Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy.

PubMed

Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi

2012-05-01

A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

The incubator and the medical discovery of the premature infant.

PubMed

Baker, J P

2000-01-01

The invention of the incubator in 1880 ignited a dramatic outpouring of popular and professional excitement over the prospect of reducing premature infant mortality. Yet the technology itself progressed slowly and fitfully over the next 50 years. The story is worth examining not so much from the standpoint of technological progress, but from the perspective of how responsibility for the newborn shifted from mothers to obstetricians and eventually pediatricians. It also illustrates how the history of technology involves more than invention. The invention of the incubator itself was less significant than the development of a system to support the device.

Polymer-Carbon Nanotube Composites, A Literature Review

DTIC Science & Technology

2004-08-01

have led to improvements in product controllability, yield, and cost . Other aspects of nanotube synthesis currently under scrutiny include study of...progress in many areas of characterization and applications was initially hindered by the high cost of production, as well as the requirement of...processing the nanotubes. In recent years, the production costs have decreased dramatically as a result of the development of new, high-throughput

Poverty among Elderly Women and Minorities. Changing Domestic Priorities Discussion Paper.

ERIC Educational Resources Information Center

Moon, Marilyn

Measured by cash income, the rate of poverty among the age 65 and older population has fallen dramatically, especially since 1974--from 25 percent in 1968 to 14.1 percent in 1983. However, this decline is the result more of an increase in poverty rates for the nonelderly in recent years than of major progress in reducing poverty for those over 65.…

Clinical Decision Support: a 25 Year Retrospective and a 25 Year Vision

PubMed Central

Sittig, D. F.; Wright, A.

2016-01-01

Summary Objective The objective of this review is to summarize the state of the art of clinical decision support (CDS) circa 1990, review progress in the 25 year interval from that time, and provide a vision of what CDS might look like 25 years hence, or circa 2040. Method Informal review of the medical literature with iterative review and discussion among the authors to arrive at six axes (data, knowledge, inference, architecture and technology, implementation and integration, and users) to frame the review and discussion of selected barriers and facilitators to the effective use of CDS. Result In each of the six axes, significant progress has been made. Key advances in structuring and encoding standardized data with an increased availability of data, development of knowledge bases for CDS, and improvement of capabilities to share knowledge artifacts, explosion of methods analyzing and inferring from clinical data, evolution of information technologies and architectures to facilitate the broad application of CDS, improvement of methods to implement CDS and integrate CDS into the clinical workflow, and increasing sophistication of the end-user, all have played a role in improving the effective use of CDS in healthcare delivery. Conclusion CDS has evolved dramatically over the past 25 years and will likely evolve just as dramatically or more so over the next 25 years. Increasingly, the clinical encounter between a clinician and a patient will be supported by a wide variety of cognitive aides to support diagnosis, treatment, care-coordination, surveillance and prevention, and health maintenance or wellness. PMID:27488402

Clinical Information Systems – From Yesterday to Tomorrow

PubMed Central

2016-01-01

Summary Objectives To review the history of clinical information systems over the past twenty-five years and project anticipated changes to those systems over the next twenty-five years. Methods Over 250 Medline references about clinical information systems, quality of patient care, and patient safety were reviewed. Books, Web resources, and the author’s personal experience with developing the HELP system were also used. Results There have been dramatic improvements in the use and acceptance of clinical computing systems and Electronic Health Records (EHRs), especially in the United States. Although there are still challenges with the implementation of such systems, the rate of progress has been remarkable. Over the next twenty-five years, there will remain many important opportunities and challenges. These opportunities include understanding complex clinical computing issues that must be studied, understood and optimized. Dramatic improvements in quality of care and patient safety must be anticipated as a result of the use of clinical information systems. These improvements will result from a closer involvement of clinical informaticians in the optimization of patient care processes. Conclusions Clinical information systems and computerized clinical decision support have made contributions to medicine in the past. Therefore, by using better medical knowledge, optimized clinical information systems, and computerized clinical decision, we will enable dramatic improvements in both the quality and safety of patient care in the next twenty-five years. PMID:27362589

Work in Progress: Gender and Politics in Late Elizabethan Progress Entertainments

ERIC Educational Resources Information Center

Kolkovich, Elizabeth Zeman

2009-01-01

This dissertation analyzes the understudied dramatic genre of Elizabethan progress entertainments, the political ideologies it conveys, and especially the female alliances it enacts. Aristocrats staged these outdoor, episodic pageants on their country estates during Elizabeth I's summer "progress" visits, 1575-1602. While previous scholars…

The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset

PubMed Central

Shoemaker, Jennifer L.; Seely, Kathryn A.; Reed, Ronald L.; Crow, John P.; Prather, Paul L.

2010-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, paralysis and death within 2–5 years of diagnosis. Currently, no effective pharmacological agents exist for the treatment of this devastating disease. Neuroinflammation may accelerate the progression of ALS. Cannabinoids produce anti-inflammatory actions via cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), and delay the progression of neuroinflammatory diseases. Additionally, CB2 receptors, which normally exist primarily in the periphery, are dramatically up-regulated in inflamed neural tissues associated with CNS disorders. In G93A-SOD1 mutant mice, the most well-characterized animal model of ALS, endogenous cannabinoids are elevated in spinal cords of symptomatic mice. Furthermore, treatment with non-selective cannabinoid partial agonists prior to, or upon, symptom appearance minimally delays disease onset and prolongs survival through undefined mechanisms. We demonstrate that mRNA, receptor binding and function of CB2, but not CB1, receptors are dramatically and selectively up-regulated in spinal cords of G93A-SOD1 mice in a temporal pattern paralleling disease progression. More importantly, daily injections of the selective CB2 agonist AM-1241, initiated at symptom onset, increase the survival interval after disease onset by 56%. Therefore, CB2 agonists may slow motor neuron degeneration and preserve motor function, and represent a novel therapeutic modality for treatment of ALS. PMID:17241118

Transmission Electron Microscopy for Nanomedicine: Novel Applications for Long-established Techniques

PubMed Central

2016-01-01

During the last twenty years, the research in nanoscience and nanotechnology has dramatically increased and, in the last decade, the interest has progressively been oriented towards biomedical applications, giving rise to a new field termed nanomedicine. Transmission electron microscopy is a valuable technique not only for the thorough physico-chemical characterization of newly synthesized nanoparticulates, but especially to explore the effects of nanocomposites on biological systems, providing essential information for the development of efficient therapeutic and diagnostic strategies. Thus, for the progress of nanotechnology in the biomedical field, experts in cell biology, histochemistry and ultramicroscopy should always support the chemists, physicists and pharmacologists engaged in the synthesis and characterization of innovative nanoconstructs. PMID:28076938

Personalized Progress Charts: An Effective Motivation for Reluctant Readers.

ERIC Educational Resources Information Center

Webre, Elizabeth C.

Progress charts are an effective means of dramatizing student effort and improvement in reading and are especially important for remedial reading students, who need concrete evidence of progress. Remedial reading students often need extrinsic reward, and since reading is a complex act, progress charts lend themselves to the element of reward and…

Inner work life: understanding the subtext of business performance.

PubMed

Amabile, Teresa M; Kramer, Steven J

2007-05-01

Anyone in management knows that employees have their good days and their bad days--and that, for the most part, the reasons for their ups and downs are unknown. Most managers simply shrug their shoulders at this fact of work life. But does it matter, in terms of performance, if people have more good days than bad days? Teresa Amabile and Steven Kramer's new stream of research, based on more than 12,000 diary entries logged by knowledge workers over three years, reveals the dramatic impact of employees' inner work lives--their perceptions, emotions, and motivation levels--on several dimensions of performance. People perform better when their workday experiences include more positive emotions, stronger intrinsic motivation (passion for the work), and more favorable perceptions of their work, their team, their leaders, and their organization. What the authors also found was that managers' behavior dramatically affects the tenor of employees' inner work lives. So what makes a difference to inner work life? When the authors compared the study participants' best days to their worst days, they found that the single most important differentiator was their sense of being able to make progress in their work. The authors also observed interpersonal events working in tandem with progress events. Praise without real work progress, or at least solid efforts toward progress, had little positive impact on people's inner work lives and could even arouse cynicism. On the other hand, good work progress without any recognition--or, worse, with criticism about trivial issues--could engender anger and sadness. Far and away, the best boosts to inner work life were episodes in which people knew they had done good work and their managers appropriately recognized that work.

Revolution…Now The Future Arrives for Five Clean Energy Technologies – 2015 Update

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

None

In 2013, the U.S. Department of Energy (DOE) released the Revolution Now report, highlighting four transformational technologies: land-based wind power, silicon photovoltaic (PV) solar modules, light-emitting diodes (LEDs), and electric vehicles (EVs). That study and its 2014 update showed how dramatic reductions in cost are driving a surge in consumer, industrial, and commercial adoption for these clean energy technologies—as well as yearly progress. In addition to presenting the continued progress made over the last year in these areas, this year’s update goes further. Two separate sections now cover large, central, utility-scale PV plants and smaller, rooftop, distributed PV systems tomore » highlight how both have achieved significant deployment nationwide, and have done so through different innovations, such as easier access to capital for utility-scale PV and reductions of non-hardware costs and third-party ownership for distributed PV. Along with these core technologies« less

[Artificial intelligence in psychiatry-an overview].

PubMed

Meyer-Lindenberg, A

2018-06-18

Artificial intelligence and the underlying methods of machine learning and neuronal networks (NN) have made dramatic progress in recent years and have allowed computers to reach superhuman performance in domains that used to be thought of as uniquely human. In this overview, the underlying methodological developments that made this possible are briefly delineated and then the applications to psychiatry in three domains are discussed: precision medicine and biomarkers, natural language processing and artificial intelligence-based psychotherapeutic interventions. In conclusion, some of the risks of this new technology are mentioned.

Portal Hypertension Over the Last 25 Years: Where Did It Go?

PubMed

Rosemurgy, Alexander; Raitano, Olivia; Srikumar, Thejal; Sawangkum, Peeraya; Luberice, Kenneth; Ryan, Carrie; Ross, Sharona

2016-06-01

Portal hypertension has seemingly vanished from surgery; this study was undertaken to determine where it has gone. Data from the Agency for Health Care Administration for 33,166,201 hospital inpatients in Florida for the periods 1988 to 1992, 1998 to 2002, and 2008 to 2012 were analyzed. Admissions with a diagnosis of portal hypertension dramatically increased: 5,473 patients from 1988 to 1992, 7,366 patients from 1998 to 2002, and 36,554 patients from 2008 to 2012. Endoscopic treatment of esophageal varices also dramatically increased. The number of decompressive shunts placed nominally increased, but application of endoscopic therapy increased significantly faster than the application of decompressive shunts (p < 0.0001). The percentage of patients who underwent shunting dramatically and significantly decreased (p < 0.0001), and surgeons undertook proportionally fewer shunts (42% in 1992 to 4% in 2012; p < 0.0001). For patients with a diagnosis of portal hypertension, in-hospital mortality progressively decreased, from 9% in 1988 to 1992 to 3% in 2008 to 2012 (p < 0.0001). In the state of Florida, over 25 years, there has been a 7-fold increase in the number of patients admitted with a diagnosis of portal hypertension, with a 65% reduction of in-hospital mortality. Application of endoscopic treatment of varices has increased dramatically. Decompressive shunts are applied to an ever-decreasing percentage of patients, and when applied, are now routinely undertaken by nonsurgeons. Therefore, portal hypertension has disappeared from the purview of surgery and has migrated toward the world of medical and endoscopic therapy, probably never to return. Copyright © 2016. Published by Elsevier Inc.

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

Gu, Meng; He, Yang; Zheng, Jianming

Silicon (Si), associated with its natural abundance, low discharge voltage vs. Li/Li+, and extremely high theoretical discharge capacity (~ 4200 mAh g-1,), has been extensively explored as anode for lithium ion battery. One of the key challenges for using Si as anode is the large volume change upon lithiation and delithiation, which causes a fast capacity fading. Over the last few years, dramatic progress has been made for addressing this issue. In this paper, we summarize the progress towards tailoring of Si as anode for lithium ion battery. The paper is organized such that it covers the fundamentals, the promisemore » offered based on nanoscale designing, and the remaining challenges that need to be attacked to allow using of Si based materials as anode for battery.« less

A Study of the Effects of Creative Dramatics on the Progress in Use of the Library, Reading Interests, Reading Achievement, Self-Concept, Creativity, and Empathy of Fourth and Fifth Grade Children.

ERIC Educational Resources Information Center

Ziegler, Elsie Mae

To appraise the value of a creative dramatics program in a public library setting was the purpose of this study. Nine public library branches comprised the setting for the experiment. At each branch there were three units: (1) creative dramatics, (2) storytelling, and (3) library usage. Storytelling and library usage were the control group. Pre…

2016 Earth System Grid Federation Annual Report

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

Williams, Dean N.

The Earth System Grid Federation (ESGF) experienced a major setback in June 2015, when it experienced a security incident that brought all systems to a halt for more than half a year. However, federation developers and management committee members turned the incident into an opportunity to dramatically upgrade the system security and functionality and to develop planning and policy documents to guide ESGF evolution and success. Moreover, despite the incident, ESGF developer working teams continue to make strong and significant progress on various enhancement projects that will help ensure ESGF can meet the needs of the climate community in themore » coming years.« less

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

The devil is in the details: maximizing revenue for daily trauma care.

PubMed

Barnes, Stephen L; Robinson, Bryce R H; Richards, J Taliesin; Zimmerman, Cindy E; Pritts, Tim A; Tsuei, Betty J; Butler, Karyn L; Muskat, Peter C; Davis, Kenneth; Johannigman, Jay A

2008-10-01

Falling reimbursement rates for trauma care demand a concerted effort of charge capture for the fiscal survival of trauma surgeons. We compared current procedure terminology code distribution and billing patterns for Subsequent Hospital Care (SHC) before and after the institution of standardized documentation. Standardized SHC progress notes were created. The note was formulated with an emphasis on efficiency and accuracy. Documentation was completed by residents in conjunction with attendings following standard guidelines of linkage. Year-to-year patient volume, length of stay (LOS), injury severity, bills submitted, coding of service, work relative value units (wRVUs), revenue stream, and collection rate were compared with and without standardized documentation. A 394% average revenue increase was observed with the standardization of SHC documentation. Submitted charges more than doubled in the first year despite a 14% reduction in admissions and no change in length of stay. Significant increases in level II and level III billing and billing volume (P < .05) were sustainable year to year and resulted in an average per patient admission SHC income increase from $91.85 to $362.31. Use of a standardized daily progress note dramatically increases the accuracy of coding and associated billing of subsequent hospital care for trauma services.

Design and fabrication of the progressive addition lenses

NASA Astrophysics Data System (ADS)

Qin, Linling; Qian, Lin; Yu, Jingchi

2011-11-01

The use of progressive addition lenses (PALs) for the correction of presbyopia has increased dramatically in recent years. These lenses are now being used as the preferred alternative to bifocal and trifocal lenses in many parts of the world. Progressive addition lenses are a kind of opthalmic lenses with freeform surface. The surface curvature of the Progressive addition lenses varies gradually from a minimum value in the upper area, to a maximum value in the lower area. Thus a PAL has a surface with three zones which have very small astigmatism: far-view zone, near-view zone, and intermediate zone. The far view zone and near view zone have relatively constant powers and connected by the intermediate zone with power varies progressively. The design and fabrication technologies of progressive addition lenses have fast progresses because of the massive development of the optical simulation software, multi-axis ultraprecision machining technologies and CNC machining technologies. The design principles of progressive addition lenses are discussed in a historic review. Several kinds of design methods are illustrated, and their advantages and disadvantages are also represented. In the current study, it is shown that the optical characteristics of the different progressive addition lenses designs are significantly different from one another. The different fabrication technologies of Progressive addition lenses are also discussed in the paper. Plastic injection molding and precision-machine turning are the common fabrication technologies for exterior PALs and Interior PALs respectively.

[Addiction and care for addicts].

PubMed

van den Brink, W; Schippers, G M

2008-01-01

In the course of the last 50 years our knowledge about the epidemiology, aetiology, pathogenesis, prevention, and treatment of addiction has increased dramatically. Since the 1980s treatment providers have had at their disposal effective psychotherapeutic interventions whereby insightful forms of treatment have been largely replaced by cognitive behavioural therapy aimed at bringing about changes in behaviour. Since the 1990s more and more pharmacological interventions have also been introduced and recently some new neurophysiological interventions have been carefully tested. Finally, considerable progress has been made in assigning patients to the most suitable forms of treatment.

Early Intervention and Nonpharmacological Therapy of Myopia in Young Adults

PubMed Central

Gładysiak, Aleksandra; Ślęzak, Daniel

2018-01-01

Myopia is a condition of the eye where parallel rays focus in front of, instead of on, the retina, which results in excessive refractive power of the cornea or the lens or eyeball elongation. Studies carried out in recent years show that the etiology of myopia is complex with genetic and environmental factors playing a role. Refraction defects decrease the quality of vision, while progressing myopia can lead to partial loss of vision, which can be particularly dramatic in young adults. Therefore, it is so crucial to take appropriate actions aimed at preventing myopia progression. This is a review of nonpharmacological therapeutic possibilities of refraction defect prevention in young adults, with special regard to myofascial therapy, osteopathy, and massage of acupuncture points surrounding the eye. PMID:29576878

The American Burn Association/Shriners Hospitals for Children Burn Outcomes Program: a progress report at 15 years.

PubMed

Tompkins, Ronald G; Liang, Matthew H; Lee, Austin F; Kazis, Lewis E

2012-09-01

The American Burn Association and the Shriners Hospitals for Children Outcomes Program has been in development for more than 15 years. Many of the tools and important findings are described in this special issue of The Journal of Trauma. This unique program in outcomes research introduces a model for outcome assessments from the patient-centered perspective with a cohort of 1,140 children with burn injury after hospitalization for up to 4 years. The findings represent a fundamental contribution to the field of burn care for monitoring outcomes from the perspective of the parent or child/adolescent. The Multi-Center Benchmarking Study of four burn centers serve as a model for collecting empiric scientific data on the variation and the expected trajectories of recovery in the most important domains of patient outcomes and can inform clinical decisions and the conduct of health service research. The dramatic progress in survival of children with severe burn injury and other advances in burn management can now move into a new phase of understanding the most cost-effective components of this care.

Stromal Androgen Receptor in Prostate Cancer Development and Progression

PubMed Central

Leach, Damien A.; Buchanan, Grant

2017-01-01

Prostate cancer development and progression is the result of complex interactions between epithelia cells and fibroblasts/myofibroblasts, in a series of dynamic process amenable to regulation by hormones. Whilst androgen action through the androgen receptor (AR) is a well-established component of prostate cancer biology, it has been becoming increasingly apparent that changes in AR signalling in the surrounding stroma can dramatically influence tumour cell behavior. This is reflected in the consistent finding of a strong association between stromal AR expression and patient outcomes. In this review, we explore the relationship between AR signalling in fibroblasts/myofibroblasts and prostate cancer cells in the primary site, and detail the known functions, actions, and mechanisms of fibroblast AR signaling. We conclude with an evidence-based summary of how androgen action in stroma dramatically influences disease progression. PMID:28117763

Hope facilitating strategies for the family of the head injury patient.

PubMed

Johnson, L H; Roberts, S L

1996-08-01

Approximately 200 new head injuries are reported per 100,000 population each year in the United States. These injuries are more common in younger men and caused most frequently by motor vehicle accidents. Head injuries occur suddenly and unexpectedly. Head injury affects not only the individual but the family as well. The family's functional abilities are threatened by the head injury of a family member. The family's adaptation to head injury and life-threatening events surrounding the injury has a significant impact on the patient's rehabilitation. A family's response of denial or lack of hope in the future has been identified as a major obstacle to successful adaptation. The hopeless family may be unable to make necessary changes at home or learn important aspects of the patient's care. Depending upon the extent of the head injury, the family needs to know that most head trauma patients make significant progress in the first six months. Progress usually continues, less dramatically, for the next two to three years.

Donor Vδ1+ γδ T cells expand after allogeneic hematopoietic stem cell transplantation and show reactivity against CMV-infected cells but not against progressing B-CLL.

PubMed

Prinz, Immo; Thamm, Kristina; Port, Matthias; Weissinger, Eva M; Stadler, Michael; Gabaev, Ildar; Jacobs, Roland; Ganser, Arnold; Koenecke, Christian

2013-05-11

γδ T lymphocytes play an important role in immune reactions towards infections and malignancies. In particular, Vγ9-Vδ1+ T lymphocytes are thought to play protective antiviral roles in human CMV infection. Recently, Vδ1+ T lymphocytes were proposed to also have anti- B-CLL reactivity. Here we report a case of 48-year-old man who received allogeneic stem cell transplantation for progressive B-CLL. Within one year after transplantation, lymphoma relapsed despite a dramatic increase of Vδ1+ T cells in the patient's blood. In vitro killing assays revealed activity of patient's γδ cells against CMV target cells, but not against the relapsing lymphoma-cells. This argues for a contribution of Vδ1+ cells in the immune reaction against CMV reactivation, but does not support a strong correlation of expanded Vδ1+ T cells and favorable disease outcome in B-CLL patients.

[An artificial heart: bridge to transplantation or permanent?].

PubMed

de Mol, Bas A J M; Lahpor, Jaap

2013-01-01

An artificial heart is a continuous-flow pump device with a constant output, which usually supports the left ventricle. Over the past five years, survival rates with an artificial heart have increased dramatically, but with an annual mortality of 10% per year compared with 6% for heart transplantation the artificial heart is mainly a 'bridge to transplantation' or an alternative for those patients who are not suitable for heart transplant, 'destination therapy'. It is anticipated that the number and severity of complications will decrease as a result of technological progress. The artificial heart could then become a long-term treatment option providing a good quality of life and thus become equivalent to a heart transplant.

Building the future an atom at a time: Realizing feynman's vision

NASA Astrophysics Data System (ADS)

Madia, William J.

2006-10-01

Since Feynman’s 1959 lecture, “There’s Plenty of Room at the Bottom,” and particularly in the last 15 years, advances in instrumentation have permitted us to observe and characterize materials at atomic scale. New and even more powerful capabilities are rapidly becoming available. At the same time, our theoretical understanding and ability to model complex systems have matured to a level that enables us to begin making useful predictions in many areas, with the promise of further progress as we approach petascale computing. Progress in making and structuring nanoscale materials in commercially useful quantities is also being made, albeit more selectively. Exploiting chemistry and biochemistry to mimic nature’s accomplishments in living systems is a promising approach that is opening new possibilities. The remarkable progress of the last few years is already producing technological advances, and more can be expected as investments in nanoscience and nanotechnology increase. Just as advances in information technology during the second half of the 20th century produced dramatic technological, economic, and societal changes, so the coming nanoscale revolution will affect virtually every aspect of life in the 21st century.

Building the future an atom at a time: Realizing Feynman's vision

NASA Astrophysics Data System (ADS)

Madia, William J.

2006-10-01

Since Feynman’s 1959 lecture, “There’s Plenty of Room at the Bottom,” and particularly in the last 15 years, advances in instrumentation have permitted us to observe and characterize materials at atomic scale. New and even more powerful capabilities are rapidly becoming available. At the same time, our theoretical understanding and ability to model complex systems have matured to a level that enables us to begin making useful predictions in many areas, with the promise of further progress as we approach petascale computing. Progress in making and structuring nanoscale materials in commercially useful quantities is also being made, albeit more selectively. Exploiting chemistry and biochemistry to mimic nature’s accomplishments in living systems is a promising approach that is opening new possibilities. The remarkable progress of the last few years is already producing technological advances, and more can be expected as investments in nanoscience and nanotechnology increase. Just as advances in information technology during the second half of the 20th century produced dramatic technological, economic, and societal changes, so the coming nanoscale revolution will affect virtually every aspect of life in the 21st century.

Three-Year Follow-Up of an Alectinib Phase I/II Study in ALK-Positive Non-Small-Cell Lung Cancer: AF-001JP.

PubMed

Tamura, Tomohide; Kiura, Katsuyuki; Seto, Takashi; Nakagawa, Kazuhiko; Maemondo, Makoto; Inoue, Akira; Hida, Toyoaki; Yoshioka, Hiroshige; Harada, Masao; Ohe, Yuichiro; Nogami, Naoyuki; Murakami, Haruyasu; Kuriki, Hiroshi; Shimada, Tadashi; Tanaka, Tomohiro; Takeuchi, Kengo; Nishio, Makoto

2017-05-10

Purpose Alectinib is an anaplastic lymphoma kinase (ALK) -specific kinase inhibitor that seems to be effective against non-small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor-naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.

Three-Year Follow-Up of an Alectinib Phase I/II Study in ALK-Positive Non–Small-Cell Lung Cancer: AF-001JP

PubMed Central

Tamura, Tomohide; Kiura, Katsuyuki; Seto, Takashi; Nakagawa, Kazuhiko; Maemondo, Makoto; Inoue, Akira; Hida, Toyoaki; Yoshioka, Hiroshige; Harada, Masao; Ohe, Yuichiro; Nogami, Naoyuki; Murakami, Haruyasu; Kuriki, Hiroshi; Shimada, Tadashi; Tanaka, Tomohiro; Takeuchi, Kengo; Nishio, Makoto

2017-01-01

Purpose Alectinib is an anaplastic lymphoma kinase (ALK) –specific kinase inhibitor that seems to be effective against non–small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor–naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment. PMID:28296581

Clocks, engines, and quarks--love, dreams, and genes. What makes development happen?

PubMed

Mayes, L C

1999-01-01

That psychological growth and maturation throughout the lifespan involve progressive linear processes is an implicit assumption of all models of development. Within psychoanalysis, a particular focus has been those processes that hinder forward development and manifest themselves as regressions or fixations or in character structure. However, the implicit assumption of progressive, linear development leaves unexplored the central question of what are the processes that govern developmental progressions. What makes psychological development happen in more or less predictable ways and yet allows for considerable individual variability? And are those developmental progressions inevitably forwardly progressive? Questions regarding what regulates and integrates development are relevant not only for understanding the normal building up of the internal world and of childhood psychopathology but also for those times of dramatic mental reorganization in adulthood surrounding events such as pregnancy and aging and for issues of psychological change during and after an analysis. Clinical material from analyses with a child and an adult and from interviews with four- to five-year-old children is used to explore individual fantasies of how development and change happens. The central role of internalization and object relations in regulating psychological development is emphasized.

Precocious puberty and large multicystic ovaries in young girls with primary hypothyroidism.

PubMed

Sanjeevaiah, Aravind Raj; Sanjay, Subbarayappa; Deepak, Tejesweni; Sharada, Ardanareshwaran; Srikanta, Sri S

2007-10-01

To describe 2 cases of primary hypothyroidism, precocious puberty, large multicystic ovaries, possible diagnostic dilemma, unilateral oophorectomies, and subsequent response to levothyroxine replacement therapy. We present the clinical, biochemical, radiologic, and histopathologic findings in 2 patients with rare cases of Van Wyk-Grumbach syndrome and megaovaries, who underwent unilateral oophorectomy. Two patients, an 8-year-old girl and a 3-year-old girl (cases 1 and 2, respectively), were referred to our center. Both patients presented with precocious puberty and vaginal bleeding and had undergone unilateral oophorectomy before referral. In the first patient (case 1), the surgical intervention was a consequence of torsion of the left megaovary, necessitating emergency oophorectomy. Oophorectomy in the second patient (case 2) was a result of initial diagnostic confusion, inasmuch as a sexcord stromal tumor was suspected. A detailed history, physical examination, and laboratory results pointed toward primary hypothyroidism due to Hashimoto's thyroiditis and thyroid dysgenesis, respectively. Serial ultrasound studies of the abdomen and pelvis revealed large multicystic ovaries, with progressive enlargement (including regrowth from an apparent ovarian "postsurgical remnant"). Both patients responded dramatically after initiation of levothyroxine replacement therapy, with no further vaginal bleeding and reversal of megaovary to normal size (in case 1). In a highly selected minority of children with untreated primary hypothyroidism, there is development of precocious puberty and progressively enlarging multicystic ovaries. The precise endocrine, neuroanatomic, and neurophysiologic bases for this phenomenon are unclear. Nevertheless, the entire clinicopathologic picture, including giant ovaries, dramatically reverts to normal status with the restoration of a euthyroid state by means of simple levothyroxine replacement therapy.

Mammalian O-Mannosylation Pathway: Glycan Structures, Enzymes, and Protein Substrates

PubMed Central

2015-01-01

The mammalian O-mannosylation pathway for protein post-translational modification is intricately involved in modulating cell–matrix interactions in the musculature and nervous system. Defects in enzymes of this biosynthetic pathway are causative for multiple forms of congenital muscular dystophy. The application of advanced genetic and biochemical technologies has resulted in remarkable progress in this field over the past few years, culminating with the publication of three landmark papers in 2013 alone. In this review, we will highlight recent progress focusing on the dramatic expansion of the set of genes known to be involved in O-mannosylation and disease processes, the concurrent acceleration of the rate of O-mannosylation pathway protein functional assignments, the tremendous increase in the number of proteins now known to be modified by O-mannosylation, and the recent progress in protein O-mannose glycan quantification and site assignment. Also, we attempt to highlight key outstanding questions raised by this abundance of new information. PMID:24786756

Accidental poisoning in childhood: five year urban population study with 15 year analysis of fatality.

PubMed Central

Pearn, J; Nixon, J; Ansford, A; Corcoran, A

1984-01-01

Patterns of accidental poisoning in children are changing dramatically. A five year population study (1977-81) was undertaken in urban children from Brisbane (population 1 000 000). A total of 2098 children were poisoned during this period with only one fatality, which represents a dramatic reduction in mortality. Over the past 15 years (1968-82) 13 children have died from accidental poisoning from this population, and two were murdered with drugs. A study of secular trends has indicated that peak incidence occurred in 1979, and the rate has been falling progressively since. The current age corrected rate of poisoning is 393 per 100 000 children per year (0-5 year olds). The rank order of poisons, drugs, and chemicals causing hospital admission and death is: petroleum distillates 13%; antihistamines 9%; benzodiazepines 9%; bleach and detergents 7%; and aspirin 6%. The ratio of fatalities to ingestions requiring hospital admission was calculated to give an index of a practical danger of noxious agents to which children are currently exposed and the rank order is: cardiotoxic drugs, one fatality to 25 ingestions; tricyclic antidepressants, one to 44; sympathomimetic drugs, one to 54; caustic soda, one to 68; aspirin, one fatality to 350 ingestions. Accidental poisoning of children leading to death has been reduced because patterns of drug prescriptions have changed, packaging of dangerous drugs has been made safer, and substances such as kerosene have been coloured blue. PMID:6140065

Toddler development.

PubMed

Colson, E R; Dworkin, P H

1997-08-01

The toddler years are ones of exciting and challenging changes in cognitive, affective, and physical growth. Physical growth is particularly remarkable for the child's increasing skills and ability to navigate the environment. Affective development is marked by the push for autonomy and independence and the highly visible nature of the child's temperament or behavioral style. The toddler also enters the wonderful years of imagination and pretend play. Perhaps most noteworthy is the child's dramatic increase in ability to communicate with others through speech and language, as evidence of the progression to symbolic thinking. The dynamic changes in children's development during the toddler years have important implications for child health supervision. Familiarity with toddler development will enable the pediatrician to monitor children's development effectively and to address common, stage-related behaviors with families during anticipatory guidance.

Targeting the androgen receptor pathway in castration-resistant prostate cancer: progresses and prospects

PubMed Central

Ferraldeschi, R; Welti, J; Luo, J; Attard, G; de Bono, JS

2015-01-01

Androgen receptor (AR) signaling is a critical pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease. However, over time, most tumors become resistant to ADT. The view of castration-resistant prostate cancer (CRPC) has changed dramatically in the last several years. Progress in understanding the disease biology and mechanisms of castration resistance led to significant advancements and to paradigm shift in the treatment. Accumulating evidence showed that prostate cancers develop adaptive mechanisms for maintaining AR signaling to allow for survival and further evolution. The aim of this review is to summarize molecular mechanisms of castration resistance and provide an update in the development of novel agents and strategies to more effectively target the AR signaling pathway. PMID:24837363

Eta Carinae’s 2014.6 Spectroscopic Event: The Extraordinary He II and N II Features

NASA Astrophysics Data System (ADS)

Davidson, Kris; Mehner, Andrea; Humphreys, Roberta M.; Martin, John C.; Ishibashi, Kazunori

2015-03-01

Eta Carinae’s spectroscopic events (periastron passages) in 2003, 2009, and 2014 differed progressively. He ii λ4687 and nearby N ii multiplet 5 have special significance because they respond to very soft X-rays and the ionizing UV radiation field (EUV). Hubble Space Telescope (HST)/STIS observations in 2014 show dramatic increases in both features compared to the previous 2009.1 event. These results appear very consistent with a progressive decline in the primary wind density, proposed years ago on other grounds. If material falls onto the companion star near periastron, the accretion rate may now have become too low to suppress the EUV. Based on observations made with the NASA/ESA Hubble Space Telescope, which is opera ted by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555.

Dramatic Decrease in Prevalence of Soil-Transmitted Helminths and New Insights Into Intestinal Protozoa in Children Living in the Chaco Region, Bolivia

PubMed Central

Macchioni, Fabio; Segundo, Higinio; Gabrielli, Simona; Totino, Valentina; Gonzales, Patricia Rojas; Salazar, Esteban; Bozo, Ricardo; Bartoloni, Alessandro; Cancrini, Gabriella

2015-01-01

We assessed the prevalence of intestinal parasites among 268 2–12-year-old children living in rural areas, small villages, and semi-urban areas of the Chaco region, south-eastern Bolivia. The overall parasitism was 69%. Only protozoa, helminths, or co-infections were observed in 89.2%, 5.9%, or 4.9% of the positive children, respectively. A significant progressive increase in overall parasite prevalence was found when passing from rural areas to small villages and semi-urban areas. The most commonly found species were Entamoeba coli (38.4%), Giardia intestinalis (37.7%), and Blastocystis spp. (16%). Hymenolepis nana was the most prevalent helminth (5.6%), followed by Ascaris lumbricoides and hookworms (1.5% and 0.4%) evidenced only in rural areas and in villages. Molecular diagnostics identified Blastocystis subtypes 9 and 2, and 5 infections by Entamoeba histolytica and 4 by Entamoeba dispar. The dramatic decrease in prevalence of soil-transmitted helminths with respect to that observed about 20 years ago (> 40%) evidences the success of the preventive chemotherapy intervention implemented in 1986. Health education and improved sanitation should be intensified to control protozoan infections. PMID:25711609

Program for Arctic Regional Climate Assessment (PARCA)

NASA Technical Reports Server (NTRS)

Gogineni, Sivaprasad; Thomas, Robert H.; Abdalati, Waleed (Editor)

1999-01-01

The Program for Arctic Regional Climate Assessment (PARCA) is a NASA-sponsored initiative with the prime objective of understanding the mass balance of the Greenland ice sheet. In October 1998, PARCA investigators met to review activities of the previous year, assess the program's progress, and plan future investigations directed at accomplishing that objective. Some exciting results were presented and discussed, including evidence of dramatic thinning of the ice sheet near the southeastern coast. Details of the investigations and many of the accomplishments are given in this report, but major highlights are given in the Executive Summary of the report.

History of solid organ transplantation and organ donation.

PubMed

Linden, Peter K

2009-01-01

Solid organ transplantation is one of the most remarkable and dramatic therapeutic advances in medicine during the past 60 years. This field has progressed initially from what can accurately be termed a "clinical experiment" to routine and reliable practice, which has proven to be clinically effective, life-saving and cost-effective. This remarkable evolution stems from a serial confluence of: cultural acceptance; legal and political evolution to facilitate organ donation, procurement and allocation; technical and cognitive advances in organ preservation, surgery, immunology, immunosuppression; and management of infectious diseases. Some of the major milestones of this multidisciplinary clinical science are reviewed in this article.

Exploiting Universality in Atoms with Large Scattering Lengths

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

Braaten, Eric

2012-05-31

The focus of this research project was atoms with scattering lengths that are large compared to the range of their interactions and which therefore exhibit universal behavior at sufficiently low energies. Recent dramatic advances in cooling atoms and in manipulating their scattering lengths have made this phenomenon of practical importance for controlling ultracold atoms and molecules. This research project was aimed at developing a systematically improvable method for calculating few-body observables for atoms with large scattering lengths starting from the universal results as a first approximation. Significant progress towards this goal was made during the five years of the project.

Influence of computational fluid dynamics on experimental aerospace facilities: A fifteen year projection

NASA Technical Reports Server (NTRS)

1983-01-01

An assessment was made of the impact of developments in computational fluid dynamics (CFD) on the traditional role of aerospace ground test facilities over the next fifteen years. With improvements in CFD and more powerful scientific computers projected over this period it is expected to have the capability to compute the flow over a complete aircraft at a unit cost three orders of magnitude lower than presently possible. Over the same period improvements in ground test facilities will progress by application of computational techniques including CFD to data acquisition, facility operational efficiency, and simulation of the light envelope; however, no dramatic change in unit cost is expected as greater efficiency will be countered by higher energy and labor costs.

Report of the Panel on Computer and Information Technology

NASA Technical Reports Server (NTRS)

Lundstrom, Stephen F.; Larsen, Ronald L.

1984-01-01

Aircraft have become more and more dependent on computers (information processing) for improved performance and safety. It is clear that this activity will grow, since information processing technology has advanced by a factor of 10 every 5 years for the past 35 years and will continue to do so. Breakthroughs in device technology, from vacuum tubes through transistors to integrated circuits, contribute to this rapid pace. This progress is nearly matched by similar, though not as dramatic, advances in numerical software and algorithms. Progress has not been easy. Many technical and nontechnical challenges were surmounted. The outlook is for continued growth in capability but will require surmounting new challenges. The technology forecast presented in this report has been developed by extrapolating current trends and assessing the possibilities of several high-risk research topics. In the process, critical problem areas that require research and development emphasis have been identified. The outlook assumes a positive perspective; the projected capabilities are possible by the year 2000, and adequate resources will be made available to achieve them. Computer and information technology forecasts and the potential impacts of this technology on aeronautics are identified. Critical issues and technical challenges underlying the achievement of forecasted performance and benefits are addressed.

Building high reliability teams: progress and some reflections on teamwork training.

PubMed

Salas, Eduardo; Rosen, Michael A

2013-05-01

The science of team training in healthcare has progressed dramatically in recent years. Methodologies have been refined and adapted for the unique and varied needs within healthcare, where once team training approaches were borrowed from other industries with little modification. Evidence continues to emerge and bolster the case that team training is an effective strategy for improving patient safety. Research is also elucidating the conditions under which teamwork training is most likely to have an impact, and what determines whether improvements achieved will be maintained over time. The articles in this special issue are a strong representation of the state of the science, the diversity of applications, and the growing sophistication of teamwork training research and practice in healthcare. In this article, we attempt to situate the findings in this issue within the broader context of healthcare team training, identify high level themes in the current state of the field, and discuss existing needs.

Long-term treatment of an addictive personality.

PubMed

Seymour, Peter M

2003-01-01

There is infrequent discussion of long-term psychotherapy of persons with addiction, particularly in the self-psychology literature. In addition, some question whether long-term psychotherapy can be helpful in severe psychiatric disorders. The author describes the treatment of a woman with multiple diagnoses, including bulimia and alcohol and drug addiction, which took place over a period of almost 7 years. These issues are addressed from a self-psychological perspective, with progression of the treatment from early facilitation of a selfobject transference to more intense selfobject transference-countertransference states. Behavioral interventions (e.g., recommendation of inpatient chemical dependency treatment) are also discussed. The author describes the patient's dramatic progress and subsequent regression. Finally, there is a discussion of the addiction from self-psychological and biological perspectives of this woman's particular developmental and treatment issues, as well as a discussion of the confrontation and limit setting in a self-psychologically oriented treatment.

Dramatic response to alectinib in inflammatory myofibroblastic tumor with anaplastic lymphoma kinase fusion gene.

PubMed

Saiki, Masafumi; Ohyanagi, Fumiyoshi; Ariyasu, Ryo; Koyama, Junji; Sonoda, Tomoaki; Nishikawa, Shingo; Kitazono, Satoru; Yanagitani, Noriko; Horiike, Atsushi; Ninomiya, Hironori; Ishikawa, Yuichi; Nishio, Makoto

2017-12-01

Inflammatory myofibroblastic tumor (IMT) is a neoplasm characterized by the proliferaton of myofibroblasts with the infiltration of inflammatory cells. There is no standard treatment for patients with recurrent or metastatic IMT. We describe here a patient with hyper-progressive IMT with an anaplastic lymphoma kinase (ALK) fusion gene that dramatically responded to alectinib without adverse events. His dramatic and enduring response supports the observation that alectinib may be considered a good treatment option for rare aggressive ALK-positive tumors. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Air Pollution: Current and Future Challenges

EPA Pesticide Factsheets

Despite the dramatic progress to date, air pollution continues to threaten Americans’ health and welfare. The main obstacles are climate change, conventional air pollution, and ozone layer depletion.

Eculizumab in paroxysmal nocturnal hemoglobinuria with Budd-Chiari syndrome progressing despite anticoagulation

PubMed Central

2012-01-01

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, life-threatening disorder characterized by chronic intravascular hemolysis caused by uncontrolled complement activation. Hepatic vein thrombosis (Budd-Chiari syndrome) is common in PNH patients. This case report describes the response to eculizumab (a humanized monoclonal antibody that inhibits terminal complement activation) in a 25-year-old male with progressive liver function deterioration despite standard anticoagulation therapy and transjugular intrahepatic porto-systemic shunt. The patient presented with anemia, severe thrombocytopenia, headache, abdominal pain, and distention. He was diagnosed with PNH, cerebral vein thrombosis, and Budd-Chiari syndrome. Despite adequate anticoagulation, diuretic administration, and placement of a transjugular shunt, additional thrombotic events and progressive liver damage were observed. Eculizumab therapy was initiated, resulting in rapid blockade of intravascular hemolysis, increased platelet counts, ascites resolution, and liver function recovery, all of which are presently sustained. Since starting eculizumab the patient has had no further thrombotic events and his quality of life has dramatically improved. This is the first report to confirm the role of complement-mediated injury in the progression of Budd-Chiari syndrome in a patient with PNH. This case shows that terminal complement blockade with eculizumab can reverse progressive thromboses and hepatic failure that is unresponsive to anticoagulation therapy and suggests that early initiation of eculizumab should be included in the therapeutic regimen of patients with PNH-related Budd-Chiari syndrome. PMID:23210433

Predictors of Progression to High-Grade Dysplasia or Adenocarcinoma in Barrett’s Esophagus

PubMed Central

Whitson, Matthew J.; Falk, Gary W.

2015-01-01

Article Synopsis The prevalence of esophageal adenocarcinoma is increasing dramatically. Barrett’s esophagus remains the most well established risk factor for the development of esophageal adenocarcinoma. There are multiple clinical, endoscopic, and pathologic factors that increase the risk of neoplastic progression to high-grade dysplasia or esophageal adenocarcinoma in Barrett’s esophagus. This article will review both risk and protective factors for neoplastic progression in patients with Barrett’s esophagus. PMID:26021196

DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia.

PubMed

Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

2016-04-01

5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple 'hits' are required for disease progression; an initial genetic abnormality followed by additional secondary 'hits'. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development.

Building cell models and simulations from microscope images.

PubMed

Murphy, Robert F

2016-03-01

The use of fluorescence microscopy has undergone a major revolution over the past twenty years, both with the development of dramatic new technologies and with the widespread adoption of image analysis and machine learning methods. Many open source software tools provide the ability to use these methods in a wide range of studies, and many molecular and cellular phenotypes can now be automatically distinguished. This article presents the next major challenge in microscopy automation, the creation of accurate models of cell organization directly from images, and reviews the progress that has been made towards this challenge. Copyright © 2015 Elsevier Inc. All rights reserved.

Dialyzer-related Thrombocytopenia due to a Polysulfone Membrane.

PubMed

Kobari, Eri; Terawaki, Hiroyuki; Takahashi, Yasuhito; Kusano, Yuki; Sakurai, Kaoru; Matsunaga, Keiko; Fukushima, Naotaro; Suzuki, Sawako; Tanaka, Ken-Ichi; Hayashi, Yoshimitsu; Watanabe, Tsuyoshi; Nakayama, Masaaki

2016-01-01

A 72-year-old Japanese woman was admitted to our hospital with rapidly progressive glomerulonephritis associated with anti-glomerular basement membrane antibody. Hemodialysis (HD) therapy was initiated on the day of admission using a biocompatible polysulfone (PS) membrane. Her platelet count (PLT; ×10(4)/μL) decreased gradually from 58.7 (day 1) to 5.8 (day 25). Considering the possibility of dialyzer-related thrombocytopenia (DRT), we measured her PLT count before and after the HD session on day 72, which revealed a dramatic decrease of 7.5 to 4.3. This finding suggested that the PS dialyzer caused PLT depletion. After discontinuation of the PS dialyzer, DRT was resolved.

Ion microscopy with resonant ionization mass spectrometry : time-of-flight depth profiling with improved isotopic precision.

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

Pellin, M. J.; Veryovkin, I. V.; Levine, J.

2010-01-01

There are four generally mutually exclusive requirements that plague many mass spectrometric measurements of trace constituents: (1) the small size (limited by the depth probed) of many interesting materials requires high useful yields to simply detect some trace elements, (2) the low concentrations of interesting elements require efficient discrimination from isobaric interferences, (3) it is often necessary to measure the depth distribution of elements with high surface and low bulk contributions, and (4) many applications require precise isotopic analysis. Resonant ionization mass spectrometry has made dramatic progress in addressing these difficulties over the past five years.

Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis.

PubMed

Hager, K; Kenklies, M; McAfoose, J; Engel, J; Münch, G

2007-01-01

Oxidative stress and neuronal energy depletion are characteristic biochemical hallmarks of Alzheimer's disease (AD). It is therefore conceivable that pro-energetic and antioxidant drugs such as alpha-lipoic acid might delay the onset or slow down the progression of the disease. In a previous study, 600mg alpha-lipoic acid was given daily to nine patients with AD (receiving a standard treatment with choline-esterase inhibitors) in an open-label study over an observation period of 12 months. The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (the mini mental state exam, MMSE and the Alzheimer's disease assessment score cognitive subscale, ADAScog). In this report, we have extended the analysis to 43 patients over an observation period of up to 48 months. In patients with mild dementia (ADAScog < 15), the disease progressed extremely slowly (ADAScog: +1.2 points/year, MMSE: -0.6 points/year), in patients with moderate dementia at approximately twice the rate. However, the progression appears dramatically lower than data reported for untreated patients or patients on choline-esterase inhibitors in the second year of long-term studies. Despite the fact that this study was not double-blinded, placebo-controlled and randomized, our data suggest that treatment with alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD. However, a state-of-the-art phase II trial is needed urgently.

Breast Cancer Patients Have Greatly Benefited from the Progress in Molecular Oncology

PubMed Central

Groner, Bernd L.; Hynes, Nancy E.

2016-01-01

Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public money, it is perfectly legitimate to ask if these large expenses are worth it. In this brief commentary, we recapitulate some of the breakthroughs that mark the history of breast cancer research over the past decades and emphasize the resulting benefits for afflicted women. In 1971, only 40% of women diagnosed with breast cancer would live another 10 years. Today, nearly 80% of women reach that significant milestone in most developed countries. This dramatic change has afforded breast cancer patients many productive years and a better quality of life. Progress resulted largely from advances in the understanding of the molecular details of the disease and their translation into innovative, rationally designed therapies. These developments are founded on the revolution in molecular and cellular biology, an entirely new array of methods and technologies, the enthusiasm, optimism, and diligence of scientists and clinicians, and the considerable funding efforts from public and private sources. We were lucky to be able to spend our productive years in a period of scientific upheaval in which methods and concepts were revolutionized and that allowed us to contribute, within the global scientific community, to the progress in basic science and clinical practice. PMID:27684370

Breast Cancer Patients Have Greatly Benefited from the Progress in Molecular Oncology.

PubMed

Groner, Bernd L; Hynes, Nancy E

2016-09-01

Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public money, it is perfectly legitimate to ask if these large expenses are worth it. In this brief commentary, we recapitulate some of the breakthroughs that mark the history of breast cancer research over the past decades and emphasize the resulting benefits for afflicted women. In 1971, only 40% of women diagnosed with breast cancer would live another 10 years. Today, nearly 80% of women reach that significant milestone in most developed countries. This dramatic change has afforded breast cancer patients many productive years and a better quality of life. Progress resulted largely from advances in the understanding of the molecular details of the disease and their translation into innovative, rationally designed therapies. These developments are founded on the revolution in molecular and cellular biology, an entirely new array of methods and technologies, the enthusiasm, optimism, and diligence of scientists and clinicians, and the considerable funding efforts from public and private sources. We were lucky to be able to spend our productive years in a period of scientific upheaval in which methods and concepts were revolutionized and that allowed us to contribute, within the global scientific community, to the progress in basic science and clinical practice.

Dramatic decrease in prevalence of soil-transmitted helminths and new insights into intestinal protozoa in children living in the Chaco region, Bolivia.

PubMed

Macchioni, Fabio; Segundo, Higinio; Gabrielli, Simona; Totino, Valentina; Gonzales, Patricia Rojas; Salazar, Esteban; Bozo, Ricardo; Bartoloni, Alessandro; Cancrini, Gabriella

2015-04-01

We assessed the prevalence of intestinal parasites among 268 2-12-year-old children living in rural areas, small villages, and semi-urban areas of the Chaco region, south-eastern Bolivia. The overall parasitism was 69%. Only protozoa, helminths, or co-infections were observed in 89.2%, 5.9%, or 4.9% of the positive children, respectively. A significant progressive increase in overall parasite prevalence was found when passing from rural areas to small villages and semi-urban areas. The most commonly found species were Entamoeba coli (38.4%), Giardia intestinalis (37.7%), and Blastocystis spp. (16%). Hymenolepis nana was the most prevalent helminth (5.6%), followed by Ascaris lumbricoides and hookworms (1.5% and 0.4%) evidenced only in rural areas and in villages. Molecular diagnostics identified Blastocystis subtypes 9 and 2, and 5 infections by Entamoeba histolytica and 4 by Entamoeba dispar. The dramatic decrease in prevalence of soil-transmitted helminths with respect to that observed about 20 years ago (> 40%) evidences the success of the preventive chemotherapy intervention implemented in 1986. Health education and improved sanitation should be intensified to control protozoan infections. © The American Society of Tropical Medicine and Hygiene.

Toward Ubiquitous BCIs

NASA Astrophysics Data System (ADS)

Allison, Brendan Z.

The preceding chapters in this book described modern BCI systems. This concluding chapter instead discusses future directions. While there are some specific predictions, I mainly analyze key factors and trends relating to practical mainstream BCI development. While I note some disruptive technologies that could dramatically change BCIs, this chapter focuses mainly on realistic, incremental progress and how progress could affect user groups and ethical issues.

Macrodystrophia lipomatosa. A case report.

PubMed

Loro, A; Francechi, F; Dal Lago, A

1995-07-01

Macrodystrophia lipomatosa, a rare form of localized gigantism of unknown cause, is characterized by a dramatic overgrowth of all the mesenchymal elements, particularly the fibroadipose tissue, of one or more digits of the foot or hand. Of the known forms, static and progressive (1), we report the case of an African patient, of Bantu origin, who had a progressive deformity of his left hand.

Type 2 Diabetes

MedlinePlus

... increasing dramatically among children, adolescents and younger adults. Prediabetes. Prediabetes is a condition in which your blood sugar ... enough to be classified as diabetes. Left untreated, prediabetes often progresses to type 2 diabetes. Gestational diabetes. ...

[Fluctuations in relative income and the baby boom in the United States].

PubMed

Bourcier De Carbon, P

1997-01-01

This work argues that fluctuations in relative income of young adults in the US after World War II coincided with the dramatically increased fertility of the baby boom and were probably a significant determining factor in its occurrence and eventual interruption. The US total fertility rate declined rapidly in the early 20th century, from 3.8 in 1900 to 2.44 in 1929 and 2.24 in 1935-36. Fertility was below replacement level in 1932-39. Its spectacular recovery from the early 1940s culminated in the year 1957, with a total fertility rate of 3.77. Fertility declined rapidly again in the late 1960s and attained its low point in 1976, with a total fertility rate of 1.74. It has slowly increased since then, especially with the arrival of increasing numbers of high-fertility immigrants from Latin America beginning in the late 1980s. Although per capita gross national product in the US rose dramatically between 1929 and 1994, income distribution also changed, as did the relative income from wages and salaries of workers under 40 years old. From the end of World War II until the late 1950s, the wage and salary income of young workers increased more rapidly than did that of older workers, so that younger workers were at an advantage during the years of the baby boom. Young workers also benefited from federal programs such as Fulbright scholarships, home loan programs, and veterans benefits. Transfer payments for pensions and higher interest rates progressively improved the position of older workers, and younger workers faced a loss of relative income in the 1960s and 1970s that coincided with the end of the baby boom and that quite likely was a causative factor. With the progressive aging of the US population, the relative loss of income of younger workers will probably intensify and be joined by a relative loss of political power, as the proportion of the electorate in the prime childbearing years shrinks further.

