigated predictors of compliance with homework recommendations and the time-varying relationship of recommendation completion with treatment response in a brief couples' intervention (N = 108). More satisfied couples and couples with more motivation to change completed more recommendations, whereas couples with children completed fewer. The association between recommendation completion and treatment response varied with the passage of time, with the strongest effect observed 6 months after the intervention, but no discernible differences at 1 year postintervention. Couples that completed more recommendations experienced more rapid treatment gains, but even those couples doing substantially fewer recommendations ultimately realized equivalent treatment effects, although they progressed more slowly. Implications are discussed. © 2015 American Association for Marriage and Family Therapy.

Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology.

PubMed

Aretz, Ina; Meierhofer, David

2016-04-27

Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology

PubMed Central

Aretz, Ina; Meierhofer, David

2016-01-01

Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology. PMID:27128910

Epigenetic regulation of female puberty.

PubMed

Lomniczi, Alejandro; Wright, Hollis; Ojeda, Sergio R

2015-01-01

Substantial progress has been made in recent years toward deciphering the molecular and genetic underpinnings of the pubertal process. The availability of powerful new methods to interrogate the human genome has led to the identification of genes that are essential for puberty to occur. Evidence has also emerged suggesting that the initiation of puberty requires the coordinated activity of gene sets organized into functional networks. At a cellular level, it is currently thought that loss of transsynaptic inhibition, accompanied by an increase in excitatory inputs, results in the pubertal activation of GnRH release. This concept notwithstanding, a mechanism of epigenetic repression targeting genes required for the pubertal activation of GnRH neurons was recently identified as a core component of the molecular machinery underlying the central restraint of puberty. In this chapter we will discuss the potential contribution of various mechanisms of epigenetic regulation to the hypothalamic control of female puberty. Copyright © 2014 Elsevier Inc. All rights reserved.

Progress and challenges in implementing the research on ESKAPE pathogens.

PubMed

Rice, Louis B

2010-11-01

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

Vaccines to Accelerate Malaria Elimination and Eventual Eradication.

PubMed

Healer, Julie; Cowman, Alan F; Kaslow, David C; Birkett, Ashley J

2017-09-01

Remarkable progress has been made in coordinated malaria control efforts with substantial reductions in malaria-associated deaths and morbidity achieved through mass administration of drugs and vector control measures including distribution of long-lasting insecticide-impregnated bednets and indoor residual spraying. However, emerging resistance poses a significant threat to the sustainability of these interventions. In this light, the malaria research community has been charged with the development of a highly efficacious vaccine to complement existing malaria elimination measures. As the past 40 years of investment in this goal attests, this is no small feat. The malaria parasite is a highly complex organism, exquisitely adapted for survival under hostile conditions within human and mosquito hosts. Here we review current vaccine strategies to accelerate elimination and the potential for novel and innovative approaches to vaccine design through a better understanding of the host-parasite interaction. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Progress in molecular-based management of differentiated thyroid cancer

PubMed Central

Xing, Mingzhao; Haugen, Bryan R; Schlumberger, Martin

2014-01-01

Substantial developments have occurred in the past 5–10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAFV600E mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine. PMID:23668556

Epilepsy and the immune system: is there a link?

PubMed

Billiau, An D; Wouters, Carine H; Lagae, Lieven G

2005-01-01

The concept that the immune system plays a role in the epileptogenic process of some epileptic syndromes was first proposed more than 20 years ago. Since then, numerous studies have reported on the existence of a variety of immunological alterations in epileptic patients, on the observation of favourable responses of refractory epilepsy syndromes to immunomodulatory treatment, and on the association of certain well-known immune-mediated disease states with epilepsy. This review comprehensively recapitulates the currently available evidence supporting or arguing against the possible involvement of the immune system in the pathogenesis of certain types of epilepsy. It is concluded that an abundance of facts is in support of this concept and that further studies should be directed at substantiating the pathogenic significance of (auto)immune responses in certain types of epilepsy. Current progress in the functional and molecular immunological research techniques will indisputably contribute to the elucidation of this link.

On the nature of carbon-hydrogen bond activation at rhodium and related reactions.