Review of Real-Time Simulator and the Steps Involved for Implementation of a Model from MATLAB/SIMULINK to Real-Time

NASA Astrophysics Data System (ADS)

Mikkili, Suresh; Panda, Anup Kumar; Prattipati, Jayanthi

2015-06-01

Nowadays the researchers want to develop their model in real-time environment. Simulation tools have been widely used for the design and improvement of electrical systems since the mid twentieth century. The evolution of simulation tools has progressed in step with the evolution of computing technologies. In recent years, computing technologies have improved dramatically in performance and become widely available at a steadily decreasing cost. Consequently, simulation tools have also seen dramatic performance gains and steady cost decreases. Researchers and engineers now have the access to affordable, high performance simulation tools that were previously too cost prohibitive, except for the largest manufacturers. This work has introduced a specific class of digital simulator known as a real-time simulator by answering the questions "what is real-time simulation", "why is it needed" and "how it works". The latest trend in real-time simulation consists of exporting simulation models to FPGA. In this article, the Steps involved for implementation of a model from MATLAB to REAL-TIME are provided in detail.

Vasculitis in the very elderly.

PubMed

Turcu, Alin; Bielefeld, Philip; Besancenot, Jean-François; Lorcerie, Bernard; Pfitzenmeyer, Pierre

2002-01-01

Whatever may be their clinical presentation, vasculitis syndromes (VS) have a bad prognosis in the very elderly. The aim of this work was to study VS particularities in very old people. Most published studies on VS in elderly people concern patients older than 60 years; studies concerning very old patients are unusual. We studied retrospectively subjects older than 75 years with a diagnosis of VS from the Departments of Geriatrics and Internal Medicine at Dijon University Hospital. These subjects were hospitalized between January 1995 and December 1999. Data were obtained from the medical files of these patients. Several aspects were considered: type of VS, associated diseases, treatment, complications, and outcome. Twelve patients, 5 men and 7 women aged 79-91 (mean age 82.3) years, were included. Primary VS was observed in half of the patients and secondary VS in the others. The initial clinical presentation was often polymorphous and unspecific; 8 of the patients died, 2 developed progressive severe functional impairment, 1 was stabilized under therapy, and 1 patient with VS secondary to infection recovered. Most patients either died quickly or progressively deteriorated from infections, malnutrition, or functional impairment. The health of the majority of patients (83%) deteriorated dramatically, leading to death or severe functional impairment. Copyright 2002 S. Karger AG, Basel

Carotid artery disease progression and related neurologic events after carotid endarterectomy.

PubMed

Avgerinos, Efthymios D; Go, Catherine; Ling, Jennifer; Naddaf, Abdallah; Steinmetz, Amy; Abou Ali, Adham N; Makaroun, Michel S; Chaer, Rabih A

2016-08-01

During the last decade, there has been a dramatic improvement in best medical treatment for patients with vascular disease. Yet, there is a paucity of contemporary long-term data for restenosis and contralateral internal carotid artery (ICA) progression. This study assessed ipsilateral and contralateral disease progression and cerebrovascular events after carotid endarterectomy (CEA). A consecutive cohort of CEAs between January 1, 2000, and December 31, 2010, was retrospectively analyzed. End points were restenosis ≥50% and ≥70%, contralateral carotid disease progression (50%-69%, 70%-99%, or occlusion) and stroke. Survival analysis and Cox regression models were used to assess the effect of baseline predictors. During the 11-year study period, 1639 patients underwent 1782 CEAs (50.0% patch closure, 23.9% primary closure, 26.1% eversion, and 2.5% combined with coronary artery bypass grafting). The combined stroke/death rate was 2.6% overall and 1.8% in the asymptomatic cohort. The rate of restenosis ≥50% at 2, 5, and 10 years was 8.5%, 15.6%, 27.2%, and the rate for restenosis ≥70% was 3.4%, 6.5%, 10.2%, respectively. Restenosis ≥50% was predicted by hypertension (hazard ratio [HR], 2.09; P = .027), female gender (HR, 1.43; P = .042), and younger age (≤65 years; HR, 1.56; P = .016), but not by statins, surgical technique, symptoms, or other baseline risk factors. Restenoses remained asymptomatic in 125 of 148 (84.5%). Progression of contralateral ICA disease at 2, 5, and 10 years was estimated at 5.4%, 15.5%, and 46.8%, respectively. Contralateral progression was only predicted by smoking (HR, 1.74; P = .008). The stroke rate in patients with disease progression of the contralateral ICA was not different compared with those without progression (7.0% vs 3.3%; P = .063). Any-stroke rates at 2, 5, and 10 years were 4.6%, 7.3%, and 15.7%, respectively. Predictors were symptomatic lesion (HR, 1.48; P = .039), renal insufficiency, defined as a glomerular filtration rate (GFR) of 30 to 59 vs <30 mL/min/1.73 m 2 (HR, 0.34; P = .009) or GFR ≥60 vs GFR <30 mL/min/1.73 m 2 (HR, 0.55; P = .109), and statin use (HR, 0.59; P = .006). Restenosis or contralateral disease progression after CEA, to a level that might warrant consideration for treatment, is very low. The potentially associated stroke rates are also very low and not clearly related to disease progression. With the exception of the postoperative duplex, surveillance within short intervals of <1 or 2 years cannot be justified. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Changes of the phytoplankton community as symptoms of deterioration of water quality in a shallow lake.

PubMed

Dembowska, Ewa Anna; Mieszczankin, Tomasz; Napiórkowski, Paweł

2018-01-25

Covering more than 60% of the lake surface, macrophytes determined the taxonomic composition of phytoplankton. We have found numerous indications of ecological deterioration and an increased trophic level year to year: an increased total number of taxa; a significantly increased number of species of Chlorophyta, Bacillariophyceae and Cyanoprokaryota; a decreased number of Chrysophyceae; increased Nygaard index, and high diversity and variability of phytoplankton functional groups. Within 2 years (2002 and 2003) algal biomass doubled: from 3.616 to 7.968 mg l -1 . An increased contribution of Chlorococcales and Cyanoprokaryota indicates progressive eutrophication of the lake. The average size of planktonic algae increased, particularly Cyanoprokaryota, where small-celled decreased dramatically and were replaced by large colonies. Cyanoprokaryota remained the dominant group of phytoplankton after 10 years, and the ecosystem of the lake remained in the turbid state. This group of algae had the average biomass 9.734 mg l -1 , which constituted almost 92% of the total biomass.

DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia

PubMed Central

Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

2016-01-01

5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple ‘hits’ are required for disease progression; an initial genetic abnormality followed by additional secondary ‘hits’. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development. PMID:27035209

Clinical and Rehabilitative Management of Retinitis Pigmentosa: Up-to-Date

PubMed Central

Parmeggiani, Francesco; Sato, Giovanni; De Nadai, Katia; Romano, Mario R; Binotto, Andrea; Costagliola, Ciro

2011-01-01

The term retinitis pigmentosa (RP) indicates a heterogeneous group of genetic rare ocular diseases in which either rods or cones are prevalently damaged. RP represents the most common hereditary cause of blindness in people from 20 to 60 years old. In general, the different RP forms consist of progressive photo-receptorial neuro-degenerations, which are characterized by variable visual disabilities and considerable socio-sanitary burden. Sometimes, RP patients do not become visually impaired or legally blind until their 40-50 years of age and/or maintain a quite acceptable sight for all their life. Other individuals with RP become completely blind very early or in middle childhood. Although there is no treatment that can effectively cure RP, in some case-series the disease’s progression seems to be reducible by specific preventive approaches. In the most part of RP patients, the quality of vision can be considerably increased by means of nanometer-controlled filters. In the present review, the main aspects of the routine clinical and rehabilitative managements for RP patients are described, particularly focusing on the importance of specific referral Centers to practice a real multidisciplinary governance of these dramatic diseases. PMID:22131870

Large-Scale Preventive Chemotherapy for the Control of Helminth Infection in Western Pacific Countries: Six Years Later

PubMed Central

Montresor, Antonio; Cong, Dai Tran; Sinuon, Mouth; Tsuyuoka, Reiko; Chanthavisouk, Chitsavang; Strandgaard, Hanne; Velayudhan, Raman; Capuano, Corinne M.; Le Anh, Tuan; Tee Dató, Ah S.

2008-01-01

In 2001, Urbani and Palmer published a review of the epidemiological situation of helminthiases in the countries of the Western Pacific Region of the World Health Organization indicating the control needs in the region. Six years after this inspiring article, large-scale preventive chemotherapy for the control of helminthiasis has scaled up dramatically in the region. This paper analyzes the most recent published and unpublished country information on large-scale preventive chemotherapy and summarizes the progress made since 2000. Almost 39 million treatments were provided in 2006 in the region for the control of helminthiasis: nearly 14 million for the control of lymphatic filariasis, more than 22 million for the control of soil-transmitted helminthiasis, and over 2 million for the control of schistosomiasis. In general, control of these helminthiases is progressing well in the Mekong countries and Pacific Islands. In China, despite harboring the majority of the helminth infections of the region, the control activities have not reached the level of coverage of countries with much more limited financial resources. The control of food-borne trematodes is still limited, but pilot activities have been initiated in China, Lao People's Democratic Republic, and Vietnam. PMID:18846234

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

Bioprotective Cultures

NASA Astrophysics Data System (ADS)

Vignolo, Graciela; Fadda, Silvina; Castellano, Patricia

Although the globalization and liberalization of world food trade offers many benefits and opportunities, it also presents new risks. As food is distributed from the original points of production, processing, and packaging to locations thousands of kilometers away, there is an increased risk of cross-border transmission of infectious agents and exposure of consumers to new hazards. In the last few years, food safety concerns have increased their importance due to the dramatic impact that they have on public health. Despite the recent progress in food biotechnology, the meat industry is still under scrutiny from consumers and media due to recent food safety crises; a series of food scandals erupted involving meat and meat products, which impacted prominently on consumer confidence.

Novel Application of Extracorporeal Photopheresis as Treatment of Graft-versus-Host Disease Following Liver Transplantation.

PubMed

Brown, Timothy J; Gentry, Cathy; Hammer, Suntrea T G; Hwang, Christine S; Vusirikala, Madhuri; Patel, Prapti A; Matevosyan, Karén; Tujios, Shannan R; Mufti, Arjmand R; Collins, Robert H

2017-01-01

A 48-year-old man with hepatitis C virus (HCV) cirrhosis complicated by hepatocellular carcinoma underwent liver transplantation. His course was complicated by fever, diarrhea, abdominal pain, and pancytopenia. He developed a diffuse erythematous rash, which progressed to erythroderma. Biopsies of the colon and skin were consistent with acute graft-versus-host disease. Donor-derived lymphocytes were present in the peripheral blood. The patient was treated with corticosteroids and cyclosporine; however, he had minimal response to intensive immunosuppressive therapy. Extracorporeal photopheresis was initiated as a salvage therapy. He had a dramatic response, and his rash, diarrhea, and pancytopenia resolved. He is maintained on minimal immunosuppression 24 months later.

Progressive liver failure post acute hepatitis A, over a three-month period, resulting in hepatorenal syndrome and death

PubMed Central

Al Saadi, Tareq; Sawaf, Bisher; Alkhatib, Mahmoud; Zakaria, Mhd Ismael; Daaboul, Bisher

2017-01-01

Abstract Hepatitis A is a common viral illness worldwide. It usually results in an acute, self-limiting disease and only rarely leads to fulminant hepatic failure or any other complications. During the period of conflict in Syria, and due to the damages to water infrastructure and poor sanitation, a dramatic increase in hepatitis A virus infection has been documented. Here we report a rare case of a 14-year-old male whose hepatitis A was complicated with hepatorenal syndrome and subacute liver failure. The war condition in Syria impeded transportation of the patient to a nearby country for liver transplantation, contributing to his unfortunate death. PMID:27247182

Tinkering with meiosis

PubMed Central

Crismani, Wayne; Girard, Chloé; Mercier, Raphael

2013-01-01

Meiosis is at the heart of Mendelian heredity. Recently, much progress has been made in the understanding of this process, in various organisms. In the last fifteen years, the functional characterization of numerous genes involved in meiosis has dramatically deepened our knowledge of key events, including recombination, cell cycle and chromosome distribution. Through a constantly advancing tool set and knowledge base, a number of advances have been made that will allow manipulation of meiosis from a plant breeding perspective. This review focuses on the aspects of meiosis that can be tinkered with to create and propagate new varieties. We would like to dedicate this review to the memory of Simon W. Chan (1974-2012) http://www.plb.ucdavis.edu/labs/srchan/ PMID:23136169

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.

Dural arteriovenous fistula presenting with exophthalmos and seizures.

PubMed

Feyissa, Anteneh M; Ponce, Lucido L; Patterson, Joel T; Von Ritschl, Rudiger H; Smith, Robert G

2014-03-15

Concomitant seizures and exophthalmos in the context of a temporal dural arteriovenous fistula (dAVF) has not been described before. Here, we report a 55-year-old-male who presented with an 8-month history of progressive painless exophthalmos of his left eye, conjunctival chemosis, reduced vision and new onset complex partial seizures. Cerebral angiography demonstrated Cognard Type IIa left cerebral dAVF fed by branches from the left occipital artery and an accessory meningeal artery, with drainage to the superior ophthalmic vein. Following surgical obliteration of dAVF feeding vessels, our patient had dramatic improvement in visual acuity, proptosis and chemosis along with cessation of clinical seizures. Published by Elsevier B.V.

Muscle Functional Morphology in Paleobiology: The Past, Present, and Future of "Paleomyology".

PubMed

Perry, Jonathan M G; Prufrock, Kristen A

2018-03-01

Our knowledge of muscle anatomy and physiology in vertebrates has increased dramatically over the last two-hundred years. Today, much is understood about how muscles contract and about the functional meaning of muscular variation at multiple scales. Progress in muscle anatomy has profited from the availability of broad comparative samples, advances in microscopy have permitted comparisons at increasingly finer scales, and progress in muscle physiology has profited from many carefully designed and executed experiments. Several avenues of future work are promising. In particular, muscle ontogeny (growth and development) is poorly understood for many vertebrate groups. We consider which types of advances in muscle functional morphology are of use to paleobiologists. These are only a modest subset for muscle anatomy and a very small subset for muscle physiology. The relationship between muscle and bone - spatially and mechanically-is critical to any future advances in "paleomyology". Anat Rec, 301:538-555, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Epigenetic pathway targets for the treatment of disease: accelerating progress in the development of pharmacological tools: IUPHAR Review 11

PubMed Central

Tough, David F; Lewis, Huw D; Rioja, Inmaculada; Lindon, Matthew J; Prinjha, Rab K

2014-01-01

The properties of a cell are determined both genetically by the DNA sequence of its genes and epigenetically through processes that regulate the pattern, timing and magnitude of expression of its genes. While the genetic basis of disease has been a topic of intense study for decades, recent years have seen a dramatic increase in the understanding of epigenetic regulatory mechanisms and a growing appreciation that epigenetic misregulation makes a significant contribution to human disease. Several large protein families have been identified that act in different ways to control the expression of genes through epigenetic mechanisms. Many of these protein families are finally proving tractable for the development of small molecules that modulate their function and represent new target classes for drug discovery. Here, we provide an overview of some of the key epigenetic regulatory proteins and discuss progress towards the development of pharmacological tools for use in research and therapy. PMID:25060293

Multiscale modelling and nonlinear simulation of vascular tumour growth

PubMed Central

Macklin, Paul; Anderson, Alexander R. A.; Chaplain, Mark A. J.; Cristini, Vittorio

2011-01-01

In this article, we present a new multiscale mathematical model for solid tumour growth which couples an improved model of tumour invasion with a model of tumour-induced angiogenesis. We perform nonlinear simulations of the multi-scale model that demonstrate the importance of the coupling between the development and remodeling of the vascular network, the blood flow through the network and the tumour progression. Consistent with clinical observations, the hydrostatic stress generated by tumour cell proliferation shuts down large portions of the vascular network dramatically affecting the flow, the subsequent network remodeling, the delivery of nutrients to the tumour and the subsequent tumour progression. In addition, extracellular matrix degradation by tumour cells is seen to have a dramatic affect on both the development of the vascular network and the growth response of the tumour. In particular, the newly developing vessels tend to encapsulate, rather than penetrate, the tumour and are thus less effective in delivering nutrients. PMID:18781303

Slow Progress In Finalizing Measles And Rubella Elimination In The European Region.

PubMed

Biellik, Robin; Davidkin, Iria; Esposito, Susanna; Lobanov, Andrey; Kojouharova, Mira; Pfaff, Günter; Santos, José Ignacio; Simpson, John; Mamou, Myriam Ben; Butler, Robb; Deshevoi, Sergei; Huseynov, Shahin; Jankovic, Dragan; Shefer, Abigail

2016-02-01

All countries in the World Health Organization European Region committed to eliminating endemic transmission of measles and rubella by 2015, and disease incidence has decreased dramatically. However, there was little progress between 2012 and 2013, and the goal will likely not be achieved on time. Genuine political commitment, increased technical capacity, and greater public awareness are urgently needed, especially in Western Europe. Project HOPE—The People-to-People Health Foundation, Inc.

Role of Advanced Glycation Endproducts and Potential Therapeutic Interventions in Dialysis Patients

PubMed Central

Mallipattu, Sandeep K.; He, John C.; Uribarri, Jaime

2017-01-01

It has been nearly 100 years since the first published report of advanced glycation end products (AGEs) by the French chemist Maillard. Since then, our understanding of AGEs in diseased states has dramatically changed. Especially in the last 25 years, AGEs have been implicated in complications related to aging, neurodegenerative diseases, diabetes, and chronic kidney disease. Although AGE formation has been well characterized by both in vitro and in vivo studies, few prospective human studies exist demonstrating the role of AGEs in patients on chronic renal replacement therapy. As the prevalence of end-stage renal disease (ESRD) in the United States rises, it is essential to identify therapeutic strategies that either delay progression to ESRD or improve morbidity and mortality in this population. This article reviews the role of AGEs, especially those of dietary origin, in ESRD patients as well as potential therapeutic anti-AGE strategies in this population. PMID:22548330

Current status and patent prospective of animal models in diabetic research

PubMed Central

Dhuria, Radhey S.; Singh, Gurpreet; Kaur, Anudeep; Kaur, Ramandeep; Kaur, Tanurajvir

2015-01-01

Diabetes mellitus is a heterogeneous complex metabolic disorder with multiple etiology which characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action or both. The widespread occurrence of diabetes throughout the world has increased dramatically over the past few years. For better understanding, appropriate animal models that closely mimic the changes in humans needed, as vital tool for understanding the etiology and pathogenesis of the disease at the cellular/molecular level and for preclinical testing of drugs. This review aims to describe the animal models of type-1 diabetes (T1Ds) and T2Ds to mimic the causes and progression of the disease in humans. And also we highlight patent applications published in the last few years related to animal models in diabetes as an important milestone for future therapies that are aim to treating diabetes with specific symptoms and complications. PMID:26261819

Current status and patent prospective of animal models in diabetic research.

PubMed

Dhuria, Radhey S; Singh, Gurpreet; Kaur, Anudeep; Kaur, Ramandeep; Kaur, Tanurajvir

2015-01-01

Diabetes mellitus is a heterogeneous complex metabolic disorder with multiple etiology which characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action or both. The widespread occurrence of diabetes throughout the world has increased dramatically over the past few years. For better understanding, appropriate animal models that closely mimic the changes in humans needed, as vital tool for understanding the etiology and pathogenesis of the disease at the cellular/molecular level and for preclinical testing of drugs. This review aims to describe the animal models of type-1 diabetes (T1Ds) and T2Ds to mimic the causes and progression of the disease in humans. And also we highlight patent applications published in the last few years related to animal models in diabetes as an important milestone for future therapies that are aim to treating diabetes with specific symptoms and complications.

Cervical spondylotic myelopathy caused by violent motor tics in a child with Tourette syndrome.

PubMed

Ko, Da-Young; Kim, Seung-Ki; Chae, Jong-Hee; Wang, Kyu-Chang; Phi, Ji Hoon

2013-02-01

We report a case of a 9-year-old boy with Tourette syndrome (TS) who developed progressive quadriparesis that was more severe in the upper extremities. He had experienced frequent and violent motor tics consisting of hyperflexion and hyperextension for years. Magnetic resonance imaging (MRI) revealed a focal high-signal intensity cord lesion and adjacent cervical spondylotic changes. Initially, the patient was observed for several months because of diagnostic uncertainty; his neurological status had improved and later worsened again. Anterior cervical discectomy of C3-4 and fusion immediately followed by posterior fixation were performed. After surgery, the neck collar was applied for 6 months. His neurological signs and symptoms improved dramatically. TS with violent neck motion may cause cervical spondylotic myelopathy at an early age. The optimal management is still unclear and attempts to control tics should be paramount. Circumferential fusion with neck bracing represents a viable treatment option.

Insects as model systems in cell biology.

PubMed

Keil, Thomas A; Steinbrecht, R Alexander

2010-01-01

For almost 100 years, insects have been favorable "model systems" in biology. Just to mention a few examples: fruit flies in genetics and developmental biology; bugs and caterpillars in hormone research; houseflies, blowflies, and locusts in neurobiology; silk moths in pheromone research; honeybees and crickets in neuroethology. For more than 50 years the electron microscope (EM) has been a valuable tool in analyzing the structure of cells and organs of these creatures. However, progress in specimen preparation was relatively slow compared with mammalian material and, in 1970, it was taken for granted that insects were much more difficult to fix than mammals. Since then, methods have dramatically improved, and satisfactory results can now be obtained routinely with chemical as well as cryofixation. In this chapter we briefly demonstrate what can be achieved with insect material, and help the researcher to find the most appropriate method for her/his systems and scientific questions. Copyright © 2010 Elsevier Inc. All rights reserved.

Role of advanced glycation endproducts and potential therapeutic interventions in dialysis patients.

PubMed

Mallipattu, Sandeep K; He, John C; Uribarri, Jaime

2012-01-01

It has been nearly 100 years since the first published report of advanced glycation end products (AGEs) by the French chemist Maillard. Since then, our understanding of AGEs in diseased states has dramatically changed. Especially in the last 25 years, AGEs have been implicated in complications related to aging, neurodegenerative diseases, diabetes, and chronic kidney disease. Although AGE formation has been well characterized by both in vitro and in vivo studies, few prospective human studies exist demonstrating the role of AGEs in patients on chronic renal replacement therapy. As the prevalence of end-stage renal disease (ESRD) in the United States rises, it is essential to identify therapeutic strategies that either delay progression to ESRD or improve morbidity and mortality in this population. This article reviews the role of AGEs, especially those of dietary origin, in ESRD patients as well as potential therapeutic anti-AGE strategies in this population. © 2012 Wiley Periodicals, Inc.

Non-homogeneous harmonic analysis: 16 years of development

NASA Astrophysics Data System (ADS)

Volberg, A. L.; Èiderman, V. Ya

2013-12-01

This survey contains results and methods in the theory of singular integrals, a theory which has been developing dramatically in the last 15-20 years. The central (although not the only) topic of the paper is the connection between the analytic properties of integrals and operators with Calderón-Zygmund kernels and the geometric properties of the measures. The history is traced of the classical Painlevé problem of describing removable singularities of bounded analytic functions, which has provided a strong incentive for the development of this branch of harmonic analysis. The progress of recent decades has largely been based on the creation of an apparatus for dealing with non-homogeneous measures, and much attention is devoted to this apparatus here. Several open questions are stated, first and foremost in the multidimensional case, where the method of curvature of a measure is not available. Bibliography: 128 titles.

High-Speed Videography Overview

NASA Astrophysics Data System (ADS)

Miller, C. E.

1989-02-01

The field of high-speed videography (HSV) has continued to mature in recent years, due to the introduction of a mixture of new technology and extensions of existing technology. Recent low frame-rate innovations have the potential to dramatically expand the areas of information gathering and motion analysis at all frame-rates. Progress at the 0 - rate is bringing the battle of film versus video to the field of still photography. The pressure to push intermediate frame rates higher continues, although the maximum achievable frame rate has remained stable for several years. Higher maximum recording rates appear technologically practical, but economic factors impose severe limitations to development. The application of diverse photographic techniques to video-based systems is under-exploited. The basics of HSV apply to other fields, such as machine vision and robotics. Present motion analysis systems continue to function mainly as an instant replay replacement for high-speed movie film cameras. The interrelationship among lighting, shuttering and spatial resolution is examined.

Rapidly progressive Scheuermann's disease in an adolescent after pectus bar placement treated with posterior vertebral-column resection: case report and review of the literature.

PubMed

Sugrue, Patrick A; OʼShaughnessy, Brian A; Blanke, Kathy M; Lenke, Lawrence G

2013-02-15

Case report and review of the literature. This case illustrates the importance of the costosternal complex in maintaining the stability and alignment of the thoracic spine. The patient was iatrogenically destabilized by placement of a pectus bar leading to rapid symptomatic progression of his Scheuermann's kyphosis, ultimately requiring surgical correction. Scheuermann's kyphosis is a disease process defined by strict radiographical and clinical criteria. Surgical treatment is generally recommended for curves greater than 75°. This case demonstrates the critical role of the costosternal complex in maintaining the stability of the thoracic spine. The patient described in this report underwent placement of a pectus bar for correction of symptomatic pectus excavatum. He subsequently developed a progressive symptomatic Scheuermann's kyphosis as a result of the destabilization of his costosternal complex. This patient ultimately required removal of the pectus bar and posterior instrumented kyphosis correction. Progressive symptomatic Scheuermann's kyphosis (105°) corrected by removal of the pectus bar, T11 posterior vertebral-column resection and T4-L3 instrumented posterior spinal fusion. The patient had an uneventful immediate postoperative course. He was discharged neurologically intact with dramatic kyphosis correction and significant symptomatic improvement. Radiographs obtained 3 years postoperatively reveal stable thoracolumbar correction. The costosternal complex plays a critically important role in the intrinsic stability of the thoracic spine. Iatrogenic disruption of the costosternal complex can result in rapid progression of thoracic/thoracolumbar kyphosis in the setting of Scheuermann's disease.

Create new research directions in comparative endocrinology from Asia and Oceania.

PubMed

Tsutsui, Kazuyoshi

2013-01-15

The Asia and Oceania Society for Comparative Endocrinology (AOSCE) was founded in 1987, when the first congress was held in Nagoya, Japan. The purpose of the AOSCE is to progress scientific activities in the field of comparative endocrinology in Asia and Oceania and to establish a deep relationship among the members. For this purpose, the AOSCE holds a congress or an intercongress symposium every 2 years, which organizes an attractive scientific program covering the latest progress in the broad aspect of comparative endocrinology. 2012 was the 25th anniversary of AOSCE. Our scientific activities have increased dramatically during the past 25 years. The 7th AOSCE congress was held in Kuala Lumpur, Malaysia in 2012. The theme of this congress was "Overcoming challenges in the 21st century". To overcome challenges in the 21st century, we further need to create new research directions in comparative endocrinology from Asia and Oceania. This paper describes a brief history of the AOSCE and also highlights the discovery of gonadotropin-inhibitory hormone (GnIH) and the progress of GnIH research as one of new research directions in comparative endocrinology. In 2000, GnIH was discovered in Japan and now more than 50 laboratories are working on GnIH in the world. The discovery of GnIH has changed our understanding about regulation of the reproductive axis drastically in the past decade. Copyright © 2012 Elsevier Inc. All rights reserved.

Third nature: the co-evolution of human behavior, culture, and technology.

PubMed

Johnston, William A

2005-07-01

Within a dynamical-systems framework, human behavior is seen as emergent from broad evolutionary processes associated with three basic forms of nature. First nature, matter, emerged from the big bang some 12-15 billion years ago; second nature, life, from the first bacteria up to 4 billion years ago; third nature, ideology and cultural artifacts (e.g., institutions and technology), with a shift to self-reflective, symbolic thought and agrarianism in humans some 8-40 thousand years ago. The co-evolution of these three natures has dramatically altered human behavior and its relationship to the whole planet. Third nature has infused human minds with several powerful ideas, or memes, including the idea of progress. These ideas have fueled the evolution of a complex institutional order (e.g., political systems and technology) and myriad attendant global problems (e.g., wars and environmental degradation). The human brain/mind is seen as the primary medium by which third nature governs human behavior and, therefore, self perpetuates.

Translating Mechanism-Based Strategies to Break the Obesity-Cancer Link: A Narrative Review.

PubMed

Smith, Laura A; O'Flanagan, Ciara H; Bowers, Laura W; Allott, Emma H; Hursting, Stephen D

2018-04-01

Prevalence of obesity, an established risk factor for many cancers, has increased dramatically over the past 50 years in the United States and across the globe. Relative to normoweight cancer patients, obese cancer patients often have poorer prognoses, resistance to chemotherapies, and are more likely to develop distant metastases. Recent progress on elucidating the mechanisms underlying the obesity-cancer connection suggests that obesity exerts pleomorphic effects on pathways related to tumor development and progression and, thus, there are multiple opportunities for primary prevention and treatment of obesity-related cancers. Obesity-associated alterations, including systemic metabolism, adipose inflammation, growth factor signaling, and angiogenesis, are emerging as primary drivers of obesity-associated cancer development and progression. These obesity-associated host factors interact with the intrinsic molecular characteristics of cancer cells, facilitating several of the hallmarks of cancer. Each is considered in the context of potential preventive and therapeutic strategies to reduce the burden of obesity-related cancers. In addition, this review focuses on emerging mechanisms behind the obesity-cancer link, as well as relevant dietary interventions, including calorie restriction, intermittent fasting, low-fat diet, and ketogenic diet, that are being implemented in preclinical and clinical trials, with the ultimate goal of reducing incidence and progression of obesity-related cancers. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Carnitine deficiency presenting with a decreased mental state in a patient with amyotrophic lateral sclerosis receiving long-term tube feeding: a case report.

PubMed

Isse, Naohi; Miura, Yoh; Obata, Toshiyuki; Takahara, Noriko

2013-12-30

L-carnitine is an important metabolic mediator involved in fatty acid transport. It is obtained from the diet, particularly from animal products, such as red meat. Previous reports have revealed that long-term tube feeding with a commercial product containing no or low levels of carnitine can lead to an altered mental state caused by hyperammonemia. A 72-year-old Japanese man had a 12-year history of amyotrophic lateral sclerosis. He was bedridden and had required mechanical ventilation and enteral tube feeding for 10 years at home. His main enteral solution was a commercial product that contained low carnitine levels, and he sometimes received coffee and homemade products such as miso soup. Our patient's ability to communicate gradually deteriorated over a period of one year. His serum total carnitine level was abnormally low, at 26.7μmol/L (normal range, 45 to 91μmol/L), but his ammonium level was normal. His mental state improved dramatically after starting L-carnitine supplementation (600mg twice daily). This case highlights the importance of avoiding carnitine deficiency in patients with amyotrophic lateral sclerosis undergoing long-term tube feeding. These patients experience progressive muscle atrophy that might cause impaired carnitine storage and might manifest as communication difficulties. Carnitine deficiency can be misdiagnosed as a progression of systemic muscle atrophy. Clinicians should be aware of this disorder and should consider periodically measuring carnitine levels, regardless of the patient's serum ammonium levels.

[Treatment of early-onset generalized dystonia by chronic bilateral stimulation of the internal globus pallidus. Apropos of a case].

PubMed

Coubes, P; Echenne, B; Roubertie, A; Vayssière, N; Tuffery, S; Humbertclaude, V; Cambonie, G; Claustres, M; Frerebeau, P

1999-05-01

Dystonia musculorum deformans is an inherited severe disease, with a wide clinical polymorphism. The most severe clinical forms with early onset carry a high risk of life-threatening complications. In the absence of any efficient medical treatment, bilateral pallidotomy has previously been reported to be of value in the management of this disease. We report the first clinical case of a severe early-onset generalized dystonia dramatically improved by a bilateral stimulation of the internal globus pallidus. In November 1996, we proposed this neurosurgical procedure for a 8-year-old girl, who had suffered since the age of 3 from severe generalized dystonia, and who progressively became totally dependent and bedridden. She had been under sedation and permanent controlled respiratory assistance for the last two months. The etiology of the disease remained unknown (the DYT1 mutation was absent). Under general anesthesia, we bilaterally implanted a four-contacts electrode in the internal globus pallidus, using the Leksell's stereotactic frame and a 1.5 tesla MRI control. A dramatic improvement was noted 6 weeks later and led us to connect the two electrodes to neurostimulators inserted under the abdominal skin.

Combined Orthodontic and Surgical Approach in the Correction of a Class III Skeletal Malocclusion with Mandibular Prognathism and Vertical Maxillary Excess Using Bimaxillary Osteotomy.

PubMed

Jose Cherackal, George; Thomas, Eapen; Prathap, Akhilesh

2013-01-01

For patients whose orthodontic problems are so severe that neither growth modification nor camouflage offers a solution, surgery to realign the jaws or reposition dentoalveolar segments is the only possible treatment. Surgery is not a substitute for orthodontics in these patients. Instead, it must be properly coordinated with orthodontics and other dental treatments to achieve good overall results. Dramatic progress in recent years has made it possible for combined surgical orthodontic treatment to be carried out successfully for patients with a severe dentofacial problem of any type. This case report provides an overview of the current treatment methodology in managing a combination of asymmetrical mandibular prognathism and vertical maxillary excess.

Business, society, and the Reagan revolution.

PubMed

Post, J E

1983-01-01

When Ronald Reagan first came to power two years ago, many Americans believed that his administration would bring about dramatic and fundamental changes in American politics. In this paper, the author contends that although it is still too early to fully assess the effects of "Reaganism" on the country in general, it is not too early to evaluate the results in terms of the altered relationships between government, business, and society. The author goes on to say that the 1982 congressional election results already show that the American people are fast becoming disillusioned with the Reagan administration. In conclusion, the author maintains that only when the U.S. chooses a visionary leader who is capable of defining--or redefining--"progress." will American politics undergo a real revolutionary change.

Binary black holes, gravitational waves, and numerical relativity

NASA Astrophysics Data System (ADS)

Centrella, Joan M.; Baker, John G.; Boggs, William D.; Kelly, Bernard J.; McWilliams, Sean T.; van Meter, James R.

2007-07-01

The final merger of comparable mass binary black holes produces an intense burst of gravitational radiation and is one of the strongest sources for both ground-based and space-based gravitational wave detectors. Since the merger occurs in the strong-field dynamical regime of general relativity, numerical relativity simulations of the full Einstein equations in 3-D are required to calculate the resulting gravitational dynamics and waveforms. While this problem has been pursued for more than 30 years, the numerical codes have long been plagued by various instabilities and, overall, progress was incremental. Recently, however, dramatic breakthrough have occurred, resulting in robust simulations of merging black holes. In this paper, we examine these developments and the exciting new results that are emerging.

Nox2-dependent ROS signaling protects against skeletal ageing

USDA-ARS?s Scientific Manuscript database

Bone remodeling is age-dependently regulated and changes dramatically during the course of development. Progressive accumulation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and hydroxyl radicals, has been suspected to be the leading cause of many inflammatory and degen...

Dramatic Contrasts in Arctic vs Antarctic Sea Ice Trends in 3-D Visualizations and Compilations of Monthly Record Highs and Lows

NASA Technical Reports Server (NTRS)

Parkinson, Claire L.; DiGirolamo, Nicolo E.

2016-01-01

New visualizations dramatically display the decreases in Arctic sea ice coverage over the years 1979-2015, apparent in each month of the year, with not a single record high in ice extents occurring in any month since 1986, a time period with 75 monthly record lows. Results are less dramatic in the Antarctic, but intriguingly in the opposite direction, with only 6 record lows since 1986 and 45 record highs.

Acute rheumatic fever and rheumatic heart disease

PubMed Central

Carapetis, Jonathan R.; Beaton, Andrea; Cunningham, Madeleine W.; Guilherme, Luiza; Karthikeyan, Ganesan; Mayosi, Bongani M.; Sable, Craig; Steer, Andrew; Wilson, Nigel; Wyber, Rosemary; Zühlke, Liesl

2018-01-01

Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances — including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life — give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty. PMID:27188830

Liver transplant in ethylmalonic encephalopathy: a new treatment for an otherwise fatal disease.

PubMed

Dionisi-Vici, Carlo; Diodato, Daria; Torre, Giuliano; Picca, Stefano; Pariante, Rosanna; Giuseppe Picardo, Sergio; Di Meo, Ivano; Rizzo, Cristiano; Tiranti, Valeria; Zeviani, Massimo; De Ville De Goyet, Jean

2016-04-01

Ethylmalonic encephalopathy is a fatal, rapidly progressive mitochondrial disorder caused by ETHE1 mutations, whose peculiar clinical and biochemical features are due to the toxic accumulation of hydrogen sulphide and of its metabolites, including thiosulphate. In mice with ethylmalonic encephalopathy, liver-targeted adeno-associated virus-mediated ETHE1 gene transfer dramatically improved both clinical course and metabolic abnormalities. Reasoning that the same achievement could be accomplished by liver transplantation, we performed living donor-liver transplantation in an infant with ethylmalonic encephalopathy. Unlike the invariably progressive deterioration of the disease, 8 months after liver transplantation, we observed striking neurological improvement with remarkable achievements in psychomotor development, along with dramatic reversion of biochemical abnormalities. These results clearly indicate that liver transplantation is a viable therapeutic option for ETHE1 disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Aspartic proteases involved in Alzheimer's disease.

PubMed

Schmidt, Boris

2003-05-09

Alzheimer's disease afflicts every tenth human aged over 65. Despite the dramatic progress that has been made in understanding the disease, the exact cause of Alzheimer's disease is still unknown. Most gene mutations associated with Alzheimer's disease point at the same culprits: amyloid precursor protein and ultimately amyloid beta. The enigmatic proteases alpha-,beta-, and gamma-secretase are the three executioners of amyloid precursor protein processing, and disruption of their delicate balance is suspected to result in Alzheimer's disease. Significant progress has been made in the selective control of these proteases, regardless of the availability of structural information. Not even the absence of a robust cell-free assay for gamma-secretase could hamper the identification of nonpeptidic inhibitors of this enzyme for long. Within five years, four distinctly different structural moieties were developed and the first drug candidates are in clinical trials. Unfortunately, selective inhibition of amyloid beta formation remains a crucial issue because fundamental fragments of the gamma-secretase complex are important for other signaling events. This problem makes beta-secretase inhibition and alpha-secretase induction even more appealing.

High precision optical spectroscopy and quantum state selected photodissociation of ultracold 88Sr2 molecules in an optical lattice

NASA Astrophysics Data System (ADS)

McDonald, Mickey

2017-04-01

Over the past several decades, rapid progress has been made toward the accurate characterization and control of atoms, epitomized by the ever-increasing accuracy and precision of optical atomic lattice clocks. Extending this progress to molecules will have exciting implications for chemistry, condensed matter physics, and precision tests of physics beyond the Standard Model. My thesis describes work performed over the past six years to establish the state of the art in manipulation and quantum control of ultracold molecules. We describe a thorough set of measurements characterizing the rovibrational structure of weakly bound 88Sr2 molecules from several different perspectives, including determinations of binding energies; linear, quadratic, and higher order Zeeman shifts; transition strengths between bound states; and lifetimes of narrow subradiant states. Finally, we discuss measurements of photofragment angular distributions produced by photodissociation of molecules in single quantum states, leading to an exploration of quantum-state-resolved ultracold chemistry. The images of exploding photofragments produced in these studies exhibit dramatic interference effects and strongly violate semiclassical predictions, instead requiring a fully quantum mechanical description.

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.

The Impact of Agribusiness on Rural Education.

ERIC Educational Resources Information Center

Theobald, Paul

The dramatic growth of multinational agribusiness corporations has led to all types of rural decline--social, demographic, institutional, and environmental. Historically, rural inhabitants and rural land have been abused and neglected in the name of progress. Rural development efforts often attract small assembly or light manufacturing plants that…

The Effectiveness of Creative Dramatics and Storytelling in a Library Setting

ERIC Educational Resources Information Center

Amato, Anthony; And Others

1973-01-01

This 2-year study involving 298 grade school pupils investigates the comparative effectiveness of creative dramatics and storytelling. While the results indicate neither had an effect on children's interests and reading achievement, there is indication that storytelling may have more influence than creative dramatics on self-image and empathy.…

KSC-2013-3030

NASA Image and Video Library

2013-07-11

CAPE CANAVERAL, Fla. -- At NASA’s Kennedy Space Center in Florida, a technician monitors the progress as a forklift is used to move the Optical Payload for Lasercomm Science, or OPALS, experiment to the air lock entrance at the Space Station Processing Facility. The optical technology demonstration experiment arrived from the agency’s Jet Propulsion Laboratory in Pasadena, Calif. NASA will use the International Space Station to test OPALS’ communications technology that could dramatically improve spacecraft communications, enhance commercial missions and strengthen transmission of scientific data. The experiment is slated to fly later this year aboard a SpaceX Dragon commercial resupply mission to the space station. The mission is expected to run 90 days after installation on the outside of the station. For more information about OPALS, visit: http://go.nasa.gov/10MMPDO. Photo credit: NASA/Jim Grossmann

KSC-2013-3033

NASA Image and Video Library

2013-07-11

CAPE CANAVERAL, Fla. -- At NASA’s Kennedy Space Center in Florida, a technicians monitor the progress as a forklift is used to lower the Optical Payload for Lasercomm Science, or OPALS, experiment near the air lock entrance at the Space Station Processing Facility. The optical technology demonstration experiment arrived from the agency’s Jet Propulsion Laboratory in Pasadena, Calif. NASA will use the International Space Station to test OPALS’ communications technology that could dramatically improve spacecraft communications, enhance commercial missions and strengthen transmission of scientific data. The experiment is slated to fly later this year aboard a SpaceX Dragon commercial resupply mission to the space station. The mission is expected to run 90 days after installation on the outside of the station. For more information about OPALS, visit: http://go.nasa.gov/10MMPDO. Photo credit: NASA/Jim Grossmann

KSC-2013-3029

NASA Image and Video Library

2013-07-11

CAPE CANAVERAL, Fla. -- At NASA’s Kennedy Space Center in Florida, a technician monitors the progress as a forklift is used to move the Optical Payload for Lasercomm Science, or OPALS, experiment to the air lock entrance at the Space Station Processing Facility. The optical technology demonstration experiment arrived from the agency’s Jet Propulsion Laboratory in Pasadena, Calif. NASA will use the International Space Station to test OPALS’ communications technology that could dramatically improve spacecraft communications, enhance commercial missions and strengthen transmission of scientific data. The experiment is slated to fly later this year aboard a SpaceX Dragon commercial resupply mission to the space station. The mission is expected to run 90 days after installation on the outside of the station. For more information about OPALS, visit: http://go.nasa.gov/10MMPDO. Photo credit: NASA/Jim Grossmann

Historical mathematics in the French eighteenth century.

PubMed

Richards, Joan L

2006-12-01

At least since the seventeenth century, the strange combination of epistemological certainty and ontological power that characterizes mathematics has made it a major focus of philosophical, social, and cultural negotiation. In the eighteenth century, all of these factors were at play as mathematical thinkers struggled to assimilate and extend the analysis they had inherited from the seventeenth century. A combination of educational convictions and historical assumptions supported a humanistic mathematics essentially defined by its flexibility and breadth. This mathematics was an expression of l'esprit humain, which was unfolding in a progressive historical narrative. The French Revolution dramatically altered the historical and educational landscapes that had supported this eighteenth-century approach, and within thirty years Augustin Louis Cauchy had radically reconceptualized and restructured mathematics to be rigorous rather than narrative.

Mutationally activated BRAF(V600E) elicits papillary thyroid cancer in the adult mouse.

PubMed

Charles, Roch-Philippe; Iezza, Gioia; Amendola, Elena; Dankort, David; McMahon, Martin

2011-06-01

Mutated BRAF is detected in approximately 45% of papillary thyroid carcinomas (PTC). To model PTC, we bred mice with adult-onset, thyrocyte-specific expression of BRAF(V600E). One month following BRAF(V600E) expression, mice displayed increased thyroid size, widespread alterations in thyroid architecture, and dramatic hypothyroidism. Over 1 year, without any deliberate manipulation of tumor suppressor genes, all mice developed PTC displaying nuclear atypia and marker expression characteristic of the human disease. Pharmacologic inhibition of MEK1/2 led to decreased thyroid size, restoration of thyroid form and function, and inhibition of tumorigenesis. Mice with BRAF(V600E)-induced PTC will provide an excellent system to study thyroid tumor initiation and progression and the evaluation of inhibitors of oncogenic BRAF signaling.

Mechanisms underlying sexual and affiliative behaviors of mice: relation to generalized CNS arousal

PubMed Central

Shelley, Deborah N.; Choleris, Elena; Kavaliers, Martin

2006-01-01

The field of social neuroscience has grown dramatically in recent years and certain social responses have become amenable to mechanistic investigations. Toward that end, there has been remarkable progress in determining mechanisms for a simple sexual behavior, lordosis behavior. This work has proven that specific hormone-dependent biochemical reactions in specific parts of the mammalian brain regulate a biologically important behavior. On one hand, this sex behavior depends on underlying mechanisms of CNS arousal. On the other hand, it serves as a prototypical social behavior. The same sex hormones and the genes that encode their receptors as are involved in lordosis, also affect social recognition. Here we review evidence for a micronet of genes promoting social recognition in mice and discuss their biological roles. PMID:18985112

Intelligent path loss prediction engine design using machine learning in the urban outdoor environment

NASA Astrophysics Data System (ADS)

Wang, Ruichen; Lu, Jingyang; Xu, Yiran; Shen, Dan; Chen, Genshe; Pham, Khanh; Blasch, Erik

2018-05-01

Due to the progressive expansion of public mobile networks and the dramatic growth of the number of wireless users in recent years, researchers are motivated to study the radio propagation in urban environments and develop reliable and fast path loss prediction models. During last decades, different types of propagation models are developed for urban scenario path loss predictions such as the Hata model and the COST 231 model. In this paper, the path loss prediction model is thoroughly investigated using machine learning approaches. Different non-linear feature selection methods are deployed and investigated to reduce the computational complexity. The simulation results are provided to demonstratethe validity of the machine learning based path loss prediction engine, which can correctly determine the signal propagation in a wireless urban setting.

Molecular structure of P2X receptors.

PubMed

Egan, Terrance M; Cox, Jane A; Voigt, Mark M

2004-01-01

P2X receptors are ligand-gated ion channels that transduce many of the physiological effects of extracellular ATP. There has been a dramatic increase in awareness of these receptors over the past 5 or so years, in great part due to their molecular cloning and characterization. The availability of cDNA clones for the various subunits has led to rapid progress in identifying their tissue-specific expression, resulting in new ideas concerning the functional roles these receptors might play in physiological and pathophysiological processes. In addition, molecular approaches have yielded much information regarding the structure and function of the receptor proteins themselves. In this review we seek to review recent findings concerning the molecular determinants of receptor-channel function, with particular focus on ligand binding and gating, ion selectivity, and subunit assembly.

Combined Orthodontic and Surgical Approach in the Correction of a Class III Skeletal Malocclusion with Mandibular Prognathism and Vertical Maxillary Excess Using Bimaxillary Osteotomy

PubMed Central

Jose Cherackal, George; Thomas, Eapen; Prathap, Akhilesh

2013-01-01

For patients whose orthodontic problems are so severe that neither growth modification nor camouflage offers a solution, surgery to realign the jaws or reposition dentoalveolar segments is the only possible treatment. Surgery is not a substitute for orthodontics in these patients. Instead, it must be properly coordinated with orthodontics and other dental treatments to achieve good overall results. Dramatic progress in recent years has made it possible for combined surgical orthodontic treatment to be carried out successfully for patients with a severe dentofacial problem of any type. This case report provides an overview of the current treatment methodology in managing a combination of asymmetrical mandibular prognathism and vertical maxillary excess. PMID:24455321

Beyond echoplaylia: promoting language in children with autism.

PubMed

Schuler, Adriana L

2003-12-01

The article was written to support the use of play as a medium to extend and enrich the communicative exchanges and, more specifically, the symbolic language of children on the autistic spectrum. The first argument in support of such use of play lies within the features of autistic communication, and particularly the extreme challenges encountered in imaginative play and narrative thought. The second argument on behalf of play lies within the selection of specific intervention strategies, which are discussed subsequently. Finally, the article presents a case illustration of how adult facilitated dramatic peer play led to a breakthrough in a range of symbolic behaviours in a 9-year-old girl with autism, who up to that point had not progressed beyond a semi-communicative use of echolalia, best described as 'situation association'.

Quick Tips for Weight Training Exercise

ERIC Educational Resources Information Center

Perez, Saul

2004-01-01

Weight training is one of the single most popular types of fitness activities in the United States. One of the reasons for its popularity is that it dramatically contributes to improved strength, muscle tone, body composition, health and appearance. Weight training is a progressive resistance exercise in which resistance is gradually increased as…

The State of Organic Teaching Laboratories

ERIC Educational Resources Information Center

Horowitz, Gail

2007-01-01

The changes that have taken place in the organic chemistry laboratory course since 1980s are reviewed with reference to the quantity and diversity of discovery-based experiments available to date. The data illustrates that significant progress is towards accomplishing dramatic changes such as the almost universal adoption of microscale, the use of…

Cultural Assumptions against Sustainability: An International Survey

ERIC Educational Resources Information Center

Gambini, Barbara

2006-01-01

Despite the great progress in increasing public awareness of and attention to the issue of sustainability, the measures taken so far fall dramatically short of halting deleterious cycles. This apparent deficiency can be ascribed to two main factors: insufficient efforts to finding viable and visible alternatives and the failure to thoroughly…

Recent progress on the structure separation of single-wall carbon nanotubes

NASA Astrophysics Data System (ADS)

Cui, Jiaming; Yang, Dehua; Zeng, Xiang; Zhou, Naigen; Liu, Huaping

2017-11-01

The mass production of single-structure, single-wall carbon nanotubes (SWCNTs) with identical properties is critical for their basic research and technical applications in the fields of electronics, optics and optoelectronics. Great efforts have been made to control the structures of SWCNTs since their discovery. Recently, the structure separation of SWCNTs has been making great progress. Various solution-sorting methods have been developed to achieve not only the separation of metallic and semiconducting species, but also the sorting of distinct (n, m) single-chirality species and even their enantiomers. This progress would dramatically accelerate the application of SWCNTs in the next-generation electronic devices. Here, we review the recent progress in the structure sorting of SWCNTs and outline the challenges and prospects of the structure separation of SWCNTs.

12-year Temporal Trend in Referral Pattern and Test Results of Stress Echocardiography in a Tertiary Care Referral Center with Moderate Volume Activities and Cath-lab Facility.

PubMed

Barbieri, Andrea; Mantovani, Francesca; Bursi, Francesca; Bartolacelli, Ylenia; Manicardi, Marcella; Lauria, Maria Giulia; Boriani, Giuseppe

2018-01-01

Data on stress echocardiography (SE) time-related changes in referral patterns and diagnostic yield for detection of inducible ischemia could enhance Echo Lab quality benchmarks and performance measures. This study aims to evaluate temporal trends in SE test results among ambulatory patients with suspected or known coronary artery disease (CAD) in a tertiary care referral center with moderate (>100/year) volume SE activities and Cath-Lab facility. From January 2004 to December 2015, 1954 patients (mean age 62 ± 12 years, 42% women, 27% with known CAD) underwent SE (1673 exercise SE, 86%, 246 pharmacological SE, 12%, 35 pacing SE, 2%). Time was grouped into three 4 year periods, where clinical data and test results were evaluated. Our series comprised low-to-intermediate pretest probability of CAD throughout the observation period (overall pretest probability of CAD 19% ± 15%). A progressive decline over time in the rate of pharmacological SE instead of a dramatic increment of exercise SE (79%-96%, P < 0.0001) was noted. The use of beta-blockers increased (from 43% to 66%, P < 0.0001), while the use of nitrates decreased (from 11% to 4%, P < 0.0001) over time. We noted a very uncommon occurrence of abnormal test results with a further decrease in the last period (from 11% to 3%, P < 0.0001). We observed, over a 12-year period, a progressive decrease in the frequency of inducible myocardial ischemia among patients with known or suspected CADe referred to our Echo Lab for SE with Cath-Lab facility, and this trend was parallel to changes in SE referral practice. These findings are particularly relevant if we consider the practical implications on diagnostic SE accuracy and risk assessment.

AJRCCM: 100-Year Anniversary.The Shifting Landscape for Lung Cancer: Past, Present, and Future

PubMed Central

Vachani, Anil; Sequist, Lecia V.

2017-01-01

The past century has witnessed a transformative shift in lung cancer from a rare reportable disease to the leading cause of cancer death among men and women worldwide. This historic shift reflects the increase in tobacco consumption worldwide, spurring public health efforts over the past several decades directed at tobacco cessation and control. Although most lung cancers are still diagnosed at a late stage, there have been significant advances in screening high-risk smokers, diagnostic modalities, and chemopreventive approaches. Improvements in surgery and radiation are advancing our ability to manage early-stage disease, particularly among patients considered unfit for traditional open resection. Arguably, the most dramatic progress has occurred on the therapeutic side, with the development of targeted and immune-based therapy over the past decade. This article reviews the major shifts in the lung cancer landscape over the past 100 years. Although many ongoing clinical challenges remain, this review will also highlight emerging molecular and imaging-based approaches that represent opportunities to transform the prevention, early detection, and treatment of lung cancer in the years ahead. PMID:28459327

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

Co-Optimization of Fuels and Engines

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

Farrell, John

2016-04-11

The Co-Optimization of Fuels and Engines (Co-Optima) initiative is a new DOE initiative focused on accelerating the introduction of affordable, scalable, and sustainable biofuels and high-efficiency, low-emission vehicle engines. The simultaneous fuels and vehicles research and development (R&D) are designed to deliver maximum energy savings, emissions reduction, and on-road vehicle performance. The initiative's integrated approach combines the previously independent areas of biofuels and combustion R&D, bringing together two DOE Office of Energy Efficiency & Renewable Energy research offices, ten national laboratories, and numerous industry and academic partners to simultaneously tackle fuel and engine research and development (R&D) to maximize energymore » savings and on-road vehicle performance while dramatically reducing transportation-related petroleum consumption and greenhouse gas (GHG) emissions. This multi-year project will provide industry with the scientific underpinnings required to move new biofuels and advanced engine systems to market faster while identifying and addressing barriers to their commercialization. This project's ambitious, first-of-its-kind approach simultaneously tackles fuel and engine innovation to co-optimize performance of both elements and provide dramatic and rapid cuts in fuel use and emissions. This presentation provides an overview of the initiative and reviews recent progress focused on both advanced spark-ignition and compression-ignition approaches.« less

Progress Toward National Aeronautics Goals

NASA Technical Reports Server (NTRS)

Russo, Carlo J.; Sehra, Arun K.

1999-01-01

NASA has made definitive progress towards achieving several bold U.S. goals in aeronautics related to air breathing engines. The advanced technologies developed towards these goals span applications from general aviation to large subsonic and supersonic aircraft. The proof of successful technology development is demonstrated through successful technology transfer to U.S. industry and projected fleet impact. Specific examples of progress are discussed that quantifies the achievement towards these goals. In addition, a more detailed vision for NASA aeronautics is defined and key strategic issues are explored which invite international and national debate and involvement especially in reduced environmental impact for subsonic and supersonic aircraft, dramatic new capabilities in general aviation engines, and reduced development cycle time and costs.

Maintenance therapy in colon cancer.

PubMed

Giuliani, F; De Vita, F; Colucci, G; Pisconti, S

2010-11-01

In the last decade dramatic improvements have been obtained in the treatment of metastatic colorectal cancer. Thanks to the introduction in the clinical practice of new drugs such as Irinotecan and Oxaliplatin, and modern biological drugs such as Bevacizumab and Cetuximab, the response rate, progression-free and overall survival are about 50-60%, 9-11 and 20-24 months respectively. Despite this progress, many questions remain unsolved especially those related to the optimal duration of treatment and the role of maintenance therapy. To treat until progression (or unacceptable toxicity) is the classical way but in the common clinical practice is frequent to perform an induction therapy (until the maximum response is obtained) followed by a complete stop and restart on progression, or by a maintenance without the drug/s responsible of the major cumulative toxicities. The following report focus on the role of different strategies respect to the classic "treatment until progression". Copyright © 2010 Elsevier Ltd. All rights reserved.

Development of BEM for ceramic composites

NASA Technical Reports Server (NTRS)

Henry, D. P.; Banerjee, P. K.; Dargush, G. F.

1990-01-01

Details on the progress made during the first three years of a five-year program towards the development of a boundary element code are presented. This code was designed for the micromechanical studies of advance ceramic composites. Additional effort was made in generalizing the implementation to allow the program to be applicable to real problems in the aerospace industry. The ceramic composite formulations developed were implemented in the three-dimensional boundary element computer code BEST3D. BEST3D was adopted as the base for the ceramic composite program, so that many of the enhanced features of this general purpose boundary element code could by utilized. Some of these facilities include sophisticated numerical integration, the capability of local definition of boundary conditions, and the use of quadratic shape functions for modeling geometry and field variables on the boundary. The multi-region implementation permits a body to be modeled in substructural parts; thus dramatically reducing the cost of the analysis. Furthermore, it allows a body consisting of regions of different ceramic matrices and inserts to be studied.

Can infections prevent or cure allergy and autoimmunity?

PubMed

Kamradt, Thomas

2005-06-01

Extract: In western countries the prevalence and incidence of allergic and autoimmune diseases have been increasing dramatically over the last 50 years. In the last two decades, significant progress has been made towards understanding the genetic basis for susceptibility to autoimmunity or allergy. Genetic factors, however, cannot explain abrupt changes in disease incidence. It is therefore likely that environmental factors, specifically environmental factors that have changed over the last two generations, are critical for the increasing incidence of allergies and autoimmune diseases. Traditionally, autoimmune diseases such as multiple sclerosis (MS), type I diabetes, or rheumatoid arthritis (RA) are believed to have resulted from aberrant immune response to pathogens. In contrast, the "hygiene hypothesis," first postulated some 20 years ago, proposes that a lack of infections, especially during early childhood, predisposes one to the aberrant immune responses against harmless foreign antigens that cause allergic diseases such as rhinitis, atopic dermatitis, and allergic asthma. Several lines of epidemiological, clinical and experimental research point to more complex connections, either protective or pathogenic, between infection, allergy and autoimmunity.

Acral keratoses and leucocytoclastic vasculitis occurring during treatment of essential thrombocythaemia with hydroxyurea.

PubMed

Worley, B; Glassman, S J

2016-03-01

Hydroxyurea is used in essential thrombocythaemia to lower thromboembolic risk. Cutaneous adverse effects from hydroxyurea are diverse. Small vessel vasculitis has been rarely reported, and the coexistence of several different morphologies has not been described. We report a case of acral keratoses, psoriasiform plaques and leucocytoclastic vasculitis (LCV) in a patient with essential thrombocythaemia. A 69-year-old woman developed a confusing array of skin lesions including keratotic papules, psoriasiform plaques and keratoderma 4 years after commencing hydroxyurea therapy. The initial diagnosis was hand and foot psoriasis, but lesions were resistant to therapy. With an increase in the dose of hydroxyurea, the lesions ulcerated. Skin biopsies taken from different sites indicated different diagnoses, including LCV. Discontinuation of hydroxyurea yielded rapid improvement. Although the most commonly reported cutaneous adverse effect from hydroxyurea is leg ulceration, this can be preceded or accompanied by less dramatic skin lesions. Unless recognized, delayed diagnosis and lesion progression can occur. © 2015 British Association of Dermatologists.

Metastatic breast cancer: The Odyssey of personalization.

PubMed

Sonnenblick, A; Pondé, N; Piccart, M

2016-10-01

Metastatic breast cancer is the most frequent cause of cancer death for women worldwide. In the last 15 years, a large number of new agents have entered clinical use, a result of the dramatic increase in our understanding of the molecular underpinnings of metastatic breast cancer. However, while these agents have led to better outcomes, they are also at the root cause of increasing financial pressure on healthcare systems. Moreover, decision making in an era where every year new agents are added to the therapeutic armamentarium has also become a significant challenge for medical oncologists. In the present article, we will provide an ample review on the most recent developments in the field of treatment of the different subtypes of metastatic breast cancer with a critical discussion on the slow progress made in identifying response biomarkers. New hopes in the form of ctDNA monitoring and functional imaging will be presented. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

The bound-state properties summary and recommendations of working group 1

NASA Astrophysics Data System (ADS)

Friar, J. L.; Frois, B.

A dozen years ago virtually nothing was known about three-nucleon forces. In the intervening years we have learned to solve routinely the trinucleon bound-state Faddeev equations for what amounts to the complete (model) nucleon-nucleon potential, and to include complicated three-nucleon forces as well. The art of constructing those forces has dramatically improved, and modern versions of these forces contain components derived from the exchange of heavy mesons, in addition to pion exchange. Experimental sophistication in probing the trinucleon ground states has made similar improvements. The recent Saclay and MIT tritium form factor experiments have finally unravelled the isospin structure of the trinucleon charge densities, and have generated new challenges for theorists. Although there are few definite conclusions yet and much remains to be done, the progress has been exceptional. Perhaps it is not too pretentious to quote the final frame of the movie 41 Destination Moon: "This is the end of the beginning."

Research on history of medicine in China in the last five years.

PubMed

Zhu, Jian-ping

2004-03-01

Since 1999, progress has been made, to varying degrees, in numerous areas of medical history research in China including history of TCM, history of western medicine, history of integrated Chinese and western medicine, history of traditional medicine of Chinese minorities, history of medicine of foreign countries, history of medical exchanges between China and other countries, and history of comparative medical history. Among others, the number of articles on history of diseases, history of specific medical disciplines, modern medical history, medical biographies, medical works, contemporary medical history, and history of medical culture has increased dramatically. In the field of history of diseases, the papers deal with diseases in gynecology and obstetrics, plague, lanhousha (scarlet fever), and nephritis; articles in the field of specific disciplines deal with history of acu-moxibustion, history of prescription-forms, and history of gynecology, endoscopic surgery, and evidence-based medicine. There are even distinguished papers appeared in these aspects. In the aspect of modern medical history, there are papers dealing with the developement of TCM, the introduction of western medicine into China, with some specific researches in these fields. Medical biographies include Tan Yun-xian, Quan Shao-qing, Du Chong-ming etc. Papers on medical works deal with the ancient unearthed literature lost yet spread and extant abroad, medical classics, canons on material medica, cold-pathogenic diseases, and formularies. While papers on history of medical culture discuss basically the influence of Confucianism, Taoism, Buddhism and I-discipline on Chinese medicine. During these five years, 300 original articles have been published in The Chinese journal of Medical History, with another 200 papers published in other Chinese journals. Forty monographs have been published and important ones are A General History of Chinese Medicine, Modern history of TCM, The Historical Development of Acupuncture, A General History of Tiberan Medicine. For the coming years, the stress points should be laid on the research on history of diseases, history of specific medical disciplines, and some specific academic topics. In addition, the weak points in the research fields of theoretical problems in studies of medical history, history of traditional medicine of Chinese minorities, medical history of communication between China and foreign countries, comparative study on medical history, and the study on history of medical also be strengthened continually. In the five years since 1999, progress has been made, more or less, in the research works in medical history in China, including history of TCM, history of western medicine, history of integrated Chinese and western medicine, history of traditional medicine of Chinese minorities, history of medicine of foreign countries, history of medical exchanges between China and other countries, and history of comparative medical history. And the number of articles on history of diseases, history of specific medical disciplines, modern medical history, medical biographies, medical works, contemporary medical history and history of medical culture has increased dramatically. The research work in ancient medical history is still progressing forcefully.

The Effectiveness of the Dramatic Activities in the Development of the Oral Performance Skills of Prep Students in English

ERIC Educational Resources Information Center

Zayed, Jihan El-Sayed Ahmed

2003-01-01

The goal of this study was to determine the effect of using some dramatic activities on developing the oral performance skills of second year prep school students in English. The dramatic activities included storytelling, story-acting, pantomime, puppetry, role-playing, reader's theater and choral reading. The oral performance skills were…

Phase I Trial and Pharmacokinetic Study of Lexatumumab in Pediatric Patients With Solid Tumors

PubMed Central

Merchant, Melinda S.; Geller, James I.; Baird, Kristin; Chou, Alexander J.; Galli, Susana; Charles, Ava; Amaoko, Martha; Rhee, Eunice H.; Price, Anita; Wexler, Leonard H.; Meyers, Paul A.; Widemann, Brigitte C.; Tsokos, Maria; Mackall, Crystal L.

2012-01-01

Purpose Lexatumumab is an agonistic, fully human monoclonal antibody against tumor necrosis factor–related apoptosis-inducing ligand receptor 2 with preclinical evidence of activity in pediatric solid tumors. Patients and Methods This phase I dose-escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab at doses up to, but not exceeding, the adult maximum-tolerated dose (3, 5, 8, and 10 mg/kg), administered once every 2 weeks to patients age ≤ 21 years with recurrent or progressive solid tumors. Results Twenty-four patients received a total of 56 cycles of lexatumumab over all four planned dose levels. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed grade 3 pneumonia with hypoxia during the second cycle. Five patients experienced stable disease for three to 24 cycles. No patients experienced complete or partial response, but several showed evidence of antitumor activity, including one patient with recurrent progressive osteosarcoma who experienced resolution of clinical symptoms and positron emission tomography activity, ongoing more than 1 year off therapy. One patient with hepatoblastoma showed a dramatic biomarker response. Conclusion Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects. PMID:23071222

A New Vision for California Higher Education: A Model Public Agenda

ERIC Educational Resources Information Center

Shulock, Nancy; Moore, Colleen; Tan, Connie

2014-01-01

This report constructs a model public agenda to address the mounting challenges facing California higher education. It is intended to inspire broad discussion potentially leading to an official public agenda for California higher education. The report describes some of the structural barriers that are preventing more dramatic progress in meeting…

Reassessing China's Higher Education Development: A Focus on Academic Culture

ERIC Educational Resources Information Center

Yang, Rui

2015-01-01

During the past three and a half decades, China has been progressing in higher education in a surprisingly dramatic manner, evidenced especially by scientific publications and sheer numbers of graduates. Such a fact has national, regional and global implications. China's higher education development and its future directions are now placed highly…

Big Gay Church: Sermons to and for an Underserved Population in Art Education Settings

ERIC Educational Resources Information Center

Rhoades, Mindi; Cosier, Kim; Davenport, Melanie G.; Sanders, James H., III; Wolfgang, Courtnie N.

2013-01-01

While the past decade shows dramatic progress in tolerance, acceptance, and support for lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) people/rights in the United States, this population remains underserved. Statistics on LGBTQ youth suicide remain troublingly high; yet, when LGBTQ youth attend schools with Gay-Straight…

Panel Recommends State-Level NAEP for 12th Graders

ERIC Educational Resources Information Center

Olson, Lynn

2004-01-01

A national commission formed to review the future of the 12th grade National Assessment of Educational Progress (NAEP) has recommended that the nation's primary barometer of student performance should expand dramatically to provide mandatory state results on the achievement of 12th graders and to measure their readiness for college, employment,…

Bullying in Schools. ERIC Digest.

ERIC Educational Resources Information Center

Banks, Ron

Bullying is a serious problem that can dramatically affect the ability of students to progress academically and socially. Bullying is comprised of direct behaviors such as teasing, taunting, threatening, hitting, and stealing that are initiated by one or more students against a victim. Bullying may also be more indirect by causing a student to be…

Rapidly Progressive Osteoarthritis: a Review of the Clinical and Radiologic Presentation.

PubMed

Flemming, Donald J; Gustas-French, Cristy N

2017-07-01

The purpose of this paper is to review the distinct clinical and radiographic features that may lead to prompt diagnosis of rapidly progressive osteoarthritis (RPOA) and thus obviate unnecessary and costly diagnostic workup. RPOA is uncommon but is more frequently seen in practice because of the aging population. RPOA is a destructive arthropathy that occurs most commonly in elderly women but can also be seen in patients that have sustained trauma. The dramatic radiologic manifestations of RPOA can lead to diagnostic confusion with other arthropathies, infection, and osteonecrosis. RPOA was originally described in the hip but may also involve the shoulder. The etiology of RPOA is not well understood, but subchondral fracture probably plays a role in the development of dramatic destruction of the joint that is seen in affected patients. Early diagnosis may reduce the complexity of surgical management. RPOA is an uncommon condition that occurs most frequently in elderly woman or in patients who have sustained trauma. Prompt recognition of the clinical and radiologic features of this arthropathy can reduce unnecessary diagnostic workup and complexity of surgical intervention.

Hsp90 activator Aha1 drives production of pathological tau aggregates

PubMed Central

Shelton, Lindsey B.; Baker, Jeremy D.; Zheng, Dali; Sullivan, Leia E.; Solanki, Parth K.; Webster, Jack M.; Sun, Zheying; Sabbagh, Jonathan J.; Nordhues, Bryce A.; Koren, John; Ghosh, Suman; Blagg, Brian S. J.; Dickey, Chad A.

2017-01-01

The microtubule-associated protein tau (MAPT, tau) forms neurotoxic aggregates that promote cognitive deficits in tauopathies, the most common of which is Alzheimer’s disease (AD). The 90-kDa heat shock protein (Hsp90) chaperone system affects the accumulation of these toxic tau species, which can be modulated with Hsp90 inhibitors. However, many Hsp90 inhibitors are not blood–brain barrier-permeable, and several present associated toxicities. Here, we find that the cochaperone, activator of Hsp90 ATPase homolog 1 (Aha1), dramatically increased the production of aggregated tau. Treatment with an Aha1 inhibitor, KU-177, dramatically reduced the accumulation of insoluble tau. Aha1 colocalized with tau pathology in human brain tissue, and this association positively correlated with AD progression. Aha1 overexpression in the rTg4510 tau transgenic mouse model promoted insoluble and oligomeric tau accumulation leading to a physiological deficit in cognitive function. Overall, these data demonstrate that Aha1 contributes to tau fibril formation and neurotoxicity through Hsp90. This suggests that therapeutics targeting Aha1 may reduce toxic tau oligomers and slow or prevent neurodegenerative disease progression. PMID:28827321

Powassan virus infection: case series and literature review from a single institution.

PubMed

Raval, Mihir; Singhal, Mayank; Guerrero, Dubert; Alonto, Augusto

2012-10-30

Powassan virus is a flavivirus related to eastern hemisphere's tick-borne encephalitis viruses. It can cause a rare but potentially life-threatening disease including encephalitis. We report four cases of POWV infection in Minnesota and North Dakota with known exposure to tick bites in 2011. Our first case was an 18-year-old male who dramatically presented with seizure and headache with positive serum analysis for Powassan virus immunoglobulin M. The second case was a 60 year old gentleman with intraparenchymal hemorrhage and was diagnosed via cerebrospinal fluid analysis. Thirdly, a 61 year old male developed altered mental status and encephalitis. Our fourth patient was a 69 year old male who had headache and non-focal weakness who was diagnosed with serum analysis. Symptoms of Powassan virus infection ranged from headaches to seizures and severe neurological symptoms. This study serves to highlight the increased detection of Powassan virus infection in the central north United States. This report focuses on the increasing incidence that can lead to increasing efforts for raising awareness regarding this infection. There is a need for clinician vigilance and public attention due to its increasing detection, westward progression and varied clinical presentations.

Cholesterol import and steroidogenesis are biosignatures for gastric cancer patient survival

PubMed Central

Chang, Wei-Chun; Huang, Shang-Fen; Lee, Yang-Ming; Lai, Hsueh-Chou; Cheng, Bi-Hua; Cheng, Wei-Chung; Ho, Jason Yen-Ping; Jeng, Long-Bin; Ma, Wen-Lung

2017-01-01

Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to that in normal counterparts, and also promoted progression. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoprotein-mediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested. PMID:27893427

Cholesterol import and steroidogenesis are biosignatures for gastric cancer patient survival.

PubMed

Chang, Wei-Chun; Huang, Shang-Fen; Lee, Yang-Ming; Lai, Hsueh-Chou; Cheng, Bi-Hua; Cheng, Wei-Chung; Ho, Jason Yen-Ping; Jeng, Long-Bin; Ma, Wen-Lung

2017-01-03

Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to that in normal counterparts, and also promoted progression. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoprotein-mediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested.

Impact of social relationships on Alzheimer's memory impairment: mechanistic studies.

PubMed

Hsiao, Ya-Hsin; Chang, Chih-Hua; Gean, Po-Wu

2018-01-11

Alzheimer's disease (AD) is characterized by progressive memory and neuronal loss culminating in cognitive impairment that not only affects a person's living ability but also becomes a society's as well as a family's economic burden. AD is the most common form of dementia in older persons. It is expected that the number of people with AD dementia will increase dramatically in the next 30 years, projecting to 75 million in 2030 and 131.5 million in 2050 worldwide. So far, no sufficient evidence is available to support that any medicine is able to prevent or reverse the progression of the disease. Early studies have shown that social environment, particularly social relationships, can affect one's behavior and mental health. A study analyzing the correlation between loneliness and risk of developing AD revealed that lonely persons had higher risk of AD compared with persons who were not lonely. On the other hand, it has been reported that we can prevent cognitive decline and delay the onset of AD if we keep mentally active and frequently participate in social activities. In this review, we focus on the impact of social behaviors on the progression of cognitive deficit in animal models of AD with a particular emphasis on a mechanistic scheme that explains how social isolation exacerbates cognitive impairment and how social interaction with conspecifics rescues AD patients' memory deficit.

Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study

PubMed Central

D'Souza, Anita; Dispenzieri, Angela; Wirk, Baldeep; Zhang, Mei-Jie; Huang, Jiaxing; Gertz, Morie A.; Kyle, Robert A.; Kumar, Shaji; Comenzo, Raymond L.; Peter Gale, Robert; Lazarus, Hillard M.; Savani, Bipin N.; Cornell, Robert F.; Weiss, Brendan M.; Vogl, Dan T.; Freytes, César O.; Scott, Emma C.; Landau, Heather J.; Moreb, Jan S.; Costa, Luciano J.; Ramanathan, Muthalagu; Callander, Natalie S.; Kamble, Rammurti T.; Olsson, Richard F.; Ganguly, Siddhartha; Nishihori, Taiga; Kindwall-Keller, Tamila L.; Wood, William A.; Mark, Tomer M.; Hari, Parameswaran

2015-01-01

Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m2 or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted. PMID:26371138

Optic nerve sheath meningiomas: visual improvement after stereotactic radiotherapy.

PubMed

Liu, James K; Forman, Scott; Hershewe, Gerard L; Moorthy, Chitti R; Benzil, Deborah L

2002-05-01

The management of primary optic nerve sheath meningioma (ONSM) is controversial. Surgery often results in postoperative blindness in the affected eye and thus has been abandoned as a treatment option for most patients. When these tumors are left untreated, however, progressive visual impairment ensues, which also leads to blindness. Recently, radiation therapy has gained wider acceptance in the treatment of these lesions. Experience with stereotactic radiotherapy (SRT) in the treatment of ONSMs is limited because of the rare incidence of this tumor. We present a series of patients with ONSM who were treated with SRT. Five patients (three women, two men), ranging in age from 40 to 73 years, presented with progressive visual loss with decreased visual field, visual acuity, and color vision affecting six eyes (one patient had tumor involving both optic nerves). One patient also presented with proptosis and diplopia. Five eyes had functional residual vision (range, 20/20 to 20/40), and one eye was completely blind. All five patients were diagnosed clinically and radiographically to have an ONSM. Three were intraorbital, one was intracanalicular as well as intraorbital, and one was a left ONSM extending through the optic foramen into the intracranial space and involving the right optic nerve. The five functional eyes were treated with SRT by use of 1.8-Gy fractions to a cumulative dose of 45 to 54 Gy. Follow-up ranged from 1 to 7 years, and serial magnetic resonance imaging revealed no changes in the size of the tumor in all five patients. Four patients experienced dramatic improvement in visual acuity, visual field, and color vision within 3 months after SRT. One patient remained stable without evidence of visual deterioration or disease progression. None had radiation-induced optic neuropathy. SRT may be a viable option for treatment of primary ONSM in patients with documented progressive visual deterioration, and it may be effective in improving or stabilizing remaining functional vision.

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).

Navigating conflicts of interest for the medical device entrepreneur.

PubMed

Donovan, Aine; Kaplan, Aaron V

2012-01-01

The past fifty years has witnessed dramatic progress in the understanding and treatment of patients suffering from cardiovascular disease leading to symptomatic relief and impressive increases in longevity. These advances have been due in large part to the development, study and implementation of new technology. Within interventional cardiology in particular, these advances have been driven by the availability of new technology in the form of medical devices. Successful device development efforts require close collaboration among basic scientist, clinician-inventors/entrepreneurs, clinician-investigators and corporations. Though the role of the clinician is central to this process, these activities present important conflicts-of-interest (COIs). The purpose of this paper is to 1) characterize these conflicts, 2) provide a context from which to approach their management and 3) recommend management strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

How Mars is losing its atmosphere on This Week @NASA – November 6, 2015

NASA Image and Video Library

2015-11-06

New findings by NASA’s Mars Atmosphere and Volatile Evolution (MAVEN) mission indicate that solar wind is currently stripping away the equivalent of about 1/4 pound of gas every second from the Martian atmosphere. MAVEN tracked a series of dramatic solar storms passing through the Martian atmosphere in March and found the loss was accelerated. This could suggest that violent solar activity in the distant past may have played a key role in the transition of the Martian climate from an early, warm and wet environment that might have supported surface life, to the cold, arid planet Mars is today. Also, 15 Years on space station, and counting!, Spacewalk for space station maintenance, NASA seeking future astronauts, Commercial Crew access tower progress and First SLS flight engine placed for testing!

Becoming Warriors: Dramatic Inquiry with 11- to 12-Year-Olds in an EBD Classroom

ERIC Educational Resources Information Center

Edmiston, Brian; Sobjack, Laura

2017-01-01

Using a dialogue format, a college professor and a teacher of 11- to 12-year-old children with emotional and behavioural difficulties (EBD) report on a case study of four children (three boys and a girl) when over a three-week period dramatic inquiry pedagogy (focused on the meaning for students of fictional violent events depicted in extracts…

Evolving medical service in the information age: a legal analysis of applying telemedicine programs in Taiwan.

PubMed

Wu, Hsing-Hao

2008-12-01

In the face of the information age, Internet and telecommunication technologies have been widely applied in various settings. These innovational technologies have been used in the areas of e-commerce, long distance learning programs, entertainment, e-government, and so on. In recent years, the evolution of Internet technology is also pervading the health care industry. This dramatic trend may significantly alter traditional medical practice as well as the means of delivery of health care. The idea of telemedicine is to use modern information technology as a means or platform to deliver health care service in remote areas and to manage medical information in digitalized forms. The progress of developing telemedicine, however, is rather slow. The main reason for this slow progress is not technological but rather legal. Health care providers are reluctant to promote this innovation in medical service mainly due to uncertain legal consequences and ethical concerns. Although there are many legal challenges surrounding telemedicine, this note will examine major legal issues including licensure, malpractice liability, and privacy protection. Furthermore, I will discuss the potential of applying telemedicine programs in Taiwan's National Health Insurance Program (hereinafter referred to as NHI).

How AIDS funding strengthens health systems: progress in pharmaceutical management.

PubMed

Embrey, Martha; Hoos, David; Quick, Jonathan

2009-11-01

In recent years, new global initiatives responding to the AIDS crisis have dramatically affected-and often significantly improved-how developing countries procure, distribute, and manage pharmaceuticals. A number of developments related to treatment scale-up, initially focused on AIDS-related products, have created frameworks for widening access to medicines for other diseases that disproportionally impact countries with limited resources and for strengthening health systems overall. Examples of such systems strengthening have come in the areas of drug development and pricing; policy and regulation; pharmaceutical procurement, distribution, and use; and management systems, such as for health information and human resources. For example, a hospital in South Africa developed new tools to decentralize provision of antiretroviral therapy to local clinics-bringing treatment closer to patients and shifting responsibility from scarce pharmacists to lower level pharmacy staff. Successful, the system was expanded to patients with other chronic conditions, such as mental illness. Progress toward universal access to HIV prevention, treatment, care, and support will continue the push to strengthen pharmaceutical sectors that serve not only HIV-related needs but all health needs; health experts can likely take these achievements further to maximize their expansion into the wider health system.

The health care industry: in evolution or revolution?

PubMed

Cleverley, W O

1999-01-01

The health care industry has experienced dramatic changes during the last 25 years and will likely undergo even more dramatic changes in the next 25 years. Many firms in the health care industry will thrive just as many firms have thrived during the last 25 years. The ultimate key to success will be management and their attention to the basics of good business management. Management has always been the key ingredient and will continue to be the most critical success factor.

Astrophysical Computation in Research, the Classroom and Beyond

NASA Astrophysics Data System (ADS)

Frank, Adam

2009-03-01

In this talk I review progress in the use of simulations as a tool for astronomical research, for education and public outreach. The talk will include the basic elements of numerical simulations as well as advances in algorithms which have led to recent dramatic progress such as the use of Adaptive Mesh Refinement methods. The scientific focus of the talk will be star formation jets and outflows while the educational emphasis will be on the use of advanced platforms for simulation based learning in lecture and integrated homework. Learning modules for science outreach websites such as DISCOVER magazine will also be highlighted.

Volcanoes of the Alaska Peninsula and Aleutian Islands, Alaska: selected photographs

USGS Publications Warehouse

Neal, Christina A.; McGimsey, Robert G.

2002-01-01

This CD-ROM contains 97 digital images of volcanoes along the Aleutian volcanic arc in Alaska. Perspectives include distant aerial shots, ground views of volcanic products and processes, and dramatic views of eruptions in progress. Each image is stored as a .PCD file in five resolutions. Brief captions, a location map, and glossary are included.

Exploring Ways that ePortfolios can Support the Progressive Development of Graduate Qualities and Professional Competencies

ERIC Educational Resources Information Center

Faulkner, Margaret; Mahfuzul Aziz, Syed; Waye, Vicki; Smith, Elizabeth

2013-01-01

Since the late-1990s, the University of South Australia has embedded seven Graduate Qualities across all programs. Subsequently, the higher education landscape has changed dramatically in terms of national policies and standards, as well as technologies available to support learning and teaching. Most higher education institutions now have their…

WORKING WOMEN AND THE AMERICAN ECONOMY.

ERIC Educational Resources Information Center

KEYSERLING, MARY DUBLIN

AMERICAN WOMEN HAVE MADE A LARGE AND GROWING CONTRIBUTION TO FAMILY INCOME PROGRESS SINCE 1940. THE NUMBER OF WOMEN IN THE WORKING FORCE HAS DOUBLED. THIS INCREASE REFLECTS THE DRAMATIC CHANGE IN WOMEN'S WORK-LIFE PATTERNS. THERE HAS BEEN A MARKED INCREASE IN THE EMPLOYMENT OF WOMEN OVER 35. THE WOMAN MOST LIKELY TO BE A WAGE EARNER IN 1967 WAS…

Women in the Progressive Era. A Unit of Study for Grades 9-12.

ERIC Educational Resources Information Center

Jason, Alli; Strickland, Louise; McMillen, Margaret

A specific dramatic episode in history that allows students to delve into the deeper meanings of selected landmark events and explore a wider context of historical narrative is represented within this supplementary teaching unit. This approach helps students materialize history as an ongoing, open-ended process that is based upon decisions made in…

Using Long-Term Time-Lapse Imaging of Mammalian Cell Cycle Progression for Laboratory Instruction and Analysis

ERIC Educational Resources Information Center

Hinchcliffe, Edward H.

2005-01-01

Cinemicrography--the capture of moving cellular sequences through the microscope--has been influential in revealing the dynamic nature of cellular behavior. One of the more dramatic cellular events is mitosis, the division of sister chromatids into two daughter cells. Mitosis has been extensively studied in a variety of organisms, both…

A visual progression of the Fort Valley Restoration Project treatments using remotely sensed imagery (P-53)

Treesearch

Joseph E. Crouse; Peter Z. Fule

2008-01-01

The landscape surrounding the Fort Valley Experimental Forest in northern Arizona has changed dramatically in the past decade due to the Fort Valley Restoration Project, a collaboration between the Greater Flagstaff Forest Partnership, Coconino National Forest, and Rocky Mountain Research Station. Severe wildfires in 1996 sparked community concern to start restoration...

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.

2008 state of the markets report

DOT National Transportation Integrated Search

2009-08-01

Wholesale natural gas and electricity prices rose : dramatically in the first half of 2008, and then : fell dramatically through the end of the year. : On average, electricity and natural gas prices in 2008 were substantially greater than prices in 2...

A Status of the Advanced Space Transportation Program from Planning to Action

NASA Technical Reports Server (NTRS)

Lyles, Garry; Griner, Carolyn

1998-01-01

A Technology Plan for Enabling Commercial Space Business was presented at the 48th International Astronautical Congress in Turin, Italy. This paper presents a status of the program's accomplishments. Technology demonstrations have progressed in each of the four elements of the program; (1) Low Cost Technology, (2) Advanced Reusable Technology, (3) Space Transfer Technology and (4) Space Transportation Research. The Low Cost Technology program element is primarily focused at reducing development and acquisition costs of aerospace hardware using a "design to cost" philosophy with robust margins, adapting commercial manufacturing processes and commercial off-the-shelf hardware. The attributes of this philosophy for small payload launch are being demonstrated at the component, sub-system, and system level. The X-34 "Fastrac" engine has progressed through major component and subsystem demonstrations. A propulsion system test bed has been implemented for system-level demonstration of component and subsystem technologies; including propellant tankage and feedlines, controls, pressurization, and engine systems. Low cost turbopump designs, commercial valves and a controller are demonstrating the potential for a ten-fold reduction in engine and propulsion system costs. The Advanced Reusable Technology program element is focused on increasing life through high strength-to-weight structures and propulsion components, highly integrated propellant tanks, automated checkout and health management and increased propulsion system performance. The validation of rocket based combined cycle (RBCC) propulsion is pro,-,ressing through component and subsystem testing. RBCC propulsion has the potential to provide performance margin over an all rocket system that could result in lower gross liftoff weight, a lower propellant mass fraction or a higher payload mass fraction. The Space Transfer Technology element of the program is pursuing technology that can improve performance and dramatically reduce the propellant and structural mass of orbit transfer and deep space systems. Flight demonstration of ion propulsion is progressing towards launch. Ion propulsion is the primary propulsion for Deep Space 1; a flyby of comet West-kohoutek-lkemura and asteroid 3352 McAuliffe. Testing of critical solar-thermal propulsion subsystems have been accomplished and planning is continuing for the flight demonstration of an electrodynamic tether orbit transfer system. The forth and final element of the program, Space Transportation Research, has progressed in several areas of propulsion research. This element of the program is focused at long-term (25 years) breakthrough concepts that could bring launch costs to a factor of one hundred below today's cost or dramatically expand planetary travel and enable interstellar travel.

A Poorly Known High-Latitude Parasitoid Wasp Community: Unexpected Diversity and Dramatic Changes through Time

PubMed Central

Boudreault, Caroline; Goulet, Henri; Hebert, Paul D. N.; Smith, Adam C.

2011-01-01

Climate change will have profound and unanticipated effects on species distributions. The pace and nature of this change is largely unstudied, especially for the most diverse elements of terrestrial communities – the arthropods – here we have only limited knowledge concerning the taxonomy and the ecology of these groups. Because Arctic ecosystems have already experienced significant increases in temperature over the past half century, shifts in community structure may already be in progress. Here we utilise collections of a particularly hyperdiverse insect group – parasitoid wasps (Hymenoptera; Braconidae; Microgastrinae) – at Churchill, Manitoba, Canada in the early and mid-twentieth century to compare the composition of the contemporary community to that present 50–70 years ago. Morphological and DNA barcoding results revealed the presence of 79 species of microgastrine wasps in collections from Churchill, but we estimate that 20% of the local fauna awaits detection. Species composition and diversity between the two time periods differ significantly; species that were most common in historic collections were not found in contemporary collections and vice versa. Using barcodes we compared these collections to others from across North America; contemporary Churchill species are most affiliated with more south-western collections, while historic collections were more affiliated with eastern collections. The past five decades has clearly seen a dramatic change of species composition within the area studied coincident with rising temperature. PMID:21897854

Unresolved antiretroviral treatment management issues in HIV-infected children.

PubMed

Heidari, Shirin; Mofenson, Lynne M; Hobbs, Charlotte V; Cotton, Mark F; Marlink, Richard; Katabira, Elly

2012-02-01

Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes. Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug-drug interactions in children to determine optimal treatment regimens for both HIV and coinfections.

An analysis of secular trends in method-specific suicides in Japan, 1950-1975.

PubMed

Yoshioka, Eiji; Saijo, Yasuaki; Kawachi, Ichiro

2017-04-05

In Japan, a dramatic rise in suicide rates was observed in the 1950s, especially among the younger population, and then the rate decreased rapidly again in the 1960s. The aim of this study was to assess secular trends in method-specific suicides by gender and age in Japan between 1950 and 1975. We paid special attention to suicides by poisoning (solid and liquid substances), and their contribution to dramatic swings in the overall suicide rate in Japan during the 1950s and 1960s. Mortality and population data were obtained from the Vital Statistics of Japan and Statistics Bureau, Ministry of Internal Affairs and Communications in Japan, respectively. We calculated method-specific age-standardized suicide rates by gender and age group (15-29, 30-49, or 50+ years). The change in the suicide rate during the research period was larger in males than females in all age groups, and was more marked among people aged 15-29 years compared to those aged 30-49 years and 50 years or over. Poisoning by solid and liquid substances overwhelmingly contributed to the dramatic change in the overall suicide rates in males and females aged 15-49 years in the 1950s and 1960s. For the peak years of the rise in poisoning suicides, bromide was the most frequently used substance. Our results for the 1950s and 1960s in Japan illustrated how assessing secular trends in method-specific suicides by gender and age could provide a deeper understanding of the dramatic swings in overall suicide rate. Although rapid increases or decreases in suicide rates have been also observed in some countries or regions recently, trends in method-specific suicides have not been analyzed because of a lack of data on method-specific suicide in many countries. Our study illustrates how the collection and analysis of method-specific data can contribute to an understanding of dramatic shifts in national suicide rates.

Is the last "man" standing in comedy the least funny? A retrospective cohort study of elite stand-up comedians versus other entertainers.

PubMed

Stewart, Simon; Wiley, Joshua F; McDermott, Cressida J; Thompson, David R

2016-10-01

This study aimed to confirm, in a large, diverse cohort of elite Stand-up Comedians and other entertainers, that there is an inverse association between comedic ability and longevity. This retrospective cohort study included 200 Stand-up Comedians (13% women), 113 Comedy Actors (17.5% women), and 184 Dramatic Actors (29.3% women) listed in the top 200 in each category in a popular online ranking website. Longevity within each group was examined adjusting for life expectancy by year of birth and within-group ranking score. Stand-up Comedians were younger than Comedy Actors (median birth year 1962 versus 1947: p<0.001) and Dramatic Actors (1962 versus 1946: p<0.001). Overall, 36/200 (18.0%), 33/114 (29.0%) and 56/184 (30.9%) of Stand-up Comedians, Comedy Actors and Dramatic Actors, respectively, had died (p=0.011). There was a significant gradient (p=0.011) in the age of death, with Stand-up Comedians dying at a younger age (67.1±21.3years) than their Comedy Actor (68.9±15.4years) and Dramatic Actor (70.7±16.6years) counterparts. Stand-up Comedians (38.9% versus 19.6%) were more likely to die prematurely compared to Dramatic Actors; p=0.043, OR 1.98; 95% CI 1.01 to 3.87). Independent of year of birth, for Stand-up Comedians alone, higher comedy rank was associated with shorter longevity (hazard ratio 0.938, 95% CI 0.880 to 0.999 for a 10-rank difference; p=0.045). These data reaffirm an adverse relationship between comedic ability and longevity, with elite Stand-up Comedians more highly rated by the public more likely to die prematurely. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Rechallenge and maintenance therapy using cetuximab and chemotherapy administered to a patient with metastatic colorectal cancer.

PubMed

Ma, Jian; Yang, Quan-Liang; Ling, Yang

2017-02-14

Cetuximab combined with chemotherapy is one of the first-line treatments of metastatic colorectal cancer. Although disease progression inevitably occurs, rechallenge and maintenance therapies using cetuximab-based regimens may be beneficial, particularly for patients with wild-type (WT) KRAS. A 47-year-old female patient who underwent right hemicolectomy presented with an ulcerative adenocarcinoma (grade 2) revealed by histopathological analysis. The patient received three cycles of adjuvant chemotherapy, but disease recurred 15 months later. Cetuximab and a FOLFOX-4 regimen were administered, followed by surgery and adjuvant chemotherapy that was administered for approximately one year. Three years after completing adjuvant therapy, her serum carcinoembryonic antigen levels rapidly increased, and enhanced computed tomography showed widespread metastases. Rechallenge with cetuximab and the FOLFIRI regimen was then initiated, and after 12 cycles, lesions in the lung and liver shrank significantly, and serum CEA levels dramatically declined. Maintenance therapy with cetuximab and capecitabine was then administered for 10 months until the metastatic lesions in the lung and liver enlarged. Rechallenge and maintenance therapy with cetuximab-based chemotherapy were relatively effective for managing a female patient with WT KRAS. Optimization of this strategy requires further in-depth investigations of more patients.

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.

Research progress and harnessing method of soil and water loss in Pisha Sandstone region

NASA Astrophysics Data System (ADS)

Xiao, P. Q.; Yang, C. X.; Jing, C. R.

2018-05-01

Pisha Sandstone region is the most vulnerable and the most dramatic area of soil erosion, severe soil erosion on the ecological bases of China’s energy security constitutes a serious challenge. Research progress of soil erosion in pisha Sandstone region was reviewed based on the need of soil and water ecological construction in Pisha Sandstone region and harnessing the yellow river including soil erosion mechanism, soil erosion dynamic monitoring and soil erosion simulation assessments. Meanwhile, the latest progress of soil and water conservation measures was analyzed, and the existing problems and future harnessing measures of soil and water loss were discussed. This study is to explore the comprehensive management method and provide scientific theory for constructing soil and water conservation project in Pisha Sandstone region.

Monitoring of KRAS-mutated ctDNA to discriminate pseudo-progression from true progression during anti-PD-1 treatment of lung adenocarcinoma

PubMed Central

Guibert, Nicolas; Mazieres, Julien; Delaunay, Myriam; Casanova, Anne; Farella, Magali; Keller, Laura; Favre, Gilles; Pradines, Anne

2017-01-01

Objectives Pseudo-progression is a rare but worrying situation for both clinicians and patients during immunotherapy. Dedicated ir-RECIST criteria have been established to improve this situation. However, this can be sometimes considered inadequate and patients experiencing true progression may then receive inefficient treatments. Additional reliable tools to discriminate pseudo from true progression are thus needed. So far, no biomarker has been identified to distinguish pseudo from true progression. We hypothesize that biomarkers associated with the molecular characteristics of the tumor may be of interest. To avoid a tumor re-biopsy, circulating markers appear to be a less invasive and reproducible procedure. As ctDNA kinetics correlate with the response to treatment in KRAS-mutated adenocarcinoma, we anticipated that this analysis could be of interest. Materials and methods We monitored the level of KRAS-mutated ctDNA by digital droplet PCR in serial plasma samples from two patients who had experienced pseudo-progression and compared the variations with those from of a patient that had true progression. Results ctDNA showed rapid and dramatic decreases in pseudo-progressive patients, whereas it was strongly increased in the progressive patient. Conclusions ddPCR of ctDNA may thus be an additional tool to discriminate pseudo-progression from true progression for tumors that harbor an oncogenic addiction. PMID:28445137

Philosophy and Methods for China's Vocational Education Curriculum Reforms in the Early Twenty-First Century

ERIC Educational Resources Information Center

Xu, Guoqing

2014-01-01

Curriculum reform is an important aspect of progress in China's vocational education in the twenty-first century. The past decade's round of reforms were unprecedented in China in terms of both the scope and depth of their impact. They have and will continue to dramatically alter the nation's vocational education curriculum and teaching methods.…

Elephantiasis nostras verrucosa: a review.

PubMed

Sisto, Krisanne; Khachemoune, Amor

2008-01-01

Elephantiasis nostras verrucosa (ENV) is a rare and dramatic sequela of chronic nonfilarial lymphedema. The condition is characterized by papules, verrucous lesions, enlargement, and woody fibrosis of the affected area. ENV is a progressive condition, and, without intervention, ongoing deformity and disability will result. Management of ENV is often challenging, but a variety of successful medical and surgical treatment strategies have been reported.

Gender Issues in Gifted Achievement: Are Girls Making Inroads While Boys Fall Behind?

ERIC Educational Resources Information Center

Rimm, Sylvia B.

2015-01-01

School and life achievement patterns for girls and women differ from those of boys and men. While girls have made dramatic progress in school, they need to be inspired to connect to lifelong achievement. Both research and clinical work at the Ohio-based Family Achievement Clinic find that more boys than girls underachieve in school. There is much…

Examining Repeaters' Performance on Second Language Proficiency Tests: A Review and a Call for Research

ERIC Educational Resources Information Center

Barkaoui, Khaled

2017-01-01

As the number of candidates who repeat English language proficiency tests more than once to meet a certain cutscore (e.g., for university admission) or to demonstrate progress (e.g., after instruction) continues to increase dramatically, there is a need for more research on the attributes and test performance of test repeaters. This article…

Improvement in Cognitive and Language Skills from Preschool to Adolescence in Autism

ERIC Educational Resources Information Center

Sigman, Marian; McGovern, Corina W.

2005-01-01

This paper reports on the developmental progression of a sample of 48 adolescents and young adults with autism who were previously assessed at preschool age and again in the mid-school period. In contrast to the earlier period when about one-third of the children made dramatic gains, cognitive and language skills tended to remain stable or decline…

Phycobilisome truncation causes widespread proteome changes in Synechocystis sp. PCC 6803

DOE PAGES

Liberton, Michelle; Chrisler, William B.; Nicora, Carrie D.; ...

2017-03-02

Here, cyanobacteria, such as Synechocystis sp. PCC 6803, utilize large antenna systems to optimize light harvesting and energy transfer to reaction centers. Understanding the structure and function of these complexes, particularly when altered, will help direct bio-design efforts to optimize biofuel production. Three specific phycobilisome (PBS) complex truncation mutants were studied, ranging from progressive truncation of phycocyanin rods in the CB and CK strains, to full removal of all phycocyanin and allophycocyanin cores in the PAL mutant. We applied comprehensive proteomic analyses to investigate both direct and downstream molecular systems implications of each truncation. Results showed that PBS truncation inmore » Synechocystis sp. PCC 6803 dramatically alters core cellular mechanisms beyond energy capture and electron transport, placing constraints upon cellular processes that dramatically altered phenotypes. This included primarily membrane associated functions and altered regulation of cellular resources (i.e., iron, nitrite/nitrate, bicarbonate). Additionally, each PBS truncation, though progressive in nature, exhibited unique phenotypes compare to WT, and hence we assert that in the current realm of extensive bioengineering and bio-design, there remains a continuing need to assess systems-wide protein based abundances to capture potential indirect phenotypic effects.« less

Phycobilisome truncation causes widespread proteome changes in Synechocystis sp. PCC 6803

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

Liberton, Michelle; Chrisler, William B.; Nicora, Carrie D.

Here, cyanobacteria, such as Synechocystis sp. PCC 6803, utilize large antenna systems to optimize light harvesting and energy transfer to reaction centers. Understanding the structure and function of these complexes, particularly when altered, will help direct bio-design efforts to optimize biofuel production. Three specific phycobilisome (PBS) complex truncation mutants were studied, ranging from progressive truncation of phycocyanin rods in the CB and CK strains, to full removal of all phycocyanin and allophycocyanin cores in the PAL mutant. We applied comprehensive proteomic analyses to investigate both direct and downstream molecular systems implications of each truncation. Results showed that PBS truncation inmore » Synechocystis sp. PCC 6803 dramatically alters core cellular mechanisms beyond energy capture and electron transport, placing constraints upon cellular processes that dramatically altered phenotypes. This included primarily membrane associated functions and altered regulation of cellular resources (i.e., iron, nitrite/nitrate, bicarbonate). Additionally, each PBS truncation, though progressive in nature, exhibited unique phenotypes compare to WT, and hence we assert that in the current realm of extensive bioengineering and bio-design, there remains a continuing need to assess systems-wide protein based abundances to capture potential indirect phenotypic effects.« less

Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology.

PubMed

Patel, Jyoti D; Krilov, Lada; Adams, Sylvia; Aghajanian, Carol; Basch, Ethan; Brose, Marcia S; Carroll, William L; de Lima, Marcos; Gilbert, Mark R; Kris, Mark G; Marshall, John L; Masters, Gregory A; O'Day, Steven J; Polite, Blasé; Schwartz, Gary K; Sharma, Sunil; Thompson, Ian; Vogelzang, Nicholas J; Roth, Bruce J

2014-01-10

Since its founding in 1964, the American Society of Clinical Oncology (ASCO) has been committed to improving cancer outcomes through research and the delivery of quality care. Research is the bedrock of discovering better treatments--providing hope to the millions of individuals who face a cancer diagnosis each year. The studies featured in "Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology" represent the invaluable contributions of thousands of patients who participate in clinical trials and the scientists who conduct basic and clinical research. The insights described in this report, such as how cancers hide from the immune system and why cancers may become resistant to targeted drugs, enable us to envision a future in which cancer will be even more controllable and preventable. The scientific process is thoughtful, deliberate, and sometimes slow, but each advance, while helping patients, now also points toward new research questions and unexplored opportunities. Both dramatic and subtle breakthroughs occur so that progress against cancer typically builds over many years. Success requires vision, persistence, and a long-term commitment to supporting cancer research and training. Our nation's longstanding investment in federally funded cancer research has contributed significantly to a growing array of effective new treatments and a much deeper understanding of the drivers of cancer. But despite this progress, our position as a world leader in advancing medical knowledge and our ability to attract the most promising and talented investigators are now threatened by an acute problem: Federal funding for cancer research has steadily eroded over the past decade, and only 15% of the ever-shrinking budget is actually spent on clinical trials. This dismal reality threatens the pace of progress against cancer and undermines our ability to address the continuing needs of our patients. Despite this extremely challenging economic environment, we continue to make progress. Maintaining and accelerating that progress require that we keep our eyes on the future and pursue a path that builds on the stunning successes of the past. We must continue to show our policymakers the successes in cancer survival and quality of life (QOL) they have enabled, emphasizing the need to sustain our national investment in the remarkably productive US cancer research enterprise. We must also look to innovative methods for transforming how we care for-and learn from-patients with cancer. Consider, for example, that fewer than 5% of adult patients with cancer currently participate in clinical trials. What if we were able to draw lessons from the other 95%? This possibility led ASCO this year to launch CancerLinQ, a groundbreaking health information technology initiative that will provide physicians with access to vast quantities of clinical data about real-world patients and help achieve higher quality, higher value cancer care. As you read the following pages, I hope our collective progress against cancer over the past year inspires you. More importantly, I hope the pride you feel motivates you to help us accelerate the pace of scientific advancement. Clifford A. Hudis, MD, FACP President American Society of Clinical Oncology.

Social neuroscience and its potential contribution to psychiatry

PubMed Central

Cacioppo, John T; Cacioppo, Stephanie; Dulawa, Stephanie; Palmer, Abraham A

2014-01-01

Most mental disorders involve disruptions of normal social behavior. Social neuroscience is an interdisciplinary field devoted to understanding the biological systems underlying social processes and behavior, and the influence of the social environment on biological processes, health and well-being. Research in this field has grown dramatically in recent years. Active areas of research include brain imaging studies in normal children and adults, animal models of social behavior, studies of stroke patients, imaging studies of psychiatric patients, and research on social determinants of peripheral neural, neuroendocrine and immunological processes. Although research in these areas is proceeding along largely independent trajectories, there is increasing evidence for connections across these trajectories. We focus here on the progress and potential of social neuroscience in psychiatry, including illustrative evidence for a rapid growth of neuroimaging and genetic studies of mental disorders. We also argue that neuroimaging and genetic research focused on specific component processes underlying social living is needed. PMID:24890058

Cervical Lymphadenopathy Mimicking Angioimmunoblastic T-Cell Lymphoma after Dapsone-Induced Hypersensitivity Syndrome

PubMed Central

Rim, Min Young; Hong, Junshik; Yo, Inku; Park, Hyeonsu; Chung, Dong Hae; Ahn, Jeong Yeal; Park, Jinny; Kim, Yun Soo; Lee, Jae Hoon

2012-01-01

A 36-year-old woman presented with erythematous confluent macules on her whole body with fever and chills associated with jaundice after 8 months of dapsone therapy. Her symptoms had developed progressively, and a physical examination revealed bilateral cervical lymphadenopathy and splenomegaly. Excisional biopsy of a cervical lymph node showed effacement of the normal architecture with atypical lymphoid hyperplasia and proliferation of high endothelial venules compatible with angioimmunoblastic T-cell lymphoma. However, it was assumed that the cervical lymphadenopathy was a clinical manifestation of a systemic hypersensitivity reaction because her clinical course was reminiscent of dapsone-induced hypersensitivity syndrome. A liver biopsy revealed drug-induced hepatitis with no evidence of lymphomatous involvement. Intravenous glucocorticoid was immediately initiated and her symptoms and clinical disease dramatically improved. The authors present an unusual case of cervical lymphadenopathy mimicking angioimmunoblastic T-cell lymphoma as an adverse reaction to dapsone. PMID:23323115

Context Matters: Volunteer Bias, Small Sample Size, and the Value of Comparison Groups in the Assessment of Research-Based Undergraduate Introductory Biology Lab Courses

PubMed Central

Brownell, Sara E.; Kloser, Matthew J.; Fukami, Tadashi; Shavelson, Richard J.

2013-01-01

The shift from cookbook to authentic research-based lab courses in undergraduate biology necessitates the need for evaluation and assessment of these novel courses. Although the biology education community has made progress in this area, it is important that we interpret the effectiveness of these courses with caution and remain mindful of inherent limitations to our study designs that may impact internal and external validity. The specific context of a research study can have a dramatic impact on the conclusions. We present a case study of our own three-year investigation of the impact of a research-based introductory lab course, highlighting how volunteer students, a lack of a comparison group, and small sample sizes can be limitations of a study design that can affect the interpretation of the effectiveness of a course. PMID:24358380

Organoids: A historical perspective of thinking in three dimensions

DOE PAGES

Simian, Marina; Bissell, Mina J.

2016-12-28

In the last ten years, there has been a dramatic surge in the number of publications where single or groups of cells are grown in substrata that have elements of basement membrane leading to the formation of tissue-like structures referred to as organoids. But, this field of research began many decades ago, when the pioneers of cell culture began to ask questions we still ask today: How does organogenesis occur? How do signals integrate to make such vastly different tissues and organs given that the sequence of the genome in our trillions of cells is identical? We summarize how workmore » over the past century generated the conceptual framework that has allowed us to make progress in the understanding of tissue-specific morphogenetic programs. The development of cell culture systems that provide accurate and physiologically relevant models are proving to be key in establishing appropriate platforms for the development of new therapeutic strategies.« less

[Interventional radiological treatment of hepatocellular carcinoma].