PubMed

Jones, William D

2005-06-27

Over the past 20 years, substantial progress has been made in the understanding of the activation of C-H and other strong bonds by reactive metal complexes in low oxidation states. This paper will present an overview of the use of pentamethylcyclopentadienyl and trispyrazolylborate rhodium complexes for the activation of arene and alkane C-H bonds. Insights into bond strengths, kinetic and thermodynamic selectivities, and the nature of the intermediates involved will be reviewed. The role of eta-2 arene complexes will be shown to be critical to the C-H activation reactions. Some information about the fleeting alkane sigma-complexes will also be presented. In addition, use of these complexes with thiophenes has shown the ability to cleave C-S bonds. Mechanistic information has been obtained indicating coordination through sulfur prior to cleavage. Relevant examples of nickel-based C-S cleavage will also be given.

Molecular ecology of hydrothermal vent microbial communities.

PubMed

Jeanthon, C

2000-02-01

The study of the structure and diversity of hydrothermal vent microbial communities has long been restricted to the morphological description of microorganisms and the use of enrichment culture-based techniques. Until recently the identification of the culturable fraction required the isolation of pure cultures followed by testing for multiple physiological and biochemical traits. However, peculiar inhabitants of the hydrothermal ecosystem such as the invertebrate endosymbionts and the dense microbial mat filaments have eluded laboratory cultivation. Substantial progress has been achieved in recent years in techniques for the identification of microorganisms in natural environments. Application of molecular approaches has revealed the existence of unique and previously unrecognized microorganisms. These have provided fresh insight into the ecology, diversity and evolution of mesophilic and thermophilic microbial communities from the deep-sea hydrothermal ecosystem. This review reports the main discoveries made through the introduction of these powerful techniques in the study of deep-sea hydrothermal vent microbiology.

Adequacy, accountability, autonomy and equity in a Middle Eastern school reform: The case of Qatar

NASA Astrophysics Data System (ADS)

Guarino, Cassandra M.; Tanner, Jeffery C.

2012-04-01

This study examines Qatar's recent and ambitious school reform in the early stages of its implementation against a set of four criteria for successful education systems drawn from guidelines developed by the international community: adequacy, accountability, autonomy and gender equity. We investigate both the initial structure of the reform and its sustainability in light of concerns that movements in these directions might be politically unfeasible. To some degree, these concerns are substantiated by the developments we trace. However, it is important to note that the reform has changed the landscape of primary and secondary education in Qatar and that many reform principles, though diluted, have been retained. This paper highlights lessons learned - both hopeful and cautionary - in the first few years of reform and presents a methodology for evaluating progress along key dimensions that can be applied to school systems in many nations.

Long-term follow-up of children conceived through assisted reproductive technology.

PubMed

Lu, Yue-hong; Wang, Ning; Jin, Fan

2013-05-01

Children conceived via assisted reproductive technologies (ART) are nowadays a substantial proportion of the population. It is important to follow up these children and evaluate whether they have elevated health risks compared to naturally conceived (NC) children. In recent years there has been a lot of work in this field. This review will summarize what is known about the health of ART-conceived children, encompassing neonatal outcomes, birth defects, growth and gonadal developments, physical health, neurological and neurodevelopmental outcomes, psychosocial developments, risk for cancer, and epigenetic abnormalities. Most of the children conceived after ART are normal. However, there is increasing evidence that ART-conceived children are at higher risk of poor perinatal outcome, birth defects, and epigenetic disorders, and the mechanism(s) leading to these changes have not been elucidated. Continuous follow-up of children after ART is of great importance as they progress through adolescence into adulthood, and new ART techniques are constantly being introduced.

Critical illness polyneuropathy and myopathy: a systematic review

PubMed Central

Zhou, Chunkui; Wu, Limin; Ni, Fengming; Ji, Wei; Wu, Jiang; Zhang, Hongliang

2014-01-01

Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or difficulty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitating neurological disease. PMID:25206749

Antibody mimetics: promising complementary agents to animal-sourced antibodies.

PubMed

Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying

2016-01-01

Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed.

Hepatitis C Virus and Antiviral Drug Resistance.