PubMed

Doros, Attila

2010-07-25

During the last years, interventional radiological treatment of hepatocellular cancer has changed dramatically. The percutaneous ethanol infiltration is partly replaced by thermoablative methods, mainly by radiofrequency ablation. Cooled-tip electrodes and volumetric therapy planning increased the treatment success. Embolisation beads made vessel occlusion more precise and predictable, while the development of the drug eluting beads led to the most effective way of chemoembolisation. The so called radioembolisation with Yttrium 90 isotopes filled into glass microbeads is slowly gaining acceptance worldwide. Thermoablation and embolisation or chemoembolisation are the main tools for downstaging tumors, or avoiding disease progression in liver transplant recipients on the waiting list. All of these therapeutic options have their well established places in well known and worldwide accepted protocols, such as the algorithm of the Barcelona group (BCLC). In the near future, further results can be expected from the combination of available treatments, including sorafenib medication.

Genome-derived vaccines.

PubMed

De Groot, Anne S; Rappuoli, Rino

2004-02-01

Vaccine research entered a new era when the complete genome of a pathogenic bacterium was published in 1995. Since then, more than 97 bacterial pathogens have been sequenced and at least 110 additional projects are now in progress. Genome sequencing has also dramatically accelerated: high-throughput facilities can draft the sequence of an entire microbe (two to four megabases) in 1 to 2 days. Vaccine developers are using microarrays, immunoinformatics, proteomics and high-throughput immunology assays to reduce the truly unmanageable volume of information available in genome databases to a manageable size. Vaccines composed by novel antigens discovered from genome mining are already in clinical trials. Within 5 years we can expect to see a novel class of vaccines composed by genome-predicted, assembled and engineered T- and Bcell epitopes. This article addresses the convergence of three forces--microbial genome sequencing, computational immunology and new vaccine technologies--that are shifting genome mining for vaccines onto the forefront of immunology research.

Sample size in psychological research over the past 30 years.

PubMed

Marszalek, Jacob M; Barber, Carolyn; Kohlhart, Julie; Holmes, Cooper B

2011-04-01

The American Psychological Association (APA) Task Force on Statistical Inference was formed in 1996 in response to a growing body of research demonstrating methodological issues that threatened the credibility of psychological research, and made recommendations to address them. One issue was the small, even dramatically inadequate, size of samples used in studies published by leading journals. The present study assessed the progress made since the Task Force's final report in 1999. Sample sizes reported in four leading APA journals in 1955, 1977, 1995, and 2006 were compared using nonparametric statistics, while data from the last two waves were fit to a hierarchical generalized linear growth model for more in-depth analysis. Overall, results indicate that the recommendations for increasing sample sizes have not been integrated in core psychological research, although results slightly vary by field. This and other implications are discussed in the context of current methodological critique and practice.

Context matters: volunteer bias, small sample size, and the value of comparison groups in the assessment of research-based undergraduate introductory biology lab courses.

PubMed

Brownell, Sara E; Kloser, Matthew J; Fukami, Tadashi; Shavelson, Richard J

2013-01-01

The shift from cookbook to authentic research-based lab courses in undergraduate biology necessitates the need for evaluation and assessment of these novel courses. Although the biology education community has made progress in this area, it is important that we interpret the effectiveness of these courses with caution and remain mindful of inherent limitations to our study designs that may impact internal and external validity. The specific context of a research study can have a dramatic impact on the conclusions. We present a case study of our own three-year investigation of the impact of a research-based introductory lab course, highlighting how volunteer students, a lack of a comparison group, and small sample sizes can be limitations of a study design that can affect the interpretation of the effectiveness of a course.

Administrative compensation of medical injuries: a hardy perennial blooms again.

PubMed

Barringer, Paul J; Studdert, David M; Kachalia, Allen B; Mello, Michelle M

2008-08-01

Periods in which the costs of personal injury litigation and liability insurance have risen dramatically have often provoked calls for reform of the tort system, and medical malpractice is no exception. One proposal for fundamental reform made during several of these volatile periods has been to relocate personal injury disputes from the tort system to an alternative, administrative forum. In the medical injury realm, a leading incarnation of such proposals in recent years has been the idea of establishing specialized administrative "health courts." Despite considerable stakeholder and policy-maker interest, administrative compensation proposals have tended to struggle for broad political acceptance. In this article, we consider the historical experience of administrative medical injury compensation proposals, particularly in light of comparative examples in the context of workplace injuries, automobile injuries, and vaccine injuries. We conclude by examining conditions that may facilitate or impede progress toward establishing demonstration projects of health courts.

Treatments for fragile X syndrome: a closer look at the data.

PubMed

Hall, Scott S

2009-01-01

Research into the determinants and developmental course of fragile X syndrome (FXS) has made remarkable progress over the last 25 years. However, treatments to ameliorate the symptoms of FXS have been less forthcoming. While there is optimism in the field that the pace of intervention research is quickening, there has been a bias toward psychopharmacological approaches to treatment. A closer look at the data from those investigations reveals a paucity of evidence that medications can improve intellectual and adaptive functioning in FXS, or decrease associated behavioral and/or emotional issues. Work in other related disorders (e.g., autism) has shown that dramatic improvements in intellectual and adaptive functioning, as well as behavioral and emotional problems, can occur if intensive behavioral treatment is begun early in the child's life. It is hoped that future research efforts will evaluate these intensive early intervention strategies in children with FXS, perhaps in combination with pharmacological approaches.

Nanobridge SQUIDs as calorimetric inductive particle detectors

NASA Astrophysics Data System (ADS)

Gallop, John; Cox, David; Hao, Ling

2015-08-01

Superconducting transition edge sensors (TESs) have made dramatic progress since their invention some 65 years ago (Andrews et al 1949 Phys. Rev. 76 154-155 Irwin and Hilton 2005 Topics Appl. Phys. 99 63-149) until now there are major imaging arrays of TESs with as many as 7588 separate sensors. These are extensively used by astronomers for some ground-breaking observations (Hattori et al 2013 Nucl. Instrum. Methods Phys. Res. A 732 299-302). The great success of TES systems has tended to overshadow other superconducting sensor developments. However there are other types (Sobolewski et al 2003 IEEE Trans. Appl. Supercond. 13 1151-7 Hadfield 2009 Nat. Photonics 3 696-705) which are discussed in papers within this special edition of the journal. Here we describe a quite different type of detector, also applicable to single photon detection but possessing possible advantages (higher sensitivity, higher operating temperature) over the conventional TES, at least for single detectors.

Giant photostriction in organic–inorganic lead halide perovskites

PubMed Central

Zhou, Yang; You, Lu; Wang, Shiwei; Ku, Zhiliang; Fan, Hongjin; Schmidt, Daniel; Rusydi, Andrivo; Chang, Lei; Wang, Le; Ren, Peng; Chen, Liufang; Yuan, Guoliang; Chen, Lang; Wang, Junling

2016-01-01

Among the many materials investigated for next-generation photovoltaic cells, organic–inorganic lead halide perovskites have demonstrated great potential thanks to their high power conversion efficiency and solution processability. Within a short period of about 5 years, the efficiency of solar cells based on these materials has increased dramatically from 3.8 to over 20%. Despite the tremendous progress in device performance, much less is known about the underlying photophysics involving charge–orbital–lattice interactions and the role of the organic molecules in this hybrid material remains poorly understood. Here, we report a giant photostrictive response, that is, light-induced lattice change, of >1,200 p.p.m. in methylammonium lead iodide, which could be the key to understand its superior optical properties. The strong photon-lattice coupling also opens up the possibility of employing these materials in wireless opto-mechanical devices. PMID:27044485

Impressions of the Meson Spectrum: Hybrids & Exotics, present and future

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

Pennington, Michael R.

2016-03-25

It has long been expected that the spectrum of hadrons in QCD would be far richer and extensive than experiment has so far revealed. While there have been experimental hints of this richness for some time, it is really only in the last few years that dramatic progress has been seen in the exploration both experimentally and in calculations on the lattice. Precision studies enabled by new technology both with detectors and high performance computations are converging on an understanding of the spectrum in strong coupling QCD. These methodologies are laying the foundation for a decade of potential discovery thatmore » electro and photoproduction experiments at Jefferson Lab, which when combined with key results on B and charmonium decays from both e+e? and pp colliders, should turn mere impressions of the light meson spectrum into a high definition picture.« less

The Role of Synthetic Biology in the Design of Microbial Cell Factories for Biofuel Production

PubMed Central

Colin, Verónica Leticia; Rodríguez, Analía; Cristóbal, Héctor Antonio

2011-01-01

Insecurity in the supply of fossil fuels, volatile fuel prices, and major concerns regarding climate change have sparked renewed interest in the production of fuels from renewable resources. Because of this, the use of biodiesel has grown dramatically during the last few years and is expected to increase even further in the future. Biodiesel production through the use of microbial systems has marked a turning point in the field of biofuels since it is emerging as an attractive alternative to conventional technology. Recent progress in synthetic biology has accelerated the ability to analyze, construct, and/or redesign microbial metabolic pathways with unprecedented precision, in order to permit biofuel production that is amenable to industrial applications. The review presented here focuses specifically on the role of synthetic biology in the design of microbial cell factories for efficient production of biodiesel. PMID:22028591

Organoids: A historical perspective of thinking in three dimensions

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

Simian, Marina; Bissell, Mina J.

In the last ten years, there has been a dramatic surge in the number of publications where single or groups of cells are grown in substrata that have elements of basement membrane leading to the formation of tissue-like structures referred to as organoids. But, this field of research began many decades ago, when the pioneers of cell culture began to ask questions we still ask today: How does organogenesis occur? How do signals integrate to make such vastly different tissues and organs given that the sequence of the genome in our trillions of cells is identical? We summarize how workmore » over the past century generated the conceptual framework that has allowed us to make progress in the understanding of tissue-specific morphogenetic programs. The development of cell culture systems that provide accurate and physiologically relevant models are proving to be key in establishing appropriate platforms for the development of new therapeutic strategies.« less

Understanding of Leaf Development-the Science of Complexity.

PubMed

Malinowski, Robert

2013-06-25

The leaf is the major organ involved in light perception and conversion of solar energy into organic carbon. In order to adapt to different natural habitats, plants have developed a variety of leaf forms, ranging from simple to compound, with various forms of dissection. Due to the enormous cellular complexity of leaves, understanding the mechanisms regulating development of these organs is difficult. In recent years there has been a dramatic increase in the use of technically advanced imaging techniques and computational modeling in studies of leaf development. Additionally, molecular tools for manipulation of morphogenesis were successfully used for in planta verification of developmental models. Results of these interdisciplinary studies show that global growth patterns influencing final leaf form are generated by cooperative action of genetic, biochemical, and biomechanical inputs. This review summarizes recent progress in integrative studies on leaf development and illustrates how intrinsic features of leaves (including their cellular complexity) influence the choice of experimental approach.

Understanding of Leaf Development—the Science of Complexity

PubMed Central

Malinowski, Robert

2013-01-01

The leaf is the major organ involved in light perception and conversion of solar energy into organic carbon. In order to adapt to different natural habitats, plants have developed a variety of leaf forms, ranging from simple to compound, with various forms of dissection. Due to the enormous cellular complexity of leaves, understanding the mechanisms regulating development of these organs is difficult. In recent years there has been a dramatic increase in the use of technically advanced imaging techniques and computational modeling in studies of leaf development. Additionally, molecular tools for manipulation of morphogenesis were successfully used for in planta verification of developmental models. Results of these interdisciplinary studies show that global growth patterns influencing final leaf form are generated by cooperative action of genetic, biochemical, and biomechanical inputs. This review summarizes recent progress in integrative studies on leaf development and illustrates how intrinsic features of leaves (including their cellular complexity) influence the choice of experimental approach. PMID:27137383

Regulation of signaling pathways by tanshinones in different cancers.

PubMed

Lin, X; Qureshi, M Z; Romero, M A; Khalid, S; Aras, A; Ozbey, U; Farooqi, A A

2017-09-30

Past several years have witnessed dramatic leaps in our understanding of rewiring of gene expression at the translation level during cancer developmentthat provides linchpin support to the transformed phenotype. Most recent and ground-breaking developments in the field of molecular oncology aredriven by an explosion in technological advancements and have started to reveal previously unimagined regulatory mechanisms and how they intricately co-ordinate to modulate cancer progression, loss of apoptosis and development of resistance against different therapeutics. However, the insights gained from work in this natural product research have far-reaching impact because of rapidly increasing repertoire of medicinally and biologically efficient phytochemicals. How Tanshinones mediate targeting of JAK-STAT, ER stress associated signaling cascade,PI3K/AKT/mTOR pathway,autophagy, TRAIL pathway and microRNAs are being discovered and will prove to be helpful in getting a step closer to personalized medicine.

Sustainable energy, economic growth and public health.

PubMed

Haines, A

2001-01-01

Dramatic economic growth over the last 50 years has been accompanied by widening inequalities world-wide in wealth and energy consumption, diminished life expectancy in some countries, and deteriorating indices of environmental sustainability including loss of bio-diversity. Raised output of carbon dioxide (CO2) and other greenhouse gases due to increased economic and industrial activity is causing progressive climate change, leading in turn to direct and indirect adverse effects on health. Emissions of greenhouse gases can be lowered by increased use of renewable energy sources, for example, wind power in the United Kingdom (UK), greater energy efficiency and other measures to promote sustainability. The experience of some developing countries shows that favourable indicators of health and development can accompany a low output of greenhouse gases. It is unclear whether contemporary political and social systems can deliver improved human development without increased use of fossil fuels and other resources.

Sequence to Structure (S2S): display, manipulate and interconnect RNA data from sequence to structure.

PubMed

Jossinet, Fabrice; Westhof, Eric

2005-08-01

Efficient RNA sequence manipulations (such as multiple alignments) need to be constrained by rules of RNA structure folding. The structural knowledge has increased dramatically in the last years with the accumulation of several large RNA structures similar to those of the bacterial ribosome subunits. However, no tool in the RNA community provides an easy way to link and integrate progress made at the sequence level using the available three-dimensional information. Sequence to Structure (S2S) proposes a framework in which an user can easily display, manipulate and interconnect heterogeneous RNA data, such as multiple sequence alignments, secondary and tertiary structures. S2S has been implemented using the Java language and has been developed and tested under UNIX systems, such as Linux and MacOSX. S2S is available at http://bioinformatics.org/S2S/.

The Management of Insect Pests in Australian Cotton: An Evolving Story.

PubMed

Wilson, Lewis J; Whitehouse, Mary E A; Herron, Grant A

2018-01-07

The Australian cotton industry progressively embraced integrated pest management (IPM) to alleviate escalating insecticide resistance issues. A systems IPM approach was used with core principles that were built around pest ecology/biology and insecticide resistance management; together, these were integrated into a flexible, year-round approach that facilitated easy incorporation of new science, strategies, and pests. The approach emphasized both strategic and tactical elements to reduce pest abundance and rationalize decisions about pest control, with insecticides as a last resort. Industry involvement in developing the approach was vital to embedding IPM within the farming system. Adoption of IPM was facilitated by the introduction of Bt cotton, availability of selective insecticides, economic validation, and an industry-wide extension campaign. Surveys indicate IPM is now embedded in industry, confirming the effectiveness of an industry-led, backed-by-science approach. The amount of insecticide active ingredient applied per hectare against pests has also declined dramatically. Though challenges remain, pest management has transitioned from reactively attempting to eradicate pests from fields to proactively managing them year-round, considering the farm within the wider landscape.

Language performance and auditory evoked fields in 2- to 5-year-old children.

PubMed

Yoshimura, Yuko; Kikuchi, Mitsuru; Shitamichi, Kiyomi; Ueno, Sanae; Remijn, Gerard B; Haruta, Yasuhiro; Oi, Manabu; Munesue, Toshio; Tsubokawa, Tsunehisa; Higashida, Haruhiro; Minabe, Yoshio

2012-02-01

Language development progresses at a dramatic rate in preschool children. As rapid temporal processing of speech signals is important in daily colloquial environments, we performed magnetoencephalography (MEG) to investigate the linkage between speech-evoked responses during rapid-rate stimulus presentation (interstimulus interval < 1 s) and language performance in 2- to 5-year-old children (n = 59). Our results indicated that syllables with this short stimulus interval evoked detectable P50m, but not N100m, in most participants, indicating a marked influence of longer neuronal refractory period for stimulation. The results of equivalent dipole estimation showed that the intensity of the P50m component in the left hemisphere was positively correlated with language performance (conceptual inference ability). The observed positive correlations were suggested to reflect the maturation of synaptic organisation or axonal maturation and myelination underlying the acquisition of linguistic abilities. The present study is among the first to use MEG to study brain maturation pertaining to language abilities in preschool children. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

The evolution of technological strategies in the prevention of dialysis water pollution: sixteen years' experience.

PubMed

Bolasco, Piergiorgio; Contu, Antonio; Meloni, Patrizia; Vacca, Dorio; Murtas, Stefano

2012-01-01

This report attempts to illustrate the positive impact on the quality of dialysis water produced over a 16-year period through the progressive optimization of technological procedures. Fundamental steps included the following: elimination of polyvinyl chloride (PVC), periodical controls, introduction of stainless steel and/or polyethylene polymer and substitution of single-pass reverse osmosis (SRO) with double-pass reverse osmosis (DRO). Daily overnight automatic thermal disinfection of distribution piping rings represented the final step. A dramatic improvement was observed in 645 water samples obtained from distribution piping. The measures applied resulted in a significant improvement of water quality, featuring levels of colony-forming units per milliliter ranging from 247.4 ± 393.7 in the presence of PVC and SRO to 14.1 ± 28.0 with stainless steel and DRO and 2.8 ± 3.2 with cross-linked polyethylene thermoplastic polymer and DRO (p < 0.01). Dialysis water should be viewed by nephrologists as a medicinal product, and every effort should be made to ensure a high-quality liquid. Copyright © 2012 S. Karger AG, Basel.

Powassan virus infection: case series and literature review from a single institution

PubMed Central

2012-01-01

Background Powassan virus is a flavivirus related to eastern hemisphere’s tick-borne encephalitis viruses. It can cause a rare but potentially life-threatening disease including encephalitis. Case presentation We report four cases of POWV infection in Minnesota and North Dakota with known exposure to tick bites in 2011. Our first case was an 18-year-old male who dramatically presented with seizure and headache with positive serum analysis for Powassan virus immunoglobulin M. The second case was a 60 year old gentleman with intraparenchymal hemorrhage and was diagnosed via cerebrospinal fluid analysis. Thirdly, a 61 year old male developed altered mental status and encephalitis. Our fourth patient was a 69 year old male who had headache and non-focal weakness who was diagnosed with serum analysis. Conclusion Symptoms of Powassan virus infection ranged from headaches to seizures and severe neurological symptoms. This study serves to highlight the increased detection of Powassan virus infection in the central north United States. This report focuses on the increasing incidence that can lead to increasing efforts for raising awareness regarding this infection. There is a need for clinician vigilance and public attention due to its increasing detection, westward progression and varied clinical presentations. PMID:23111001

Airborne Laser Hydrography II

NASA Astrophysics Data System (ADS)

Philpot, W.; Wozencraft, J.

2016-02-01

In 1985, Dr. Gary Guenther assembled the text, "Airborne Laser Hydrography" which quickly became a heavily used manual and guide for any and all scientists and engineers involved with airborne lidar bathymetry (ALB). It was a remarkable book that captured a snapshot of the state of the art of ALB and included historical developments, theoretical and modeling efforts as well as design characteristics and constraints, ending with accuracy assessment and a discussion of design tradeoffs. Known familiarly as the "Blue Book" it served the community remarkably well for many years. At 30 years of age, it is still a valued reference, but unavoidably dated in a field that has developed rapidly and nonstop over the intervening years. It is time for an update. The new text is attempt by the ALB community to update and expand upon Guenther's text. Like the original, Blue Book II reviews the historical developments in ALB, extending them into the 21st century, considers basic environmental water optical properties, theoretical developments, data processing and performance evaluation. All have progressed dramatically in the past 30 years. This paper presents an outline of the new book, a description of the contents, with emphasis on the theoretical models of the lidar waveform and its propagation through, and interaction with the water.

Mobile Manipulators for Assisted Living in Residential Settings

DTIC Science & Technology

2007-01-01

expected to grow dramatically over the next decade as the baby boom generation approaches 65 years of age. The UMass/Smith ASSIST framework aims to...is expected to grow dramatically over the next decade as the baby boom generation approaches 65 years of age. The UMass/Smith ASSIST framework aims to...functions. The vast majority of robotic rehabilitation work takes a hands-on approach where, for example, the robot aids the movement of a patient’s limb

Enhancing the Competitiveness of Vietnamese Industry Through Trade Liberalization

DTIC Science & Technology

2013-11-01

This effort was progressing well and gathering momentum up until 2008, but it slowed dramatically under the impact of the global economic slowdown...international trade. The TPP is expected have positive economic impacts for all participants and benefit Vietnam the most with an estimated 14...Vietnamese enterprises. Adjusting accounting standards to converge with IFRS will create confidence in financial analysis and allow for global comparisons

Dietary fat source alters hepatic gene expression profile and determines the type of live pathology in rats overfed via total eteral nutrtion

USDA-ARS?s Scientific Manuscript database

Non-alcoholic fatty liver disease (NAFLD) is considered a part of the 'metabolic syndrome' associated with obesity and can progress in some patients to chirrosis, loss of liver function and liver cancer. NAFLD is now the most common form of liver injury, and rates are rising dramatically as a result...

Lord Kelvin and the Age-of-the-Earth Debate: A Dramatization.

ERIC Educational Resources Information Center

Stinner, Art; Tecihman, Jurgen

2003-01-01

Presents a dramatization of a fictitious debate about the age of the earth that takes place at the Royal Institution, London, England, in the year 1872 among Sir William Thomson, T.H. Huxley, Sir Charles Lyell, and Hermann von Helmholtz. (Contains 17 references.) (Author/YDS)

Dramatic Changes in Health Care Professions in the Past 40 Years.

PubMed

Goldfield, Norbert

During the forty-year life of the Journal of Ambulatory Care Management, revolutionary transformations have occurred in the roles of existing health professions, as has the emergence of new categories of health professionals. This paper specifies the reasons for these dramatic changes, the new types of health care professions that have emerged, changes in existing professions, and suggestions of future directions. Many of these changes will be impacted by what occurs in Washington, DC in the debate over the Accountable Care Act.

Lack of significant improvements in long-term allograft survival in pediatric solid organ transplantation: A US national registry analysis.

PubMed

Dharnidharka, Vikas R; Lamb, Kenneth E; Zheng, Jie; Schechtman, Kenneth B; Meier-Kriesche, Herwig-Ulf

2015-08-01

Improvements across many facets of transplantation have led to better 1-yr outcomes of transplanted organs. In this study, we assessed whether longer-term attrition rates improved in pediatric kidney (KI), liver (LI), heart (HR) and lung (LU) transplant (TX) survival. We analyzed data between 1989 and 2008 from 5747 KI, 7348 LI, 5103 HR, and 715 LU TXs (under 18 yr of age at transplant, first solitary transplant only), from the National Scientific Registry of Transplant Recipients database in the USA. Kaplan-Meier (K-M) or ordinary least square (OLS) estimates were used to calculate median and projected survival half-lives. Attrition rates, defined as percent failing within a given time period, were stratified by year of TX. Median half-lives from 1989 TX year to 2005 TX year have shown a major improvement only in LI TX, remaining unchanged in HR and KI TX, or remaining very low in LU TX. All four organ TX types have shown a dramatic drop in first-year attrition rates from 1989 to 2008. However, longer-term attrition rates (1-3, 3-5, 5-10 yr) have remained largely unchanged for all four organ TX types. Further progress in long-term survival will need targeting end-points beyond first-year rejection and survival rates. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Blastic plasmacytoid dendritic cell neoplasm frequently shows occult central nervous system involvement at diagnosis and benefits from intrathecal therapy.

PubMed

Martín-Martín, Lourdes; Almeida, Julia; Pomares, Helena; González-Barca, Eva; Bravo, Pilar; Giménez, Teresa; Heras, Cecilia; Queizán, José-Antonio; Pérez-Ceballos, Elena; Martínez, Violeta; Alonso, Natalia; Calvo, Carlota; Álvarez, Rodolfo; Caballero, María Dolores; Orfao, Alberto

2016-03-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive myeloid neoplasm which shows a high rate of central nervous system (CNS) recurrence and overall survival (OS) of <1 year. Despite this, screening for CNS involvement is not routinely performed at diagnosis and intrathecal (IT) prophylaxis is not regularly administered in BPDCN. Here, we prospectively evaluated 13 consecutive BPDCN patients for the presence of CNS involvement by flow cytometry. Despite none of the patients presented with neurological symptoms, occult CNS involvement was detected in 6/10 cases evaluated at diagnosis and 3/3 studied at relapse/progression. BPDCN patients evaluated at diagnosis received IT treatment -either CNS prophylaxis (n = 4) or active therapy (n = 6)- and all but one remain alive (median follow-up of 20 months). In contrast, all three patients assessed at relapse/progression died. The potential benefit of IT treatment administered early at diagnosis on OS and CNS recurrence-free survival of BPDCN was further confirmed in a retrospective cohort of another 23 BPDCN patients. Our results show that BPDCN patients studied at diagnosis frequently display occult CNS involvement; moreover, they also indicate that treatment of occult CNS disease might lead to a dramatically improved outcome of BPDCN.

ANMCO/ELAS/SIBioC Consensus Document: biomarkers in heart failure

PubMed Central

Gulizia, Michele Massimo; Clerico, Aldo; Di Tano, Giuseppe; Emdin, Michele; Feola, Mauro; Iacoviello, Massimo; Latini, Roberto; Mortara, Andrea; Valle, Roberto; Misuraca, Gianfranco; Passino, Claudio; Masson, Serge; Aimo, Alberto; Ciaccio, Marcello; Migliardi, Marco

2017-01-01

Abstract Biomarkers have dramatically impacted the way heart failure (HF) patients are evaluated and managed. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological or pathogenic processes, or pharmacological responses to a therapeutic intervention. Natriuretic peptides [B-type natriuretic peptide (BNP) and N-terminal proBNP] are the gold standard biomarkers in determining the diagnosis and prognosis of HF, and a natriuretic peptide-guided HF management looks promising. In the last few years, an array of additional biomarkers has emerged, each reflecting different pathophysiological processes in the development and progression of HF: myocardial insult, inflammation, fibrosis, and remodelling, but their role in the clinical care of the patient is still partially defined and more studies are needed before to be well validated. Moreover, several new biomarkers have the potential to identify patients with early renal dysfunction and appear to have promise to help the management cardio-renal syndrome. With different biomarkers reflecting HF presence, the various pathways involved in its progression, as well as identifying unique treatment options for HF management, a closer cardiologist-laboratory link, with a multi-biomarker approach to the HF patient, is not far ahead, allowing the unique opportunity for specifically tailoring care to the individual pathological phenotype. PMID:28751838

Blastic plasmacytoid dendritic cell neoplasm frequently shows occult central nervous system involvement at diagnosis and benefits from intrathecal therapy

PubMed Central

Martín-Martín, Lourdes; Almeida, Julia; Pomares, Helena; González-Barca, Eva; Bravo, Pilar; Giménez, Teresa; Heras, Cecilia; Queizán, José-Antonio; Pérez-Ceballos, Elena; Martínez, Violeta; Alonso, Natalia; Calvo, Carlota; Álvarez, Rodolfo; Caballero, María Dolores; Orfao, Alberto

2016-01-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive myeloid neoplasm which shows a high rate of central nervous system (CNS) recurrence and overall survival (OS) of <1 year. Despite this, screening for CNS involvement is not routinely performed at diagnosis and intrathecal (IT) prophylaxis is not regularly administered in BPDCN. Here, we prospectively evaluated 13 consecutive BPDCN patients for the presence of CNS involvement by flow cytometry. Despite none of the patients presented with neurological symptoms, occult CNS involvement was detected in 6/10 cases evaluated at diagnosis and 3/3 studied at relapse/progression. BPDCN patients evaluated at diagnosis received IT treatment -either CNS prophylaxis (n = 4) or active therapy (n = 6)- and all but one remain alive (median follow-up of 20 months). In contrast, all three patients assessed at relapse/progression died. The potential benefit of IT treatment administered early at diagnosis on OS and CNS recurrence-free survival of BPDCN was further confirmed in a retrospective cohort of another 23 BPDCN patients. Our results show that BPDCN patients studied at diagnosis frequently display occult CNS involvement; moreover, they also indicate that treatment of occult CNS disease might lead to a dramatically improved outcome of BPDCN. PMID:26840087

Progress on upwelling studies in the China seas

NASA Astrophysics Data System (ADS)

Hu, Jianyu; Wang, Xiao Hua

2016-09-01

East Asian marginal seas surrounding China exhibit rich ocean upwelling, mostly in response to the southwesterly summer monsoon. Upwelling in the China seas, namely, the South China Sea, the Taiwan Strait, the East China Sea, the Yellow Sea, and the Bohai Sea, has become increasingly important because the potential changes in the upwelling may have dramatic ecosystem, socioeconomic, and climate impacts. This paper reviews the progress of upwelling studies in the China seas since the year 2000, by presenting the principal characteristics and new understanding of 12 major upwelling regions in the China seas. Upwelling exhibits long-term variability at intraseasonal to multidecadal scales as well as short-term variability frequently caused by tropical cyclones. It is also associated with the El Niño-Southern Oscillation, local environmental variation, and biogeochemical factors. The coastal upwelling around Hainan Island and the upwelling or cold dome northeast of Taiwan Island are specifically highlighted because they have attracted great interest for decades. This paper summarizes upwelling mechanisms in terms of wind, topography, tide, stratification, and background flow, with applications mostly to the China seas. Finally, we propose some topics for future upwelling research, i.e., potential intensification of coastal upwelling under global climate change, downwelling, intrusion of upwelling into coastal embayments, and the influence of upwelling on fishery and biogeochemical processes.

[Late complications of liver cirrhosis - management of gastrointestinal bleeding in the presence of portal hypertension].

PubMed

Hejda, Václav

Cirrhosis is the end stage of progressive development of different liver diseases and is associated with significant morbidity and mortality rates. Cirrhosis is associated with a number of potential complications, in particular with development of portal hypertension. Portal hypertension with the production of ascites, hepatic and gastric varices bleeding in the upper part of the gastrointestinal tract, presents the breakpoint in the natural course of cirrhosis, and it is associated with a considerably worse prognosis of patients, with a dramatically increased risk of mortality. A major progress was reached during the past 10-20 years in diagnosing liver cirrhosis (including non-invasive methods), in primary prevention of the initial episode of upper gastrointestinal bleeding and in the therapy of acute bleeding due to modern pharmacotherapy, with regard to expanding possibilities of therapeutic endoscopy and relatively new options for management of acute bleeding (esophageal stents, TIPS and suchlike). However acute upper gastrointestinal bleeding associated with portal hypertension still presents a considerable risk of premature death (15-20 %). Early diagnosing and causal treatment of numerous liver diseases may lead to slowing or regression of fibrosis and cirrhosis and possibly even of the degree of portal hypertension and thereby also the risk of bleeding.Key words: cirrhosis - esophageal varices - treatment of bleeding - portal hypertension.

Nutrient enrichment enhances black band disease progression in corals

NASA Astrophysics Data System (ADS)

Voss, Joshua D.; Richardson, Laurie L.

2006-11-01

Infectious diseases are recognized as significant contributors to the dramatic loss of corals observed worldwide. However, the causes of increased coral disease prevalence and severity are not well understood. One potential factor is elevated nutrient concentration related to localized anthropogenic activities such as inadequate waste water treatment or terrestrial runoff. In this study the effect of nutrient enrichment on the progression of black band disease (BBD) was investigated using both in situ and laboratory experiments. Experimental increases in localized nutrient availability using commercial time release fertilizer in situ resulted in doubling of BBD progression and coral tissue loss in the common reef framework coral Siderastrea siderea. Laboratory experiments in which artificially infected S. siderea colonies were exposed to increased nitrate concentrations (up to 3 μM) demonstrated similar increases in BBD progression. These findings provide evidence that the impacts of this disease on coral populations are exacerbated by nutrient enrichment and that management to curtail excess nutrient loading may be important for reducing coral cover loss due to BBD.

Negotiating for Change: Modifying Collective Bargaining Agreements for School Turnaround

ERIC Educational Resources Information Center

Weinberg, Rebecca

2011-01-01

Dramatically improving student achievement in a school that has been failing for many years requires dramatically different conditions. Only the most effective teachers and leaders should be in the building, and the leadership must have the flexibility to respond strategically to the needs of the students, with regular input from teachers.…

The Accessibility of Socio-Dramatic Play to Culturally and Linguistically Diverse Australian Preschoolers

ERIC Educational Resources Information Center

Scrafton, Eleanor; Whitington, Victoria

2015-01-01

Socio-dramatic play is preschool children's leading learning activity (Karpov 2005; Vygotsky 1978). Yet entering play often poses challenges (Corsaro 2003), particularly for culturally and linguistically diverse (CALD) children (Hruska 2007). At preschool four-year-old CALD children are both acquiring a new language, and learning new rules, social…

Teenagers' Significant Experiences in Aesthetic Areas: Some Empirical Observations Regarding the Role of Dramatic Art

ERIC Educational Resources Information Center

Finnas, Leif

2008-01-01

Fifteen sixteen-year-old Fenno-Swedish compulsory school pupils' descriptions and evaluations of significant, i.e. more or less "strong", experiences relating to dramatic art (film, theatre) were analysed and compared with reported experiences in other aesthetic areas (music, nature etc.). The drama area was represented in many…

Demographic Trends and Projections Affecting Higher Education.

ERIC Educational Resources Information Center

Zuniga, Robin Etter

1997-01-01

A dramatic increase in the pool of college-age students in the next 20 years is inevitable, but this will not necessarily lead to dramatic increases in higher education enrollment. Enrollment forecasters must ask how economic growth, tuition increases, or an increase in standardized test requirements will affect demand and be clear about…

Is All-State Guitar in Your State's Future?

ERIC Educational Resources Information Center

McCarthy, Glen

2013-01-01

The growth of guitar education in schools has been dramatic. From regional, specialized, and isolated programs just a few years ago to a broad-based movement with strong support from administrators, parents, and students, guitar classes are taught today all over North America. Colleges now offer guitar education. A dramatic indicator of guitar's…

Anthropogenic biogeochemical impacts on coral reefs in the Pacific Islands—An overview

NASA Astrophysics Data System (ADS)

Morrison, R. J.; Denton, G. R. W.; Bale Tamata, U.; Grignon, J.

2013-11-01

Coral reefs dominate the coastal environment in many Pacific Islands, being present as atolls, coral platforms, barrier and fringing reefs. With ever increasing populations and migration of people to the coast, the anthropogenic impacts on these reefs have increased dramatically in the last 30 years. While research on these impacts has been limited, some important progress has been made. This paper reviews some of the completed studies, with outcomes from American Samoa, Fiji, French Polynesia, Guam, Saipan, New Caledonia and Tonga presented. These studies indicate that the most significant impacts have been found in locations close to major urban centres or industrial and mining activities. The extent of impact varies from place to place with minimal impacts in the more isolated and less industrialised communities. Common anthropogenic impacts are contamination caused by inadequate sewage treatment, erosion from adjacent agricultural and urban expansion activities, poor waste management, eutrophication, inefficient and/or inappropriate pesticide use and hydrocarbons use, storage and management. The outcomes include contaminated sediments (trace metals, pesticides, PCBs, hydrocarbons) with some impacts on resident biota. In some instances, the edible quality of local fisheries resources has been significantly compromised.Even in locations with small populations, increasing populations and poor economic conditions have resulted in noticeable effects on the adjacent fringing reefs, including dramatic algal proliferation and declines in fish numbers resulting from increasing nutrient discharges and increased herbivore fish catches. Recovery measures including fishing bans and alternative fishing practices have been implemented to address these issues in some areas.

Cancer-associated lysosomal changes: friends or foes?

PubMed

Kallunki, T; Olsen, O D; Jäättelä, M

2013-04-18

Rapidly dividing and invasive cancer cells are strongly dependent on effective lysosomal function. Accordingly, transformation and cancer progression are characterized by dramatic changes in lysosomal volume, composition and cellular distribution. Depending on one's point of view, the cancer-associated changes in the lysosomal compartment can be regarded as friends or foes. Most of them are clearly transforming as they promote invasive growth, angiogenesis and drug resistance. The same changes can, however, strongly sensitize cells to lysosomal membrane permeabilization and thereby to lysosome-targeting anti-cancer drugs. In this review we compile our current knowledge on cancer-associated changes in lysosomal composition and discuss the consequences of these alterations to cancer progression and the possibilities they can bring to cancer therapy.

Sustaining aspen in western landscapes: Symposium proceedings; 13-15 June 2000; Grand Junction, CO

Treesearch

Wayne D. Shepperd; Dan Binkley; Dale L. Bartos; Thomas J. Stohlgren; Lane G. Eskew

2001-01-01

The current status and trend of aspen is a topic of debate; some studies have claimed dramatic reductions in aspen stands while others have found no major changes. The actual picture of aspen forests across the West is variable, and the presence of conifers and ungulates in aspen may or may not indicate a progressive loss of aspen. These proceedings summarize the state...

The Academic Achievement of Limited English Proficient (LEP) Youth in New and Established Immigrant States: Lessons from the National Assessment of Educational Progress (NAEP)

ERIC Educational Resources Information Center

Spees, Lisa P.; Potochnick, Stephanie; Perreira, Krista M.

2016-01-01

The dramatic growth and dispersal of immigrant families has changed the face of public education at a time when states are experiencing increased school accountability pressures under the No Child Left Behind Act and its recent successor, the Every Student Succeeds Act. Of particular concern is how these demographic shifts affect the academic…

The evolution of atmospheric science goals and enhanced technology needed to satisfy remote sensing requirements

NASA Astrophysics Data System (ADS)

Russell, J. M., III

2017-12-01

The era of satellite observations of Earth's atmosphere has undergone a remarkable and dramatic evolution since temperature measurements were first made from the Nimbus 3 satellite launched in April 1969. Since those early days of discovery, amazing progress has occurred in scientific understanding of the atmosphere. The launch of Nimbus 7 in October 1978 provided an explosion of information on the composition of the stratosphere revealing for the first time the global distributions of stratospheric O3, H2O, CH4, CO, NO, NO2, HNO3 and aerosols. The SAGE series of satellites begun in 1979 and the Upper Atmosphere Research Satellite deployed from the Space Shuttle in October 1991 added new and more tenuous stratospheric gases especially in the odd chlorine family. Measurements of stratospheric ozone destroying chlorine and bromine compounds have continued with the EOS suite of satellites. Measurements from the TIMED satellite have provided a 15-year data set for study of the energetics, chemistry and dynamics of the mesosphere and lower thermosphere and vertical coupling between atmospheric regions. The AIM satellite has provided a 10-year data base of the tenuous layer of mesopause level noctilucent clouds and horizontal coupling between hemispheres. This progression of knowledge and measurement capability has evolved together as the needs developed to observe and characterize less abundant but more important atmospheric constituents and processes. This talk summarizes some of the key science results, the technology challenges that had to be overcome to enable the measurements and a view toward the future to meet new science requirements.

A multicentre, randomized, double-blind placebo-controlled trial evaluating rosiglitazone for the prevention of atherosclerosis progression after coronary artery bypass graft surgery in patients with type 2 diabetes. Design and rationale of the VeIn-Coronary aTherOsclerosis and Rosiglitazone after bypass surgerY (VICTORY) trial

PubMed Central

Bertrand, Olivier F; Poirier, Paul; Rodés-Cabau, Josep; Rinfret, Stéphane; Title, Lawrence; Dzavik, Vladimir; Natarajan, Madhu; Angel, Juan; Batalla, Nuria; Alméras, Natalie; Costerousse, Olivier; De Larochellière, Robert; Roy, Louis; Després, Jean-Pierre

2009-01-01

BACKGROUND: The number of patients with coronary artery disease and type 2 diabetes will increase dramatically over the next decade. Diabetes has been related to accelerated atherosclerosis and many patients with diabetes will require coronary artery bypass graft (CABG) surgery utilizing saphenous vein grafts. After CABG, accelerated atherosclerosis in saphenous vein grafts leads to graft failure in approximately 50% of cases over a 10-year period. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, has been shown to improve multiple metabolic parameters in patients with type 2 diabetes. However, its role in the prevention of atherosclerosis progression is uncertain. STUDY DESIGN: VeIn-Coronary aTherOsclerosis and Rosiglitazone after bypass surgerY (VICTORY) is a cardiometabolic trial in which patients with type 2 diabetes, one to 10 years after CABG, will be randomly assigned to receive rosiglitazone (up to 8 mg/day) or a placebo after qualifying angiography and intravascular ultrasound of a segment of one vein graft with or without a native anastomosed coronary artery. A comprehensive set of athero-thrombo-inflammatory markers will be serially assessed during the 12-month follow-up period. Body fat distribution and body composition will be assessed by computed tomography and dual energy x-ray absorptiometry, respectively, at baseline, six months and 12 months follow-up. For atherosclerosis progression evaluation, repeat angiography and intravascular ultrasound will be performed after 12 months follow-up. The primary end point of the study will be the change in atherosclerotic plaque volume in a 40 mm or longer segment of one vein graft. CONCLUSIONS: The VICTORY trial is the first cardiometabolic study to evaluate the antiatherosclerotic and metabolic effects of rosiglitazone in post-CABG patients with type 2 diabetes. PMID:19746240

Celiac disease: progress towards diagnosis and definition of pathogenic mechanisms.

PubMed

Rossi, Mauro; Bot, Adrian

2011-08-01

The current issue of the International Reviews of Immunology is dedicated entirely to Celiac Disease (CD). Recent development of additional biomarkers and diagnostics resulted in a sharp revision of the prevalence of this condition, with a previously unrecognized subclinical occurrence in the adult population. This was paralleled by groundbreaking progress in understanding its molecular pathogenesis: while gluten-derived peptides activate the innate immunity, post-translationally modified gluten elicits an adaptive immunity. These arms amplify each other, resulting in a self- perpetuating autoimmune condition, influenced by disturbances of the gut flora and mucus chemistry. The process evolves dramatically in a subset of patients with vulnerable immune homeostasis (eg. Treg cells) explaining the progressive, aggravating syndrome in the clinically overt version of CD. In depth understanding of the pathogenesis of CD thus creates the premises of developing novel, more accurate animal models that should support a rationale development of new prophylactic and therapeutic interventions.

First Report of Dramatic Tumor Responses with Ramucirumab and Paclitaxel After Progression on Pembrolizumab in Two Cases of Metastatic Gastroesophageal Adenocarcinoma.

PubMed

Chakrabarti, Sakti; Dong, Haidong; Paripati, Harshita R; Ross, Helen J; Yoon, Harry H

2018-04-19

Checkpoint inhibitors targeted at programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) can result in significant benefit to a small proportion of patients with cancer, including those with tumors of the stomach and gastroesophageal junction. These drugs are now approved for several solid tumors, including the recent accelerated approval of pembrolizumab for gastroesophageal adenocarcinomas in the third-line setting and beyond based on the KEYNOTE-059 phase II trial. Data are lacking on the efficacy of chemotherapy after progression on PD-1 blockade in metastatic gastroesophageal adenocarcinoma. This report describes the exceptional response of two patients who received ramucirumab plus paclitaxel after progressive disease on pembrolizumab. This early clinical observation suggests that the sequence of administration of PD-1 blockade and chemotherapy may be important in this disease. © AlphaMed Press 2018.

Age-Specific Malaria Mortality Rates in the KEMRI/CDC Health and Demographic Surveillance System in Western Kenya, 2003–2010

PubMed Central

Desai, Meghna; Buff, Ann M.; Khagayi, Sammy; Byass, Peter; Amek, Nyaguara; van Eijk, Annemieke; Slutsker, Laurence; Vulule, John; Odhiambo, Frank O.; Phillips-Howard, Penelope A.; Lindblade, Kimberly A.; Laserson, Kayla F.; Hamel, Mary J.

2014-01-01

Recent global malaria burden modeling efforts have produced significantly different estimates, particularly in adult malaria mortality. To measure malaria control progress, accurate malaria burden estimates across age groups are necessary. We determined age-specific malaria mortality rates in western Kenya to compare with recent global estimates. We collected data from 148,000 persons in a health and demographic surveillance system from 2003–2010. Standardized verbal autopsies were conducted for all deaths; probable cause of death was assigned using the InterVA-4 model. Annual malaria mortality rates per 1,000 person-years were generated by age group. Trends were analyzed using Poisson regression. From 2003–2010, in children <5 years the malaria mortality rate decreased from 13.2 to 3.7 per 1,000 person-years; the declines were greatest in the first three years of life. In children 5–14 years, the malaria mortality rate remained stable at 0.5 per 1,000 person-years. In persons ≥15 years, the malaria mortality rate decreased from 1.5 to 0.4 per 1,000 person-years. The malaria mortality rates in young children and persons aged ≥15 years decreased dramatically from 2003–2010 in western Kenya, but rates in older children have not declined. Sharp declines in some age groups likely reflect the national scale up of malaria control interventions and rapid expansion of HIV prevention services. These data highlight the importance of age-specific malaria mortality ascertainment and support current strategies to include all age groups in malaria control interventions. PMID:25180495

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study.

PubMed

Cunningham, Miles G; Yadollahikhales, Golnaz; Vitaliano, Gordana; van Horne, Craig

2016-11-15

Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression. The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. Five years after initiating DBS, during a routine battery change, an apparent electrical event occurred that triggered the rapid onset of severe depression. Anti-seizure and antidepressant medications were ineffective, and the patient was offered a course of electroconvulsive therapy (ECT), which resulted in complete reversal of her depressive episode. Parkinson's syndrome can be seen after a single closed head injury event. Post-traumatic parkinsonism is responsive to DBS; however, DBS has been associated with an infrequent occurrence of dramatic disruption in mood. ECT is a therapeutic option for patients who develop intractable depressive illness associated with DBS.

Meniscal Extrusion or Subchondral Damage Characterize Incident Accelerated Osteoarthritis: Data from the Osteoarthritis Initiative

PubMed Central

Driban, Jeffrey B.; Ward, Robert J.; Eaton, Charles B.; Lo, Grace H.; Price, Lori Lyn; Lu, Bing; McAlindon, Timothy E.

2015-01-01

Introduction Knee osteoarthritis (KOA) is typically a slowly progressive disorder; however, a subset of knees progress with dramatic rapidity. We aimed to describe magnetic resonance imaging (MRI) findings that are associated with accelerated KOA. Materials and Methods We conducted a longitudinal descriptive study in the Osteoarthritis Initiative (OAI) cohort. We selected participants who had no radiographic KOA at baseline with one of the following in the most severe knee: 1) accelerated KOA (progressed to end-stage KOA within 48 months), 2) common KOA, and 3) no KOA at all visits. We enriched the sample by selecting knees with a self-reported or suspected knee injury. A musculoskeletal radiologist blinded to group assignments but not to time sequence performed MRI readings for the visit before and after an injury. Results We assessed 38 participants (knees), 66% were female, mean age 61 (9) years, and mean body mass index 28.5 (4.9) kg/m2. Fifteen of 20 knees with no or common KOA, had no incident findings consistent with acute damage. Among the 18 knees with accelerated KOA most had incident findings: 13 (72%) had incident medial meniscal pathology with extrusion and 5 (28%) knees had subchondral damage. Conclusions Incident MRI findings that are associated with incident accelerated KOA are characterized by structural damage that compromises subchondral bone or the function of the meniscus. Recognizing meniscal extrusion and/or change in shape, lateral meniscal tear, or acute subchondral damage may be vital for identifying individuals at risk for accelerated KOA. PMID:26149125

How to Know when Dramatic Change Is on Track: Leading Indicators of School Turnarounds

ERIC Educational Resources Information Center

Kowal, Julie; Ableidinger, Joe

2011-01-01

In recent years, national policymakers have placed new emphasis on "school turnarounds" as a strategy for rapid, dramatic improvement in chronically failing schools, calling on education leaders to turn around performance in the 5,000 lowest-achieving schools nationwide. This goal may seem daunting, given the dismal success rates of…

Comprehensive proteomic profiles of mouse AApoAII amyloid fibrils provide insights into the involvement of lipoproteins in the pathology of amyloidosis.

PubMed

Miyahara, Hiroki; Sawashita, Jinko; Ishikawa, Eri; Yang, Mu; Ding, Xin; Liu, Yingye; Hachiya, Naomi; Kametani, Fuyuki; Yazaki, Masahide; Mori, Masayuki; Higuchi, Keiichi

2018-02-10

Amyloidosis is a disorder characterized by extracellular fibrillar deposits of misfolded proteins. The amyloid deposits commonly contain several non-fibrillar proteins as amyloid-associated proteins, but their roles in amyloidosis pathology are still unknown. In mouse senile amyloidosis, apolipoprotein A-II (ApoA-II) forms extracellular amyloid fibril (AApoAII) deposits with other proteins (AApoAII-associated proteins) in many organs. We previously reported that R1.P1-Apoa2 c mice provide a reproducible model of AApoAII amyloidosis. In order to investigate the sequential alterations of AApoAII-associated protein, we performed a proteomic analysis of amyloid fibrils extracted from mouse liver tissues that contained different levels of AApoAII deposition. We identified 6 AApoAII-associated proteins that constituted 20 of the top-ranked proteins in mice with severe AApoAII deposition. Although the amount of AApoAII-associated proteins increased with the progression of amyloidosis, the relative abundance of AApoAII-associated proteins changed little throughout the progression of amyloidosis. On the other hand, plasma levels of these proteins showed dramatic changes during the progression of amyloidosis. In addition, we confirmed that AApoAII-associated proteins were significantly associated with lipid metabolism based on functional enrichment analysis, and lipids were co-deposited with AApoAII fibrils from early stages of development of amyloidosis. Thus, these results demonstrate that lipoproteins are involved in AApoAII amyloidosis pathology. This study presented proteomic profiles of AApoAII amyloidosis during disease progression and it revealed co-deposition of lipids with AApoAII deposits based on functional analyses. The relative abundance of AApoAII-associated proteins in the amyloid fibril fractions did not change over the course of development of AApoAII amyloidosis pathology. However, their concentrations in plasma changed dramatically with progression of the disease. Interestingly, several AApoAII-associated proteins have been found as constituents of lipid-rich lesions of other degenerative diseases, such as atherosclerosis and age-related macular degeneration. The common protein components among these diseases with lipid-rich deposits could be accounted for by a lipoprotein retention model. Copyright © 2017 Elsevier B.V. All rights reserved.

Transcriptomic indices of fast and slow disease progression in two mouse models of amyotrophic lateral sclerosis.

PubMed

Nardo, Giovanni; Iennaco, Raffaele; Fusi, Nicolò; Heath, Paul R; Marino, Marianna; Trolese, Maria C; Ferraiuolo, Laura; Lawrence, Neil; Shaw, Pamela J; Bendotti, Caterina

2013-11-01

Amyotrophic lateral sclerosis is heterogeneous with high variability in the speed of progression even in cases with a defined genetic cause such as superoxide dismutase 1 (SOD1) mutations. We reported that SOD1(G93A) mice on distinct genetic backgrounds (C57 and 129Sv) show consistent phenotypic differences in speed of disease progression and life-span that are not explained by differences in human SOD1 transgene copy number or the burden of mutant SOD1 protein within the nervous system. We aimed to compare the gene expression profiles of motor neurons from these two SOD1(G93A) mouse strains to discover the molecular mechanisms contributing to the distinct phenotypes and to identify factors underlying fast and slow disease progression. Lumbar spinal motor neurons from the two SOD1(G93A) mouse strains were isolated by laser capture microdissection and transcriptome analysis was conducted at four stages of disease. We identified marked differences in the motor neuron transcriptome between the two mice strains at disease onset, with a dramatic reduction of gene expression in the rapidly progressive (129Sv-SOD1(G93A)) compared with the slowly progressing mutant SOD1 mice (C57-SOD1(G93A)) (1276 versus 346; Q-value ≤ 0.01). Gene ontology pathway analysis of the transcriptional profile from 129Sv-SOD1(G93A) mice showed marked downregulation of specific pathways involved in mitochondrial function, as well as predicted deficiencies in protein degradation and axonal transport mechanisms. In contrast, the transcriptional profile from C57-SOD1(G93A) mice with the more benign disease course, revealed strong gene enrichment relating to immune system processes compared with 129Sv-SOD1(G93A) mice. Motor neurons from the more benign mutant strain demonstrated striking complement activation, over-expressing genes normally involved in immune cell function. We validated through immunohistochemistry increased expression of the C3 complement subunit and major histocompatibility complex I within motor neurons. In addition, we demonstrated that motor neurons from the slowly progressing mice activate a series of genes with neuroprotective properties such as angiogenin and the nuclear factor (erythroid-derived 2)-like 2 transcriptional regulator. In contrast, the faster progressing mice show dramatically reduced expression at disease onset of cell pathways involved in neuroprotection. This study highlights a set of key gene and molecular pathway indices of fast or slow disease progression which may prove useful in identifying potential disease modifiers responsible for the heterogeneity of human amyotrophic lateral sclerosis and which may represent valid therapeutic targets for ameliorating the disease course in humans.

CP violation in the B system.

PubMed

Gershon, T; Gligorov, V V

2017-04-01

The phenomenon of CP violation is crucial to understand the asymmetry between matter and antimatter that exists in the Universe. Dramatic experimental progress has been made, in particular in measurements of the behaviour of particles containing the b quark, where CP violation effects are predicted by the Kobayashi-Maskawa mechanism that is embedded in the standard model. The status of these measurements and future prospects for an understanding of CP violation beyond the standard model are reviewed.

The Cancer Family Caregiving Experience: An Updated and Expanded Conceptual Model

PubMed Central

Fletcher, Barbara Swore; Miaskowski, Christine; Given, Barbara; Schumacher, Karen

2011-01-01

Objective The decade from 2000–2010 was an era of tremendous growth in family caregiving research specific to the cancer population. This research has implications for how cancer family caregiving is conceptualized, yet the most recent comprehensive model of cancer family caregiving was published ten years ago. Our objective was to develop an updated and expanded comprehensive model of the cancer family caregiving experience, derived from concepts and variables used in research during past ten years. Methods A conceptual model was developed based on cancer family caregiving research published from 2000–2010. Results Our updated and expanded model has three main elements: 1) the stress process, 2) contextual factors, and 3) the cancer trajectory. Emerging ways of conceptualizing the relationships between and within model elements are addressed, as well as an emerging focus on caregiver-patient dyads as the unit of analysis. Conclusions Cancer family caregiving research has grown dramatically since 2000 resulting in a greatly expanded conceptual landscape. This updated and expanded model of the cancer family caregiving experience synthesizes the conceptual implications of an international body of work and demonstrates tremendous progress in how cancer family caregiving research is conceptualized. PMID:22000812

[Stem cell-based cardiac regeneration after myocardial infarction].

PubMed

Reinsch, M; Weinberger, F

2018-03-01

Myocardial infarction leads to an irreversible loss of vital myocardial cells. The transplantation of new cardiomyocytes into the heart was first described over 20 years ago and represents a straightforward approach to remuscularize a damaged heart. Due to the lack of human cells a clinical application seemed ambitious; however, dramatic progress in stem cell biology over the last two decades has paved the way towards a clinical application. This is especially important as the prognosis for patients with terminal heart failure is still poor. The transplantation of either cardiomyocytes or engineered heart tissue derived from pluripotent stem cells (either embryonic stem cells or induced pluripotent stem cells) might represent a new regenerative approach. Transplantation of either cells or tissue constructs has now been evaluated in several preclinical models, which have demonstrated that an injured heart can be (partially) remuscularized; however, major hurdles towards a clinical application are the transplantation-related occurrence of arrhythmia, the potential tumorigenicity of pluripotent cells and the required immunosuppression. Several groups are working hard to solve these problems and we are optimistic that the first clinical studies will take place within the next few years.

[A long-term survival case of progressive breast cancer detected in gastric metastasis].

PubMed

Hayashi, Keiko; Sengoku, Norihiko; Kosaka, Yoshimasa; Enomoto, Takumo; Kajita, Sabine; Kondo, Yasushi; Kuranami, Masaru; Watanabe, Masahiko

2010-11-01

A 51-year-old postmenopausal woman was diagnosed as having adenocarcinoma (gastric cancer type 4) from gastric biopsy by upper endoscopy. Her chief complaint was abdominal dilatation. Meanwhile, a breast CT suggested tumor in her left breast and was diagnosed as an invasive lobular carcinoma based on a core needle biopsy. After gastric biopsy, tissues are stained by ER and PgR in immunohistochemistry. The diagnosis was modified from gastric cancer to T2N1M1, stage IV left breast cancer, accompanied by a treatment. Chemotherapy with EC 6 course consisted of a weekly PTX 4 course (epirubicin, cyclophosphamide-weekly paclitaxel) was performed. After the chemotherapy, breast mass, ascites and tumor marker were dramatically improved. Then hormonal therapy was administered. She passed away 2 and 1/2 years after her first visit to the hospital. Metastatic gastric tumors simulating type 4 advanced gastric cancer (MGTS type 4) and invasive lobular carcinoma are known to have an unfavorable prognosis. There is no doubt, however, that the multidisciplinary treatments have brought a satisfaction to her and family. We should keep in mind a possibility of gastric metastasis of breast cancer, when consulting a female patient with gastric cancer type 4.

New developments in low temperature physics New developments in low temperature physics

NASA Astrophysics Data System (ADS)

Hallock, Bob; Paalanenn, Mikko

2009-04-01

Below you will find part of the activity report to the IUPAP General Assembly, October 2008, by the present and previous Chairmen of C5. It provides an overview of the most important and recent developments in low temperature physics, much in line with the program of LT25. For the field of experimental low temperature physics, the ability to conduct research has been damaged by the dramatic increase in the price of liquid helium. In the USA, for example, the price of liquid helium has approximately doubled over the past two years. This has led to a reduction in activity in many laboratories as the funding agencies have not quickly increased support in proportion. The increase in price of liquid helium has accelerated interest in the development and use of alternative cooling systems. In particular, pulse-tube coolers are now available that will allow cryostats with modest cooling needs to operate dilution refrigerators without the need for repeated refills of liquid helium from external supply sources. Solid helium research has seen a dramatic resurgence. Torsional oscillator experiments have been interpreted to show that solid helium may undergo a transition to a state in which some of the atoms in the container do not follow the motion of the container, e.g. may be 'supersolid'. The observation is robust, but the interpretation is controversial. The shear modulus of solid helium undergoes a similar signature with respect to temperature. Experiments that should be expected to cause helium to flow give conflicting results. Theory predicts that a perfect solid cannot show supersolid behavior, but novel superfluid-like behavior should be seen in various defects that can exist in the solid, and vorticity may play a significant role. And, recently there have been reports of unusual mass decoupling in films of pure 4He on graphite surfaces as well as 3He- 4He mixture films on solid hydrogen surfaces. These may be other examples of unusual superfluid-like behavior. There is continued interest in superfluid turbulence, where there has been progress in the use of very sensitive ultra-cold detectors as well as the use of injected ions. Interesting progress is being made in understanding how quantum turbulence resembles classical turbulence. New evidence shows that turbulence can develop by the entanglement of vortex rings. It now appears possible to control the transition to quantum turbulence in 4He. High temperature and unconventional superconductivity continues to show progress. Over the past few years we have seen new work on the coexistence of superconductivity and ferromagnetism in the uranium compounds. Discovery of superconductivity in layered iron-arsenic compounds may lead to a new generation of high temperature superconductors and holds great promise. There has also been strong progress in the possible use of layered transition metal oxide materials as the basis for the discovery of new superconductors. The visualization via STM of the electronic states of high transition temperature materials continue to provide new insights into the pairing that takes place in such materials. There is also emerging new work that shows that in a two dimensional superconducting system with patterned holes, pairing may exist in the insulating state. Graphene has been a very hot topic due to the ability to readily create atomically thin sheets of carbon, which has given rise to investigation in a number of settings via many techniques. These thin sheets, unknown until a few years ago, reveal remarkable electronic and optical properties, which are only beginning to be understood and explored. There has also been continuing progress in the area of carbon nanotubes where there have been developments in the study of the spin and orbital motion of electrons, which have implications for spintronics applications. There has been progress in the area of qubits, where it now seems possible to communicate quantum information between qubits using photons. Thus emerges the possibility of using superconducting integrated circuits to carry out experimental studies in quantum optics. In addition, small Josephson junctions are being used to study quantum coherence in ways not possible previously. Device-driven research continues to show remarkable new results. The use of SQUID detection has allowed the possibility of very low magnetic field magnetic imaging (MRI) with the ability to resolve structures to a higher degree than previously possible. There has also been work in the area of nano-mechanical resonators, which may allow the future study of squeezed states in a mechanical system. In addition, there continues to be work on nanomagnets, which show self-assembly properties and unusual temperature dependence to the magnetization. Ultra-cold gases continue to see dramatic progress due to the unprecedented ability of the realm of cold-atom physics to manipulate atoms and their environment. Optical superlattices have allowed studies of superexchange interactions and open the possibility of further investigation of the dynamical behavior of quantum spin systems. Such cold gas experiments have allowed unprecedented opportunity to study quantum degenerate Fermi gases and the realization of superfluidity with unusual interactions. Also in this area it has been possible to create controlled disorder and subsequently directly observe localization phenomena in one dimension, with the expectation that this can be extended to higher dimensions.

NEW DEVELOPMENTS IN LOW TEMPERATURE PHYSICS : Part of the Activity Report to the IUPAP General Assembly

NASA Astrophysics Data System (ADS)

Hallock, Bob; Paalanen, Mikko

2009-03-01

Below you find part of the Activity Report to the IUPAP General Assembly, October 2008, by the present and previous Chairmen of C5. It provides an overview of the most important and recent developments in low temperature physics, much in line with the program of LT25. For the field of experimental low temperature physics, the ability to conduct research has been damaged by the dramatic increase in the price of liquid helium. In the United States for example, the price of liquid helium has approximately doubled over the past two years. This has led to a reduction in activity in many laboratories as the funding agencies have not quickly increased support in proportion. The increase in price of liquid helium has accelerated interest in the development and use of alternative cooling systems. In particular, pulse tube coolers are now available that will allow cryostats with modest cooling needs to operate dilution refrigerators without the need for repeated refills of liquid helium from external supply sources. Solid helium research has seen a dramatic resurgence. Torsional oscillator experiments have been interpreted to show that solid helium may undergo a transition to a state in which some of the atoms in the container do not follow the motion of the container, e.g. may be 'supersolid'. The observation is robust, but the interpretation is controversial. The shear modulus of solid helium undergoes a similar signature with respect to temperature. Experiments that should be expected to cause helium to flow give conflicting results. Theory predicts that a perfect solid cannot show supersolid behavior, but novel superfluid-like behavior should be seen in various defects that can exist in the solid, and vorticity may play a significant role. And, recently there have been reports of unusual mass decoupling in films of pure 4He on graphite surfaces as well as 3He-4He mixture films on solid hydrogen surfaces. These may be other examples of unusual superfluid-like behavior. There is continued interest in superfluid turbulence, where there has been progress in the use of very sensitive ultra-cold detectors as well as the use of injected ions. Interesting progress is being made in understanding how quantum turbulence resembles classical turbulence. New evidence shows that turbulence can develop by the entanglement of vortex rings. It now appears possible to control the transition to quantum turbulence in 4He. High temperature and unconventional superconductivity continues to show progress. Over the past few years we have seen new work on the coexistence of superconductivity and ferromagnetism in the Uranium compounds. Discovery of superconductivity in layered iron-arsenic compounds may lead to a new generation of high temperature superconductors and holds great promise. There has also been strong progress in the possible use of layered transition metal oxide materials as the basis for the discovery of new superconductors. The visualization via STM of the electronic states of high transition temperature materials continue to provide new insights into the pairing that takes place in such materials. There is also emerging new work that shows that in a two dimensional superconducting system with patterned holes, pairing may exist in the insulating state. Graphene has been a very hot topic due to the ability to readily create atomically thin sheets of carbon, which has given rise to investigation in a number of settings via many techniques. These thin sheets, unknown until a few years ago, reveal remarkable electronic and optical properties, which are only beginning to be understood and explored. There has also been continuing progress in the area of carbon nanotubes where there have been developments in the study of the spin and orbital motion of electrons, which have implications for spintronics applications. There has been progress in the area of qubits, where it now seems possible to communicate quantum information between qubits using photons. Thus emerges the possibility of using superconducting integrated circuits to carry out experimental studies in quantum optics. In addition, small Josephson junctions are being used to study quantum coherence in ways not possible previously. Device-driven research continues to show remarkable new results. The use of SQUID detection has allowed the possibility of very low magnetic field magnetic imaging (MRI) with the ability to resolve structures to a higher degree than previously possible. There has also been work in the area of nano-mechanical resonators, which may allow future study of squeezed states in a mechanical system. In addition, there continues to be work on nanomagnets, which show self-assembly properties and unusual temperature dependence to the magnetization. Ultra-cold gasses continue to see dramatic progress due to the unprecedented ability of the realm of cold-atom physics to manipulate atoms and their environment. Optical superlattices have allowed studies of superexchange interactions and open the possibility of further investigation of the dynamical behavior of quantum spin systems. Such cold gas experiments have allowed unprecedented opportunity to study quantum degenerate Fermi gasses and the realization of superfluidity with unusual interactions. Also in this area it has been possible to create controlled disorder and subsequently directly observe localization phenomena in one dimension, with the expectation that this can be extended to higher dimensions. Bob Hallock University of Massachusetts, USA Mikko Paalanen Helsinki University of Technology, Finland

Nature's combinatorial biosynthesis and recently engineered production of nucleoside antibiotics in Streptomyces.

PubMed

Chen, Shawn; Kinney, William A; Van Lanen, Steven

2017-04-01

Modified nucleosides produced by Streptomyces and related actinomycetes are widely used in agriculture and medicine as antibacterial, antifungal, anticancer and antiviral agents. These specialized small-molecule metabolites are biosynthesized by complex enzymatic machineries encoded within gene clusters in the genome. The past decade has witnessed a burst of reports defining the key metabolic processes involved in the biosynthesis of several distinct families of nucleoside antibiotics. Furthermore, genome sequencing of various Streptomyces species has dramatically increased over recent years. Potential biosynthetic gene clusters for novel nucleoside antibiotics are now apparent by analysis of these genomes. Here we revisit strategies for production improvement of nucleoside antibiotics that have defined mechanisms of action, and are in clinical or agricultural use. We summarize the progress for genetically manipulating biosynthetic pathways for structural diversification of nucleoside antibiotics. Microorganism-based biosynthetic examples are provided and organized under genetic principles and metabolic engineering guidelines. We show perspectives on the future of combinatorial biosynthesis, and present a working model for discovery of novel nucleoside natural products in Streptomyces.

Damage resistant optics for a mega-joule solid-state laser

NASA Astrophysics Data System (ADS)

Campbell, J. H.; Rainer, F.; Kozlowski, M. R.; Wolfe, C. R.; Thomas, I.; Milanovich, F.

1990-12-01

Research on Inertial Confinement Fusion (ICF) has progressed rapidly in the past several years. As a consequence, LLNL is developing plans to upgrade the current 120 kJ solid state (Nd3+ phosphate glass) Nova laser to a 1.5 to 2 megajoule system with the goal of achieving fusion ignition. The design of the planned Nova Upgrade is briefly discussed. Because of recent improvements in the damage resistance of optical materials it is now technically and economically feasible to build a megajoule-class solid state laser. Specifically, the damage threshold of Nd(+3)-doped phosphate laser glass, multilayer dielectric coatings, and non-linear optical crystals (e.g., KDP) have been dramatically improved. These materials now meet the fluence requirements for a 1.5 to 2 MJ Nd(+3)-glass laser operating at 1054 and 351 nm and at a pulse length of 3 ns. The recent improvements in damage thresholds are reviewed; threshold data at both 1064 and 355 nm and the measured pulse length scaling are presented.

Damage resistant optics for a megajoule solid state laser

NASA Astrophysics Data System (ADS)

Campbell, Jack H.; Rainer, Frank; Kozlowski, Mark R.; Wolfe, C. Robert; Thomas, Ian M.; Milanovich, Fred P.

1991-06-01

Research on Inertial Confinement Fusion (ICF) has progressed rapidly in the past several years. As a consequence LLNL is developing plans to upgrade the current 120 kJ solid state (Nd3-phosphate glass) Nova laser to a 1 . 5 to 2 megajoule system with the goal of achieving fusion ignition. The design of the planned Nova Upgrade is briefly discussed. Because of recent improvements in the damage resistance of optical materials it is now technically and economically feasible to build a megajoule-class solid state laser. Specifically the damage threshold of Nd3- doped phosphate laser glass muliilayer dielectric coatings and non-linear optical crystals (e. g. KDP) have been dramatically improved. These materials now meet the fluence requirements for a 1. 5-2 MJ Nd3-glass laser operating at 1054 and 351 nm and at a pulse length of 3 ns. The recent improvements in damage thresholds are reviewed threshold data at both 1064 and 355 nm and the measured pulse length scaling are presented. 1.

Progress and challenges for abiotic stress proteomics of crop plants.

PubMed

Barkla, Bronwyn J; Vera-Estrella, Rosario; Pantoja, Omar

2013-06-01

Plants are continually challenged to recognize and respond to adverse changes in their environment to avoid detrimental effects on growth and development. Understanding the mechanisms that crop plants employ to resist and tolerate abiotic stress is of considerable interest for designing agriculture breeding strategies to ensure sustainable productivity. The application of proteomics technologies to advance our knowledge in crop plant abiotic stress tolerance has increased dramatically in the past few years as evidenced by the large amount of publications in this area. This is attributed to advances in various technology platforms associated with MS-based techniques as well as the accessibility of proteomics units to a wider plant research community. This review summarizes the work which has been reported for major crop plants and evaluates the findings in context of the approaches that are widely employed with the aim to encourage broadening the strategies used to increase coverage of the proteome. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

I want you to pretend to be sincere.

PubMed

Hynes, Julia

2016-12-01

Medical education has changed dramatically since the inception of this journal 50 years ago and is indeed a work in progress: there is now heavy emphasis on the character of the physician, in particular, and professionalism, in general. The subjects of communications skills and the teaching of sincerity, empathy and compassion are relative newcomers to the stage: they are not even as old as this journal itself. Nevertheless, these topics arose in an ancient debate dating from classical antiquity. 'Can we teach virtue?' Plato wondered in the Meno. Not exactly, he concluded. Aristotle believed that acquirement of the virtues enables one to attain the human good, which, in turn, spills over to any profession in which the human being decides to engage. Aristotle, along with his successor, Thomas Aquinas, the 13th century philosopher, argued that the virtues cannot be taught but only acquired, with practice and time, in the real situation. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Wind Energy Deployment in Isolated Islanded Power Systems: Challenges & Realities (Poster)

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

Baring-Gould, I.

Rising costs of fuels, energy surety, and the carbon impacts of diesel fuel are driving remote and islanded communities dependent on diesel power generation to look for alternatives. Over the past few years, interest in using wind energy to reduce diesel fuel consumption has increased dramatically, potentially providing economic, environmental, social, and security benefits to the energy supply of isolated and islanded communities. However, the task of implementing such systems has remained elusive and subject to many cases of lower-than-expected performance. This poster describes the current status of integrating higher contribution wind technology into islanded power systems, the progress ofmore » recent initiatives implemented by the U.S. Department of Energy and Interior, and some of the lingering technical and commercial challenges. Operating experience from a number of power systems is described. The worldwide market for wind development in islanded communities (some of these supplying large domestic loads) provides a strong market niche for the wind industry, even in the midst of a slow global recovery.« less

Foreword to the Special Issue on Ejecta

DOE PAGES

Buttler, William Tillman; Williams, Robin J. R.; Najjar, Fady M.

2017-05-22

We report that ejecta physics is a young field, having developed over the last 60 years or so. Essentially, ejecta forms as a spray of dense particles generated from the free surface of metals subjected to strong shocks, but the detailed mechanisms controlling the properties of this particulate ejecta are only now being fully elucidated. The field is dynamic and rapidly growing, with military and industrial applications, and applications to areas such as fusion research. This Special Issue on Ejecta reports the current state of the art in ejecta physics, describing experimental, theoretical and computational work by research groups aroundmore » the world. While much remains to be done, the dramatic recent progress in the field, some of it first reported here, means that this volume provides a particularly timely review. In this foreword, we provide a brief historical overview of the development of ejecta physics, to define the context for the work in the rest of this Special Issue.« less

Millimeter-wave MMIC technology for smart weapons

NASA Astrophysics Data System (ADS)

Seashore, Charles R.

1994-12-01

Millimeter wave MMIC component technology has made dramatic progress over the last ten years largely due to funding stimulation received under the ARPA Tri-Service MIMIC program. In several smart weapon systems, MMIC components are now specified as the baseline approach for millimeter wave radar transceiver hardware. Availability of this new frontier in microelectronics has also enabled realization of sensor fusion for multispectral capability to defeat many forms of known countermeasures. The current frequency range for these MMIC-based components is approximately 30 to 100 GHz. In several cases, it has been demonstrated that the MMIC component performance has exceeded that available from hybrid microstrip circuits using selected discrete devices. However, challenges still remain in chip producibility enhancement and cost reduction since many of the essential device structure candidates are themselves emerging technologies with a limited wafer fabrication history and accumulated test databases. It is concluded that smart weapons of the future will rely heavily on advanced microelectronics to satisfy performance requirements as well as meeting stringent packaging and power source constraints.

[Dropped head syndrome as first manifestation of primary hyperparathyroid myopathy].

PubMed

Ota, Kiyobumi; Koseki, Sayo; Ikegami, Kenji; Onishi, Iichiroh; Tomimitsu, Hiyoryuki; Shintani, Shuzo

2018-03-28

75 years old woman presented with 6-month history of progressive dropped head syndrome. Neurological examination revealed moderate weakness of flexor and extensor of neck and mild weakness of proximal appendicular muscles with normal deep tendon reflexes. The needle electromyography showed short duration and low amplitude motor unit potential. No fibrillation potentials or positive sharp waves were seen. Biopsy of deltoid muscle was normal. Laboratory studies showed elevated levels of serum calcium (11.8 mg/dl, upper limit of normal 10.1) and intact parathyroid hormone (104 pg/ml, upper limit of normal 65), and decreased level of serum phosphorus (2.3 mg/dl, lower limit of normal 2.7). Ultrasonography and enhanced computed tomography revealed a parathyroid tumor. The tumor was removed surgically. Pathological examination proved tumor to be parathyroid adenoma. Dropped head and weakness of muscles were dramatically improved within a week after the operation. Although hyperparathyroidism is a rare cause of dropped head syndrome, neurologists must recognize hyperparathyroidism as a treatable cause of dropped head syndrome.

Perianal Crohn disease.

PubMed

Asma, Sioud Dhrif; Soumaya, Youssef; Kahena, Jaber; Raouf, Dhaoui Mohamed; Nejib, Doss

2006-12-10

Crohn disease is a chronic inflammatory disease characterized by sharply demarcated segments of gastrointestinal involvement from mouth to anus. Its perineal manifestations are among the most devastating and mutilating complications. They occur at any time and may precede the intestinal manifestations. Their most common presentations are perineal ulceration, fistula, and abscess. Proliferative and polypoid morphology of the cutaneous lesions mimicking warts and condyloma are rarely described. We report a 25-year-old woman with a 4-month history of confluent plaques of the perineal region with vegetant surfaces, suspected to be genital warts. The lesions progressed to fistulas, inducing deep ulcerations surrounded by pseudocondylomatous tumors. About 2 months prior to presentation she began to suffer from gastrointestinal symptoms and noted weight loss. Physical examination, endoscopic examination, and pathological interpretation led to the diagnosis of Crohn disease with perineal involvement being the initial presenting sign. Significant improvement was induced with prednisone (45 mg daily) and azathioprine. Our observation is notable for the pseudocondylomatous appearance and the dramatic response to medical treatment despite severe involvement.

The role of markup for enabling interoperability in health informatics.

PubMed

McKeever, Steve; Johnson, David

2015-01-01

Interoperability is the faculty of making information systems work together. In this paper we will distinguish a number of different forms that interoperability can take and show how they are realized on a variety of physiological and health care use cases. The last 15 years has seen the rise of very cheap digital storage both on and off site. With the advent of the Internet of Things people's expectations are for greater interconnectivity and seamless interoperability. The potential impact these technologies have on healthcare are dramatic: from improved diagnoses through immediate access to a patient's electronic health record, to in silico modeling of organs and early stage drug trials, to predictive medicine based on top-down modeling of disease progression and treatment. We will begin by looking at the underlying technology, classify the various kinds of interoperability that exist in the field, and discuss how they are realized. We conclude with a discussion on future possibilities that big data and further standardizations will enable.

Black-Hole Binaries, Gravitational Waves, and Numerical Relativity

NASA Technical Reports Server (NTRS)

Kelly, Bernard J.; Centrella, Joan; Baker, John G.; Kelly, Bernard J.; vanMeter, James R.

2010-01-01

Understanding the predictions of general relativity for the dynamical interactions of two black holes has been a long-standing unsolved problem in theoretical physics. Black-hole mergers are monumental astrophysical events ' releasing tremendous amounts of energy in the form of gravitational radiation ' and are key sources for both ground- and spacebased gravitational wave detectors. The black-hole merger dynamics and the resulting gravitational waveforms can only he calculated through numerical simulations of Einstein's equations of general relativity. For many years, numerical relativists attempting to model these mergers encountered a host of problems, causing their codes to crash after just a fraction of a binary orbit cnuld be simulated. Recently ' however, a series of dramatic advances in numerical relativity has ' for the first time, allowed stable / robust black hole merger simulations. We chronicle this remarkable progress in the rapidly maturing field of numerical relativity, and the new understanding of black-hole binary dynamics that is emerging. We also discuss important applications of these fundamental physics results to astrophysics, to gravitationalwave astronomy, and in other areas.

On the Path to SunShot - Emerging Opportunities and Challenges in U.S. Solar Manufacturing

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

Chung, Donald; Horowitz, Kelsey; Kurup, Parthiv

Innovation-driven cost and performance improvements, along with strong projected solar demand in the United States and across the Americas, could increase the attractiveness of U.S.-based solar manufacturing (see Chung et al. 2016). Although improvements to standard PV modules have produced deep cost reductions over the past 5 years, the returns on such incremental improvements appear to be diminishing, and more dramatic innovations in module design and manufacturing are required to continue along the path of rapid progress. At the same time, major opportunities exist for innovation to unlock the potential of CSP technologies. This need for innovation could benefit U.S.more » PV and CSP manufacturers. The United States has been rated one of the world’s most competitive and innovative countries as well as one of the best locations for PV manufacturing. It is a global leader in PV and CSP R&D and patent production, and U.S. PV manufacturers are already pursuing highly differentiated innovations.« less

Inspiration in the harness of daily labor. Darwin, botany, and the triumph of evolution, 1859-1868.

PubMed

Bellon, Richard

2011-09-01

Charles Darwin hoped that a large body of working naturalists would embrace evolution after the Origin of Species appeared in late 1859. He was disappointed. His evolutionary ideas at first made painfully little progress in the scientific community. But by 1863 the tide had turned dramatically, and within five years evolution became scientific orthodoxy in Britain. The Origin's reception followed this peculiar trajectory because Darwin had not initially tied its theory to productive original scientific investigation, which left him vulnerable to charges of reckless speculation. The debate changed with his successful application of evolution to original problems, most notably orchid fertilization, the subject of a well-received book in 1862. Most of Darwin's colleagues found the argument of the Origin convincing when they realized that it functioned productively in the day-to-day work of science-and not before. The conceptual force of the Origin, however outwardly persuasive, acquired full scientific legitimacy only when placed "in the harness of daily labour".

Algorithmic methods to infer the evolutionary trajectories in cancer progression

PubMed Central

Graudenzi, Alex; Ramazzotti, Daniele; Sanz-Pamplona, Rebeca; De Sano, Luca; Mauri, Giancarlo; Moreno, Victor; Antoniotti, Marco; Mishra, Bud

2016-01-01

The genomic evolution inherent to cancer relates directly to a renewed focus on the voluminous next-generation sequencing data and machine learning for the inference of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly stemming from the dramatic heterogeneity of the disease. In this paper, we build on our recent work on the “selective advantage” relation among driver mutations in cancer progression and investigate its applicability to the modeling problem at the population level. Here, we introduce PiCnIc (Pipeline for Cancer Inference), a versatile, modular, and customizable pipeline to extract ensemble-level progression models from cross-sectional sequenced cancer genomes. The pipeline has many translational implications because it combines state-of-the-art techniques for sample stratification, driver selection, identification of fitness-equivalent exclusive alterations, and progression model inference. We demonstrate PiCnIc’s ability to reproduce much of the current knowledge on colorectal cancer progression as well as to suggest novel experimentally verifiable hypotheses. PMID:27357673

The Changes They are A-Timed: Metabolism, Endogenous Clocks, and the Timing of Puberty

PubMed Central

Tolson, Kristen P.; Chappell, Patrick E.

2012-01-01

Childhood obesity has increased dramatically over the last several decades, particularly in industrialized countries, often accompanied by acceleration of pubertal progression and associated reproductive abnormalities (Biro et al., 2006; Rosenfield et al., 2009). The timing of pubertal initiation and progression in mammals is likely influenced by nutritional and metabolic state, leading to the hypothesis that deviations from normal metabolic rate, such as those seen in obesity, may contribute to observed alterations in the rate of pubertal progression. While several recent reviews have addressed the effects of metabolic disorders on reproductive function in general, this review will explore previous and current models of pubertal timing, outlining a potential role of endogenous timing mechanisms such as cellular circadian clocks in the initiation of puberty, and how these clocks might be altered by metabolic factors. Additionally, we will examine recently elucidated neuroendocrine regulators of pubertal progression such as kisspeptin, explore models detailing how the mammalian reproductive axis is silenced during the juvenile period and reactivated at appropriate developmental times, and emphasize how metabolic dysfunction such as childhood obesity may alter timing cues that advance or delay pubertal progression, resulting in diminished reproductive capacity. PMID:22645521

Recent Advances in Nanotechnology for Diabetes Treatment

PubMed Central

DiSanto, Rocco Michael; Subramanian, Vinayak; Gu, Zhen

2015-01-01

Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to “closed-loop” insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels. “Closing the loop” between blood glucose level (BGL) measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed. PMID:25641955

KENNEDY SPACE CENTER, FLA. - Capt. Charles Plumb (USNR retired) dramatically describes some of his six years as a prisoner of war in Vietnam. Plumb was keynote speaker for the kickoff of Spaceport Super Safety and Health Day at KSC, an annual event dedicated to reinforcing safe and healthful behaviors in the workforce.

NASA Image and Video Library

2003-10-15

KENNEDY SPACE CENTER, FLA. - Capt. Charles Plumb (USNR retired) dramatically describes some of his six years as a prisoner of war in Vietnam. Plumb was keynote speaker for the kickoff of Spaceport Super Safety and Health Day at KSC, an annual event dedicated to reinforcing safe and healthful behaviors in the workforce.

Innovating aging: promises and pitfalls on the road to life extension

PubMed Central

Vijg, Jan; de Grey, Aubrey D.N.J.

2014-01-01

One of the main benefits from the dramatic technological progress over the last two centuries is the enormous increase in human life expectancy, which has now reached record highs. After conquering most childhood diseases and a fair fraction of the diseases that plague adulthood, medical technology is now mainly pre-occupied by age-related disorders. Further progress is dependent on circumventing the traditional medical focus on individual diseases and instead targeting aging as a whole as the ultimate cause of the health problems that affect humankind at old age. In principle, a major effort to control the gradual accumulation of molecular and cellular damage – considered by many as the ultimate cause of intrinsic aging – may rapidly lead to interventions for regenerating aged and worn-out tissues and organs. While considered impossible by many, there really is no reason to reject this as scientifically implausible. However, as we discuss, it is not only scientific progress that is currently a limiting factor, but societal factors that hinder and may ultimately prevent further progress in testing and adopting the many possible interventions to cure aging. PMID:24732067

Organ Bioprinting: Are We There Yet?

PubMed

Gao, Guifang; Huang, Ying; Schilling, Arndt F; Hubbell, Karen; Cui, Xiaofeng

2018-01-01

About 15 years ago, bioprinting was coined as one of the ultimate solutions to engineer vascularized tissues, which was impossible to accomplish using the conventional tissue fabrication approaches. With the advances of 3D-printing technology during the past decades, one may expect 3D bioprinting being developed as much as 3D printing. Unfortunately, this is not the case. The printing principles of bioprinting are dramatically different from those applied in industrialized 3D printing, as they have to take the living components into account. While the conventional 3D-printing technologies are actually applied for biological or biomedical applications, true 3D bioprinting involving direct printing of cells and other biological substances for tissue reconstruction is still in its infancy. In this progress report, the current status of bioprinting in academia and industry is subjectively evaluated. The progress made is acknowledged, and the existing bottlenecks in bioprinting are discussed. Recent breakthroughs from a variety of associated fields, including mechanical engineering, robotic engineering, computing engineering, chemistry, material science, cellular biology, molecular biology, system control, and medicine may overcome some of these current bottlenecks. For this to happen, a convergence of these areas into a systemic research area "3D bioprinting" is needed to develop bioprinting as a viable approach for creating fully functional organs for standard clinical diagnosis and treatment including transplantation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

AIDS vaccines that allow HIV-1 to infect and escape immunologic control: a mathematic analysis of mass vaccination.

PubMed

van Ballegooijen, Marijn; Bogaards, Johannes A; Weverling, Gerrit-Jan; Boerlijst, Maarten C; Goudsmit, Jaap

2003-10-01

Cytotoxic T lymphocyte (CTL)-based HIV vaccine concepts shown to reduce viremia and postpone disease but not to prevent infection in monkeys are currently in human phase 1 trials. To evaluate the potential efficacy of vaccines that cannot prevent HIV-1 to infect and escape immunologic control, we designed a mathematic model that correlates the level of viremia to both infectiousness and disease progression. We speculate that vaccinees will have a virologic set point and disease progression rates comparable to untreated HIV-1-infected individuals with the best prognosis. Our model (illustrated with R0 = 3) shows that a sexually active population can ultimately be reduced to 26% of its initial size as a result of AIDS-related mortality in the absence of treatment or vaccination. Start of vaccination when HIV-1 prevalence is still low might postpone the peak incidence of infection and the dramatic decline in population size by up to 22 years. In conclusion, CTL-based vaccines that do not prevent HIV-1 infection but do postpone the time to onset of AIDS have considerable potential to curb the spread of HIV-1 and to postpone high AIDS-related mortality on a population level. The number of long-term survivors is substantially increased only when vaccination is initiated early in an AIDS epidemic, however.

Report of the Defense Science Board Task Force on Globalization and Security.

DTIC Science & Technology

1999-12-01

adversaries, such as North Korea’s progress in ballistic missiles. The leveling effect of globalization is a thread that runs through the Task Force...globalization are manifold. Increased use of the commercial sector cannot be separated from the effects of globalization. Nor is increased DoD reliance...enhance dramatically DSB Task Force on Globalization and Security DoD’s organizational efficiency and effectiveness . This could allow DoD to cut

Raytheon dual-use long life cryocooler

NASA Astrophysics Data System (ADS)

Kirkconnell, Carl S.; Ross, Bradley A.

2005-05-01

Raytheon has manufactured closed-cycle cryocoolers for both tactical military and space applications for over thirty years. Tactical and space cryocooler technologies have historically been treated as distinct both at Raytheon and throughout the industry. Differing technical requirements, operating lifetimes, and order quantities have driven these types of coolers to dramatically different design approaches and cost levels. For example, a typical space cryocooler system today costs approximately 2M as compared to roughly 10,000 for a tactical cryocooler. However, stimuli from both the tactical and space cooler user communities are driving the markets together. Tactical cryocooler requirements are starting to push towards operating lifetime requirements more characteristic of the space coolers (e.g., 20,000+ hours). Space cryocooler users, in particular Missile Defense Agency, are pushing for substantial cost reduction. In response, Raytheon is developing a low cost space cryocooler with an intended dual-use capability to also serve the tactical marketplace. This cooler leverages proven flexure-suspension technology to achieve long life, and a low cost concentric pulse tube cold head design has been developed that can be packaged into the existing Standard Advanced Dewar Assembly, Type One (SADA-I). The cooler meets or exceeds the SADA-I operational requirements (capacity, efficiency, etc.) as well. For the space-version of the cooler, the electronics cost has been reduced by an estimated 80% versus current designs, largely by approaching the vibration cancellation requirement from a dramatically different perspective. Fabrication of the brassboard expander is nearly complete, and the prototype design is well underway. The design approach, development progress, and proposed applications are presented.

Thin-film semiconductor perspective of organometal trihalide perovskite materials for high-efficiency solar cells

DOE PAGES

Xiao, Zhengguo; Yuan, Yongbo; Wang, Qi; ...

2016-02-19

Organolead trihalide perovskites (OTPs) are arising as a new generation of low-cost active materials for solar cells with efficiency rocketing from 3.5% to over 20% within only five years. From “dye” in dye sensitized solar cells to “hole conductors” and “electron conductors” in mesoscopic heterojunction solar cells, there has been a dramatic conceptual evolution on the function of OTPs in photovoltaic devices. OTPs were originally used as dyes in Gratzel cells, achieving a high efficiency above 15% which, however, did not manifest the excellent charge transport properties of OTPs. An analogy of OTPs to traditional semiconductors was drawn after themore » demonstration of highly efficient planar heterojunction structure OTP devices and the observation of their excellent bipolar transport properties with a large diffusion length exceeding 100 nm in CH 3NH 3PbI 3 (MAPbI 3) polycrystalline thin films. Here, this review aims to provide the most recent advances in the understanding of the origin of the high OTP device efficiency. Specifically we will focus on reviewing the progress in understanding 1) the characterization of fantastic optoelectronic property of OTPs, 2) the unusual defect physics that originate the optoelectronic property; 3) morphology control of the perovskite film from fabrication process and film post-treatment, and 4) device interface and charge transport layers that dramatically impact device efficiency in the OTP thin film devices; 5) photocurrent hysteresis; 6) tandem solar cells; 7) stability of the perovskite materials and solar cell devices.« less

Proteoglycan depletion and size reduction in lesions of early grade chondromalacia of the patella.

PubMed

Väätäinen, U; Häkkinen, T; Kiviranta, I; Jaroma, H; Inkinen, R; Tammi, M

1995-10-01

To determine the content and molecular size of proteoglycans (PGs) in patellar chondromalacia (CM) and control cartilages as a first step in investigating the role of matrix alterations in the pathogenesis of this disease. Chondromalacia tissue from 10 patients was removed with a surgical knife. Using identical techniques, apparently healthy cartilage of the same site was obtained from 10 age matched cadavers (mean age 31 years in both groups). Additional pathological cartilage was collected from 67 patients with grades II-IV CM (classified according to Outerbridge) using a motorised shaver under arthroscopic control. The shaved cartilage chips were collected with a dense net from the irrigation fluid of the shaver. The content of tissue PGs was determined by Safranin O precipitation or uronic acid content, and the molecular size by mobility on agarose gel electrophoresis. The mean PG content of the CM tissue samples with a knife was dramatically reduced, being only 15% of that in controls. The cartilage chips collected from shaving operations of grades II, III, and IV CM showed a decreasing PG content: 9%, 5%, and 1% of controls, respectively. Electrophoretic analysis of PGs extracted with guanidium chloride from the shaved tissue samples suggested a significantly reduced size of aggrecans in the mild (grade II) lesions. These data show that there is already a dramatic and progressive depletion of PGs in CM grade II lesions. This explains the softening of cartilage, a typical finding in the arthroscopic examination of CM. The PG size reduction observed in grade II implicates proteolytic attack as a factor in the pathogenesis of CM.

150 years since Babbage's ophthalmoscope.

PubMed

Keeler, C R

1997-11-01

The discovery of the ophthalmoscope in 1851 is rightly attributed to Hermann von Helmholtz. However, 4 years earlier, in 1847, Charles Babbage nearly invented the instrument that was to revolutionize ophthalmological examination so dramatically.

Impaired fetal muscle development and JAK-STAT activation mark disease onset and progression in a mouse model for merosin-deficient congenital muscular dystrophy.

PubMed

Nunes, Andreia M; Wuebbles, Ryan D; Sarathy, Apurva; Fontelonga, Tatiana M; Deries, Marianne; Burkin, Dean J; Thorsteinsdóttir, Sólveig

2017-06-01

Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a dramatic neuromuscular disease in which crippling muscle weakness is evident from birth. Here, we use the dyW mouse model for human MDC1A to trace the onset of the disease during development in utero. We find that myotomal and primary myogenesis proceed normally in homozygous dyW-/- embryos. Fetal dyW-/- muscles display the same number of myofibers as wildtype (WT) muscles, but by E18.5 dyW-/- muscles are significantly smaller and muscle size is not recovered post-natally. These results suggest that fetal dyW-/- myofibers fail to grow at the same rate as WT myofibers. Consistent with this hypothesis between E17.5 and E18.5 dyW-/- muscles display a dramatic drop in the number of Pax7- and myogenin-positive cells relative to WT muscles, suggesting that dyW-/- muscles fail to generate enough muscle cells to sustain fetal myofiber growth. Gene expression analysis of dyW-/- E17.5 muscles identified a significant increase in the expression of the JAK-STAT target gene Pim1 and muscles from 2-day and 3-week old dyW-/- mice demonstrate a dramatic increase in pSTAT3 relative to WT muscles. Interestingly, myotubes lacking integrin α7β1, a laminin-receptor, also show a significant increase in pSTAT3 levels compared with WT myotubes, indicating that α7β1 can act as a negative regulator of STAT3 activity. Our data reveal for the first time that dyW-/- mice exhibit a myogenesis defect already in utero. We propose that overactivation of JAK-STAT signaling is part of the mechanism underlying disease onset and progression in dyW-/- mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Novel Antibacterial Compounds and their Drug Targets - Successes and Challenges.

PubMed

Kaczor, Agnieszka A; Polski, Andrzej; Sobótka-Polska, Karolina; Pachuta-Stec, Anna; Makarska-Bialokoz, Magdalena; Pitucha, Monika

2017-01-01

Infectious diseases are one of the most important and urgent health problems in the world. According to the World Health Organization (WHO) statistics, infectious and parasitic diseases are a cause of about 16% of all deaths worldwide and over 40% of deaths in Africa. A considerable progress that has been made during last hundred years in the fight against infectious diseases, in particular bacterial infections, can be attributed mainly to three factors: (1) the general improvement of living conditions, in particular sanitation; (2) development of vaccines and (3) development of efficient antibacterial drugs. Although considerable progress in reduction of the number of cases of bacterial infections, especially in lethal cases, has been made, continued cases and outbreaks of these diseases persist, which is caused by different contributing factors. Indeed, during last sixty years antibacterial drugs were used against various infectious diseases caused by bacterial pathogens with an undoubtable success. The most fruitful period for antibiotic development lasted from 40's to 60's of the last century and resulted in the majority of antibiotics currently on the market, which were obtained by screening actinomycetes derived from soil. Although the market for antibacterial drugs is nowadays greater than 25 billion US dollars per year, novel antibacterial drugs are still demanded due to developed resistance of many pathogenic bacteria against current antibiotics. In the last five years, one can observe a dramatic increase in cases of resistant bacteria strains (e.g. Klebsiella pneumoniae and E. coli) which are responsible for difficult to treat pneumonia and infections of urinary tract. The development of resistant bacteria strains is a side effect of antibiotic application for treatment: the infections become untreatable as a result of the existence of antibiotic-tolerant persisters. In this review, we discuss the challenges in antibacterial drug discovery, including the molecular basis of drug resistance, drug targets for novel antibacterial drugs, and new compounds (since year 2010) from different chemical classes with antibacterial activity, focusing on structure-activity relationships. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Political and Social History of HIV in South Africa.

PubMed

Simelela, Nono; Venter, W D Francois; Pillay, Yogan; Barron, Peter

2015-06-01

For the past 25 years, South Africa has had to deal with the inexorable and monumental rise of HIV. From one or two isolated cases, in the late 1980s, South Africa now has an estimated 6.4 million people infected with HIV, with high rates of concomitant tuberculosis, which will profoundly affect the country for decades to come. For nearly 10 years, the South African government's response to the HIV epidemic was described as denialist, which was estimated to have resulted in the deaths of 330,000 people because lifesaving antiretroviral therapy (ART) was not provided (Chigwedere et al. J Acquir Immune Defic Syndr. 49:410-15, 2008; Heywood 2004). However, the story of the HIV and AIDS response in South Africa over the past 5 years is one of great progress after almost a decade of complex and tragic denialism that united civil society in a way not seen since the opposition to apartheid. Today, South Africa can boast of close to 3 million people on ART, by far the largest number in the world. Prevention efforts appear to be yielding results but there continues to be large numbers of new infections, with a profound peak in incidence in young women aged 15 to 24 years. In addition, infections occur across the gender spectrum in older age groups. As a result of the massive increase in access to ART after 2004 and particularly after 2008 as political will towards the HIV ART programme improved, there has been a marked increase in life expectancy, from 56 to 61 years in the period 2009-2012 alone; the aggressive expansion of the prevention of mother to child transmission (PMTCT) to HIV-positive pregnant women has been accompanied by dramatic decrease in HIV transmission to infants; and a 25 % decrease in child and infant mortality rates in the period 2009-2012. This progress in access is significantly due to a civil society movement that was prepared to pose a rights-based challenge to a governing party in denial and to brave health officials, politicians and clinicians working in a hostile system to bring about change.

2222 kidney transplantations at the University Hospital Basel: a story of success and new challenges.

PubMed

Wehmeier, Caroline; Georgalis, Argyrios; Hirt-Minkowski, Patricia; Amico, Patrizia; Hoenger, Gideon; Voegele, Thomas; Brun, Nicole; Bock, Andreas; Wolff, Thomas; Guerke, Lorenz; Bachmann, Alexander; Hopfer, Helmut; Dickenmann, Michael; Steiger, Jürg; Schaub, Stefan

2016-01-01

The aim was to investigate changes in kidney allograft donor/recipient characteristics and outcomes at our centre. We retrospectively reviewed all 2222 kidney transplantations performed between 1967 and 2015. The population was divided into four eras on the basis of time intervals corresponding to major changes in immunosuppression and pretransplant risk stratification: (i.) 1967-1980 (n = 231), (ii.) 1981-1997 (n = 883), (iii.) 1998-2004 (n = 437), (iv.) 2005-2015 (n = 671). In deceased donor transplants, we observed a continuous increase of the median recipient (45, 51, 56 and 58 years; p <0.0001) and donor (26, 36, 49 and 54 years; p <0.0001) age. Notably, the frequency of expanded criteria donors increased dramatically (1%, 10%, 28%, 40%, p <0.0001). Graft survival at 1 year (63%, 82%, 89%, 95%), 5 years (46%, 66%, 72%, 78%) and 10 years (27%, 46%, 48%, 61%) significantly improved (p <0.0001). Patient survival also significantly improved and remained stable at a high level within the last three eras (1 year: 97%; 5 years: 87%; 10 years: 71%). Similar trends along with slightly better outcomes were noticed in living donor transplantations. In the most recent era, graft losses in elderly patients were in 81% of cases related to the patient's death, whereas in young patients 83% of graft losses were caused by transplant failure (mainly rejection). Allograft function at the time of patients' deaths would have allowed for calculated 10 additional years with an estimated glomerular filtration rate >15 ml/min. Despite increasing donor and recipient age, outcomes improved, illustrating ongoing progress in kidney transplantation. A major new challenge is to match the functional capacity of the donor organ with the anticipated lifespan of the recipient.

Frontline treatment of acute myeloid leukemia in adults

PubMed Central

Tamamyan, Gevorg; Kadia, Tapan; Ravandi, Farhad; Borthakur, Gautam; Cortes, Jorge; Jabbour, Elias; Daver, Naval; Ohanian, Maro; Kantarjian, Hagop; Konopleva, Marina

2017-01-01

Recent years have highlighted significant progress in understanding the underlying genetic and epigenetic signatures of acute myeloid leukemia(AML). Most importantly, novel chemotherapy and targeted strategies have led to improved outcomes in selected genetic subsets. AML is a remarkably heterogeneous disease, and individualized therapies for disease-specific characteristics (considering patients’ age, cytogenetics, and mutations) could yield better outcomes. Compared with the historical 5-to 10-year survival rate of 10%, the survival of patients who undergo modern treatment approaches reaches up to 40–50%, and for specific subsets, the improvements are even more dramatic; for example, in acute promyelocytic leukemia, the use of all-trans retinoic acid and arsenic trioxide improved survival from 30–40% up to 80–90%. Similar progress has been documented in core-binding-factor-AML, with an increase in survival from 30% to 80% upon the use of high-dose cytarabine/fludarabine/granulocyte colony-stimulating factor combination regimens. AML treatment was also recently influenced by the discovery of the superiority of regimens with higher dose Ara-C and nucleoside analogues compared with the “7+3” regimen, with about a 20% improvement in overall survival. Despite these significant differences, most centers continue to use the “7+3” regimen, and greater awareness will improve the outcome. The discovery of targetable molecular abnormalities and recent studies of targeted therapies (gemtuzumab ozagomycin, FLT3 inhibitors, isocitrate dehydrogenase inhibitors, and epigenetic therapies), future use of checkpoint inhibitors and other immune therapies such as chimeric antigen receptor T-cells, and maintenance strategies based on the minimal residual disease evaluation represent novel, exciting clinical leads aimed to improve AML outcomes in the near future. PMID:28109402

A Year of Progress: NASA's Space Launch System Approaches Critical Design Review

NASA Technical Reports Server (NTRS)

Askins, Bruce; Robinson, Kimberly

2015-01-01

NASA's Space Launch System (SLS) made significant progress on the manufacturing floor and on the test stand in 2014 and positioned itself for a successful Critical Design Review in mid-2015. SLS, the world's only exploration-class heavy lift rocket, has the capability to dramatically increase the mass and volume of human and robotic exploration. Additionally, it will decrease overall mission risk, increase safety, and simplify ground and mission operations - all significant considerations for crewed missions and unique high-value national payloads. Development now is focused on configuration with 70 metric tons (t) of payload to low Earth orbit (LEO), more than double the payload of the retired Space Shuttle program or current operational vehicles. This "Block 1" design will launch NASA's Orion Multi-Purpose Crew Vehicle (MPCV) on an uncrewed flight beyond the Moon and back and the first crewed flight around the Moon. The current design has a direct evolutionary path to a vehicle with a 130t lift capability that offers even more flexibility to reduce planetary trip times, simplify payload design cycles, and provide new capabilities such as planetary sample returns. Every major element of SLS has successfully completed its Critical Design Review and now has hardware in production or testing. In fact, the SLS MPCV-to-Stage-Adapter (MSA) flew successfully on the Exploration Flight Test (EFT) 1 launch of a Delta IV and Orion spacecraft in December 2014. The SLS Program is currently working toward vehicle Critical Design Review in mid-2015. This paper will discuss these and other technical and programmatic successes and challenges over the past year and provide a preview of work ahead before the first flight of this new capability.

Current status of x-ray mask manufacturing at the Microlithographic Mask Development Center

NASA Astrophysics Data System (ADS)

Kimmel, Kurt R.; Hughes, Patrick J.

1996-07-01

The Microlithographic Mask Development Center (MMD) has been the focal point of X-ray mask development efforts in the United States since its inception in 1993. Funded by the Advanced Research Projects Agency (ARPA), and with technical support from the Proximity X-ray Lithography Association (AT&T, IBM, Loral Federal Systems, and Motorola) the MMD has recently made dramatic advances in mask fabrication. Numerous defect-free 64Mb and 256Mb DRAM masks have been made on both boron-doped silicon and silicon carbide substrates. Image-placement error of less than 35nm 3 sigma is achieved with high yield. Image-size (critical dimension) control of 25nm 3 sigma on 250nm nominal images is representative performance. This progress is being made in a manufacturing environment with significant volumes, multiple customers, multiple substrate configurations, and fast turnaround-time (TAT) requirements. The MMD state-of-the-art equipment infrastructure has made much of this progress possible. This year the MMD qualified the EL-4, an IBM-designed-and-built variable-shaped-spot e-beam system. The fundamental performance parameters of this system will be described. Operational techniques of multiple partial exposure writing and product specific emulation (PSE) have been implemented to improve image-placement accuracy with remarkable success. Image-size control was studied in detail with contributory components separated. Defect density was systematically reduced to yield defect-free masks while simultaneously tightening inspection criteria. Information about these and other recent engineering highlights will be reported. An outline of the primary engineering challenges and goals for 1996 and status of progress toward 100 nm design rule capability will also be given.

The Pathophysiology of Repetitive Concussive Traumatic Brain Injury in Experimental Models; New Developments and Open Questions

PubMed Central

Brody, David L; Benetatos, Joseph; Bennett, Rachel E; Klemenhagen, Kristen C; Donald, Christine L Mac

2015-01-01

In recent years, there has been an increasing interest in the pathophysiology of repetitive concussive traumatic brain injury (rcTBI) in large part due to the association with dramatic cases of progressive neurological deterioration in professional athletes, military personnel, and others. However, our understanding of the pathophysiology of rcTBI is less advanced than for more severe brain injuries. Most prominently, the mechanisms underlying traumatic axonal injury, microglial activation, amyloid-beta accumulation, and progressive tau pathology are not yet known. In addition, the role of injury to dendritic spine cytoskeletal structures, vascular reactivity impairments, and microthrombi are intriguing and subjects of ongoing inquiry. Methods for quantitative analysis of axonal injury, dendritic injury, and synaptic loss need to be refined for the field to move forward in a rigorous fashion. We and others are attempting to develop translational approaches to assess these specific pathophysiological events in both animals and humans to facilitate clinically relevant pharmacodynamic assessments of candidate therapeutics. In this article, we review and discuss several of the recent experimental results from our lab and others. We include new initial data describing the difficulty in modeling progressive tau pathology in experimental rcTBI, and results demonstrating that sertraline can alleviate social interaction deficits and depressive-like behaviors following experimental rcTBI plus foot shock stress. Furthermore, we propose a discrete set of open, experimentally tractable questions that may serve as a framework for future investigations. In addition, we also raise several important questions that are less experimentally tractable at this time, in hopes that they may stimulate future methodological developments to address them. PMID:25684677

Progress towards malaria control targets in relation to national malaria programme funding

PubMed Central

2013-01-01

Background Malaria control has been dramatically scaled up the past decade, mainly thanks to increasing international donor financing since 2003. This study assessed progress up to 2010 towards global malaria impact targets, in relation to Global Fund, other donor and domestic malaria programme financing over 2003 to 2009. Methods Assessments used domestic malaria financing reported by national programmes, and Global Fund/OECD data on donor financing for 90 endemic low- and middle-income countries, WHO estimates of households owning one or more insecticide-treated mosquito net (ITN) for countries in sub-Saharan Africa, and WHO-estimated malaria case incidence and deaths in countries outside sub-Saharan Africa. Results Global Fund and other donor funding is concentrated in a subset of the highest endemic African countries. Outside Africa, donor funding is concentrated in those countries with highest malaria mortality and case incidence rates over the years 2000 to 2003. ITN coverage in 2010 in Africa, and declines in case and death rates per person at risk over 2004 to 2010 outside Africa, were greatest in countries with highest donor funding per person at risk, and smallest in countries with lowest donor malaria funding per person at risk. Outside Africa, all-source malaria programme funding over 2003 to 2009 per case averted ($56-5,749) or per death averted ($58,000-3,900,000) over 2004 to 2010 tended to be lower (more favourable) in countries with higher donor malaria funding per person at risk. Conclusions Increases in malaria programme funding are associated with accelerated progress towards malaria control targets. Associations between programme funding per person at risk and ITN coverage increases and declines in case and death rates suggest opportunities to maximize the impact of donor funding, by strategic re-allocation to countries with highest continued need. PMID:23317000

Consequences of dramatic reductions in state tobacco control funds: Florida, 1998-2000.