PubMed

Kim, Seungtaek; Han, Kwang-Hyub; Ahn, Sang Hoon

2016-11-15

Since its discovery in 1989, hepatitis C virus (HCV) has been intensively investigated to understand its biology and develop effective antiviral therapies. The efforts of the previous 25 years have resulted in a better understanding of the virus, and this was facilitated by the development of in vitro cell culture systems for HCV replication. Antiviral treatments and sustained virological responses have also improved from the early interferon monotherapy to the current all-oral regimens using direct-acting antivirals. However, antiviral resistance has become a critical issue in the treatment of chronic hepatitis C, similar to other chronic viral infections, and retreatment options following treatment failure have become important questions. Despite the clinical challenges in the management of chronic hepatitis C, substantial progress has been made in understanding HCV, which may facilitate the investigation of other closely related flaviviruses and lead to the development of antiviral agents against these human pathogens.

Recent advancements of wide-angle polarization analysis with 3He neutron spin filters

NASA Astrophysics Data System (ADS)

Chen, W. C.; Gentile, T. R.; Ye, Q.; Kirchhoff, A.; Watson, S. M.; Rodriguez-Rivera, J. A.; Qiu, Y.; Broholm, C.

2016-09-01

Wide-angle polarization analysis with polarized 3He based neutron spin filters (NSFs) has recently been employed on the Multi-Axis Crystal Spectrometer (MACS) at the National Institute of Standards and Technology Center for Neutron Research (NCNR). Over the past several years, the apparatus has undergone many upgrades to address the fundamental requirements for wide angle polarization analysis using spin exchange optical pumping based 3He NSFs. In this paper, we report substantial improvements in the on-beam-line performance of the apparatus and progress toward routine user capability. We discuss new standard samples used for 3He NSF characterization and the flipping ratio measurement on MACS. We further discuss the management of stray magnetic fields produced by operation of superconducting magnets on the MACS instrument, which can significantly reduce the 3He polarization relaxation time. Finally, we present the results of recent development of horseshoe-shaped wide angle cells.

Discussion on a Public Hospital's Practice in Culture Shaping and Innovative Development.

PubMed

Zhang, Peiying

2015-05-01

Culture shaping is an important part of a hospital's quality management to enhance its medical service, improve doctor-patient relations, and cement its brand image (Jianping and Hong in Chinese Hospital Management 29(1):36-37, 2009). First built in 1953, Xuzhou Central Hospital is a tertiary general hospital in the Huaihai Economic Zone and has won a series of honorary titles for its reforms, innovations, and the level of medical services provided. In recent years, the hospital has increased its efforts in culture shaping through the construction of special departments, medical services, hospital culture, and professional ethics. This has resulted in substantial progress in the hospital's medical capabilities and service quality, and laid a solid foundation to achieve its ambitious goal of becoming a nationally prestigious hospital, among the best in Jiangsu and a regional healthcare center in the Huaihai Economic Zone.

Integrating internal and external bioanalytical support to deliver a diversified pharmaceutical portfolio.

PubMed

Summerfield, Scott G; Evans, Christopher; Spooner, Neil; Dunn, John A; Szapacs, Matthew E; Yang, Eric

2014-05-01

The portfolios of pharmaceutical companies have diversified substantially over recent years in recognition that monotherapies and/or small molecules are less suitable for modulating many complex disease etiologies. Furthermore, there has been increased pressure on drug-development budgets over this same period. This has placed new challenges in the path of bioanalytical scientists, both within the industry and with contract research organizations (CROs). Large pharmaceutical, biotechnology and small-medium healthcare enterprises have had to make important decisions on what internal capabilities they wish to retain and where CROs offers a significant strategic benefit to their business model. Our journey has involved asking where we believe an internal bioanalytical facility offers the greatest benefit to progressing drug candidates through the drug-development cycle and where externalization can help free up internal resources, adding flexibility to our organization in order to deal with the inevitable peaks and troughs in workload.

Sacubitril/Valsartan: From Clinical Trials to Real-world Experience.