PubMed

Niederdeppe, J; Farrelly, M C; Hersey, J C; Davis, K C

2008-06-01

This study assessed whether dramatic funding reductions to the Florida Tobacco Control Program (FTCP) influenced trends in recall of the Florida "truth" anti-smoking media campaign, anti-industry attitudes and non-smoking intentions among Florida teens. We used an interrupted time series technique to test for differences in the rates of change in Florida "truth" recall, anti-industry beliefs and non-smoking intentions before and after the FTCP budget cuts using the Florida Anti-tobacco Media Evaluation (FAME) survey, a repeated cross-sectional telephone survey of Florida teens. Recall of the Florida "truth" anti-smoking campaign, anti-industry attitudes, and non-smoking intentions increased dramatically between April 1998 and May 1999. Florida "truth" recall declined after FTCP budget cuts in June 1999. Anti-industry beliefs and non-smoking intentions plateaued or began to decline after the budget cuts. The launch of the national "truth" campaign in February 2000 may have offset otherwise deleterious effects of the budget cuts on anti-industry beliefs, but not smoking intentions. Reductions in tobacco control funding have immediate effects on programme exposure and cognitive precursors to smoking initiation. There is a critical need to maintain and enhance funding for state tobacco control programmes to continue nationwide progress in preventing youth from initiating cigarette smoking.

Emerging players in the initiation of eukaryotic DNA replication

PubMed Central

2012-01-01

Faithful duplication of the genome in eukaryotes requires ordered assembly of a multi-protein complex called the pre-replicative complex (pre-RC) prior to S phase; transition to the pre-initiation complex (pre-IC) at the beginning of DNA replication; coordinated progression of the replisome during S phase; and well-controlled regulation of replication licensing to prevent re-replication. These events are achieved by the formation of distinct protein complexes that form in a cell cycle-dependent manner. Several components of the pre-RC and pre-IC are highly conserved across all examined eukaryotic species. Many of these proteins, in addition to their bona fide roles in DNA replication are also required for other cell cycle events including heterochromatin organization, chromosome segregation and centrosome biology. As the complexity of the genome increases dramatically from yeast to human, additional proteins have been identified in higher eukaryotes that dictate replication initiation, progression and licensing. In this review, we discuss the newly discovered components and their roles in cell cycle progression. PMID:23075259

Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease

PubMed Central

Rousseaux, Maxime W. C.; Marcogliese, Paul C.; Qu, Dianbo; Hewitt, Sarah J.; Seang, Sarah; Kim, Raymond H.; Slack, Ruth S.; Schlossmacher, Michael G.; Lagace, Diane C.; Mak, Tak W.; Park, David S.

2012-01-01

DJ-1 mutations cause autosomal recessive early-onset Parkinson disease (PD). We report a model of PD pathology: the DJ1-C57 mouse. A subset of DJ-1–nullizygous mice, when fully backcrossed to a C57BL/6J background, display dramatic early-onset unilateral loss of dopaminergic (DA) neurons in their substantia nigra pars compacta, progressing to bilateral degeneration of the nigrostriatal axis with aging. In addition, these mice exhibit age-dependent bilateral degeneration at the locus ceruleus nucleus and display mild motor behavior deficits at aged time points. These findings effectively recapitulate the early stages of PD. Therefore, the DJ1-C57 mouse provides a tool to study the preclinical aspects of neurodegeneration. Importantly, by exome sequencing, we identify candidate modifying genes that segregate with the phenotype, providing potentially critical clues into how certain genes may influence the penetrance of DJ-1–related degeneration in mice. PMID:23019375

Pulsatile crizotinib treatment for brain metastasis in a patient with non-small-cell lung cancer.

PubMed

Wang, S; Chen, J; Xie, Z; Xia, L; Luo, W; Li, J; Li, Q; Yang, Z

2017-10-01

Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is a distinct subtype with patients showing peculiar clinicopathological features and dramatic responses to the ALK tyrosine kinase inhibitor crizotinib. Patients with this cancer variant have a dismal prognosis and limited treatment options when it has progressed to intracranial metastasis because of inadequate drug penetration into the central nervous system (CNS). Factors associated with response to TKI therapy have been reported to include pharmacokinetic and biodynamic resistance phenomena. In our NSCLC patient with multiple intracranial metastases, we administered high-dose pulsatile crizotinib therapy (1000 mg/d) on a one-day-on/one-day-off basis. A significant central nervous system (CNS) response was achieved, and time to neurological progression was prolonged to 6 months. High-dose pulsatile therapy may be an effective dosing strategy for crizotinib in NSCLC showing progression to metastasis in the brain. © 2017 John Wiley & Sons Ltd.

Progressive Primary Pulmonary Tuberculosis Presenting as the Sudden Unexpected Death in Infancy: A Case Report

PubMed Central

Dempers, Johan; Sens, Mary Ann; Wadee, Shabbir Ahmed; Kinney, Hannah C.; Odendaal, Hein J.; Wright, Colleen A.

2010-01-01

The classification of an unexpected infant death as the sudden infant death syndrome (SIDS) depends upon a complete autopsy and death scene investigation to exclude known causes of death. Here we report the death of a four-month-old infant in a tuberculosis endemic area that presented as a sudden unexpected death in infancy (SUDI) with no apparent explanation based on the death scene characteristics. The autopsy, however, revealed progressive primary pulmonary tuberculosis with intrathoracic adenopathy, compression of the tracheobronchial tree and miliary lesions in the liver. This case underscores the clinical difficulties in the diagnosis of infantile tuberculosis, as well as the possibility of sudden death as part of its protean manifestations. The pathology and clinical progression of tuberculosis in infants differs from older children and adults due to the immature immune response in infants. This case dramatically highlights the need for complete autopsies in all sudden and unexpected infant deaths, as well as the public health issues in a sentinel infant tuberculosis diagnosis. PMID:20705406

Optimizing management of actinic keratosis and photodamaged skin: utilizing a stepwise approach.

PubMed

Lee, Andrew D; Jorizzo, Joseph L

2009-09-01

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

Renin-Angiotensin-Aldosterone System Blockade in Diabetic Nephropathy. Present Evidences

PubMed Central

Lozano-Maneiro, Luz; Puente-García, Adriana

2015-01-01

Diabetic Kidney Disease (DKD) is the leading cause of chronic kidney disease in developed countries and its prevalence has increased dramatically in the past few decades. These patients are at an increased risk for premature death, cardiovascular disease, and other severe illnesses that result in frequent hospitalizations and increased health-care utilization. Although much progress has been made in slowing the progression of diabetic nephropathy, renal dysfunction and the development of end-stage renal disease remain major concerns in diabetes. Dysregulation of the renin-angiotensin-aldosterone system (RAAS) results in progressive renal damage. RAAS blockade is the cornerstone of treatment of DKD, with proven efficacy in many arenas. The theoretically-attractive option of combining these medications that target different points in the pathway, potentially offering a more complete RAAS blockade, has also been tested in clinical trials, but long-term outcomes were disappointing. This review examines the “state of play” for RAAS blockade in DKD, dual blockade of various combinations, and a perspective on its benefits and potential risks. PMID:26569322

Dramatic response to temozolomide, irinotecan, and bevacizumab for recurrent medulloblastoma with widespread osseous metastases.

PubMed

Bonney, Phillip A; Santucci, Joshua A; Maurer, Adrian J; Sughrue, Michael E; McNall-Knapp, Rene Y; Battiste, James D

2016-04-01

There is little evidence to guide the choice of chemotherapeutic agents for osseous metastases in medulloblastoma. Recently, triple therapy with temozolomide, irinotecan, and bevacizumab has been reported to have efficacy in recurrent medulloblastoma, and this regimen alone and in combination with other agents has been tested in several early-phase clinical trials. Here we report a 20-year-old woman with multiply-relapsed medulloblastoma with numerous osseous metastases 8 years after original diagnosis who responded dramatically to temozolomide, irinotecan, and bevacizumab therapy. This case highlights the potential for this regimen in treating osseous metastases in medulloblastoma. Copyright © 2016. Published by Elsevier Ltd.

A young-onset frontal dementia with dramatic calcifications due to a novel CSF1R mutation.

PubMed

Gore, Ethan; Manley, Andrew; Dees, Daniel; Appleby, Brian S; Lerner, Alan J

2016-06-01

Neuroimaging and genomic analysis greatly aid in the identification of young-onset dementia antemortem. We present the case of a 33-year-old female with a 2-year rapid decline to dementia and immobility marked by personality change, executive deficits including compulsions, attention deficit, apraxia, Parkinsonism, and pyramidal signs. She had unique and dramatic calcifications and confluent white matter changes on imaging and was found to have a novel mutation in the colony stimulating factor 1 receptor gene causing adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Here, we review ALSP and briefly discuss differential diagnoses.

The solid-state signaling pathway from extracellular matrix to nuclear matrix: The critical role of three-dimensional architecture for functional differentiation

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

Lelievre, S.; Bissell, M.J.

Breast cells are useful experimental subjects for cell biologists because the mammary gland is one of the few tissues that undergoes dramatic changes in form and function after adulthood. Recently, the study in our laboratory of a human breast tumor progression series has allowed for the analysis of changes in cellular architecture (including nuclear architecture) when phenotypically normal cells become tumorigenic. This research aims to participate in the battle against breast cancer by helping to understand tumor progression and to identify new therapeutic markers for cancer treatment. This article explores the advantages and challenges of using high resolution X-ray computedmore » microtomography for the study of 3-dimensional organization of breast tissue architecture.« less

[The glymphatic system: concept, function and research progresses].

PubMed

Wang, Lin-Hui; Wang, Zi-Lan; Chen, Wen-Yue; Chen, Ming-Jia; Xu, Guang-Yin

2018-02-25

The glymphatic system is a cerebrospinal fluid-interstitial fluid exchange system dependent on the water channel aquaporin-4 polarized on astrocyte endfeet, which is proposed to account for the clearance of abnormal proteins (e.g. β-amyloid) and metabolites (e.g. lactate) from the brain. Accumulating studies have revealed that glymphatic activity during sleep and general anesthesia is dramatically enhanced, while its function is significantly damaged during aging, traumatic brain injury, Alzheimer's disease, stroke, and diabetes. The glymphatic hypothesis is a breakthrough in the field of neuroscience recently, which would considerably enhance our comprehension on the cerebrospinal fluid circulation and its role in the maintenance of brain homeostasis. In this review, we briefly introduced the conceptualization of glymphatic system, summarized the recent progresses, and prospected its future investigation and potential clinical application.

The Final Merger of Black-Hole Binaries

NASA Technical Reports Server (NTRS)

Kelly, Bernard J.; Centrealla, Joan; Baker, John G.; Kelly, Bernard J.; vanMeter, James R.

2010-01-01

Recent breakthroughs in the field of numerical relativity have led to dramatic progress in understanding the predictions of General Relativity for the dynamical interactions of two black holes in the regime of very strong gravitational fields. Such black-hole binaries are important astrophysical systems and are a key target of current and developing gravitational-wave detectors. The waveform signature of strong gravitational radiation emitted as the black holes fall together and merge provides a clear observable record of the process. After decades of slow progress / these mergers and the gravitational-wave signals they generate can now be routinely calculated using the methods of numerical relativity. We review recent advances in understanding the predicted physics of events and the consequent radiation, and discuss some of the impacts this new knowledge is having in various areas of astrophysics

[Analysis of relation between the development of study and literatures about benign positional paroxysmal vertigo published international and domestic].

PubMed

Jia, Jianping; Sun, Xiaohui; Dai, Song; Sang, Yuehong

2016-01-01

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder that causes vertigo. Study of BPPV has dramatically rapid progress in recent years. We analyze the BPPV growth We searched the international data quantity year by year in database of PubMed, ScienceDirect and WILEY before 2014 respectively, then we searched the domestic data quantity year by year in database of CNKI, VIP and Wanfang Data before 2015 by selecting "Benign paroxysmal positional vertigo" as the keywords. Then we carried out regression analysis with the gathered results in above databases to determine data growth regularity and main factors that affect future development of BPPV. Also, we analyzes published BPPV papers in domestic and international journals. PubMed database contains 808 literatures, ScienceDirect contains 177 database and WILEY contains 46 literatures, All together we collected 1 038 international articles. CNKI contains 440 literatures, VIP contains 580 literatures and WanFang data contains 449 literatures. All together we collected 1 469 domestic literatures. It shows the rising trend of the literature accumulation amount of BPPV. The scattered point diagram of BPPV shows an exponential growing trend, which was growing slowly in the early time but rapidly in recent years. It shows that the development of BPPV has three stages from international arical: exploration period (before 1985), breakthrough period (1986-1998). The deepening stage (after 1998), Chinese literature also has three stages from domestic BPPV precess. Blank period (before the year of 1982), the enlightenment period (1982-2004), the deepening stage (after the year of 2004). In the pregress of BPPV, many outsantding sccholars played an important role in domestic scitifction of researching, which has produced a certain influence in the worldwide.

[Endocrine complications of cystic fibrosis in childhood].

PubMed

Castanet, M; Wieliczko, M-C

2012-05-01

Since the 20 last years, the median age of survival has dramatically improved in children suffering from cystic fibrosis and complications such as growth retardation, pubertal delay and low bone mineral density are now more often than not observed in affected adolescents. The severity of the disease and the poor nutritional status due to pancreatic insufficiency and malabsorption are commonly implicated but recent data suggest that the disease could also play a role though the alteration of the chlore chanel (CFTR). Furthermore an increase prevalence of glucose intolerance and diabetes due to the progressive β cells destruction is observed in these children that make the life sometimes difficult for these adolescents already affected by an heavy chronic disease. The monitoring of the children should thus now become pluridisciplinary and include regular clinical evaluation of height and pubertal status, mineral bone density by DEXA and OGTT every two years since 10 years of age. Therefore, in addition to the standard treatment of cystic fibrosis is now added the vitamin D supplementation, the subcutaneous insulin therapy and may be the growth hormone that could be a new therapeutic demonstrating beneficial effects in these chronic disease. However further studies need to be performed to improve the management of these new endocrine complications more and more frequent in children and adolescents suffering from cystic fibrosis. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Dengue vaccine: come let's fight the menace.

PubMed

Chawla, Sumit; Sahoo, Soumya Swaroop; Singh, Inderjeet; Verma, Madhur; Gupta, Vikas; Kumari, Sneh

2015-01-01

Although dengue has a global distribution, the World Health Organization (WHO) South-East Asia region together with Western Pacific region bears nearly 75% of the current global disease burden. Globally, the societal burden has been estimated to be approximately 528 to 1300 disability-adjusted life years (DALY) per million to populations in endemic regions Dengue is believed to infect 50 to 100 million people worldwide a year with half a million life-threatening infections requiring hospitalization, resulting in approximately 12,500 to 25,000 deaths. Despite being known for decades and nearly half the world's population is at risk for infection with as many as 100 million cases occurring annually, the pitiable state is that we still have no antiviral drugs to treat it and no vaccines to prevent it. In recent years, however, the development of dengue vaccines has accelerated dramatically in tandem with the burgeoning dengue problem with a rejuvenated vigour. However, recent progress in molecular-based vaccine strategies, as well as a renewed commitment by the World Health Organization (WHO) to co-ordinate global efforts on vaccine development, finally provides hope that control of this serious disease may be at hand. Today, several vaccines are in various stages of advanced development, with clinical trials currently underway on 5 candidate vaccines. Trials in the most advanced stages are showing encouraging preliminary data, and the leading candidate could be licensed as early as 2015.

Cancer therapy based on oncogene addiction.

PubMed

McCormick, Frank

2011-05-01

Tumor cells contain multiple mutations, yet they often depend on continued expressed of a single oncoprotein for survival. Targeting these proteins has led to dramatic responses. Unfortunately, patients usually progress, through drug resistance or adaptive resistance through reprogramming of signaling networks. The Ras-MAPK pathway provides examples of these successes and failures, and has revealed unexpected degrees of oncogene addiction and signaling complexity that are likely to be useful lessons for the future of targeted therapy. Copyright © 2011 Wiley-Liss, Inc.

The Envy of Scholars: Applying the Lessons of the Framingham Heart Study to the Prevention of Chronic Kidney Disease.

PubMed

Wasser, Walter G; Gil, Amnon; Skorecki, Karl L

2015-07-30

During the past 50 years, a dramatic reduction in the mortality rate associated with cardiovascular disease has occurred in the US and other countries. Statistical modeling has revealed that approximately half of this reduction is the result of risk factor mitigation. The successful identification of such risk factors was pioneered and has continued with the Framingham Heart Study, which began in 1949 as a project of the US National Heart Institute (now part of the National Heart, Lung, and Blood Institute). Decreases in total cholesterol, blood pressure, smoking, and physical inactivity account for 24%, 20%, 12%, and 5% reductions in the mortality rate, respectively. Nephrology was designated as a recognized medical professional specialty a few years later. Hemodialysis was first performed in 1943. The US Medicare End-Stage Renal Disease (ESRD) Program was established in 1972. The number of patients in the program increased from 5,000 in the first year to more than 500,000 in recent years. Only recently have efforts for risk factor identification, early diagnosis, and prevention of chronic kidney disease (CKD) been undertaken. By applying the approach of the Framingham Heart Study to address CKD risk factors, we hope to mirror the success of cardiology; we aim to prevent progression to ESRD and to avoid the cardiovascular complications associated with CKD. In this paper, we present conceptual examples of risk factor modification for CKD, in the setting of this historical framework.

Observations on self-incineration characteristics in 24 years (1993-2016) of autopsies in the city of Milan.

PubMed

Amadasi, Alberto; Boracchi, Michele; Gentile, Guendalina; Maciocco, Francesca; Maghin, Francesca; Zoja, Riccardo

2018-01-01

Self-incineration is one of the most dramatic and lethal suicide methods. It is rarely reported in Western countries and is more frequent in developing regions. We illustrate the forensic cases of self-immolation occurring over 24 years in the city of Milan, Italy, highlighting the main issues of such a complex and rare suicide. We selected 33 cases of self-incineration among 23,417 autopsies (4022 suicides) performed at the Department of Legal Medicine of the University of Milan over a period of 24 years (1993-2016). Several parameters were included and analysed: gender and age of the victims, pathological history, previous suicide intentions/attempts, duration of burning, place of death or discovery of the corpse, circumstantial data of fatal events and autopsy findings, with particular attention to thermal injuries. Self-incineration was found in 0.8% of total suicides and 0.14% of total autopsies. One of these cases involved a complex modality (association with plastic-bag suffocation). The typical characteristics of the victim were an Italian man with psychiatric illness, frequently moved by passion, existential discomfort and economic problems. During the 24-year period, the number of cases of self-incineration progressively reduced. This study provides a general overview in one of the biggest metropolitan Italian areas and is one of the few works performed on this topic. It may be helpful in understanding and studying such an unusual manner of suicide.

Rectal cancer surgery: a brief history.

PubMed

Galler, Avi S; Petrelli, Nicholas J; Shakamuri, Shanthi P

2011-12-01

In the last 250 years, the treatment of rectal cancer has changed dramatically. Once considered an incurable disease, combined modality therapy has improved mortality from 100% to less than 4% for locally advanced rectal cancer. This dramatic reduction paralleled surgical techniques based on a growing understanding of anatomy and disease pathology. In order to understand modern treatment, it is necessary to recognize the achievements of preceding surgeons. Copyright © 2010 Elsevier Ltd. All rights reserved.

Atrial fibrillation was changed into sinus bradycardia in a ROS1-positive advanced lung adenocarcinoma patient who achieved durable response to Crizotinib: A case report and literature review.

PubMed

Liu, Lan; Wu, Jing; Zhao, Wei; Huang, Mei-Juan

2017-05-01

The c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearrangements represent a new and rare genetic subtype of non-small-cell lung cancer. In recent years, the use of crizotinib in ROS1-rearranged lung cancer exhibits significant clinical efficacy. Crizotinib is generally well tolerated and the most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac, and endocrine abnormalities. From a cardiac perspective, crizotinib is associated with 2 main cardiac effects, QT interval prolongation and bradycardia. We reported a case of a 67-year-old man with ROS1-rearranged advanced lung adenocarcinoma. Crizotinib was initiated as first-line treatment, combined with whole brain radiation therapy. Interestingly, after treatment of crizotinib, the patient suffered a transient QTc interval prolongation and his persistent atrial fibrillation was changed into sinus bradycardia. Only 22 days after crizotinib treatment, the patient's tumor achieved a partial response. So far the patient has taken crizotinib for >19 months with no evidence of disease progression. The present study demonstrates dramatic benefit of crizotinib for patients with ROS1 rearrangement. Besides, we should caution the cardiac effects caused by crizotinb and our case provides evidence that crizotinib may be safe for patients with atrial fibrillation under close monitoring.

West Nile Virus Encephalitis 16 Years Later.

PubMed

Kleinschmidt-DeMasters, Bette K; Beckham, J David

2015-09-01

Arboviruses (Arthropod-borne viruses) include several families of viruses (Flaviviridae, Togaviradae, Bunyaviradae, Reoviradae) that are spread by arthropod vectors, most commonly mosquitoes, ticks and sandflies. The RNA genome allows these viruses to rapidly adapt to ever-changing host and environmental conditions. Thus, these virus families are largely responsible for the recent expansion in geographic range of emerging viruses including West Nile virus (WNV), dengue virus and Chikungunya virus. This review will focus on WNV, especially as it has progressively spread westward in North America since its introduction in New York in 1999. By 2003, WNV infections in humans had reached almost all lower 48 contiguous United States (US) and since that time, fluctuations in outbreaks have occurred. Cases decreased between 2008 and 2011, followed by a dramatic flair in 2012, with the epicenter in the Dallas-Fort Worth region of Texas. The 2012 outbreak was associated with an increase in reported neuroinvasive cases. Neuroinvasive disease continues to be a problem particularly in the elderly and immunocompromised populations, although WNV infections also represented the second most frequent cause of pediatric encephalitis in these same years. Neuropathological features in cases from the 2012 epidemic highlight the extent of viral damage that can occur in the CNS. © 2015 International Society of Neuropathology.

A novel, long-lived, and highly engraftable immunodeficient mouse model of mucopolysaccharidosis type I.

PubMed

Mendez, Daniel C; Stover, Alexander E; Rangel, Anthony D; Brick, David J; Nethercott, Hubert E; Torres, Marissa A; Khalid, Omar; Wong, Andrew Ms; Cooper, Jonathan D; Jester, James V; Monuki, Edwin S; McGuire, Cian; Le, Steven Q; Kan, Shih-Hsin; Dickson, Patricia I; Schwartz, Philip H

2015-01-01

Mucopolysaccharidosis type I (MPS I) is an inherited α-L-iduronidase (IDUA, I) deficiency in which glycosaminoglycan (GAG) accumulation causes progressive multisystem organ dysfunction, neurological impairment, and death. Current MPS I mouse models, based on a NOD/SCID (NS) background, are short-lived, providing a very narrow window to assess the long-term efficacy of therapeutic interventions. They also develop thymic lymphomas, making the assessment of potential tumorigenicity of human stem cell transplantation problematic. We therefore developed a new MPS I model based on a NOD/SCID/Il2rγ (NSG) background. This model lives longer than 1 year and is tumor-free during that time. NSG MPS I (NSGI) mice exhibit the typical phenotypic features of MPS I including coarsened fur and facial features, reduced/abnormal gait, kyphosis, and corneal clouding. IDUA is undetectable in all tissues examined while GAG levels are dramatically higher in most tissues. NSGI brain shows a significant inflammatory response and prominent gliosis. Neurological MPS I manifestations are evidenced by impaired performance in behavioral tests. Human neural and hematopoietic stem cells were found to readily engraft, with human cells detectable for at least 1 year posttransplantation. This new MPS I model is thus suitable for preclinical testing of novel pluripotent stem cell-based therapy approaches.

A novel, long-lived, and highly engraftable immunodeficient mouse model of mucopolysaccharidosis type I

PubMed Central

Mendez, Daniel C; Stover, Alexander E; Rangel, Anthony D; Brick, David J; Nethercott, Hubert E; Torres, Marissa A; Khalid, Omar; Wong, Andrew MS; Cooper, Jonathan D; Jester, James V; Monuki, Edwin S; McGuire, Cian; Le, Steven Q; Kan, Shih-hsin; Dickson, Patricia I; Schwartz, Philip H

2015-01-01

Mucopolysaccharidosis type I (MPS I) is an inherited α-L-iduronidase (IDUA, I) deficiency in which glycosaminoglycan (GAG) accumulation causes progressive multisystem organ dysfunction, neurological impairment, and death. Current MPS I mouse models, based on a NOD/SCID (NS) background, are short-lived, providing a very narrow window to assess the long-term efficacy of therapeutic interventions. They also develop thymic lymphomas, making the assessment of potential tumorigenicity of human stem cell transplantation problematic. We therefore developed a new MPS I model based on a NOD/SCID/Il2rγ (NSG) background. This model lives longer than 1 year and is tumor-free during that time. NSG MPS I (NSGI) mice exhibit the typical phenotypic features of MPS I including coarsened fur and facial features, reduced/abnormal gait, kyphosis, and corneal clouding. IDUA is undetectable in all tissues examined while GAG levels are dramatically higher in most tissues. NSGI brain shows a significant inflammatory response and prominent gliosis. Neurological MPS I manifestations are evidenced by impaired performance in behavioral tests. Human neural and hematopoietic stem cells were found to readily engraft, with human cells detectable for at least 1 year posttransplantation. This new MPS I model is thus suitable for preclinical testing of novel pluripotent stem cell-based therapy approaches. PMID:26052536

Multiscale assessment of micro-seismicity and slow earthquakes

NASA Astrophysics Data System (ADS)

Yuen, David A.; Ni, Sidao; Wang, Yibo; Xu, Chang; Veveakis, Manny

2017-03-01

Today we witness the economical throes and uncertainties created by the dramatic cratering of oil prices in 2014 from 115 dollars per barrel to 38 dollars. This dramatic nonlinear phenomenon reminds earth scientists of the disintegration of the Laurentide ice sheet, some 14,000 years ago. One of the contributing factors of the precipitous drop in oil prices is super-fracking. This is used for oil as well as for gas production and became economically feasible about .twenty years ago. Thanks to this technological breakthrough Americans had enjoyed a renaissance in oil production since 2005. This process, however, has some drawbacks, such as the induced earthquakes occurring in rejuvenated or new fields (Fig. 1).

Comparison of Glaucoma Progression Detection by Optical Coherence Tomography and Visual Field.

PubMed

Zhang, Xinbo; Dastiridou, Anna; Francis, Brian A; Tan, Ou; Varma, Rohit; Greenfield, David S; Schuman, Joel S; Huang, David

2017-12-01

To compare longitudinal glaucoma progression detection using optical coherence tomography (OCT) and visual field (VF). Validity assessment. We analyzed subjects with more than 4 semi-annual follow-up visits (every 6 months) in the multicenter Advanced Imaging for Glaucoma Study. Fourier-domain optical coherence tomography (OCT) was used to map the thickness of the peripapillary retinal nerve fiber layer (NFL) and ganglion cell complex (GCC). OCT-based progression detection was defined as a significant negative trend for either NFL or GCC. VF progression was reached if either the event or trend analysis reached significance. The analysis included 356 glaucoma suspect/preperimetric glaucoma (GS/PPG) eyes and 153 perimetric glaucoma (PG) eyes. Follow-up length was 54.1 ± 16.2 months for GS/PPG eyes and 56.7 ± 16.0 for PG eyes. Progression was detected in 62.1% of PG eyes and 59.8% of GS/PPG eyes by OCT, significantly (P < .001) more than the detection rate of 41.8% and 27.3% by VF. In severity-stratified analysis of PG eyes, OCT had significantly higher detection rate than VF in mild PG (63.1% vs. 38.7%, P < .001), but not in moderate and advanced PG. The rate of NFL thinning slowed dramatically in advanced PG, but GCC thinning rate remained relatively steady and allowed good progression detection even in advanced disease. The Kaplan-Meier time-to-event analyses showed that OCT detected progression earlier than VF in both PG and GS/PPG groups. OCT is more sensitive than VF for the detection of progression in early glaucoma. While the utility of NFL declines in advanced glaucoma, GCC remains a sensitive progression detector from early to advanced stages. Copyright © 2017 Elsevier Inc. All rights reserved.

The First Year Experience in Australian Universities: Findings from Two Decades, 1994-­2014

ERIC Educational Resources Information Center

Baik, Chi; Naylor, Ryan; Arkoudis, Sophie

2015-01-01

This report provides an analysis of trends over a twenty year period in the attitudes and experiences of first year students in Australian universities. It is based on the national survey of first year students undertaken by the Melbourne Centre for the Study of Higher Education at five-yearly intervals since 1994. Dramatic changes have taken…

Ayurvedic medicinal plants for Alzheimer's disease: a review

PubMed Central

2012-01-01

Alzheimer's disease is an age-associated, irreversible, progressive neurodegenerative disease that is characterized by severe memory loss, unusual behavior, personality changes, and a decline in cognitive function. No cure for Alzheimer's exists, and the drugs currently available to treat the disease have limited effectiveness. It is believed that therapeutic intervention that could postpone the onset or progression of Alzheimer's disease would dramatically reduce the number of cases in the next 50 years. Ayurvedic medicinal plants have been the single most productive source of leads for the development of drugs, and over a hundred new products are already in clinical development. Indeed, several scientific studies have described the use of various Ayurvedic medicinal plants and their constituents for treatment of Alzheimer's disease. Although the exact mechanism of their action is still not clear, phytochemical studies of the different parts of the plants have shown the presence of many valuable compounds, such as lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids, that show a wide spectrum of pharmacological activities, including anti-inflammatory, anti-amyloidogenic, anti-cholinesterase, hypolipidemic, and antioxidant effects. This review gathers research on various medicinal plants that have shown promise in reversing the Alzheimer's disease pathology. The report summarizes information concerning the phytochemistry, biological, and cellular activities and clinical applications of these various plants in order to provide sufficient baseline information that could be used in drug discovery campaigns and development process, thereby providing new functional leads for Alzheimer's disease. PMID:22747839

Aging in America in the Twenty-first Century: Demographic Forecasts from the MacArthur Foundation Research Network on an Aging Society

PubMed Central

Olshansky, S Jay; Goldman, Dana P; Zheng, Yuhui; Rowe, John W

2009-01-01

Context: The aging of the baby boom generation, the extension of life, and progressive increases in disability-free life expectancy have generated a dramatic demographic transition in the United States. Official government forecasts may, however, have inadvertently underestimated life expectancy, which would have major policy implications, since small differences in forecasts of life expectancy produce very large differences in the number of people surviving to an older age. This article presents a new set of population and life expectancy forecasts for the United States, focusing on transitions that will take place by midcentury. Methods: Forecasts were made with a cohort-components methodology, based on the premise that the risk of death will be influenced in the coming decades by accelerated advances in biomedical technology that either delay the onset and age progression of major fatal diseases or that slow the aging process itself. Findings: Results indicate that the current forecasts of the U.S. Social Security Administration and U.S. Census Bureau may underestimate the rise in life expectancy at birth for men and women combined, by 2050, from 3.1 to 7.9 years. Conclusions: The cumulative outlays for Medicare and Social Security could be higher by $3.2 to $8.3 trillion relative to current government forecasts. This article discusses the implications of these results regarding the benefits and costs of an aging society and the prospect that health disparities could attenuate some of these changes. PMID:20021588

Correction of Spinal Deformity on a Lung Transplantation Recipient.

PubMed

Andrés Peiró, José Vicente; Granell, Joan Bagó; Moret, Montserrat Feliu; Galdó, Antonio Moreno

2017-01-01

The coexistence of lung disease and scoliosis entails a dramatic situation. There are no papers reporting scoliosis surgery in patients who suffered lung transplantation. To describe the case of a patient who underwent surgery to correct progressive spinal deformity after two consecutive lung transplants. Case report, including review of patient records, imaging and pulmonary function tests, and literature review. A 9-year-old woman diagnosed of idiopathic pulmonary fibrosis and progressive scoliosis underwent lung transplant. Retransplantation of right lung was performed at the age of 14 due to chronic rejection. When she was 16, respiratory function was stable and spinal deformity severely impaired her quality of life. Patient and family demanded a surgical correction. At that moment, she had severe osteoporosis and immunosuppression as a result of anti-rejection therapy. The pattern was a severe double thoracic curve T1-T6 89° and T7-L1 139°. To correct it, a posterior instrumented spine fusion from T2 to L4 using a hybrid configuration was performed. No significant complications occurred in perioperative, postoperative, and midterm follow-up periods. Solid fusion was achieved and patient was satisfied with surgery. Unfortunately, chronic lung graft rejection worsened her long-term general status. Scoliosis surgery on lung transplant recipients is feasible, regardless of potential complications related to immunosuppression and osteoporosis. The goal is to improve quality of life. Copyright © 2016 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Accelerated measles control in the Western Pacific region.

PubMed

McFarland, Jeffrey W; Mansoor, Osman David; Yang, Baoping

2003-05-15

By the 1990s, an immunization program in the western Pacific had dramatically reduced measles morbidity and mortality. Building on the region's successful elimination of polio, several countries and areas achieved or are close to measles elimination, thus showing the potential for global eradication. The diverse challenges for measles control in different parts of the region have produced lessons that will help with future control, including the need for surveillance of sufficient standard to guide and monitor progress. A group of experts recognized both the potential and the challenges of the measles immunization program and proposed regional elimination as the appropriate disease control target for the region. No date was recommended for its achievement. If progress continues at the present rate, the western Pacific region should soon be able to set a target date for measles elimination.

Role of the Polarity Determinant Crumbs in Suppressing Mammalian Epithelial Tumor Progression

PubMed Central

Karp, Cristina M.; Tan, Ting Ting; Mathew, Robin; Nelson, Deidre; Mukherjee, Chandreyee; Degenhardt, Kurt; Karantza-Wadsworth, Vassiliki; White, Eileen

2009-01-01

Most tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial (iBMK) cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity and contact inhibition, while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila. PMID:18519669

Proteoglycan depletion and size reduction in lesions of early grade chondromalacia of the patella.

PubMed Central

Väätäinen, U; Häkkinen, T; Kiviranta, I; Jaroma, H; Inkinen, R; Tammi, M

1995-01-01

OBJECTIVE--To determine the content and molecular size of proteoglycans (PGs) in patellar chondromalacia (CM) and control cartilages as a first step in investigating the role of matrix alterations in the pathogenesis of this disease. METHODS--Chondromalacia tissue from 10 patients was removed with a surgical knife. Using identical techniques, apparently healthy cartilage of the same site was obtained from 10 age matched cadavers (mean age 31 years in both groups). Additional pathological cartilage was collected from 67 patients with grades II-IV CM (classified according to Outerbridge) using a motorised shaver under arthroscopic control. The shaved cartilage chips were collected with a dense net from the irrigation fluid of the shaver. The content of tissue PGs was determined by Safranin O precipitation or uronic acid content, and the molecular size by mobility on agarose gel electrophoresis. RESULTS--The mean PG content of the CM tissue samples with a knife was dramatically reduced, being only 15% of that in controls. The cartilage chips collected from shaving operations of grades II, III, and IV CM showed a decreasing PG content: 9%, 5%, and 1% of controls, respectively. Electrophoretic analysis of PGs extracted with guanidium chloride from the shaved tissue samples suggested a significantly reduced size of aggrecans in the mild (grade II) lesions. CONCLUSION--These data show that there is already a dramatic and progressive depletion of PGs in CM grade II lesions. This explains the softening of cartilage, a typical finding in the arthroscopic examination of CM. The PG size reduction observed in grade II implicates proteolytic attack as a factor in the pathogenesis of CM. Images PMID:7492223

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.

Chemotherapy and target therapy in the management of adult high- grade gliomas.

PubMed

Spinelli, Gian Paolo; Miele, Evelina; Lo Russo, Giuseppe; Miscusi, Massimo; Codacci-Pisanelli, Giovanni; Petrozza, Vincenzo; Papa, Anselmo; Frati, Luigi; Della Rocca, Carlo; Gulino, Alberto; Tomao, Silverio

2012-10-01

Adult high grade gliomas (HGG) are the most frequent and fatal primary central nervous system (CNS) tumors. Despite recent advances in the knowledge of the pathology and the molecular features of this neoplasm, its prognosis remains poor. In the last years temozolomide (TMZ) has dramatically changed the life expectancy of these patients: the association of this drug with radiotherapy (RT), followed by TMZ alone, is the current standard of care. However, malignant gliomas often remain resistant to chemotherapy (CHT). Therefore, preclinical and clinical research efforts have been directed on identifying and understanding the different mechanisms of chemo-resistance operating in this subset of tumors,in order to develop effective strategies to overcome resistance. Moreover, the evidence of alterations in signal transduction pathways underlying tumor progression, has increased the number of trials investigating molecular target agents, such as anti-epidermal growth factor receptor (EGFR) and anti- vascular endothelial growth factor (VEGF) signaling. The purpose of this review is to point out the current standard of treatment and to explore new available target therapies in HGG.

Current status of gene therapy trials for Parkinson's disease.

PubMed

Fiandaca, Massimo; Forsayeth, John; Bankiewicz, Krystof

2008-01-01

The incidence of Parkinson's disease (PD) increases greatly with age, and the baby-boomer population can expect to generate a large number of individuals with the disease, all of whom will have significantly increased medical care needs over periods of 20 years or more. This emerging healthcare burden to our society calls for accelerated efforts to understand this disease better and treat it more effectively. The growing interest in gene therapy grew out of a recognition that new medicines may be needed to combat the relentless progression of the disease in the face of conventional pharmaco-therapies and surgical interventions that have so far failed to offer more than palliative relief. The potential of gene therapy to alter dramatically the course of the disease lies very much with the challenge of converting a research tool into a medical option, a process that clearly requires a unique combination of rigor and flexibility. In this review, we examine the unique aspects of gene therapy that make its use in PD attractive, but also analyze the difficulties of employing a medicine that acts for the rest of the patient's life.

Management of reproduction and pregnancy complications in maternal obesity: which role for dietary polyphenols?

PubMed

Santangelo, Carmela; Varì, Rosaria; Scazzocchio, Beatrice; Filesi, Carmelina; Masella, Roberta

2014-01-01

Obesity is a global and dramatic public health problem; maternal obesity represents one of the main risk factors of infertility and pregnancy complications as it is associated with adverse maternal and offspring outcomes. In the last few years, adipose tissue dysfunction associated with altered adipocytokine secretion has been suggested to play a critical role in all the phases of reproductive process. Obesity is a nutrition-related disorder. In this regard, dietary intervention strategies, such as high intake of fruit and vegetables, have shown significant effects in both preserving health and counteracting obesity-associated diseases. Evidence has been provided that polyphenols, important constituents of plant-derived food, can influence developmental program of oocyte and embryo, as well as pregnancy progression by modulating several cellular pathways. This review will examine the controversial results so far obtained on adipocytokine involvement in fertility impairment and pregnancy complications. Furthermore, the different effects exerted by polyphenols on oocyte, embryo, and pregnancy development will be also taken in account. © 2013 International Union of Biochemistry and Molecular Biology.

Avoiding the Enumeration of Infeasible Elementary Flux Modes by Including Transcriptional Regulatory Rules in the Enumeration Process Saves Computational Costs

PubMed Central

Jungreuthmayer, Christian; Ruckerbauer, David E.; Gerstl, Matthias P.; Hanscho, Michael; Zanghellini, Jürgen

2015-01-01

Despite the significant progress made in recent years, the computation of the complete set of elementary flux modes of large or even genome-scale metabolic networks is still impossible. We introduce a novel approach to speed up the calculation of elementary flux modes by including transcriptional regulatory information into the analysis of metabolic networks. Taking into account gene regulation dramatically reduces the solution space and allows the presented algorithm to constantly eliminate biologically infeasible modes at an early stage of the computation procedure. Thereby, computational costs, such as runtime, memory usage, and disk space, are extremely reduced. Moreover, we show that the application of transcriptional rules identifies non-trivial system-wide effects on metabolism. Using the presented algorithm pushes the size of metabolic networks that can be studied by elementary flux modes to new and much higher limits without the loss of predictive quality. This makes unbiased, system-wide predictions in large scale metabolic networks possible without resorting to any optimization principle. PMID:26091045

Exposure ethics: does HIV pre-exposure prophylaxis raise ethical problems for the health care provider and policy maker?

PubMed

Venter, Francois; Allais, Lucy; Richter, Marlise

2014-07-01

The last few years have seen dramatic progress in the development of HIV pre-exposure prophylaxis (PrEP). These developments have been met by ethical concerns. HIV interventions are often thought to be ethically difficult. In a context which includes disagreements over human rights, controversies over testing policies, and questions about sexual morality and individual responsibility, PrEP has been seen as an ethically complex intervention. We argue that this is mistaken, and that in fact, PrEP does not raise new ethical concerns. Some of the questions posed by PrEP are not specific to HIV prophylaxis, but simply standard public health considerations about resource allocation and striking a balance between individual benefit and public good. We consider sexual disinhibition in the context of private prescriptions, and conclude that only unjustified AIDS-exceptionalism or inappropriate moralism about sex supports thinking that PrEP raises new ethical problems. This negative conclusion is significant in a context where supposed ethical concerns about PrEP have been raised, and in the context of HIV exceptionalism. © 2013 John Wiley & Sons Ltd.

Central nervous system and muscle involvement in an adolescent patient with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.

PubMed

Ishii, Kiyoko; Komaki, Hirofumi; Ohkuma, Aya; Nishino, Ichizo; Nonaka, Ikuya; Sasaki, Masayuki

2010-09-01

We report an adolescent case of late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by intermittent nausea and depressive state as early symptoms. At the age of 12 years and 11 months, the patient experienced intermittent nausea and vomiting, and depressive state. She was on medication for depression for 5 months but it was ineffective. Brain magnetic resonance imaging showed disseminated high-intensity areas in the periventricular white matter and in the splenium of the corpus callosum on T2-weighted images and fluid-attenuated inversion-recovery images. Progressive muscle weakness occurred and blood creatine kinase level was found to be elevated. The muscle biopsy revealed lipid storage myopathy. Urine organic acid analysis and mutation analysis of the ETFDH gene confirmed the diagnosis of MADD. With oral supplements of riboflavin and l-carnitine, in addition to a high-calorie and reduced-fat diet, her clinical symptoms improved dramatically. Early diagnosis is important because riboflavin treatment has been effective in a significant number of patients with MADD. Copyright 2009 Elsevier B.V. All rights reserved.

Trapped ventricle after laser ablation of a subependymal giant cell astrocytoma complicated by intraventricular gadolinium extravasation: case report.

PubMed

Karsy, Michael; Patel, Daxa M; Bollo, Robert J

2018-05-01

Magnetic resonance imaging-guided stereotactic laser ablation of intracranial targets, including brain tumors, has expanded dramatically over the past decade, but there have been few reports of complications, especially those occurring in a delayed fashion. Laser ablation of subependymal giant cell astrocytomas (SEGAs) is an attractive alternative to maintenance immunotherapy in some children with tuberous sclerosis complex (TSC); however, the effect of treatment on disease progression and the nature and frequency of potential complications remains largely unknown. The authors report the case of a 5-year-old boy with TSC who underwent stereotactic laser ablation of a SEGA at the right foramen of Monro on 2 separate occasions. After the second ablation, immediate posttreatment MRI revealed gadolinium extravasation from the tumor into the lateral ventricle. Nine months later, the patient presented with papilledema and delayed obstructive hydrocephalus secondary to intraventricular adhesions causing a trapped right lateral ventricle. This was successfully treated with endoscopic septostomy. The authors discuss the potential cause and clinical management of a delayed complication not previously reported after a relatively novel surgical therapy.

[Streptococcus milleri: An unusual cause of skull extensive osteomyelitis in an immunocompetent patient].

PubMed

Duquenne, C; Dernis, E; Zehrouni, A; Bizon, A; Duquenne, M

2017-09-01

Streptococcus milleri (Streptococcus anginosus, intermedius and constellatus) are commensal organisms, which can become pathogenic and cause infection with frequent abscess formation, local or metastatic extension. Osteomyelitis of the skull has been rarely reported in this type of infection. Skull osteomyelitis due to Streptococcus milleri is reported in a 61-year-old immunocompetent man without any medical history, occurring 10 months after a head injury without any wound or complication at initial presentation. A progressive right parieto-occipital headache with worsening and increased acute phase reactants evoked a giant cell arteritis. After few days of corticosteroid therapy (0.5 mg/kg/day), diagnosis of subcutaneous abscess associated to an extensive osteomyelitis of the skull due to Streptococcus milleri was diagnosed. The outcome was favorable after drainage of one liter of pus, irrigation, debridement and antibiotherapy by amoxicillin for 8 weeks. It is necessary to discuss the differential diagnosis of giant cell arteritis particularly when symptoms are unusual. Even a short-term corticosteroid therapy may dramatically exacerbate an undetected infection. Copyright © 2017. Published by Elsevier SAS.

Lost, a desert river and its native fishes: A historical perspective of the lower Colorado River

USGS Publications Warehouse

Mueller, Gordon A.; Marsh, Paul C.

2002-01-01

The Colorado River had one of the most unique fish communities in the world. Seventy-five percent of those species were found no where else in the world. Settlement of the lower basin brought dramatic changes to both the river and its native fish. Those changes began more than 120 years ago as settlers began stocking nonnative fishes. By 1930, nonnative fish had spread throughout the lower basin and replaced native communities. All resemblance of historic river conditions faded with the construction of Hoover Dam in 1935 and other large water development projects. Today, few remember what the Colorado River was really like. Seven of the nine mainstream fishes are now federally protected as endangered. Federal and state agencies are attempting to recover these fish; however, progress has been frustrated due to the severity of human impact. This report presents testimony, old descriptions, and photographs describing the changes that have taken place in hopes that it will provide managers, biologists, and the interested public a better appreciation of the environment that shaped these unique fish.

New concepts concerning prostate cancer screening.

PubMed

Fillmore, Rebecca A; Kojima, Chinatsu; Johnson, Chevaun; Kolcun, Georgina; Dangott, Lawrence J; Zimmer, Warren E

2014-07-01

Prostate Cancer (CaP) is rapidly becoming a worldwide health issue. While CaP mortality has decreased in recent years, coincident with the widespread use of Prostate-Specific Antigen (PSA) screening, it remains the most common solid tumor in men and is the second leading cause of cancer death in the United States. The frequency of CaP is growing not only in western cultures, but also its incidence is dramatically increasing in eastern nations. Recently, examination of data from long-term trials and follow up has cast a shadow on the effectiveness of employing PSA as a primary screening tool for CaP. In this review, we not only summarize opinions from this examination and synthesize recommendations from several groups that suggest strategies for utilizing PSA as a tool, but also call for research into biomarkers for CaP diagnosis and disease progression. We also describe our recent work that identified a smooth muscle contractile protein in prostate epithelia, namely smooth muscle gamma actin, and indicate the potential for this molecule as a new unique footprint and as a CaP marker. © 2014 by the Society for Experimental Biology and Medicine.

Strategies to Screen for Diabetic Retinopathy in Chinese Patients with Newly Diagnosed Type 2 Diabetes: A Cost-Effectiveness Analysis.

PubMed

Wu, Bin; Li, Jin; Wu, Haixiang

2015-11-01

To investigate the cost-effectiveness of different screening intervals for diabetic retinopathy (DR) in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). Chinese healthcare system.Chinese general clinical setting. A cost-effectiveness model was developed to simulate the disease course of Chinese population with newly diagnosed with diabetes. Different DR screening programs were modeled to project economic outcomes. To develop the economic model, we calibrated the progression rates of DR that fit Chinese epidemiologic data derived from the published literature. Costs were estimated from the perspective of the Chinese healthcare system, and the analysis was run over a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. Total costs, vision outcomes, costs per quality-adjusted life year (QALY), the incremental cost-effectiveness ratio (ICER) of screening strategies compared to no screening. DR screening is effective in Chinese patients with newly diagnosed T2DM, and screen strategies with ≥4-year intervals were cost-effective (ICER <$7,485 per QALY) compared to no screening. Screening every 4 years produced the greatest increase in QALYs (11.066) among the cost-effective strategies. The screening intervals could be varied dramatically by age at T2DM diagnosis. Probabilistic sensitivity analyses demonstrated the consistency and robustness of the cost-effectiveness of the 4-year interval screening strategy. The findings suggest that a 4-year interval screening strategy is likely to be more cost-effective than screening every 1 to 3 years in comparison with no screening in the Chinese setting. The screening intervals might be tailored according to the age at T2DM diagnosis.

Secreted phosphoprotein 24 kD (Spp24) inhibits growth of human pancreatic cancer cells caused by BMP-2

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

Li, Chen-Shuang; Tian, Haijun, E-mail: haijuntianmd@gmail.com; Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA

The emerging role of bone morphogenetic proteins (BMPs) in the initiation and progression of multiple cancers has drawn great attention in cancer research. In this study, we report that BMP-2 can promote the proliferation of the pancreatic tumor cell line, PANC-1. Secreted phosphoprotein 24 kD (Spp24), a BMP binding protein, did not affect the proliferation of the cells but promoted the apoptosis of the cells in vitro. In a xeneograft tumor model using PANC-1 cells, BMP-2 dramatically promoted tumor growth, while Spp24 not only abolished the effect of BMP-2, but also dramatically induced tumor shrinking when used alone. Activation of Smad1/5/8 participatedmore » in this process as demonstrated by immunohistochemical staining of phosphorylated Smad 1/5/8. We conclude that Spp24 can be developed into a therapeutic agent that could be employed in clinical situations where the inhibition of BMPs and related proteins is advantageous. - Highlights: • Spp24 effectively inhibited the in vivo tumor growth of PANC-1. • BMP-2 dramatically promoted tumor growth by promoting PANC-1 proliferation. • Spp24 abolished the tumor growth effect of BMP-2 by promoting PANC-1 apoptosis. • Spp24 may be a candidate as a therapeutic agent of pancreatic cancer.« less

Increasing methylation of the calcitonin gene during disease progression in sequential samples from CML patients.

PubMed

Mills, K I; Guinn, B A; Walsh, V A; Burnett, A K

1996-09-01

In chronic myeloid leukaemia (CML), disease progression from the initial chronic phase to the acute phase or blast crisis has previously been shown to be correlated with progressive increases in hyper-methylation of the calcitonin gene, located at chromosome 11p15. However, sequential studies of individual patients were not performed in these investigations. We have analysed 44 samples from nine patients with typical Philadelphia chromosome positive CML throughout their disease progression to determine the methylation state of the calcitonin gene at these time points. Densitometry was used to quantitate the ratio of the normal 2.0 kb Hpa II fragments, indicating normal methylation status of the gene, compared to the intensity of the abnormal, hyper-methylated, 2.6-3.1 kb Hpa II fragments. We found a gradual increase in the ratio of methylated:unmethylated calcitonin gene during chronic phase with a dramatic rise at blast crisis. Further, the ratio of the abnormal hypermethylated 3.1 kb fragments to the methylated 2.6 kb fragment resulted in the identification of a clonal expansion of abnormally methylated cells. This expansion of cells with hypermethylation of the calcitonin gene during chronic phase was shown to coincide with the presence of a mutation in the p53 gene. The data presented in this study would suggest that an increased methylation status of the calcitonin gene during disease progression may indicate the expansion of abnormal blast cell populations and subsequent progression to blast crisis.

1954 Annual Report

Treesearch

Philip A. Briegleb

1954-01-01

1954 completed the fiftieth year of operation of the U. S. Forest Service and the thirty-fourth year for the Southern Forest Experiment Station. The half century just past has brought dramatic changes in the forests of the South and to the people and industries dependent upon them.

Spine oncology: Daedalus, Theseus, and the Minotaur.

PubMed

Donthineni, Rakesh; Ofluoglu, Onder

2009-01-01

Over the past three decades, progress has been dramatic in the management of spine tumors. For example, advanced imaging technologies made available at manageable costs have lowered the threshold for scanning. CT, MRI, and PET imaging modalities have greatly enhanced the ability of the surgeon to accurately delineate the extension of the lesion within the bone, the soft tissue, and the spinal canal. Such enhancements have led to great leaps forward in preoperative planning and postoperative evaluation, including improved reconstruction options are resulting in improved outcomes. This article introduces the theme of this volume.

Operative treatment of sternal fractures.

PubMed

Al-Qudah, Abdullah

2006-10-01

Four patients with displaced sternal fractures complained of intractable pain following road traffic accidents. They all had bone deformities, but only one had associated traumatic injuries. All patients underwent operative reduction and fixation of the fractured sternum using a T-shaped compression-tension stainless steel plate and screws. Pain relief was often dramatic and all patients progressed to sternal union. None required reoperation. No infections occurred. Two plates have subsequently been removed. On follow-up, all patients had excellent results. Sternal plating, which is based on the tension-band principle, is an effective treatment for displaced sternal fractures.

Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

PubMed

Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

2009-01-01

Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

Immunotherapy for Ovarian Cancer: What's Next?

PubMed Central

Kandalaft, Lana E.; Powell, Daniel J.; Singh, Nathan; Coukos, George

2011-01-01

In the past decade, we have witnessed important gains in the treatment of ovarian cancer; however, additional advances are required to reduce mortality. With compelling evidence that ovarian cancers are immunogenic tumors, immunotherapy should be further pursued and optimized. The dramatic advances in laboratory and clinical procedures in cellular immunotherapy, along with the development of powerful immunomodulatory antibodies, create new opportunities in ovarian cancer therapeutics. Herein, we review current progress and future prospects in vaccine and adoptive T-cell therapy development as well as immunomodulatory therapy tools available for immediate clinical testing. PMID:21079136

Tools for Understanding Space Weather Impacts to Satellites

NASA Astrophysics Data System (ADS)

Green, J. C.; Shprits, Y.; Likar, J. J.; Kellerman, A. C.; Quinn, R. A.; Whelan, P.; Reker, N.; Huston, S. L.

2017-12-01

Space weather causes dramatic changes in the near-Earth radiation environment. Intense particle fluxes can damage electronic components on satellites, causing temporary malfunctions, degraded performance, or a complete system/mission loss. Understanding whether space weather is the cause of such problems expedites investigations and guides successful design improvements resulting in a more robust satellite architecture. Here we discuss our progress in developing tools for satellite designers, manufacturers, and decision makers - tools that summarize space weather impacts to specific satellite assets and enable confident identification of the cause and right solution.

Overcoming barriers to membrane protein structure determination.

PubMed

Bill, Roslyn M; Henderson, Peter J F; Iwata, So; Kunji, Edmund R S; Michel, Hartmut; Neutze, Richard; Newstead, Simon; Poolman, Bert; Tate, Christopher G; Vogel, Horst

2011-04-01

After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988-2011): A Population-Based Study of French Adolescents.

PubMed

Ghione, Silvia; Sarter, Hélène; Fumery, Mathurin; Armengol-Debeir, Laura; Savoye, Guillaume; Ley, Delphine; Spyckerelle, Claire; Pariente, Benjamin; Peyrin-Biroulet, Laurent; Turck, Dominique; Gower-Rousseau, Corinne

2018-02-01

Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period. Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification. 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/10 5 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/10 5 (+126%; P<0.001) and for UC, from 1.6 to 4.1/10 5 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC. In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

[Epidemiology of myopia].

PubMed

Hopf, S; Pfeiffer, N

2017-01-01

Myopia is the most common cause for impaired vision in children and young adults with increasing tendency. Although myopia is hereditary, genetic findings do not explain the full extent of its recent increase. Epidemiologic studies are required to investigate the prevalence and incidence of this disease. The prevalence, incidence and progression of myopia with its economic impact are emphasized to review the distribution and consequences of the development and progression of myopia. A systematic literature search was conducted in MEDLINE. The global prevalence of myopia is currently 28.3 % and is dramatically increasing. In 2050, half of the world population will be affected. Myopia starts earlier and exhibits a peak prevalence in young Asian adults. High myopia indicates a similar development. Interventions to slow the development and progression of myopia are strongly required due to the medical and socio-economic drawbacks for the individuals and for society. Myopia is already a ubiquitous phenomenon in some parts of the world. One out of ten persons will be at a relevant risk of becoming blind as a result of myopia in the future. Preventive measures have not shown sweeping success.

Science Update: Inorganic Chemistry.

ERIC Educational Resources Information Center

Rawls, Rebecca

1981-01-01

Describes areas of inorganic chemistry which have changed dramatically in the past year or two, including photochemistry, electrochemistry, organometallic complexes, inorganic reaction theory, and solid state chemistry. (DS)

Survival of multiple myeloma patients aged 65-70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network.

PubMed

Ozaki, Shuji; Harada, Takeshi; Saitoh, Takayuki; Shimazaki, Chihiro; Itagaki, Mitsuhiro; Asaoku, Hideki; Kuroda, Yoshiaki; Chou, Takaaki; Yoshiki, Yumiko; Suzuki, Kenshi; Murakami, Hirokazu; Hayashi, Kunihiko; Mina, Roberto; Palumbo, Antonio; Shimizu, Kazuyuki

2014-01-01

Novel agents such as thalidomide, lenalidomide and bortezomib have dramatically changed the treatment paradigm of multiple myeloma (MM). However, it is not clear whether these agents improve the prognosis of elderly patients who have undergone autologous stem cell transplantation (auto-SCT). We retrospectively analyzed the outcome of 318 newly diagnosed patients aged 65–70 years who were treated between January 1, 2004, and December 31, 2009. As initial therapy, 192 patients were treated with conventional chemotherapy,88 with novel agent-containing regimens, 21 with conventional chemotherapy plus auto-SCT and the remaining 17 with novel agents plus auto-SCT. The median progression-free survival was 19.1, 24.5, 26.8 and 35.2 months, respectively, and the 5-year overall survival (OS) was 40, 62, 63 and 87%, respectively. Initial therapy with novel agents (p < 0.001) or auto-SCT (p < 0.02) significantly improved OS compared with the group without these treatment modalities. Salvage therapy with novel agents also significantly improved survival after relapse compared with conventional chemotherapy alone (p < 0.04). In a multivariate analysis, the use of novel agents was an independent prognostic factor significantly associated with extended OS(p < 0.003). These results indicate that novel agents and auto-SCT had a major impact on OS in eligible patients in this subgroup of MM. © 2014 S. Karger AG, Basel

Promoting fundamental clinical skills: a competency-based college approach at the University of Washington.

PubMed

Goldstein, Erika A; Maclaren, Carol F; Smith, Sherilyn; Mengert, Terry J; Maestas, Ramoncita R; Foy, Hugh M; Wenrich, Marjorie D; Ramsey, Paul G

2005-05-01

The focus on fundamental clinical skills in undergraduate medical education has declined over the last several decades. Dramatic growth in the number of faculty involved in teaching and increasing clinical and research commitments have contributed to depersonalization and declining individual attention to students. In contrast to the close teaching and mentoring relationship between faculty and students 50 years ago, today's medical students may interact with hundreds of faculty members without the benefit of a focused program of teaching and evaluating clinical skills to form the core of their four-year curriculum. Bedside teaching has also declined, which may negatively affect clinical skills development. In response to these and other concerns, the University of Washington School of Medicine has created an integrated developmental curriculum that emphasizes bedside teaching and role modeling, focuses on enhancing fundamental clinical skills and professionalism, and implements these goals via a new administrative structure, the College system, which consists of a core of clinical teachers who spend substantial time teaching and mentoring medical students. Each medical student is assigned a faculty mentor within a College for the duration of his or her medical school career. Mentors continuously teach and reflect with students on clinical skills development and professionalism and, during the second year, work intensively with them at the bedside. They also provide an ongoing personal faculty contact. Competency domains and benchmarks define skill areas in which deepening, progressive attention is focused throughout medical school. This educational model places primary focus on the student.

[A patient with thyroid cancer evaluated according to Response Evaluation Criteria in Solid Tumors during treatment for breast cancer recurrence in hepatic and cervical lymph nodes].

PubMed

Hayashi, Keiko; Enomoto, Takumo; Oshida, Sayuri; Habiro, Takeyoshi; Hatate, Kazuhiko; Sengoku, Norihiko; Watanabe, Masahiko

2013-11-01

We describe a case of a 69-year-old woman who underwent left breast-preserving surgery and axillary dissection for left-sided breast cancer at 60 years of age. The histopathological diagnosis was papillotubular carcinoma, luminal A (pathological T1N0M0).In the eighth year after surgery, computed tomography (CT) revealed recurrence in the liver and cervical lymph node metastasis. The patient did not respond to 3 months of treatment with letrozole (progressive disease [PD]). Six courses of chemotherapy with epirubicin and cyclophosphamide (EC) were administered. Subsequently, the attending physician was replaced while the patient was receiving paclitaxel( PTX).After 4 courses of treatment with PTX, the liver metastasis disappeared (complete response [CR]).However, the cervical lymph nodes did not shrink (PD).The cytological diagnosis was papillary thyroid cancer with associated cervical lymph node metastasis. Total thyroidectomy and D3b cervical lymph node dissection were performed. The pathological diagnosis was pEx0T1bN1Mx, pStage IVA disease. Replacement of the attending physician is a critical turning point for patients. During chemotherapy or hormone therapy for breast cancer, each organ should be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).In the case of our patient, thyroid cancer was diagnosed according to RECIST. Cancer specialists should bear in mind that the treatment policy may change dramatically depending on the results of RECIST assessment.

AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

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

Xi, Yu; Department of General Surgery, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang 832008; Niu, Jianhua

The AGC kinase family is important cell proliferation and survival. Dysregulation of this family contributes to gastric cancer progression. Here, we evaluated the potential activity of AT13148, a first-in-class multi-AGC kinase inhibitor, against gastric cancer cells. Our results showed that AT13148 exerted potent cytotoxic and anti-proliferative activities against a panel human gastric cancer cell lines (HGC-27, AGS, SNU-601, N87 and MKN-28), possibly via inducing cancer cell apoptotic death. Apoptosis inhibition by the Caspase blockers dramatically attenuated AT13148-caused cytotoxicity against gastric cancer cells. Intriguingly, same AT13148 treatment was not cytotoxic/pro-apoptotic to the non-cancerous human gastric epithelial GEC-1 cells. At the signaling level,more » AT13148 treatment in gastric cancer cells dramatically suppressed activation of multiple AGC kinases, including Akt (at p-Thr-308), p70S6 kinase (p70S6K), glycogen synthase kinase 3β (GSK-3β) and p90 ribosomal S6 kinase (RSK). Our in vivo studies demonstrated that daily oral gavage of AT13148 at well-tolerated doses significantly inhibited HGC27 xenograft tumor growth in nude mice. AGC activity was also dramatically decreased in AT13148-administrated HGC27 tumors. Therefore, targeting AGC kinases by AT13148 demonstrates superior anti-gastric cancer activity both in vitro and in vivo. The preclinical results of this study support the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate. - Highlights: • AT13148 is cytotoxic and anti-proliferative to human gastric cancer cells. • AT13148 induces gastric cancer cell apoptotic death, inhibited by Caspase inhibitors. • AT13148 inactivates multiple AGC kinases in human gastric cancer cells. • AT13148 oral administration suppresses HGC27 xenograft growth in nude mice. • AT13148 oral administration inhibits multiple AGC kinases in HGC27 xenograft tumors.« less

Bariatric Surgery Prior to Total Joint Arthroplasty May Not Provide Dramatic Improvements In Post Arthroplasty Surgical Outcomes

PubMed Central

Paxton, Elizabeth W.; Fisher, David; Li, Robert A.; Barber, Thomas C.; Singh, Jasvinder A.

2014-01-01

This study compared the total joint arthroplasty (TJA) surgical outcomes of patients who had bariatric surgery prior to TJA to TJA patients who were candidates but did not have bariatric surgery. Patients were retrospectively grouped into: Group 1 (n=69), those with bariatric surgery >2 years prior to TJA, Group 2 (n=102), those with surgery within 2 years of TJA, and Group 3 (n=11,032), those without bariatric surgery. In Group 1, 2.9% (95%CI 0.0–6.9%) had complications within 1 year compared to 5.9% (95%CI 1.3–10.4%) in Group 2, and 4.1% (95%CI 3.8–4.5%) in Group 3. 90-day readmission (7.2%, 95%CI 1.1–13.4%) and revision density (3.4/100 years of observation) was highest in Group 1. Bariatric surgery prior to TJA may not provide dramatic improvements in post-operative TJA surgical outcomes. PMID:24674730

Dramatic pretend play games uniquely improve emotional control in young children.

PubMed

Goldstein, Thalia R; Lerner, Matthew D

2017-09-15

Pretense is a naturally occurring, apparently universal activity for typically developing children. Yet its function and effects remain unclear. One theorized possibility is that pretense activities, such as dramatic pretend play games, are a possible causal path to improve children's emotional development. Social and emotional skills, particularly emotional control, are critically important for social development, as well as academic performance and later life success. However, the study of such approaches has been criticized for potential bias and lack of rigor, precluding the ability to make strong causal claims. We conducted a randomized, component control (dismantling) trial of dramatic pretend play games with a low-SES group of 4-year-old children (N = 97) to test whether such practice yields generalized improvements in multiple social and emotional outcomes. We found specific effects of dramatic play games only on emotional self-control. Results suggest that dramatic pretend play games involving physicalizing emotional states and traits, pretending to be animals and human characters, and engaging in pretend scenarios in a small group may improve children's emotional control. These findings have implications for the function of pretense and design of interventions to improve emotional control in typical and atypical populations. Further, they provide support for the unique role of dramatic pretend play games for young children, particularly those from low-income backgrounds. A video abstract of this article can be viewed at: https://youtu.be/2GVNcWKRHPk. © 2017 John Wiley & Sons Ltd.

EDITORIAL: Progress in applications of magnetic nanoparticles in biomedicine Progress in applications of magnetic nanoparticles in biomedicine

NASA Astrophysics Data System (ADS)

O'Grady, Kevin

2009-11-01

In 2003 Journal of Physics D: Applied Physics published three sequential review articles on the subject of biomedical applications of magnetic nanoparticles. At that time there was growing interest in basic research on the potential of magnetic nanoparticles in biomedicine, including the appropriate methods to synthesize the particles and how to functionalize them. Following that initial publication the field has burgeoned and is now of a scale that could never have been envisaged in 2003. In the original review articles the authors anticipated applications in three specific technical areas of drug delivery and cell separation, MRI contrast enhancement and hyperthermic heating of biological materials, either for cell destruction or to increase the efficacy of other associated treatments such as chemotherapy. Six years later, significant progress has been made in all three areas, with applications already having been realized. More significantly, in vivo applications of both MRI contrast and hyperthermic cell heating have been achieved in human patients. This rapid progress in such a complex field is due to the need for non-invasive therapies and more effective management of serious conditions than is possible by the simple use of drugs alone. Imaging techniques such as MRI have also improved beyond all expectation and hence the possibility of improved contrast is particularly appealing. However, none of these applications could have been realized without dramatic progress beyond the state of the art in 2003 in the areas of particle synthesis and functionalization. Hence, remarkable progress has been made in all areas of the physics, chemistry and biochemistry of this subject, leading to many publications and perhaps a ten-fold increase in the number of those actively involved in research in this area. In 2003 we were most fortunate to have several expert authors review the subject. Quentin Pankhurst, Puerto Morales and Catherine Berry are now recognized as leaders within their own areas of the field. Because that field is moving rapidly and has now become a major subject of study, we believe that a collection of updated reviews would be highly appropriate and beneficial to the community. We have been fortunate in getting the same authors to provide six-year updates of their original works. This offers continuity and also allows those who may be new to this area to refer back to the original reviews for a full description of the basic science. In the interests of economy and to avoid repetition, this new set of reviews should be read in conjunction with the original works. The Editorial Board of J. Phys D is particularly grateful to the authors for agreeing to write a second work for our journal. We are aware that the production of reviews is an onerous task and acknowledge their efforts in making available such clear and high quality papers. We trust these new works will prove as beneficial to readers and as successful for their authors as were their original reviews.

The State Fiscal Situation: The Lost Decade

ERIC Educational Resources Information Center

National Governors Association, 2009

2009-01-01

The fiscal condition of states deteriorated dramatically over the last two years because of the depth and length of the economic downturn, and state officials do not expect this situation to improve any time soon. Previous downturns have proven that the worst budget years for a state are the two years after the national recession is declared over.…

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.

Toward Active X-ray Telescopes II

NASA Technical Reports Server (NTRS)

O'Dell, Stephen L.; Aldroft, Thomas L.; Atkins, Carolyn; Button, Timothy W.; Cotroneo, Vincenzo; Davis, William N.; Doel, Peter; Feldman, Charlotte H.; Freeman, Mark D.; Gubarev, Mikhail V.;

Controlling interactions between highly magnetic atoms with Feshbach resonances.

PubMed

Kotochigova, Svetlana

2014-09-01

This paper reviews current experimental and theoretical progress in the study of dipolar quantum gases of ground and meta-stable atoms with a large magnetic moment. We emphasize the anisotropic nature of Feshbach resonances due to coupling to fast-rotating resonant molecular states in ultracold s-wave collisions between magnetic atoms in external magnetic fields. The dramatic differences in the distribution of resonances of magnetic (7)S3 chromium and magnetic lanthanide atoms with a submerged 4f shell and non-zero electron angular momentum is analyzed. We focus on dysprosium and erbium as important experimental advances have been recently made to cool and create quantum-degenerate gases for these atoms. Finally, we describe progress in locating resonances in collisions of meta-stable magnetic atoms in electronic P-states with ground-state atoms, where an interplay between collisional anisotropies and spin-orbit coupling exists.

EGF Induced Centrosome Separation Promotes Mitotic Progression and Cell Survival

PubMed Central

Mardin, Balca R.; Isokane, Mayumi; Cosenza, Marco R.; Krämer, Alwin; Ellenberg, Jan; Fry, Andrew M.; Schiebel, Elmar

2014-01-01

Summary Timely and accurate assembly of the mitotic spindle is critical for the faithful segregation of chromosomes and centrosome separation is a key step in this process. The timing of centrosome separation varies dramatically between cell types; however, the mechanisms responsible for these differences and its significance are unclear. Here, we show that activation of epidermal growth factor receptor (EGFR) signaling determines the timing of centrosome separation. Premature separation of centrosomes decreases the requirement for the major mitotic kinesin Eg5 for spindle assembly, accelerates mitosis and decreases the rate of chromosome missegregation. Importantly, EGF stimulation impacts upon centrosome separation and mitotic progression to different degrees in different cell lines. Cells with high EGFR levels fail to arrest in mitosis upon Eg5 inhibition. This has important implications for cancer therapy since cells with high centrosomal response to EGF are more susceptible to combinatorial inhibition of EGFR and Eg5. PMID:23643362

The Burn Wound Microenvironment

PubMed Central

Rose, Lloyd F.; Chan, Rodney K.

2016-01-01

Significance: While the survival rate of the severely burned patient has improved significantly, relatively little progress has been made in treatment or prevention of burn-induced long-term sequelae, such as contraction and fibrosis. Recent Advances: Our knowledge of the molecular pathways involved in burn wounds has increased dramatically, and technological advances now allow large-scale genomic studies, providing a global view of wound healing processes. Critical Issues: Translating findings from a large number of in vitro and preclinical animal studies into clinical practice represents a gap in our understanding, and the failures of a number of clinical trials suggest that targeting single pathways or cytokines may not be the best approach. Significant opportunities for improvement exist. Future Directions: Study of the underlying molecular influences of burn wound healing progression will undoubtedly continue as an active research focus. Increasing our knowledge of these processes will identify additional therapeutic targets, supporting informed clinical studies that translate into clinical relevance and practice. PMID:26989577

Basics of particle therapy I: physics

PubMed Central

Park, Seo Hyun

2011-01-01

With the advance of modern radiation therapy technique, radiation dose conformation and dose distribution have improved dramatically. However, the progress does not completely fulfill the goal of cancer treatment such as improved local control or survival. The discordances with the clinical results are from the biophysical nature of photon, which is the main source of radiation therapy in current field, with the lower linear energy transfer to the target. As part of a natural progression, there recently has been a resurgence of interest in particle therapy, specifically using heavy charged particles, because these kinds of radiations serve theoretical advantages in both biological and physical aspects. The Korean government is to set up a heavy charged particle facility in Korea Institute of Radiological & Medical Sciences. This review introduces some of the elementary physics of the various particles for the sake of Korean radiation oncologists' interest. PMID:22984664

The Light and Shadow of Senescence and Inflammation in Cardiovascular Pathology and Regenerative Medicine

PubMed Central

Dal Sasso, Eleonora; Schirone, Leonardo; Forte, Maurizio; Palmerio, Silvia; Gerosa, Gino; Sciarretta, Sebastiano

2017-01-01

Recent epidemiologic studies evidence a dramatic increase of cardiovascular diseases, especially associated with the aging of the world population. During aging, the progressive impairment of the cardiovascular functions results from the compromised tissue abilities to protect the heart against stress. At the molecular level, in fact, a gradual weakening of the cellular processes regulating cardiovascular homeostasis occurs in aging cells. Atherosclerosis and heart failure are particularly correlated with aging-related cardiovascular senescence, that is, the inability of cells to progress in the mitotic program until completion of cytokinesis. In this review, we explore the intrinsic and extrinsic causes of cellular senescence and their role in the onset of these cardiovascular pathologies. Additionally, we dissect the effects of aging on the cardiac endogenous and exogenous reservoirs of stem cells. Finally, we offer an overview on the strategies of regenerative medicine that have been advanced in the quest for heart rejuvenation. PMID:29118467

Candesartan: widening indications for this angiotensin II receptor blocker?

PubMed

Mendis, B; Page, S R

2009-08-01

Candesartan cilexetil is one of a number of drugs of the angiotensin II receptor blocker (ARB) class. Their principal mode of action involves competitive blockade of the angiotensin II type 1 receptor, thereby modulating the activity of the rennin-angiotensin-aldosterone system. Angiotensin II receptor blocker therapy has been proven to be well tolerated and effective in the management of hypertension, chronic heart failure with left ventricular dysfunction and the prevention and progression of diabetic renal disease. Candesartan is a highly potent, long-acting and selective angiotensin II type 1 receptor blocker. It was launched in 1998 for the treatment of hypertension. Its use has increased dramatically, with recently published data suggesting benefit in the treatment of stroke, heart failure, diabetic renal disease and most recently in preventing the development of or delaying the progression of diabetic retinopathy. In this article we review the literature on the use of ARB drugs in general before focusing on candesartan.

Segmentation and classification of cell cycle phases in fluorescence imaging.

PubMed

Ersoy, Ilker; Bunyak, Filiz; Chagin, Vadim; Cardoso, M Christina; Palaniappan, Kannappan

2009-01-01

Current chemical biology methods for studying spatiotemporal correlation between biochemical networks and cell cycle phase progression in live-cells typically use fluorescence-based imaging of fusion proteins. Stable cell lines expressing fluorescently tagged protein GFP-PCNA produce rich, dynamically varying sub-cellular foci patterns characterizing the cell cycle phases, including the progress during the S-phase. Variable fluorescence patterns, drastic changes in SNR, shape and position changes and abundance of touching cells require sophisticated algorithms for reliable automatic segmentation and cell cycle classification. We extend the recently proposed graph partitioning active contours (GPAC) for fluorescence-based nucleus segmentation using regional density functions and dramatically improve its efficiency, making it scalable for high content microscopy imaging. We utilize surface shape properties of GFP-PCNA intensity field to obtain descriptors of foci patterns and perform automated cell cycle phase classification, and give quantitative performance by comparing our results to manually labeled data.

Childhood Stuttering – Where are we and Where are we going?

PubMed Central

Smith, Anne; Weber, Christine

2017-01-01

Remarkable progress has been made over the past two decades in expanding our understanding of the behavioral, peripheral physiological, and central neurophysiological bases of stuttering in early childhood. It is clear that stuttering is a neurodevelopmental disorder characterized by atypical development of speech motor planning and execution networks. The speech motor system must interact in complex ways with neural systems mediating language, other cognitive, and emotional processes. During the time window when stuttering typically appears and follows its path to either recovery or persistence, all of these neurobehavioral systems are undergoing rapid and dramatic developmental changes. We summarize our current understanding of the various developmental trajectories relevant for the understanding of stuttering in early childhood. We also present theoretical and experimental approaches that we believe will be optimal for even more rapid progress toward developing better and more targeted treatment for stuttering in the preschool children who are more likely to persist in stuttering. PMID:27701705

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.

A Markov model to evaluate cost-effectiveness of antiangiogenesis therapy using bevacizumab in advanced cervical cancer.

PubMed

Minion, Lindsey E; Bai, Jiaru; Monk, Bradley J; Robin Keller, L; Ramez, Eskander N; Forde, Gareth K; Chan, John K; Tewari, Krishnansu S

2015-06-01

To evaluate the cost-effectiveness of bevacizumab in recurrent/persistent and metastatic cervical cancer using recently reported updated survival and toxicology data. A Markov decision tree based on the Gynecologic Oncology Group 240 randomized trial was created. The 2013 MediCare Services Drug Payment Table and Physician Fee Schedule provided costs. In the 5-year model subjects transitioned through the following states: response, progression, minor complications, severe complications, and death. Patients experiencing a health utility per month according to treatment effectiveness were calculated. Because cervical cancer survival is measured in months rather than years, results were reported in both quality adjusted cervical cancer life months and years (QALmonth, QALY), adjusted from a baseline of having advanced cervical cancer during a month. The estimated total cost of therapy with bevacizumab is approximately 13.2 times that for chemotherapy alone, adding $73,791 per 3.5months (0.29year) of life gained, resulting in an incremental cost-effectiveness ratio (ICER) of $21.083 per month of added life. The ICER increased to $5775 per month of added life and $24,597/QALmonth ($295,164/QALY) due to the smaller difference in QALmonths. With 75% bevacizumab cost reduction, the ICER is $6737/QALmonth ($80,844/QALY), which translates to $23,580 for the 3.5month (0.29year) gain in OS. Increased costs are primarily related to the cost of drug and not the management of bevacizumab-induced complications. Cost reductions in bevacizumab result in dramatic declines in the ICER, suggesting that cost reconciliation in advanced cervical cancer may be possible through the availability of biosimilars, and/or less expensive, equally efficacious anti-angiogenesis agents. Copyright © 2015 Elsevier Inc. All rights reserved.

Coupled Environmental Processes in the Mojave Desert and Implications for ET Covers as Stable Landforms

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

D. Shafer; M. Y oung; S. Zitzer

2006-01-18

Monolayer evapotranspiration (ET) covers are the baseline method for closure of disposal sites for low-level radioactive waste (LLW), mixed LLW, and transuranic (TRU) waste at the Nevada Test Site (NTS). The regulatory timeline is typically 1,000 years for LLW and 10,000 years for TRU waste. Covers for such waste have different technical considerations than those with shorter timelines because they are subject to environmental change for longer periods of time, and because the environmental processes are often coupled. To evaluate these changes, four analog sites (approximately 30, 1,000 to 2,000, 7,000 to 12,500, and 125,000 years in age) on themore » NTS were analyzed to address the early post-institutional control period (the youngest site), the 1,000-year compliance period for disposal of LLW, and the 10,000-year period for TRU waste. Tests included soil texture, structure, and morphology; surface soil infiltration and hydraulic conductivity; vegetation and faunal surveys; and literature reviews. Separate measurements were made in plant undercanopy and intercanopy areas. The results showed a progressive increase in silt and clay content of surface soils with age. Changes in soil texture and structure led to a fivefold decline in saturated hydraulic conductivity in intercanopy areas, but no change in undercanopies, which were subject to bioturbation. These changes may have been responsible for the reduction in total plant cover, most dramatically in intercanopy areas, primarily because more precipitation either runs off the site or is held nearer to the surface where plant roots are less common. The results suggest that covers may evolve over longer timeframes to stable landforms that minimize the need for active maintenance.« less

Long-term effects of chronic light pollution on seasonal functions of European blackbirds (Turdus merula).

PubMed

Dominoni, Davide M; Quetting, Michael; Partecke, Jesko

2013-01-01

Light pollution is known to affect important biological functions of wild animals, including daily and annual cycles. However, knowledge about long-term effects of chronic exposure to artificial light at night is still very limited. Here we present data on reproductive physiology, molt and locomotor activity during two-year cycles of European blackbirds (Turdus merula) exposed to either dark nights or 0.3 lux at night. As expected, control birds kept under dark nights exhibited two regular testicular and testosterone cycles during the two-year experiment. Control urban birds developed testes faster than their control rural conspecifics. Conversely, while in the first year blackbirds exposed to light at night showed a normal but earlier gonadal cycle compared to control birds, during the second year the reproductive system did not develop at all: both testicular size and testosterone concentration were at baseline levels in all birds. In addition, molt sequence in light-treated birds was more irregular than in control birds in both years. Analysis of locomotor activity showed that birds were still synchronized to the underlying light-dark cycle. We suggest that the lack of reproductive activity and irregular molt progression were possibly the results of i) birds being stuck in a photorefractory state and/or ii) chronic stress. Our data show that chronic low intensities of light at night can dramatically affect the reproductive system. Future studies are needed in order to investigate if and how urban animals avoid such negative impact and to elucidate the physiological mechanisms behind these profound long-term effects of artificial light at night. Finally we call for collaboration between scientists and policy makers to limit the impact of light pollution on animals and ecosystems.

Why Leadership Matters: One School's Journey to Success

ERIC Educational Resources Information Center

Ward, Cheryl James

2013-01-01

In the following study, the researcher, an experienced leadership coach and former principal, observed the leadership practices of a first-year principal over the course of one year as student achievement at his school increased dramatically. Employing participant observation, document analysis, interviewing, and administration of a teacher…

Academe's Increased Reliance on Legal Advice Documented by College Attorneys' Association.

ERIC Educational Resources Information Center

Fields, Cheryl M.

1985-01-01

In 25 years, litigation and lawyers' influence on campuses has increased dramatically and so has the National Association of College and University Attorneys group's membership. A review of the past 25 years of legal changes and increased reliance on lawyers is presented. (MLW)

Total Recall

ERIC Educational Resources Information Center

American School & University, 2007

2007-01-01

For 25 years, "American School & University" has been publishing a special issue dedicated to the best in education design. Although design has changed dramatically over the years, one will find that the jury criteria for award-winning projects has remained consistent. The first jury was looking for technical innovation, and 1986's…

Defining Human-Centered System Issues for Verifying and Validating Air Traffic Control Systems

DOT National Transportation Integrated Search

1993-01-01

Over the past 40 years, the application of automation to the U.S. air traffic : control (ATC) system has grown enormously to meet significant increases in air : traffic volume. The next ten years will witness a dramatic overhaul of computer : hardwar...

Growth and Your 13-to 18-Year-Old

MedlinePlus

... is a time of dramatic change for both boys and girls. Hormone-driven changes are accompanied by growth spurts ... ages 12 and 15. The growth spurt of boys is, on average, about 2 years later than that of girls. By age 16, most boys have stopped growing, ...

Male Psychopaths and Their Criminal Careers.

ERIC Educational Resources Information Center

Hare, Robert D.; And Others

1988-01-01

Examined criminal histories of male psychopaths and nonpsychopaths, exploring time in prison and conviction rates for five-year periods between ages of 16 and 45. Criminal activities of nonpsychopaths were relatively constant over years; activities of psychopaths remained high until around age 40, then declined dramatically. Results are consistent…

2013 Annual Survey of Journalism Mass Communication Enrollments: Enrollments Decline for Third Consecutive Year

ERIC Educational Resources Information Center

Becker, Lee Bernard; Vlad, Tudor; Simpson, Holly Anne

2014-01-01

Enrollments in journalism and mass communication programs in the United States in the fall of 2013 were down from a year earlier for the third year in a row. Enrollments dropped at the bachelor's, master's, and doctoral levels, and the number of freshmen and sophomores were down dramatically from a year earlier. Enrollments in the…

Countdown to 2015 country case studies: what can analysis of national health financing contribute to understanding MDG 4 and 5 progress?

PubMed

Mann, Carlyn; Ng, Courtney; Akseer, Nadia; Bhutta, Zulfiqar A; Borghi, Josephine; Colbourn, Tim; Hernández-Peña, Patricia; Huicho, Luis; Malik, Muhammad Ashar; Martinez-Alvarez, Melisa; Munthali, Spy; Salehi, Ahmad Shah; Tadesse, Mekonnen; Yassin, Mohammed; Berman, Peter

2016-09-12

Countdown to 2015 (Countdown) supported countries to produce case studies that examine how and why progress was made toward the Millennium Development Goals (MDGs) 4 and 5. Analysing how health-financing data explains improvements in RMNCH outcomes was one of the components to the case studies. This paper presents a descriptive analysis on health financing from six Countdown case studies (Afghanistan, Ethiopia, Malawi, Pakistan, Peru, and Tanzania), supplemented by additional data from global databases and country reports on macroeconomic, health financing, demographic, and RMNCH outcome data as needed. It also examines the effect of other contextual factors presented in the case studies to help interpret health-financing data. Dramatic increases in health funding occurred since 2000, where the MDG agenda encouraged countries and donors to invest more resources on health. Most low-income countries relied on external support to increase health spending, with an average 20-64 % of total health spending from 2000 onwards. Middle-income countries relied more on government and household spending. RMNCH funding also increased since 2000, with an average increase of 119 % (2005-2010) for RMNH expenditures (2005-2010) and 165 % for CH expenditures (2005-2011). Progress was made, especially achieving MDG 4, even with low per capita spending; ranging from US$16 to US$44 per child under 5 years among low-income countries. Improvements in distal factors were noted during the time frame of the analysis, including rapid economic growth in Ethiopia, Peru, and Tanzania and improvements in female literacy as documented in Malawi, which are also likely to have contributed to MDG progress and achievements. Increases in health and RMNCH funding accompanied improvements in outcomes, though low-income countries are still very reliant on external financing, and out-of-pocket comprising a growing share of funds in middle-income settings. Enhancements in tracking RMNCH expenditures across countries are still needed to better understand whether domestic and global health financing initiatives lead to improved outcomes as RMNCH continues to be a priority under the Sustainable Development Goals.

Progress towards the 'Golden Age' of biotechnology.

PubMed

Gartland, K M A; Bruschi, F; Dundar, M; Gahan, P B; Viola Magni, M p; Akbarova, Y

2013-07-01

Biotechnology uses substances, materials or extracts derived from living cells, employing 22 million Europeans in a € 1.5 Tn endeavour, being the premier global economic growth opportunity this century. Significant advances have been made in red biotechnology using pharmaceutically and medically relevant applications, green biotechnology developing agricultural and environmental tools and white biotechnology serving industrial scale uses, frequently as process feedstocks. Red biotechnology has delivered dramatic improvements in controlling human disease, from antibiotics to overcome bacterial infections to anti-HIV/AIDS pharmaceuticals such as azidothymidine (AZT), anti-malarial compounds and novel vaccines saving millions of lives. Green biotechnology has dramatically increased food production through Agrobacterium and biolistic genetic modifications for the development of 'Golden Rice', pathogen resistant crops expressing crystal toxin genes, drought resistance and cold tolerance to extend growth range. The burgeoning area of white biotechnology has delivered bio-plastics, low temperature enzyme detergents and a host of feedstock materials for industrial processes such as modified starches, without which our everyday lives would be much more complex. Biotechnological applications can bridge these categories, by modifying energy crops properties, or analysing circulating nucleic acid elements, bringing benefits for all, through increased food production, supporting climate change adaptation and the low carbon economy, or novel diagnostics impacting on personalized medicine and genetic disease. Cross-cutting technologies such as PCR, novel sequencing tools, bioinformatics, transcriptomics and epigenetics are in the vanguard of biotechnological progress leading to an ever-increasing breadth of applications. Biotechnology will deliver solutions to unimagined problems, providing food security, health and well-being to mankind for centuries to come. Copyright © 2013 Elsevier Ltd. All rights reserved.

Geophysical analysis of the recent sinkhole trend at Ghor-Haditha (Dead Sea, Jordan)

NASA Astrophysics Data System (ADS)

Camerlynck, Christian; Bodet, Ludovic; Galibert, Pierre-Yves; Boucher, Marie; Al-Zoubi, Abdallah

2013-04-01

For essentially the last 30 year the water level of the Dead Sea has highly dropped. One of the major associated facts is sinkhole occurrences along the shoreline both in Jordan and Israel. As the principal invoked mechanism, many studies have concluded that sinkhole formation results from the dissolution of a previously immersed salt layer, progressively in contact with fresh to brackish water. In Jordan, the triggering of this phenomenon could also be the result of particular tectonic settings, associated with the Jordan-Dead Sea transform fault system. At Ghor Haditha (south-est Jordan), the consequences have been dramatic for farmers with the shrinking of temporary available lands and industry with the closing of at least one factory. The shallow material in this area is heterogeneous and composed of intercalated sand and clay layers of alluvial-colluvial origin, over a salty substratum, whose precise depth and thickness are yet partially hypothesized. Between 2005 and 2008, a multi-method high-resolution geophysical survey was performed, approximately over a 1 km2 area at Ghor Haditha, associating mainly electromagnetic soundings, magnetic resonance soundings (MRS), and seismic profiling, ground-penetrating radar and electrical resistivity tomography. At the same time, this specific area was the location of a dramatic evolution of sinkhole occurences, regularly followed by geodetic measurements. Over the 3 years period, about 120 TEM (Transient ElectroMagnetic) soundings allow to map precisely the depth of the conductive layers below the resistive overburden. Two conductive layer are then revealed, the latter showing the lowest resistivity below 1 Ohm.m corresponding to the saline substratum. Several MRS (3 in 2005, repeated in 2007 and 12 additional soundings) show an east-west hydraulic gradient towards the Dead. However, the main sinkhole trend coincides with both: - a clear low transmissivity axis determined from MRS measurements; - the western side of a depression into the top of the most conductive layer. This shows so clearly a correlation between the recent sinkhole phenomenon and the current water circulations, but paleo-topography below the Pleistocene deposits mays equally be a clue in the sinkhole hazard.

Progress on the International Space Station - We're Part Way up the Mountain

NASA Technical Reports Server (NTRS)

Fortenberry, Lindy; Bartoe, John-David F.; Holloway, Thomas

2001-01-01

The first phase of the International Space Station construction has been completed, and research has begun. Russian, U.S., and Canadian hardware is on orbit, and Italian logistics modules have visited often. With the delivery of the U.S. Laboratory, Destiny, significant research capability is in place, and dozens of U.S. and Russian experiments have been conducted. Crew members have been on orbit continuously since November 2000. Several "bumps in the road" have occurred along the way, and each has been systematically overcome. Enormous amounts of hardware and software are being developed by the International Space Station partners and participants around the world and are largely on schedule for launch. Significant progress has been made in the testing of completed elements at launch sites in the United States and Kazakhstan. Over 250,000 kilograms of flight hardware have been delivered to the Kennedy Space Center and integrated testing of several elements wired together has progressed extremely well. Mission control centers are fully functioning in Houston, Moscow, and Canada, and operations centers Darmstadt, Tsukuba, Turino, and Huntsville will be going on line as they are required. Extensive coordination efforts continue among the space agencies of the five partners and two participants, involving 16 nations. All of them continue to face their own challenges and have achieved significant successes. This paper will discuss the contributions of the International Space Station partners and participants, their accomplished milestones, and upcoming events. The International Space Station program, the largest and most complicated peacetime project in history, has progressed part way up the mountain, and the partners are continuing their journey to the top. The International Space Station (ISS) is unprecedented in its technological, engineering, and management complexity, and is one of the largest international collaborations ever undertaken. The ISS is a dramatic example of the ability of nations to work together as a team toward common goals and dreams. The challenges encountered and overcome by the international ISS team have been likened to climbing a mountain. Construction of the ISS has progressed rapidly in the past year. ISS is now a functioning microgravity laboratory in space hosting a permanent human presence, prompting the characterization that we are "part way up the mountain, and the team continues its climb."

Into the Curriculum. Creative Dramatics: Valentine Lip Sync Book Charades; Language Arts/Social Studies: Found Poetry from Primary Sources; Reading/Language Arts: A Thematic Activity To Herald in the New Year; Science: Asian Elephant Life Cycles; Social Studies: Conservation of Animal Species-Asian Elephants; Social Studies: What Makes a Leader?

ERIC Educational Resources Information Center

Shugar, Candace; Robinson, Alice A.

2003-01-01

Provides six fully developed library media activities that are designed for use with specific curriculum units in creative dramatics, language arts, social studies, reading, and science. Library media skills, curriculum objectives, grade levels, resources, instructional roles, activities and procedures, evaluation, and follow-up are described for…

Graduate Student Teacher Training: Still Relevant (And Missing?) 20 Years Later

ERIC Educational Resources Information Center

Blouin, David D.; Moss, Alison R.

2015-01-01

Twenty years ago, Pescosolido and Milkie (1995) reported that 50 percent of U.S. and Canadian sociology graduate programs offered formal teacher training. Despite pronouncements that offerings have increased substantially, no similarly thorough and direct investigation has been published since. In this time of dramatic change and increasing…

Walnuts and Berries for the Brain

USDA-ARS?s Scientific Manuscript database

Average lifespans have increased dramatically over the last century and by the year 2050 fully 30% of the total population will be over 65 years of age. There is a high probability that these people will be exhibiting the most common behavioral changes that occur in “normal” aging - impaired mobilit...

DEVELOPMENT OF AN EPA METHOD FOR PERFLUOROCALKYL COMPOUNDS IN DRINKING WATER

EPA Science Inventory

Perfluoroalkyl compounds (PFCs) have been manufactured for over 50 years and their use has dramatically increased over the years. Due to their unique properties of repelling both water and oil, PFCs have been used in a wide variety of applications. In 2001, identification of or...

The State of Enrollment Management in Journalism and Mass Communication Programs.

ERIC Educational Resources Information Center

Rawlins, Brad L.; Soenksen, Roger; Jensen, Matt

Some programs in journalism and mass communication have been forced to incorporate limited enrollment strategies, as undergraduate interest in these programs continues to grow. After 4 years of moderate growth, undergraduate enrollments in journalism and mass communication programs increased dramatically in the year 2000. Some of the limited…

Florida Community College Finance: Update. Report 2.

ERIC Educational Resources Information Center

Florida State Postsecondary Education Planning Commission, Tallahassee.

In Florida, community college enrollments have increased by 41% over the past 5 years. The use of a 3-year average to fund enrollment has penalized those colleges which have grown dramatically. This report analyzes the range of community college expenditures by instructional program; the relationship of instructional expenditures to support…

Predictive Modeling: Linking Enrollment and Budgeting

ERIC Educational Resources Information Center

Trusheim, Dale; Rylee, Carol

2011-01-01

The hard choices that must be made to balance budgets at higher education institutions can be painful and have dramatic consequences that may linger for years. If enrollment projections and therefore tuition income/budgeting projections for future years are inaccurate, then the result may be unnecessary or insufficient budget reductions, both of…

Urban Adolescents' Postschool Aspirations and Awareness

ERIC Educational Resources Information Center

Scanlon, David; Saxon, Karyn; Cowell, Molly; Kenny, Maureen E.; Perez-Gualdron, Leyla; Jernigan, Maryam

2008-01-01

The young adult years (approximately the age when one leaves high school to age 23) are pivotal to adult life success. They are the years when adolescents typically assume dramatic increases in responsibility for self-direction in areas such as socialization, independent living, citizenship, employment, education, and mental and physical health.…

Forest Thrives In Sludge Application Tests

Treesearch

Dale G. Brockway

1988-01-01

A six-year, state and federal research-demonstration project to recycle treated municipal wastewater sludge on forest lands has resulted in dramatic growth increase of trees, groundcover and wildlife populations.

KENNEDY SPACE CENTER, FLA. - Capt. Charles Plumb (USNR retired) begins his dramatic presentation of his six years as a prisoner of war in Vietnam. The block of light on the stage represented the size of the cell he was confined in. Plumb was keynote speaker for the kickoff of Spaceport Super Safety and Health Day at KSC, an annual event dedicated to reinforcing safe and healthful behaviors in the workforce.

NASA Image and Video Library

2003-10-15

KENNEDY SPACE CENTER, FLA. - Capt. Charles Plumb (USNR retired) begins his dramatic presentation of his six years as a prisoner of war in Vietnam. The block of light on the stage represented the size of the cell he was confined in. Plumb was keynote speaker for the kickoff of Spaceport Super Safety and Health Day at KSC, an annual event dedicated to reinforcing safe and healthful behaviors in the workforce.

Forward to the Special Issue in Physics of the Earth and Planetary Interiors on Multiscale Assessment of Micro-Seismicity and Slow Earthquakes

NASA Astrophysics Data System (ADS)

Yuen, David A.; Ni, Sidao; Wang, Yibo; Xu, Chang; Veveakis, Manny

2016-12-01

Today we witness the economical throes and uncertainties created by the dramatic cratering of oil prices in 2014 from 115 dollars per barrel to 38 dollars. This dramatic nonlinear phenomenon reminds earth scientists of the disintegration of the Laurentide ice sheet, some 14,000 years ago. One of the contributing factors of the precipitous drop in oil prices is super-fracking. This is used for oil as well as for gas production and became economically feasible about .twenty years ago. Thanks to this technological breakthrough Americans had enjoyed a renaissance in oil production since 2005. This process, however, has some drawbacks, such as the induced earthquakes occurring in rejuvenated or new fields (Fig. 1).

Case Study: The Use of Massage Therapy to Relieve Chronic Low-Back Pain.

PubMed

Allen, Laura

2016-09-01

To study the effects of massage on chronic low-back pain in a patient with four different diagnoses: osteoarthritis, scoliosis, spinal stenosis, and degenerative disc disease. The patient's goal was to cut down on the amount of pain medication he takes. A 63-year-old man with chronic back pain received four massages across a twenty-day period. Progress was recorded using the Oswestry Low Back Pain Scale, as he self-reported on levels of pain and interference with his activities of daily living. Improvement was noted in 9 out of 10 measurements of self-reported pain and activities of daily living, with the only exception being his ability to lift heavy objects, which remained unchanged. The most dramatic differences were improvements in his ability to walk, and in the changing degrees of pain. The client also self-reported being able to decrease his pain medication and the ability to ride his bicycle for the first time in years. Massage therapy is a promising treatment for chronic low-back pain for patients who may have multiple pathologies, any one of which could be responsible for the condition. Further study is encouraged to determine the efficacy of massage therapy as a readily accessible, lower-cost alternative to more invasive therapies and as an adjunct to regular medical care, when appropriate.

Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

PubMed

Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E

2017-01-01

Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

Waist-to-height ratio is a useful index for nonalcoholic fatty liver disease in children and adolescents: a secondary data analysis.

PubMed

Lin, Ming-Shyan; Lin, Tsai-Hui; Guo, Su-Er; Tsai, Ming-Horng; Chiang, Ming-Shin; Huang, Tung-Jung; Chen, Mei-Yen

2017-10-30

Nonalcoholic fatty liver disease (NAFLD) is a global problem and pediatric obesity has risen dramatically. Early NAFLD might progress to nonalcoholic steatohepatitis (NASH) or liver cirrhosis and significantly increase liver disease-related mortality. We looked for NAFLD predictors in children and adolescents. This community-based, cross-sectional study ran from December 2012 to September 2013 in southwestern Taiwan. Children <10 and >19 years old, with detected hepatic diseases, or who drank alcohol were excluded. The diagnosis of NAFLD was based on ultrasound: age, sex, anthropometric measurements, and laboratory data were evaluated for associated risks by using logistic regression analysis. Receiver operating characteristic (ROC) curves were used to determine cutoff values. We enrolled one thousand, two hundred and ten children (594 males; 616 females; mean age: 15.5 ± 2.8 years). Age, anthropometric measurements, and laboratory data were significantly higher in children with NAFLD. The association between NAFLD and the waist-to-height ratio (WHtR) was significant (adjusted odds ratio: 2.6; 95% confidence interval: 1.909-3.549; P < 0.001). It indicated highly suspicion of NAFLD (sensitivity: 70.1%; specificity 76.9%) when the WHtR for children and adolescents is above the cutoff value of 0.469. The WHtR might be a powerful index of the severity of pediatric NAFLD.

Treatment of hemophilia in the near future.

PubMed

Peyvandi, Flora; Garagiola, Isabella

2015-11-01

Advancements and debacles have characterized hemophilia treatment over the past 50 years. The 1970s saw the availability of plasma-derived concentrates making prophylaxis and home therapy possible. This optimistic perception changed extremely in the early 1980s, when most people with hemophilia were infected with HIV and hepatitis viruses. Then, also in the 1980s, the rapid progress in molecular biology led to the development of recombinant therapeutic products. This important advancement was a huge technological leap fresh off from the earlier 1980s disaster. Now in the 21st century, the newer bioengineering drugs open a new hopeful phase for the management of hemophilia. The current efforts are concentrated on producing novel coagulation factors with prolonged bioavailability, increased potency, and resistance to inactivation and potentially reduced immunogenicity; this phase of evolution is improving very quickly. 2014 is the year of marketing approval by the Food and Drug Administration of the first bioengineered FVIII and FIX long-acting drugs, using Fc-fusion strategy. This represents the first significant advance in the hemophilia therapy that dramatically transforms patient management by substantially reducing the frequency of injections, improving compliance, and simplifying prophylaxis and, in turn, refining the quality of life of hemophilia patients, offering them a nearly normal life expectancy, particularly to newborns with hemophilia B. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Syringomyelia caused by an arachnoid web in a patient with shunted Dandy-Walker malformation.

PubMed

Lee, Hee Chang; Choi, Jung Won; Lee, Ji Yeoun; Phi, Ji Hoon; Kim, Seung-Ki; Cho, Byung-Kyu; Wang, Kyu-Chang

2017-04-01

Dandy-Walker malformation (DWM) is a congenital brain anomaly characterized by dysgenesis of the cerebellar vermis and the presence of a posterior fossa cyst. The association of syringomyelia with DWM is extremely rare. A 10-year-old patient who was diagnosed with DWM in infancy presented with progressive scoliosis and fecal incontinence. He had been treated with cystoventriculoperitoneal shunting with a Y-connection during infancy, which was followed by a revision 6 years later. During the revision surgery, intraventricular bleeding occurred and was managed conservatively. Imaging studies for the current visit revealed syringomyelia along the cervicothoracic spinal cord and a membranous structure around the cervicomedullary junction. Phase-contrast cine magnetic resonance imaging (MRI) revealed disturbed cerebrospinal fluid (CSF) flow across the membrane. We excised the arachnoid web that was tethering the brainstem and blocking CSF flow. Postoperatively, the patient experienced symptom relief, and the follow-up imaging study demonstrated a dramatic decrease in the size of the syringomyelia. We suggest that syrinx formation in this patient was possibly caused by disturbed CSF flow and tethering of the brainstem. We experienced an unusual case of DWM with syringomyelia which was caused by an arachnoid web blocking CSF flow and tethering the brainstem. The arachnoid web seems to be formed by previous bleeding which occurred at the time of shunt revision. After excision of the arachnoid web, the patient showed good outcome.

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

Riesen, Rolf E.; Bridges, Patrick G.; Stearley, Jon R.

Next-generation exascale systems, those capable of performing a quintillion (10{sup 18}) operations per second, are expected to be delivered in the next 8-10 years. These systems, which will be 1,000 times faster than current systems, will be of unprecedented scale. As these systems continue to grow in size, faults will become increasingly common, even over the course of small calculations. Therefore, issues such as fault tolerance and reliability will limit application scalability. Current techniques to ensure progress across faults like checkpoint/restart, the dominant fault tolerance mechanism for the last 25 years, are increasingly problematic at the scales of future systemsmore » due to their excessive overheads. In this work, we evaluate a number of techniques to decrease the overhead of checkpoint/restart and keep this method viable for future exascale systems. More specifically, this work evaluates state-machine replication to dramatically increase the checkpoint interval (the time between successive checkpoint) and hash-based, probabilistic incremental checkpointing using graphics processing units to decrease the checkpoint commit time (the time to save one checkpoint). Using a combination of empirical analysis, modeling, and simulation, we study the costs and benefits of these approaches on a wide range of parameters. These results, which cover of number of high-performance computing capability workloads, different failure distributions, hardware mean time to failures, and I/O bandwidths, show the potential benefits of these techniques for meeting the reliability demands of future exascale platforms.« less

Effects of precipitation changes on switchgrass photosynthesis, growth, and biomass: A mesocosm experiment.

PubMed

Hui, Dafeng; Yu, Chih-Li; Deng, Qi; Dzantor, E Kudjo; Zhou, Suping; Dennis, Sam; Sauve, Roger; Johnson, Terrance L; Fay, Philip A; Shen, Weijun; Luo, Yiqi

2018-01-01

Climate changes, including chronic changes in precipitation amounts, will influence plant physiology and growth. However, such precipitation effects on switchgrass, a major bioenergy crop, have not been well investigated. We conducted a two-year precipitation simulation experiment using large pots (95 L) in an environmentally controlled greenhouse in Nashville, TN. Five precipitation treatments (ambient precipitation, and -50%, -33%, +33%, and +50% of ambient) were applied in a randomized complete block design with lowland "Alamo" switchgrass plants one year after they were established from tillers. The growing season progression of leaf physiology, tiller number, height, and aboveground biomass were determined each growing season. Precipitation treatments significantly affected leaf physiology, growth, and aboveground biomass. The photosynthetic rates in the wet (+50% and +33%) treatments were significantly enhanced by 15.9% and 8.1%, respectively, than the ambient treatment. Both leaf biomass and plant height were largely increased, resulting in dramatically increases in aboveground biomass by 56.5% and 49.6% in the +50% and +33% treatments, respectively. Compared to the ambient treatment, the drought (-33% and -50%) treatments did not influence leaf physiology, but the -50% treatment significantly reduced leaf biomass by 37.8%, plant height by 16.3%, and aboveground biomass by 38.9%. This study demonstrated that while switchgrass in general is a drought tolerant grass, severe drought significantly reduces Alamo's growth and biomass, and that high precipitation stimulates its photosynthesis and growth.

Can loss and grief activate latent neoplasia? A clinical case of possible interaction between genetic risk and stress in breast cancer.