PubMed

Joly, Joanna M; Desai, Akshay S

2018-04-23

Compared to enalapril, use of angiotensin-receptor blocker and neprilysin inhibitor sacubitril/valsartan to treat patients with heart failure and reduced ejection fraction (HFrEF) is associated with substantial reductions in both cardiovascular mortality and heart failure progression. The purpose of this review is to discuss the real-world experience of sacubitril/valsartan. In the years following the publication of the landmark PARADIGM-HF trial in 2014 and its subsequent FDA approval, a growing evidence base supports the safety and efficacy of sacubitril/valsartan in a broad spectrum of patients with HFrEF. Updated clinical practice guidelines have embraced the use of sacubitril/valsartan in preference to ACE inhibitors or ARBs in selected patients. In this review, we highlight the clinical trials that led to these key updates to clinical guidelines, offer practical strategies for patient selection and utilization in clinical practice, and identify important areas of uncertainty that require future research.

Overview of magnetospheric research

NASA Technical Reports Server (NTRS)

Ashour-Abdalla, Maha

1994-01-01

During the funding period for NASA Grant NAG5-1480 which prior to December, 1, 1990 was known as NASA Grant NAGW-78, the group has made substantial progress on the various topics originally proposed. The research performed has resulted in two Ph.D. Theses, more than 50 refereed papers in various journals and conference proceedings, and 31 invited and 104 contributed talks at conferences and symposia throughout the world. The main results from this work are summarized in each of the sections outlined in the original proposal, followed by a complete list of the group publications associated with this grant, a list of all invited talks given during the last three years, and finally a listing of the contributed talks. Research topics include global magnetohydrodynamic simulations, structure of the dayside magnetopause, merging at the dayside magnetopause, polar wind, plasma waves in the distant magnetotail, slow shocks in the distant magnetotail, collisionless tearing instabilities in the magnetotail, and other problems.

Upgrades for the CMS simulation

DOE PAGES

Lange, D. J.; Hildreth, M.; Ivantchenko, V. N.; ...

2015-05-22

Over the past several years, the CMS experiment has made significant changes to its detector simulation application. The geometry has been generalized to include modifications being made to the CMS detector for 2015 operations, as well as model improvements to the simulation geometry of the current CMS detector and the implementation of a number of approved and possible future detector configurations. These include both completely new tracker and calorimetry systems. We have completed the transition to Geant4 version 10, we have made significant progress in reducing the CPU resources required to run our Geant4 simulation. These have been achieved throughmore » both technical improvements and through numerical techniques. Substantial speed improvements have been achieved without changing the physics validation benchmarks that the experiment uses to validate our simulation application for use in production. As a result, we will discuss the methods that we implemented and the corresponding demonstrated performance improvements deployed for our 2015 simulation application.« less

[Professor Kazimierz Jaegermann--forensic pathologist--scientist--thinker].

PubMed

Nasiłowski, Władysław

2009-01-01

Professor Kazimierz Jaegermann, a founder of the theory of medico-legal opinionating, passed away 20 years ago. Numerous specialists in forensic medicine and an ever increasing number of lawyers substantiate the importance and value of the creative thought and the entire research work of Professor Jaegermann that have been an inspiration of progress in forensic medicine and in the science of applied law. His unique ability to perform a scientific synthesis leading to recognizing forensic medicine as an applied bridging knowledge points to the eminently creative role played by Professor Jaegermann in development of forensic medicine. There is an urgent need to recall his research activities and to publish a complete collection of his articles and publications. With this idea in mind, I present below an article based on the text published in No. 1 of the Zeszyty Naukowe Katedry Medycyny Sadowej Slaskiej Akademii Medycznej in 1995.

Modifying Science Grammatically and Conceptually

NASA Astrophysics Data System (ADS)

Kelly, B. P.

2017-12-01

Many adjectives—including normal, traditional, incremental, natural, social, system, actionable, and Arctic—are employed to distinguish types of science. How useful are those modifiers? For example, how is "Arctic" research different from other varieties? What conjunctions are useful among these types of research? In other words, do we benefit from "normal science" and "actionable science" or must we choose between them? Clarity about how we talk about science has substantial implications for how we think about science, how we integrate science with other epistemologies, and how science is regarded among policy makers. The importance of actionable science was highlighted during the last International Polar Year, and the Study of Environmental Arctic Change and others have taken up the challenge. As we make our knowledge actionable, however, we must remain clear about the essential nature of what Thomas Kuhn called normal science. Being clear about how science progresses would seem a prerequisite to the elusive challenge of integration with other ways of knowing.

The role of luteinizing hormone-releasing hormone in the diagnosis of constitutional delayed puberty

PubMed Central

Sagel, Julius; Distiller, Larry A.; Joffe, Barry I.

1975-01-01

The presumptive diagnosis of constitutional delayed adolescence is difficult to substantiate. Clinical examination and routine biochemical testing are not sufficient to exclude isolated gonadotrophin deficiency. Seven males are reported who presented with delayed puberty. These patients were given 100 μg luteinizing hormone-releasing hormone (LH-RH) intravenously, and the luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses were measured. Three of four males who were completely prepubertal (Stage 1) had a normal adult male response. These three patients have progressed further into puberty several months after this diagnostic test. The fourth patient in stage 1 puberty had a prepubertal LH response. A year later the response became adult in type, and 3 months thereafter stage 2 puberty was evident. The LH response to LH-RH thus appears to have some prognostic value in the assessment of males presenting with delayed puberty. PMID:1105498

Cerebral Microbleeds: A Field Guide to their Detection and Interpretation

PubMed Central

Greenberg, Steven M.; Vernooij, Meike W.; Cordonnier, Charlotte; Viswanathan, Anand; Salman, Rustam Al-Shahi; Warach, Steven; Launer, Lenore J.; Van Buchem, Mark A.; Breteler, Monique M.B.

2012-01-01

Summary Cerebral microbleeds (CMB) are increasingly recognized neuroimaging findings, occurring with cerebrovascular disease, dementia, and normal aging. Recent years have seen substantial progress, particularly in developing newer MRI methodologies for CMB detection and applying them to population-based elderly samples. This review focuses on these recent developments and their impact on two major questions: how CMB are detected, and how they should be interpreted. There is now ample evidence that prevalence and number of detected CMB varies with MRI characteristics such as pulse sequence, sequence parameters, spatial resolution, magnetic field strength, and post-processing, underlining the importance of MRI technique in interpreting studies. Recent investigations using sensitive techniques find the prevalence of CMB detected in community-dwelling elderly to be surprisingly high. We propose procedural guidelines for identifying CMB and suggest possible future approaches for elucidating the role of these common lesions as markers for, and potential contributors to, small vessel brain disease. PMID:19161908

A Conceptual Framework for Addressing Residual Atherosclerotic Cardiovascular Disease Risk in the Era of Precision Medicine.

PubMed

Patel, Kershaw V; Pandey, Ambarish; de Lemos, James A

2018-04-11

Until recently, therapies to mitigate atherosclerotic cardiovascular disease (ASCVD) risk have been limited to lifestyle interventions, blood pressure lowering medications, high intensity statin therapy, antiplatelet agents, and in select patients, coronary artery revascularization. Despite administration of these evidence-based therapies, substantial residual risk for cardiovascular events persists, particularly among individuals with known ASCVD. Moreover, the current guideline-based approach does not adequately account for patient-specific, causal pathways that lead to ASCVD progression and complications. In the past few years, multiple new pharmacological agents, targeting conceptually distinct pathophysiological targets, have been shown in large and well-conducted clinical trials to lower cardiovascular risk among patients with established ASCVD receiving guideline directed medical care. These evidenced-based therapies reduce event rates, and in some cases all-cause and cardiovascular mortality; these benefits confirm important new disease targets and challenge the adequacy of the current "standard of care" for secondary prevention.

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.

One Year Later: Assessing Our Progress | NOAA Gulf Spill Restoration

Science.gov Websites

Archive Home One Year Later: Assessing Our Progress One Year Later: Assessing Our Progress oil in the wake Restoration Area A year ago, the Deepwater Horizon drilling rig sank, starting an oil spill that became the samples, surveyed thousands of miles of shoreline for oil, posted more than 60 work plans and other data

Measles and rubella elimination: learning from polio eradication and moving forward with a diagonal approach.

PubMed

Goodson, James L; Alexander, James P; Linkins, Robert W; Orenstein, Walter A

2017-12-01

In 1988, an estimated 350,000 children were paralyzed by polio and 125 countries reported polio cases, the World Health Assembly passed a resolution to achieve polio eradication by 2000, and the Global Polio Eradication Initiative (GPEI) was established as a partnership focused on eradication. Today, following eradication efforts, polio cases have decreased >99% and eradication of all three types of wild polioviruses is approaching. However, since polio resources substantially support disease surveillance and other health programs, losing polio assets could reverse progress toward achieving Global Vaccine Action Plan goals. Areas covered: As the end of polio approaches and GPEI funds and capacity decrease, we document knowledge, experience, and lessons learned from 30 years of polio eradication. Expert commentary: Transitioning polio assets to measles and rubella (MR) elimination efforts would accelerate progress toward global vaccination coverage and equity. MR elimination feasibility and benefits have long been established. Focusing efforts on MR elimination after achieving polio eradication would make a permanent impact on reducing child mortality but should be done through a 'diagonal approach' of using measles disease transmission to identify areas possibly susceptible to other vaccine-preventable diseases and to strengthen the overall immunization and health systems to achieve disease-specific goals.

Enuresis and encopresis: ten years of progress.

PubMed

Mikkelsen, E J

2001-10-01

To review the progress made over the past decade with regard to the treatment of enuresis and encopresis, as well as advances in the understanding of etiological mechanisms. Separate computerized literature (English language only) searches of Medline and PsycINFO databases were conducted under the parameter of enuresis and children-adolescents, as well as encopresis and children-adolescents. There has been a substantial decrease in published research concerning the use of imipramine to treat enuresis compared with the prior two decades, accompanied by a corresponding increase in the number of papers concerning desmopressin acetate (DDAVP), which has become the primary pharmacological treatment. Genetic studies of large pedigrees have further confirmed the importance of heritable factors. With regard to encopresis, the research has focused primarily on pathophysiological factors related to the colon and anal sphincter. The widespread use of DDAVP has been the primary addition to treatment strategies over the past decade. The bell-and-pad method of conditioning, the only major treatment that has enduring benefit after being withdrawn, is the most cost-effective and appears to be underutilized. Research into etiological mechanisms has focused primarily on the mechanism of action of DDAVP and advances in the understanding of genetic factors. Advances in the treatment and etiological understanding of encopresis have been less impressive.

The scorecard on globalization 1980-2000: its consequences for economic and social well-being.

PubMed

Weisbrot, Mark; Baker, Dean; Kraev, Egor; Chen, Judy

2002-01-01

The era of globalization has brought substantially less progress than was achieved in the preceding 20 years. This study by the Center for Economic and Policy Research concludes that the data provide no evidence that the policies associated with globalization have improved outcomes for developing countries, and its findings challenge economists and policymakers who cite globalization as an engine of growth while pressing for policies that strengthen the trend. The study also served as a backdrop to the release of the United Nations Development Program's Human Development Report on July 11, 2001. Using standard measures of economic growth, health outcomes, education, and literacy, the CEPR study compares the progress achieved during the period preceding globalization, 1960-80, with the period from 1980 to 2000, which was characterized by the reduction of tariff and nontariff barriers to trade, the removal of restrictions on international investment flows, and increasing intervention by the International Monetary Fund and World Bank on a wide range of economic and policy issues. While the evidence presented here does not prove that the policies associated with globalization were responsible for the deterioration in economic performance, it does present a very strong prima facie case that some structural and policy changes implemented during the last two decades are at least partly responsible for these declines.

Relating plastic in the ocean to ecological harm, a review of recent progress in risk analysis

NASA Astrophysics Data System (ADS)

Schuyler, Q. A.; Hardesty, B. D.; Wilcox, C.; van Sebille, E.; Mallos, N. J.; Leonard, G. H.

2016-02-01

Plastic pollution in the ocean is emerging as a global environmental concern. Estimates suggest that we dump on the order of 8.4 million tons of plastic in the ocean each year. This plastic reaches substantial concentrations, with at sea sampling measuring densities over 580,000 items per square kilometer. However, it is difficult to relate this exposure to resulting ecological impacts. Animals dying due to plastic ingestion or entanglement may not was ahsore, and sampling at sea is expensive and infrequent. Thus demonstrating a direct relationship between plastic in the envioronment and harm to marine wildlife is challenging. Here we review current progress on risk assessment for impacts to marine wildlife from plastic pollution. The analyses we review range from expert elicitation to integrated statistical and physical models. They range widely in scope, from estimates at the individual level to who taxa analysis. Some of the analyses reach only to exposure to the pressure, whie others carry through to estimate demographic impacts and even mortality due to ingestion of or entanglement in plastic debris in the ocean. We summarize the results of these studies, and provide a roadmap for future contributions toward estimating the actual ecological impact of plastic pollution.

Integrated health and social care in England--Progress and prospects.

PubMed

Humphries, Richard

2015-07-01

This paper reviews recent policy initiatives in England to achieve the closer integration of health and social care. This has been a policy goal of successive UK governments for over 40 years but overall progress has been patchy and limited. The coalition government has a new national framework for integrated care and variety of new policy initiatives including the 'pioneer' programme, the introduction of a new pooled budget--the 'Better Care Fund'--and a new programme of personal commissioning. Further change is likely as the NHS begins to develop new models of care delivery. There are significant tensions between these very different policy levers and styles of implementation. It is too early to assess their combined impact. Expectations that integration will achieve substantial financial savings are not supported by evidence. Local effort alone will be insufficient to overcome the fundamental differences in entitlement, funding and delivery between the NHS and the social care system. With a national election set to take place in May 2015, all political parties are committed to the integration of health and social care but clear evidence about the best means to achieve it is likely to remain as elusive as ever. Copyright © 2015 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.

The new chiropractic.

PubMed

Walker, Bruce F

2016-01-01

Physical manipulation and manual therapies are thousands of years old. The most popular western world iteration of these therapies is delivered by chiropractors. It can be argued that the collective public health benefit from chiropractic for spinal pain has been very substantial, however as chiropractic has transitioned from craft to profession it has encountered many internally and externally driven machinations that have retarded its progress to a fully accepted allied health profession. This article sets out a ten point plan for a new chiropractic that will achieve full acceptance for this troubled profession. This article is based on a keynote speech known as the FG Roberts Memorial Address delivered on October 10, 2015, in Melbourne, Australia at the Chiropractic & Osteopathic College of Australasia and Chiropractic Australia national conference. The ten point plan consists of the following: improving the pre-professional education of chiropractors, establishing a progressive identity, developing a special interest for the profession, marginalising the nonsensical elements of the profession, being pro-public health, supporting the legitimate organised elements of the profession, improving clinical practice, embracing evidence based practice, supporting research and showing personal leadership. Adherence to this fresh ten point plan will, over time, see the chiropractic profession gain full legitimacy in the allied health field and acceptance by other health providers, policy makers and the public at large.

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

PubMed

Pichler, Raimund H; de Boer, Ian H

2010-08-01

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

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

PubMed

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

2013-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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

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

Treesearch

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

2003-01-01

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

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

Treesearch

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

2003-01-01

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

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

ERIC Educational Resources Information Center

Stanley-Hermanns, Melinda; Engebretson, Joan

2010-01-01

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

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

ERIC Educational Resources Information Center

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

2006-01-01

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

[Integral assessment of learning subjects difficulties].

PubMed

Grebniak, N P; Shchudro, S A

2010-01-01

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

ORNL Annual Sustainability Report

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

Lapsa, Melissa Voss; Nichols, Teresa A.

2014-02-01

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

Higher Education Research Community in Taiwan: An Emerging Field

ERIC Educational Resources Information Center

Chan, Sheng-Ju; Chan, Ying

2015-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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

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

ERIC Educational Resources Information Center

Zwick, Rebecca

2010-01-01

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

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

ERIC Educational Resources Information Center

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

2013-01-01

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

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

ERIC Educational Resources Information Center

Thille, Candace; Smith, Joel

2011-01-01

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