PubMed

Biondi, M; Costantini, A; Parisi, A

1996-01-01

Nineteenth-century physicians working with cancer patients frequently reported that severe emotional losses and grief occurred in some cases before cancer. Research on psychoneuroimmunology seems to reactivate this interest and could give a possible convincing background. We recently observed the case of a 45-year-old woman who developed symptoms of breast cancer (ductal infiltrating carcinoma, T1, N1, M0) 3 years after the loss of her only child. The affection for the child compensated inadequacies of her marriage, which became increasingly unstable. The child died in a dramatic accident at home, while his mother was near him but unable to help. The patient had a moderate genetic-familial risk of mammary cancer. Animal studies strongly suggest that stress, through neuroimmunomodulatory mediatory mechanisms, can significantly affect appearance and progression of mammary cancer. The patient developed long-lasting intense grief, despair and hopelessness. We discuss the case from three main standpoints: genetic and risk factors for breast cancer; findings which demonstrated a relationship between stress, neuroimmunomodulation and cancer in animals; data from autopsy studies which found foci of latent breast cancer in 20% of healthy women in the same age range. Stress does not create cancer. However we hypothesize that in this case it could have contributed by the activation of a latent neoplasia and/or by impairing immunosurveillance during a critical life phase.

Mechanism of Action and Toxicities of Purgatives Used for Colonoscopy Preparation

PubMed Central

Adamcewicz, Margaret; Bearelly, Dilip; Porat, Gail; Friedenberg, Frank K.

2011-01-01

Importance of the field In developed countries colonoscopy volume has increased dramatically over the past 15 years and is the principle method used to screen for colon cancer. Preparations used for colon cleaning have evolved over the past 30 years. Some preparations have been shown to be unsafe and are now used on a limited basis. There has been progress on limiting the volume required and on taste improvement. Areas covered in this review This review provides an account of preparations used from 1980 when polyethylene glycol-based preparations became widely available, until the present day. The review highlights their mechanism of action and principle toxicities. The handling of solutes and solute-free fluid by the colon is also reviewed. What the reader will gain The reader will gain a perspective on the factors considered in developing colonic purgatives and the rationale for choosing selected preparations based on patient factors such as age, co-morbidities, and concomitant medications. Take home message Although generally safe and effective, colonic purgatives have both acute and permanent toxicities. The safest preparations utilize polyethylene glycol combined with a balanced electrolyte solution. Limitations of this preparation center on the volume required and poor taste. Alternative formulations are now available; however those using sodium phosphate have fallen out of favor due to a risk of renal toxicity. PMID:21162694

A five year view on the contribution of snowmelt to flow in the Willamette River using water stable isotopes

EPA Science Inventory

Much of the water that people in Western Oregon rely on come from the snowpack in the Cascade Mountains, and this snowpack is expected to decrease in coming years with climate change. In fact, the past five years have shown dramatic variation in snowpack from a high of 174% of n...

Common MRI acquisition non-idealities significantly impact the output of the boundary shift integral method of measuring brain atrophy on serial MRI.

PubMed

Preboske, Gregory M; Gunter, Jeff L; Ward, Chadwick P; Jack, Clifford R

2006-05-01

Measuring rates of brain atrophy from serial magnetic resonance imaging (MRI) studies is an attractive way to assess disease progression in neurodegenerative disorders, particularly Alzheimer's disease (AD). A widely recognized approach is the boundary shift integral (BSI). The objective of this study was to evaluate how several common scan non-idealities affect the output of the BSI algorithm. We created three types of image non-idealities between the image volumes in a serial pair used to measure between-scan change: inconsistent image contrast between serial scans, head motion, and poor signal-to-noise (SNR). In theory the BSI volume difference measured between each pair of images should be zero and any deviation from zero should represent corruption of the BSI measurement by some non-ideality intentionally introduced into the second scan in the pair. Two different BSI measures were evaluated, whole brain and ventricle. As the severity of motion, noise, and non-congruent image contrast increased in the second scan, the calculated BSI values deviated progressively more from the expected value of zero. This study illustrates the magnitude of the error in measures of change in brain and ventricle volume across serial MRI scans that can result from commonly encountered deviations from ideal image quality. The magnitudes of some of the measurement errors seen in this study exceed the disease effect in AD shown in various publications, which range from 1% to 2.78% per year for whole brain atrophy and 5.4% to 13.8% per year for ventricle expansion (Table 1). For example, measurement error may exceed 100% if image contrast properties dramatically differ between the two scans in a measurement pair. Methods to maximize consistency of image quality over time are an essential component of any quantitative serial MRI study.

Whipple’s disease: misdiagnosed as sarcoidosis with further tricuspid valve endocarditis and pulmonary embolism – a case report

PubMed Central

Berent, Robert; Auer, Johann; Lassnig, Elisabeth; von Duvillard, Serge P; Crouse, Stephen F; Tuppy, Herwig; Eber, Bernd

2009-01-01

GH Whipple described a 36-year-old physician in 1907 with gradual loss of weight and strength, stools consisting chiefly of neutral fat and fatty acids, indefinite abdominal signs and a peculiar multiple arthritis. The patient died of this progressive illness. Whipple called it intestinal lipodystrophy since he observed accumulation of large masses of neutral fats and fatty acids in the lymph spaces. It was renamed Whipple’s disease in 1949. An infectious aetiology was suspected as early as Whipple’s initial report. However, successful treatment with antibiotics was not reported until 1952, which resulted in dramatic clinical responses. The cause is now known to be Tropheryma whipplei. Light and electron microscopy of infected tissue identified a gram-positive, non-acid-fast, periodic acid-Schiff (PAS) positive bacillus with a characteristic trilamellar plasma membrane resembling that of gram-negative bacteria. Whipple’s disease is extremely rare. It is a systemic infectious disorder affecting mostly middle-aged white men. The clinical presentation is often non-specific, which may make its diagnosis difficult. The four cardinal clinical manifestations are arthralgias, weight loss, diarrhoea and abdominal pain. The frequently vague articular symptoms can precede the diagnosis of Whipple’s disease by an average of 6–8 years. Lymph nodes and other tissues may present diagnostic problems, since the changes in routinely stained sections may mimic those of sarcoidosis. The detection of PAS-positive histiocytes in the small intestine remains the mainstay of the diagnosis, although Whipple’s disease without gastrointestinal involvement is described. We illustrate a case in which, retrospectively, the clinical presentation would have been typical for Whipple’s disease. However, the clinical presentation and the histological examinations of lymph nodes, liver biopsies and ascites initially were misinterpreted as sarcoidosis with consecutive immunosuppressive therapy and progressive worsening of the patient’s health presenting at least as sepsis with endocarditis. PMID:21686811

Fish biorobotics: kinematics and hydrodynamics of self-propulsion.

PubMed

Lauder, George V; Anderson, Erik J; Tangorra, James; Madden, Peter G A

2007-08-01

As a result of years of research on the comparative biomechanics and physiology of moving through water, biologists and engineers have made considerable progress in understanding how animals moving underwater use their muscles to power movement, in describing body and appendage motion during propulsion, and in conducting experimental and computational analyses of fluid movement and attendant forces. But it is clear that substantial future progress in understanding aquatic propulsion will require new lines of attack. Recent years have seen the advent of one such new avenue that promises to greatly broaden the scope of intellectual opportunity available to researchers: the use of biorobotic models. In this paper we discuss, using aquatic propulsion in fishes as our focal example, how using robotic models can lead to new insights in the study of aquatic propulsion. We use two examples: (1) pectoral fin function, and (2) hydrodynamic interactions between dorsal and caudal fins. Pectoral fin function is characterized by considerable deformation of individual fin rays, as well as spanwise (along the length) and chordwise (across the fin) deformation and area change. The pectoral fin can generate thrust on both the outstroke and instroke. A robotic model of the pectoral fin replicates this result, and demonstrates the effect of altering stroke kinematics on the pattern of force production. The soft dorsal fin of fishes sheds a distinct vortex wake that dramatically alters incoming flow to the tail: the dorsal fin and caudal fin act as dual flapping foils in series. This design can be replicated with a dual-foil flapping robotic device that demonstrates this phenomenon and allows examination of regions of the flapping performance space not available to fishes. We show how the robotic flapping foil device can also be used to better understand the significance of flexible propulsive surfaces for locomotor performance. Finally we emphasize the utility of self-propelled robotic devices as a means of understanding how locomotor forces are generated, and review different conceptual designs for robotic models of aquatic propulsion.

Age-related macular degeneration—emerging pathogenetic and therapeutic concepts

PubMed Central

GEHRS, KAREN M.; ANDERSON, DON H.; JOHNSON, LINCOLN V.; HAGEMAN, GREGORY S.

2014-01-01

Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage ‘wet’ form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common ‘dry’ AMD, except for the use of antioxidants that delay progression in 20%–25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene—which encodes the major inhibitor of the complement alternative pathway—is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel diagnostic and therapeutic approaches for this disease that will dramatically improve the quality of our prolonged lifespan. PMID:17101537

Tilted orthodontic micro implants: a photoelastic stress analysis.

PubMed

Çehreli, Seçil; Özçırpıcı, Ayça Arman; Yılmaz, Alev

2013-10-01

The aim of this study was to examine peri-implant stresses around orthodontic micro implants upon torque-tightening and static load application by quasi-three-dimensional photoelastic stress analysis. Self-tapping orthodontic micro implants were progressively inserted into photoelastic models at 30, 45, 70, and 90 degrees and insertion torques were measured. Stress patterns (isochromatic fringe orders) were recorded by the quasi-three-dimensional photoelastic method using a circular polariscope after insertion and 250 g static force application. Torque-tightening of implants generated peri-implant stresses. Upon insertion, 90 degree placed implants displayed the lowest and homogeneous stress distribution followed by 30, 70, and 45 degree tilted implants. Static loading did not dramatically alter stress fields around the implants tested. The highest alteration in stress distribution was observed for the 90 degree placed implant, while 70 degree tilted implant had the lowest stresses among tilted implants. Torque-tightening of orthodontic micro implants creates a stress field that is not dramatically altered after application of static lateral moderate orthodontic loads, particularly at the cervical region of tilted implants.

Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages.

PubMed

Lichtenstein, Laeticia; Mattijssen, Frits; de Wit, Nicole J; Georgiadi, Anastasia; Hooiveld, Guido J; van der Meer, Roelof; He, Yin; Qi, Ling; Köster, Anja; Tamsma, Jouke T; Tan, Nguan Soon; Müller, Michael; Kersten, Sander

2010-12-01

Dietary saturated fat is linked to numerous chronic diseases, including cardiovascular disease. Here we study the role of the lipoprotein lipase inhibitor Angptl4 in the response to dietary saturated fat. Strikingly, in mice lacking Angptl4, saturated fat induces a severe and lethal phenotype characterized by fibrinopurulent peritonitis, ascites, intestinal fibrosis, and cachexia. These abnormalities are preceded by a massive acute phase response induced by saturated but not unsaturated fat or medium-chain fat, originating in mesenteric lymph nodes (MLNs). MLNs undergo dramatic expansion and contain numerous lipid-laden macrophages. In peritoneal macrophages incubated with chyle, Angptl4 dramatically reduced foam cell formation, inflammatory gene expression, and chyle-induced activation of ER stress. Induction of macrophage Angptl4 by fatty acids is part of a mechanism that serves to reduce postprandial lipid uptake from chyle into MLN-resident macrophages by inhibiting triglyceride hydrolysis, thereby preventing macrophage activation and foam cell formation and protecting against progressive, uncontrolled saturated fat-induced inflammation. Copyright © 2010 Elsevier Inc. All rights reserved.

Disparity changes in 370 Ma Devonian fossils: the signature of ecological dynamics?

PubMed

Girard, Catherine; Renaud, Sabrina

2012-01-01

Early periods in Earth's history have seen a progressive increase in complexity of the ecosystems, but also dramatic crises decimating the biosphere. Such patterns are usually considered as large-scale changes among supra-specific groups, including morphological novelties, radiation, and extinctions. Nevertheless, in the same time, each species evolved by the way of micro-evolutionary processes, extended over millions of years into the evolution of lineages. How these two evolutionary scales interacted is a challenging issue because this requires bridging a gap between scales of observation and processes. The present study aims at transferring a typical macro-evolutionary approach, namely disparity analysis, to the study of fine-scale evolutionary variations in order to decipher what processes actually drove the dynamics of diversity at a micro-evolutionary level. The Late Frasnian to Late Famennian period was selected because it is punctuated by two major macro-evolutionary crises, as well as a progressive diversification of marine ecosystem. Disparity was estimated through this period on conodonts, tooth-like fossil remains of small eel-like predators that were part of the nektonic fauna. The study was focused on the emblematic genus of the period, Palmatolepis. Strikingly, both crises affected an already impoverished Palmatolepis disparity, increasing risks of random extinction. The major disparity signal rather emerged as a cycle of increase and decrease in disparity during the inter-crises period. The diversification shortly followed the first crisis and might correspond to an opportunistic occupation of empty ecological niche. The subsequent oriented shrinking in the morphospace occupation suggests that the ecological space available to Palmatolepis decreased through time, due to a combination of factors: deteriorating climate, expansion of competitors and predators. Disparity changes of Palmatolepis thus reflect changes in the structure of the ecological space itself, which was prone to evolve during this ancient period where modern ecosystems were progressively shaped.

Research progress on electronic phase separation in low-dimensional perovskite manganite nanostructures

PubMed Central

2014-01-01

Perovskite oxide manganites with a general formula of R1-x AxMnO3 (where R is a trivalent rare-earth element such as La, Pr, Sm, and A is a divalent alkaline-earth element such as Ca, Sr, and Ba) have received much attention due to their unusual electron-transport and magnetic properties, which are indispensable for applications in microelectronic, magnetic, and spintronic devices. Recent advances in the science and technology have resulted in the feature sizes of microelectronic devices based on perovskite manganite oxides down-scaling into nanoscale dimensions. At the nanoscale, low-dimensional perovskite manganite oxide nanostructures display novel physical properties that are different from their bulk and film counterparts. Recently, there is strong experimental evidence to indicate that the low-dimensional perovskite manganite oxide nanostructures are electronically inhomogeneous, consisting of different spatial regions with different electronic orders, a phenomenon that is named as electronic phase separation (EPS). As the geometry sizes of the low-dimensional manganite nanostructures are reduced to the characteristic EPS length scale (typically several tens of nanometers in manganites), the EPS is expected to be strongly modulated, leading to quite dramatic changes in functionality and more emergent phenomena. Therefore, reduced dimensionality opens a door to the new functionalities in perovskite manganite oxides and offers a way to gain new insight into the nature of EPS. During the past few years, much progress has been made in understanding the physical nature of the EPS in low-dimensional perovskite manganite nanostructures both from experimentalists and theorists, which have a profound impact on the oxide nanoelectronics. This nanoreview covers the research progresses of the EPS in low-dimensional perovskite manganite nanostructures such as nanoparticles, nanowires/nanotubes, and nanostructured films and/or patterns. The possible physical origins of the EPS are also discussed from the signatures of electronic inhomogeneities as well as some theoretical scenarios, to shed light on understanding this phenomenon. Finally, the perspectives to the future researches in this area are also outlined. PMID:25024686

Disparity Changes in 370 Ma Devonian Fossils: The Signature of Ecological Dynamics?

PubMed Central

Girard, Catherine; Renaud, Sabrina

2012-01-01

Early periods in Earth's history have seen a progressive increase in complexity of the ecosystems, but also dramatic crises decimating the biosphere. Such patterns are usually considered as large-scale changes among supra-specific groups, including morphological novelties, radiation, and extinctions. Nevertheless, in the same time, each species evolved by the way of micro-evolutionary processes, extended over millions of years into the evolution of lineages. How these two evolutionary scales interacted is a challenging issue because this requires bridging a gap between scales of observation and processes. The present study aims at transferring a typical macro-evolutionary approach, namely disparity analysis, to the study of fine-scale evolutionary variations in order to decipher what processes actually drove the dynamics of diversity at a micro-evolutionary level. The Late Frasnian to Late Famennian period was selected because it is punctuated by two major macro-evolutionary crises, as well as a progressive diversification of marine ecosystem. Disparity was estimated through this period on conodonts, tooth-like fossil remains of small eel-like predators that were part of the nektonic fauna. The study was focused on the emblematic genus of the period, Palmatolepis. Strikingly, both crises affected an already impoverished Palmatolepis disparity, increasing risks of random extinction. The major disparity signal rather emerged as a cycle of increase and decrease in disparity during the inter-crises period. The diversification shortly followed the first crisis and might correspond to an opportunistic occupation of empty ecological niche. The subsequent oriented shrinking in the morphospace occupation suggests that the ecological space available to Palmatolepis decreased through time, due to a combination of factors: deteriorating climate, expansion of competitors and predators. Disparity changes of Palmatolepis thus reflect changes in the structure of the ecological space itself, which was prone to evolve during this ancient period where modern ecosystems were progressively shaped. PMID:22558396

Dramatic and concerted conformational changes enable rhodocetin to block α2β1 integrin selectively

PubMed Central

Orriss, George L.; Niland, Stephan; Johanningmeier, Benjamin; Pohlentz, Gottfried; Meier, Markus; Karrasch, Simone; Estevão-Costa, Maria Inacia; Martins Lima, Augusto; Stetefeld, Jörg

2017-01-01

The collagen binding integrin α2β1 plays a crucial role in hemostasis, fibrosis, and cancer progression amongst others. It is specifically inhibited by rhodocetin (RC), a C-type lectin-related protein (CLRP) found in Malayan pit viper (Calloselasma rhodostoma) venom. The structure of RC alone reveals a heterotetramer arranged as an αβ and γδ subunit in a cruciform shape. RC specifically binds to the collagen binding A-domain of the integrin α2 subunit, thereby blocking collagen-induced platelet aggregation. However, until now, the molecular basis for this interaction has remained unclear. Here, we present the molecular structure of the RCγδ-α2A complex solved to 3.0 Å resolution. Our findings show that RC undergoes a dramatic structural reorganization upon binding to α2β1 integrin. Besides the release of the nonbinding RCαβ tandem, the RCγ subunit interacts with loop 2 of the α2A domain as result of a dramatic conformational change. The RCδ subunit contacts the integrin α2A domain in the “closed” conformation through its helix C. Combined with epitope-mapped antibodies, conformationally locked α2A domain mutants, point mutations within the α2A loop 2, and chemical modifications of the purified toxin protein, this molecular structure of RCγδ-α2A complex explains the inhibitory mechanism and specificity of RC for α2β1 integrin. PMID:28704364

AYA in the USA. International Perspectives on AYAO, Part 5

PubMed Central

2013-01-01

Within the past decade, the discipline of adolescent and young adult (AYA) oncology has taken root in the United States. It arose from the observation that survival improvements for 15–39-year-olds have lagged behind those of both children and older adults. Rapid progress in this new area has resulted from energetic work by researchers, clinicians, and non-profit organizations focusing on AYA-aged cancer patients and survivors. The term “AYA” is now well recognized within both pediatric and medical oncology, and AYA-specific aims are increasingly included in clinical trials and also basic and translational oncology research. The AYA oncology movement in the United States was spearheaded by the LIVESTRONG Young Adult Alliance (the Alliance), a coalition of AYA-focused non-profit organizations and academic institutions that has recently transitioned into a successor organization—Critical Mass: The Young Adult Cancer Alliance, composed of individual AYAO professionals. The work of groups such as the Alliance/Critical Mass and key collaborators—including the National Cancer Institute, National Comprehensive Cancer Network, Children's Oncology Group, and advocacy organizations—provides a useful platform for the discussion of progress in AYA oncology in the United States, including advances in (1) research and tool development; (2) public and professional education; (3) advocacy and patient support; (4) awareness; and (5) service delivery. AYA oncology programs are now burgeoning dramatically throughout the United States, and many well-established U.S. programs share distinctive features in clinical programming. The United States is now entering an era of larger-scale coordinated efforts in research, advocacy, and clinical care for AYAs with cancer. PMID:24380035

AYA in the USA. International Perspectives on AYAO, Part 5.

PubMed

Johnson, Rebecca H

2013-12-01

Within the past decade, the discipline of adolescent and young adult (AYA) oncology has taken root in the United States. It arose from the observation that survival improvements for 15-39-year-olds have lagged behind those of both children and older adults. Rapid progress in this new area has resulted from energetic work by researchers, clinicians, and non-profit organizations focusing on AYA-aged cancer patients and survivors. The term "AYA" is now well recognized within both pediatric and medical oncology, and AYA-specific aims are increasingly included in clinical trials and also basic and translational oncology research. The AYA oncology movement in the United States was spearheaded by the LIVESTRONG Young Adult Alliance (the Alliance), a coalition of AYA-focused non-profit organizations and academic institutions that has recently transitioned into a successor organization-Critical Mass: The Young Adult Cancer Alliance, composed of individual AYAO professionals. The work of groups such as the Alliance/Critical Mass and key collaborators-including the National Cancer Institute, National Comprehensive Cancer Network, Children's Oncology Group, and advocacy organizations-provides a useful platform for the discussion of progress in AYA oncology in the United States, including advances in (1) research and tool development; (2) public and professional education; (3) advocacy and patient support; (4) awareness; and (5) service delivery. AYA oncology programs are now burgeoning dramatically throughout the United States, and many well-established U.S. programs share distinctive features in clinical programming. The United States is now entering an era of larger-scale coordinated efforts in research, advocacy, and clinical care for AYAs with cancer.

Personalized Medicine for Chronic Respiratory Infectious Diseases: Tuberculosis, Nontuberculous Mycobacterial Pulmonary Diseases, and Chronic Pulmonary Aspergillosis.

PubMed

Salzer, Helmut J F; Wassilew, Nasstasja; Köhler, Niklas; Olaru, Ioana D; Günther, Gunar; Herzmann, Christian; Kalsdorf, Barbara; Sanchez-Carballo, Patricia; Terhalle, Elena; Rolling, Thierry; Lange, Christoph; Heyckendorf, Jan

2016-01-01

Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections. © 2016 S. Karger AG, Basel.

Use of intravenous lipid emulsion to reverse central nervous system toxicity of an iatrogenic local anesthetic overdose in a patient on peritoneal dialysis.

PubMed

Lange, D Bruce; Schwartz, Daniel; DaRoza, Gerald; Gair, Robert

2012-12-01

To describe a case of severe central nervous system toxicity after an overdose of lidocaine by local infiltration in a peritoneal dialysis patient and subsequent treatment of the toxicity with lipid emulsion. A 31-year-old male received an iatrogenic overdose of 1600 mg of lidocaine 2% by infiltration during an attempt to remove and replace a peritoneal dialysis catheter. Within 10 minutes after the last lidocaine injection, the patient exhibited features of local anesthetic toxicity, which included tachycardia, hypertension, shortness of breath, dizziness, and a choking sensation that progressed to hallucinations, dysarthria, and uncoordinated, weak limb movement. Within 10 minutes after administration of a single 1.5-mg/kg intravenous bolus of 1.5 mL/kg [corrected], the patient improved dramatically. After observation overnight in a monitored care setting, the patient was discharged home with no apparent neurologic sequelae. Systemic toxicity due to regional anesthesia with local anesthetic agents such as lidocaine has been well described in the medical literature. The use of lipid emulsion as an antidote to the toxicity of local anesthetics and other lipophilic drugs has been suggested as a valuable intervention in both early, rapidly progressive toxicity, as well as toxicity that is refractory to standard treatment. Patients with advanced chronic kidney disease may be more susceptible to systemic effects of lidocaine due to decreased drug elimination. Central nervous system toxicity due to an overdose of lidocaine was quickly reversed by intravenous lipid emulsion in our patient.

[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.

Muscle assembly: a titanic achievement?

PubMed

Gregorio, C C; Granzier, H; Sorimachi, H; Labeit, S

1999-02-01

The formation of perfectly aligned myofibrils in striated muscle represents a dramatic example of supramolecular assembly in eukaryotic cells. Recently, considerable progress has been made in deciphering the roles that titin, the third most abundant protein in muscle, has in this process. An increasing number of sarcomeric proteins (ligands) are being identified that bind to specific titin domains. Titin may serve as a molecular blueprint for sarcomere assembly and turnover by specifying the precise position of its ligands within each half-sarcomere in addition to functioning as a molecular spring that maintains the structural integrity of the contracting myofibrils.

Syntactic Metals: A Survey of Current Technology

NASA Technical Reports Server (NTRS)

Erikson, Ray

2003-01-01

Syntactic metals are a relatively new development in materials science. Several approaches to synthesizing these materials have been tried, and the handful of researchers in this field are beginning to make progress in defining useful compositions and processes. Syntactic metals can provide materials with dramatically improved specific strength and stiffness over their parent alloys, while retaining the isotropy that makes ordinary metals preferable to fiber-reinforced laminated composites in many applications. This paper reviews syntactic material concepts in general, the current state of the art (including the author's own work in syntactic aluminum), and the direction of future developments.

[Means and methods of acoustic protection in aviation: current status and outlook for development].

PubMed

Soldatov, S K; Bogomolov, A V; Zinkin, V N; Aver'ianov, A A; Rossel's, A V; Patskin, G A; Sokolov, B A

2011-01-01

Analysis of the current status of acoustic protection in aviation shows that despite the material progress in the field, risk of professional pathologies in flying and technical personnel is still high. The situation is dramatized by the lack of effective personal and crew acoustic protectors. The authors speculate on applicability of innovative materials and technologies, ingenious designs of earphones and modular prefabricated demountable structures. Tests of proposed personal protectors demonstrated their competitiveness with foreign analogs. Prospective lines of development, e.g. incorporation of active sound absorption systems in existing passive protectors are discussed.

3D Simulations of Convection: From the Sun Toward Evolved Stars

NASA Astrophysics Data System (ADS)

Höfner, Susanne

2018-04-01

Basic physical considerations and detailed numerical simulations predict a dramatic increase in the sizes of convection cells during late phases of stellar evolution. The recent progress in high-angular-resolution techniques has made it possible to observe surface structures on several nearby giants and supergiants for a wide range of wavelengths. Such observations provide much-needed checkpoints for convection theory, in addition to the detailed comparisons of models and observations for the sun. In this talk I will give an overview of current 3D convection models for different types of stars and discuss related observable phenomena.

Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats

PubMed Central

Huang, Cao; Tong, Jianbin; Bi, Fangfang; Zhou, Hongxia; Xia, Xu-Gang

2011-01-01

Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration, which ultimately leads to paralysis and death. Mutation of TAR DNA binding protein 43 (TDP-43) has been linked to the development of an inherited form of ALS. Existing TDP-43 transgenic animals develop a limited loss of motor neurons and therefore do not faithfully reproduce the core phenotype of ALS. Here, we report the creation of multiple lines of transgenic rats in which expression of ALS-associated mutant human TDP-43 is restricted to either motor neurons or other types of neurons and skeletal muscle and can be switched on and off. All of these rats developed progressive paralysis reminiscent of ALS when the transgene was switched on. Rats expressing mutant TDP-43 in motor neurons alone lost more spinal motor neurons than rats expressing the disease gene in varying neurons and muscle cells, although these rats all developed remarkable denervation atrophy of skeletal muscles. Intriguingly, progression of the disease was halted after transgene expression was switched off; in rats with limited loss of motor neurons, we observed a dramatic recovery of motor function, but in rats with profound loss of motor neurons, we only observed a moderate recovery of motor function. Our finding suggests that mutant TDP-43 in motor neurons is sufficient to promote the onset and progression of ALS and that motor neuron degeneration is partially reversible, at least in mutant TDP-43 transgenic rats. PMID:22156203

Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia.

PubMed

Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano

2014-01-01

Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

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.

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

Assessing climate change impacts on soil salinity development with proximal and satellite sensors

USDA-ARS?s Scientific Manuscript database

Changes in climate patterns have dramatically influenced some agricultural areas. Examples include the historic 5-year drought in California’s San Joaquin Valley (SJV) and the 20-year above average annual rainfall in the Red River Valley (RRV) of the Midwestern USA. Climate change may have impacted ...

Trends and Research Issues in Educational Technology

ERIC Educational Resources Information Center

Spector, J. Michael

2013-01-01

If one looks back at the last 50 years or so at educational technologies, one will notice several things. First, the pace of innovation has increased dramatically with many developments in the application of digital technologies to learning and instruction, following by a few years developments in the sciences and engineering disciplines that are…

What Educators Need to Know about Bullying

ERIC Educational Resources Information Center

Graham, Sandra

2011-01-01

Peer victimization--or what's known as harassment or bullying--is not a new problem in American schools, though it appears to have taken on more epic proportions in recent years. The research about peer victimization has increased dramatically in the past 10 years, but there are still many myths about bullying. This article discusses six myths…

Child Care: Federal Funding for Fiscal Year 1997.

ERIC Educational Resources Information Center

General Accounting Office, Washington, DC. Health, Education, and Human Services Div.

The number of working women with children has increased dramatically in the past 20 years, increasing the demand for child care services to help working families secure and maintain their economic self-sufficiency. As more welfare families will be expected to seek and keep jobs, demand for child care services will increase. Because Congress is…

The effects of nutrition on cognition and motor function in aging

USDA-ARS?s Scientific Manuscript database

Average lifespans have increased dramatically over the last century and by the year 2050 fully 30% of the total population will be over 65 years of age. There is a high probability that these people will be exhibiting the most common behavioral changes that occur in “normal” aging - impaired mobilit...

Dramatic Experiences for Future Middle Level Teachers

ERIC Educational Resources Information Center

Weilbacher, Gary; LeMasters, Julie; Gill, Lana; Wisniewski, Jessica; Arnold, Christine

2005-01-01

During the last three years, Lincoln Middle School has been the site of a Professional Development School partnership in conjunction with the Illinois State University Middle School Department. With more than 90% of its 400-plus students receiving free or reduced price lunches, Lincoln is an eight-year-old, "Title I" building whose…

Pathways to Performance: An Examination of Entry Pathway and First-Year University Results

ERIC Educational Resources Information Center

Diamond, Mark R.; O'Brien-Malone, Angela

2018-01-01

Although diversity at universities has increased dramatically over the past 150 years, many groups are still under-represented relative to their proportion in the general population. Initiatives to improve diversity have included the increased use of entry pathways other than direct admission from secondary school. As admissions via these…

"Diplomas Now" Offers Potential Dropouts Lots of Help

ERIC Educational Resources Information Center

Gewertz, Catherine

2009-01-01

Feltonville School of Arts and Sciences, a 750-student middle school in upper north Philadelphia, is a showcase for a comprehensive approach to dropout prevention. It produced such dramatic improvements in attendance, behavior, and course-passing rates last year that it's being tried this year in 11 more middle or high schools in Chicago, Los…

Exploring Prejudice in Young Adult Literature through Drama and Role Play.

ERIC Educational Resources Information Center

Bontempo, Barbara T.

1995-01-01

States that the adolescent years are timely years for addressing problems of discrimination, prejudice, and cultural differences. Argues that dramatization of the thoughts, feelings, and experiences of characters can provide students with an understanding of those issues. Uses Mildred Taylor's "Roll of Thunder, Hear My Cry" as an example, and…

Predictors of Online Learning Success in a Rural Community College

ERIC Educational Resources Information Center

McPhaul-Moore, Elizabeth

2013-01-01

The number of courses offered online and the level of students enrolled in online courses has dramatically increased over the last several years. The National Education Center for Education Statistics reports that during the 2006-2007 school term, 97% of public two-year institutions across the nation offered college-level distance learning…

In Wake of Riots, France Refashions Priority Zones

ERIC Educational Resources Information Center

Hendrie, Caroline

2006-01-01

This article deals with an initiative embarked upon by the government of France one year after widespread youth violence broke out in many disadvantaged communities in France. The initiative is aimed at adapting its 25-year-old "priority education" program to a landscape that has dramatically changed. The initiative is the centerpiece of…

The Founding Entrepreneurs: America's Prosperity

ERIC Educational Resources Information Center

Gunderson, Gerald

2007-01-01

The American economy has had the fastest and most dramatic development of all the world's major economies. Four hundred years ago, the economic output of the area that became the United States was negligible by world standards. Yet only 250 years later, the U.S. economy had become the largest in the world, surpassing all other countries, including…

Efficiency and Equity in the Time Pattern of Teacher Pension Benefits: An Analysis of Four State Systems. Working Paper 2007-01

ERIC Educational Resources Information Center

Costrell, Robert M.; Podgursky, Michael J.

2007-01-01

Defined Benefit pension plans often generate odd time patterns of benefits. One typical pattern exhibits low accrual in early years, accelerating in mid-late years, followed by dramatic decline, or even negative returns in years that are relatively young for retirement. We consider four states for specific analysis: Arkansas, Missouri, California…

Tissue banking in South Africa: a 19-year history.

PubMed

Lindeque, B G P; Lindeque, A M; Hausner, H; Le Roux, T L B

2005-01-01

The establishment of a Tissue Bank and the science of Tissue Banking in South Africa started in the 1960s and is still developing. This article describes the development and growth of Tissue Banking in South Africa. The current emphasis is to supply viable bone products that have been produced under the best possible quality controlled circumstances; with the collaboration between different Organ Donation Organisations. Through collaboration, a dramatic increase in the number of donors was noted over the years. Concurrently, there was a dramatic increase in the usage of different allograft products and now necessitates the development of new graft materials for expanding patient options. As an ongoing concern, the Tissue Bank in South Africa experienced an ever increase in costs to enhance quality/safety controls: increase in historical patient information, documentation and serological testing in a population struggling to control HIV. To date, the South African Tissue Bank has not experienced any untoward patient incidence since the 1960s and currently is getting over 500 donors per year.

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

Periprosthetic osteolysis after AES total ankle replacement: Conventional radiography versus CT-scan.

PubMed

Viste, Anthony; Al Zahrani, Nader; Brito, Nuno; Lienhart, Christophe; Fessy, Michel Henri; Besse, Jean-Luc

2015-09-01

The aim of this study was to compare conventional X-rays and CT-scan in detecting peri-prosthetic osteolytic lesions, a major concern after total ankle replacement (TAR). We prospectively assessed 50 patients (mean age 56 years), consecutively operated on by the same senior surgeon, between 2003 and 2006 and with a mean follow-up period of 4 years (range, 2-6.2). The component used was AES total ankle replacement. The etiologies for total ankle arthroplasty were: posttraumatic in 50%, osteoarthritis secondary to instability in 36%. Plain radiographs were analyzed by 4 independent observers, using a 10-zone protocol (location) and 5 size categories. At 4-year follow-up, all patients had been CT-scan assessed with the same protocol by 2 independent observers. Plain radiographs showed dramatic progression of severe periprosthetic lyses (>10mm): from 14% to 36% of interface cysts for the tibial component respectively at 2 and 4-year follow-up and from 4% to 30% for the talar implant. The talar component was more accurately assessed by CT-scan (mean frontal and sagittal talar lesion: from 270 mm2 to 288 mm2 for CT-scan versus 133 mm2 to 174 mm2 for X-rays). For tibial cysts, axial views showed larger lesions (313 mm2 than frontal (194 mm2) or sagittal (213.5 mm2) views. At 4-year follow-up, 24% of patients had revision with curetage or arthrodesis, and at 7 years follow-up 38% were revised. These results are similar to recent AES series, justifying withdrawal of this device. CT-scan was more accurate than X-rays for detecting and quantifying periprosthetic osteolysis. We recommend a yearly radiological control and CT-scan in case of lesion on X-rays. Copyright © 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Suspended animation extends survival limits of Caenorhabditis elegans and Saccharomyces cerevisiae at low temperature.

PubMed

Chan, Kin; Goldmark, Jesse P; Roth, Mark B

2010-07-01

The orderly progression through the cell division cycle is of paramount importance to all organisms, as improper progression through the cycle could result in defects with grave consequences. Previously, our lab has shown that model eukaryotes such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Danio rerio all retain high viability after prolonged arrest in a state of anoxia-induced suspended animation, implying that in such a state, progression through the cell division cycle is reversibly arrested in an orderly manner. Here, we show that S. cerevisiae (both wild-type and several cold-sensitive strains) and C. elegans embryos exhibit a dramatic decrease in viability that is associated with dysregulation of the cell cycle when exposed to low temperatures. Further, we find that when the yeast or worms are first transitioned into a state of anoxia-induced suspended animation before cold exposure, the associated cold-induced viability defects are largely abrogated. We present evidence that by imposing an anoxia-induced reversible arrest of the cell cycle, the cells are prevented from engaging in aberrant cell cycle events in the cold, thus allowing the organisms to avoid the lethality that would have occurred in a cold, oxygenated environment.

Charting a Course for Precision Oncology

DOE PAGES

Kusnezov, Dimitri; Paragas, Jason

2017-02-09

Here, the fields of science have undergone dramatic reorganizations as they have come to terms with the realities of the growing complexities of their problem set, the costs, and the breadth of skills needed to make major progress. A field such as particle physics transformed from principal investigator-driven research supported by an electron synchrotron in the basement of your physics building in the 1950s, to regional centers when costs became prohibitive to refresh technology everywhere, driving larger teams of scientists to cooperate in the 1970s, to international centers where multinational teams work together to achieve progress. The 2013 Nobel Prizemore » winning discovery of the Higgs boson would have been unlikely without such team science. Other fields such as the computational sciences are well on their way through such a transformation. Today, we see precision medicine as a field that will need to come to terms with new organizational principles in order to make major progress, including everyone from individual medical researchers to pharma. Interestingly, the Cancer Moonshot has helped move thinking in that direction for part of the community and now the initiative has been transformed into law.« less

Suspended Animation Extends Survival Limits of Caenorhabditis elegans and Saccharomyces cerevisiae at Low Temperature

PubMed Central

Chan, Kin; Goldmark, Jesse P.

2010-01-01

The orderly progression through the cell division cycle is of paramount importance to all organisms, as improper progression through the cycle could result in defects with grave consequences. Previously, our lab has shown that model eukaryotes such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Danio rerio all retain high viability after prolonged arrest in a state of anoxia-induced suspended animation, implying that in such a state, progression through the cell division cycle is reversibly arrested in an orderly manner. Here, we show that S. cerevisiae (both wild-type and several cold-sensitive strains) and C. elegans embryos exhibit a dramatic decrease in viability that is associated with dysregulation of the cell cycle when exposed to low temperatures. Further, we find that when the yeast or worms are first transitioned into a state of anoxia-induced suspended animation before cold exposure, the associated cold-induced viability defects are largely abrogated. We present evidence that by imposing an anoxia-induced reversible arrest of the cell cycle, the cells are prevented from engaging in aberrant cell cycle events in the cold, thus allowing the organisms to avoid the lethality that would have occurred in a cold, oxygenated environment. PMID:20462960

Changes in cardiac output and tibial artery flow during and after progressive LBNP

NASA Technical Reports Server (NTRS)

1980-01-01

A 3.0 MHz Pulsed Doppler velocity meter (PD) was used to determine blood velocities in the ascending aorta from the suprasternal notch before, during and after progressive 5 min stages of lower body negative pressure (LBNP) in 7 subjects. Changes in stroke volume were calculated from the systolic velocity integrals. A unique 20 MHz PD was used to estimate bloodflow in the posterior tibial artery. With -20 torr mean stroke volume fell 11% and then continued to decline by 48% before LBNP was terminated. Mean tibial flow fell progressively with LBNP stress, due to an increase in reverse flow component and a reduction in peak forward flow and diameter. Stroke volume increased and heart rate fell dramatically during the first 15 sec of recovery. The LBNP was terminated early in 2 subjects because of vasovagal symptons (V). During V the stroke volume rose 86% which more than compensated for the drop in heart rate. This implies that V is accompanied by a paradoxical increase in venous return and that the reduction in HR is the primary cardiovascular event. During the first 15 sec of recovery these 2 subjects had a distinctive marked rise to heart rate reminiscent of the Bainbridge reflex.

Agricultural pesticide exposure and the molecular connection to lymphomagenesis

PubMed Central

Agopian, Julie; Navarro, Jean-Marc; Gac, Anne-Claire; Lecluse, Yannick; Briand, Mélanie; Grenot, Pierre; Gauduchon, Pascal; Ruminy, Philippe; Nadel, Bertrand; Roulland, Sandrine

2009-01-01

The t(14;18) translocation constitutes the initiating event of a causative cascade leading to follicular lymphoma (FL). t(14;18) translocations are present in blood from healthy individuals, but there is a trend of increased prevalence in farmers exposed to pesticides, a group recently associated with higher risk of t(14;18)+ non-Hodgkin's lymphoma development. A direct connection between agricultural pesticide use, t(14;18) in blood, and malignant progression, however, has not yet been demonstrated. We followed t(14;18) clonal evolution over 9 yr in a cohort of farmers exposed to pesticides. We show that exposed individuals bear particularly high t(14;18) frequencies in blood because of a dramatic clonal expansion of activated t(14;18)+ B cells. We further demonstrate that such t(14;18)+ clones recapitulate the hallmark features of developmentally blocked FL cells, with some displaying aberrant activation-induced cytidine deaminase activity linked to malignant progression. Collectively, our data establish that expanded t(14;18)+ clones constitute bona fide precursors at various stages of FL development, and provide a molecular connection between agricultural pesticide exposure, t(14;18) frequency in blood, and clonal progression. PMID:19506050

Charting a Course for Precision Oncology

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

Kusnezov, Dimitri; Paragas, Jason

Here, the fields of science have undergone dramatic reorganizations as they have come to terms with the realities of the growing complexities of their problem set, the costs, and the breadth of skills needed to make major progress. A field such as particle physics transformed from principal investigator-driven research supported by an electron synchrotron in the basement of your physics building in the 1950s, to regional centers when costs became prohibitive to refresh technology everywhere, driving larger teams of scientists to cooperate in the 1970s, to international centers where multinational teams work together to achieve progress. The 2013 Nobel Prizemore » winning discovery of the Higgs boson would have been unlikely without such team science. Other fields such as the computational sciences are well on their way through such a transformation. Today, we see precision medicine as a field that will need to come to terms with new organizational principles in order to make major progress, including everyone from individual medical researchers to pharma. Interestingly, the Cancer Moonshot has helped move thinking in that direction for part of the community and now the initiative has been transformed into law.« less

Long noncoding RNA LINC01296 promotes tumor growth and progression by sponging miR-5095 in human cholangiocarcinoma.

PubMed

Zhang, Dawei; Li, Haiyan; Xie, Juping; Jiang, Decan; Cao, Liangqi; Yang, Xuewei; Xue, Ping; Jiang, Xiaofeng

2018-06-01

The aim of the present study was to elucidate whether, and how, long intergenic non-protein coding RNA 1296 (LINC01296) is involved in the modulation of human cholangiocarcinoma (CCA) development and progression. Microarray data analysis and reverse transcription-quantitative polymerase chain reaction analysis demonstrated that LINC01296 was significantly upregulated in human CCA compared with nontumor tissues. Furthermore, the expression of LINC01296 in human CCA was positively associated with tumor severity and clinical stage. Knockdown of LINC01296 dramatically suppressed the viability, migration and invasion of RBE and CCLP1 cells, and promoted cell apoptosis in vitro. Furthermore, LINC01296 knockdown inhibited tumor growth in a xenograft model. Mechanistically, LINC01296 was demonstrated to sponge microRNA-5095 (miR-5095), which targets MYCN proto-oncogene bHLH transcription factor (MYCN) mRNA in human CCA. By inhibition of miR-5095, LINC01296 overexpression upregulated the expression of MYCN and promoted cell viability, migration and invasion in CCA cells. The results reveal that the axis of LINC01296/miR-5095/MYCN may be a mechanism to regulate CCA development and progression.

Impact of Four Years of Annual Mass Drug Administration on Prevalence and Intensity of Schistosomiasis among Primary and High School Children in Western Kenya: A Repeated Cross-Sectional Study

PubMed Central

Abudho, Bernard O.; Ndombi, Eric M.; Guya, Bernard; Carter, Jennifer M.; Riner, Diana K.; Kittur, Nupur; Karanja, Diana M. S.; Secor, W. Evan; Colley, Daniel G.

2018-01-01

Abstract. Schistosomiasis remains a major public health problem in Kenya. The World Health Organization recommends preventive chemotherapy with praziquantel (PZQ) to control morbidity due to schistosomiasis. Morbidity is considered linked to intensity of infection, which along with prevalence is used to determine the frequency of mass drug administration (MDA) to school-age children. We determined the impact of annual school-based MDA on children across all primary and high school years using a repeated cross-sectional study design in five schools near Lake Victoria in western Kenya, an area endemic for Schistosoma mansoni. At baseline and for the following four consecutive years, between 897 and 1,440 school children in Grades 1–12 were enrolled and evaluated by Kato-Katz for S. mansoni and soil-transmitted helminths (STH), followed by annual MDA with PZQ and albendazole. Four annual rounds of MDA with PZQ were associated with reduced S. mansoni prevalence in all school children (44.7–14.0%; P < 0.001) and mean intensity of infection by 91% (90.4 to 8.1 eggs per gram [epg] of stool; P < 0.001). Prevalence of high-intensity infection (≥ 400 epg) decreased from 6.8% at baseline to 0.3% by the end of the study. Soil-transmitted helminth infections, already low at baseline, also decreased significantly over the years. In this high prevalence area, annual school-based MDA with high coverage across all Grades (1–12) resulted in rapid and progressive declines in overall prevalence and intensity of infection. This decrease was dramatic in regard to heavy infections in older school-attending children. PMID:29532768

Impact of Four Years of Annual Mass Drug Administration on Prevalence and Intensity of Schistosomiasis among Primary and High School Children in Western Kenya: A Repeated Cross-Sectional Study.

PubMed

Abudho, Bernard O; Ndombi, Eric M; Guya, Bernard; Carter, Jennifer M; Riner, Diana K; Kittur, Nupur; Karanja, Diana M S; Secor, W Evan; Colley, Daniel G

2018-05-01

Schistosomiasis remains a major public health problem in Kenya. The World Health Organization recommends preventive chemotherapy with praziquantel (PZQ) to control morbidity due to schistosomiasis. Morbidity is considered linked to intensity of infection, which along with prevalence is used to determine the frequency of mass drug administration (MDA) to school-age children. We determined the impact of annual school-based MDA on children across all primary and high school years using a repeated cross-sectional study design in five schools near Lake Victoria in western Kenya, an area endemic for Schistosoma mansoni . At baseline and for the following four consecutive years, between 897 and 1,440 school children in Grades 1-12 were enrolled and evaluated by Kato-Katz for S. mansoni and soil-transmitted helminths (STH), followed by annual MDA with PZQ and albendazole. Four annual rounds of MDA with PZQ were associated with reduced S. mansoni prevalence in all school children (44.7-14.0%; P < 0.001) and mean intensity of infection by 91% (90.4 to 8.1 eggs per gram [epg] of stool; P < 0.001). Prevalence of high-intensity infection (≥ 400 epg) decreased from 6.8% at baseline to 0.3% by the end of the study. Soil-transmitted helminth infections, already low at baseline, also decreased significantly over the years. In this high prevalence area, annual school-based MDA with high coverage across all Grades (1-12) resulted in rapid and progressive declines in overall prevalence and intensity of infection. This decrease was dramatic in regard to heavy infections in older school-attending children.

The first ten years: achievements and challenges of the Brazilian program of universal access to HIV/AIDS comprehensive management and care, 1996-2006.

PubMed

Hacker, Mariana A; Kaida, Angela; Hogg, Robert S; Bastos, Francisco I

2007-01-01

A review was carried out of papers published between 1996 and 2006, documenting the introduction of highly active anti-retroviral therapy (HAART) in Brazil. Papers indexed in the MEDLINE and SciELO databases were retrieved using different combinations of keywords related to the management and care of AIDS in the post-HAART era: opportunistic diseases and co-infections, adherence to therapy, survival in the pre- and post-HAART eras, adverse events and side-effects, emergence and possible transmission of resistant viral strains, metabolic and cardiovascular disorders, and issues related to access to care and equity. The review documents the dramatic changes in HIV/AIDS disease progression in the post-HAART era, including an increase in survival and quality of life and a pronounced decrease in the episodes of opportunistic diseases. Notwithstanding such major achievements, new challenges have emerged, including slow evolving co-infections (such as hepatitis C, metabolic and cardiovascular disorders), the emergence of viral resistance, with consequences at the individual level (virological failure) and the community level (primary/secondary resistance at the population level), and impacts on the cost of new therapeutic regimens.

Hungry Horse Dam Fisheries Mitigation : Fish Passage and Habitat Improvement in the Upper Flathead River Basin, 1991-1996 Progress Report.

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

Knotek, W.Ladd; Deleray, Mark; Marotz, Brian L.

1997-08-01

In the past 50 years, dramatic changes have occurred in the Flathead Lake and River system. Degradation of fishery resources has been evident, in part due to deterioration of aquatic habitat and introduction of non-endemic fish and invertebrate species. Habitat loss has been attributed to many factors including the construction and operation of Hungry Horse Dam, unsound land use practices, urban development, and other anthropogenic and natural disturbances. Fish migration has also been limited by barriers such as dams and impassible culverts. Cumulatively, these factors have contributed to declines in the distribution and abundance of native fish populations. Recovery ofmore » fish populations requires that a watershed approach be developed that incorporates long-term aquatic habitat needs and promotes sound land use practices and cooperation among natural resource management agencies. In this document, the authors (1) describe completed and ongoing habitat improvement and fish passage activities under the Hungry Horse Fisheries Mitigation Program, (2) describe recently identified projects that are in the planning stage, and (3) develop a framework for identifying prioritizing, implementing, and evaluating future fish habitat improvement and passage projects.« less

A case of mitochondrial encephalomyopathy associated with a muscle coenzyme Q10 deficiency.

PubMed

Boitier, E; Degoul, F; Desguerre, I; Charpentier, C; François, D; Ponsot, G; Diry, M; Rustin, P; Marsac, C

1998-01-01

We report severe coenzyme Q10 deficiency of muscle in a 4-year-old boy presenting with progressive muscle weakness, seizures, cerebellar syndrome, and a raised cerebro-spinal fluid lactate concentration. State-3 respiratory rates of muscle mitochondria with glutamate, pyruvate, palmitoylcarnitine, and succinate as respiratory substrates were markedly reduced, whereas ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine were oxidized normally. The activities of complexes I, II, III and IV of the electron transport chain were normal, but the activities of complexes I+III and II+III, both systems requiring coenzyme Q10 as an electron carrier, were dramatically decreased. These results suggested a defect in the mitochondrial coenzyme Q10 content. This was confirmed by the direct assessment of coenzyme Q10 level by high-performance liquid chromatography in patient's muscle homogenate and isolated mitochondria, revealing levels of 16% and 6% of the control values, respectively. We did not find any impairment of the respiratory chain either in a lymphoblastoid cell line or in skin cultured fibroblasts from the patient, suggesting that the coenzyme Q10 depletion was tissue-specific. This is a new case of a muscle deficiency of mitochondrial coenzyme Q in a patient suffering from an encephalomyopathy.

Successful rechallenge with ceritinib after leukocytoclastic vasculitis during ceritinib treatment for non-small cell lung cancer harboring the EML4-ALK fusion protein.

PubMed

Okimoto, Tamio; Tsubata, Yukari; Hotta, Takamasa; Hamaguchi, Megumi; Okuno, Takae; Shiratsuki, Yohei; Kodama, Akari; Nakao, Mika; Amano, Yoshihiro; Hamaguchi, Shunichi; Kurimoto, Noriaki; Tobita, Reiko; Isobe, Takeshi

2018-04-13

Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKIs) dramatically improve progression-free survival compared to cytotoxic agents. It is therefore important to manage patients with ALK-TKIs until drug resistance occurs. Leukocytoclastic vasculitis (LCV) is a rare complication during cancer treatment and is associated with a variety of factors. Currently, it is unclear whether we should withdraw a treatment when drug-induced LCV develops. We report a 40-year-old man with advanced pulmonary adenocarcinoma harboring the EML4-ALK fusion protein who developed LCV during ceritinib treatment. Four weeks after withdrawing ceritinib, we could successfully perform rechallenge with ceritinib at the normal dose. Rapid and massive tumor apoptosis due to ceritinib treatment may lead to neoantigen release and immune complexes deposition. To the best of our knowledge, we report the first case of LCV in a patient during ALK-TKI treatment. Following this occurrence, we were able to successfully perform rechallenge with ceritinib. Therefore, key drugs used in a patient's treatment regimen should not be discontinued without careful evaluation, and we should also consider the possibility of rechallenge.

Induction of Oral Tolerance with Transgenic Plants Expressing Antigens for Prevention/Treatment of Autoimmune, Allergic and Inflammatory Diseases.

PubMed

Ma, Shengwu; Liao, Yu-Cai; Jevnikar, Anthony M

2015-01-01

The prevalence and incidence of autoimmune and allergic diseases have increased dramatically over the last several decades, especially in the developed world. The treatment of autoimmune and allergic diseases is typically with the use of non-specific immunosuppressive agents that compromise the integrity of the host immune system and therefore, increase the risk of infections. Antigenspecific immunotherapy by reinstating immunological tolerance towards self antigens without compromising immune functions is a much desired goal for the treatment of autoimmune and allergic diseases. Mucosal administration of antigen is a long-recognized method of inducing antigen-specific immune tolerance known as oral tolerance, which is viewed as having promising potential in the treatment of autoimmune and allergic diseases. Plant-based expression and delivery of recombinant antigens provide a promising new platform to induce oral tolerance, having considerable advantages including reduced cost and increased safety. Indeed, in recent years the use of tolerogenic plants for oral tolerance induction has attracted increasing attention, and considerable progress has been made. This review summarizes recent advances in using plants to deliver tolerogens for induction of oral tolerance in the treatment of autoimmune, allergic and inflammatory diseases.

Thrombolytic therapy for mitral valve thrombosis.

PubMed

Lin, T K; Tsai, L M; Chen, J H; Yang, Y J

1997-05-01

A 44-year-old man with a St. Jude mitral valve was admitted because of progressive pulmonary edema. He was diagnosed with prosthetic heart valve thrombosis (PHVT) based on the findings of "muffled" prosthetic valve clicks. Doppler echocardiographic evidence of severe mitral stenosis and transesophageal echocardiographic evidence of limited mitral valve motility. Because the patient hesitated to undergo our recommended surgical treatment, he was immediately treated with intravenous recombinant tissue plasminogen activator (100 mg over 3 h) followed by heparinization. Two hours after the thrombolytic therapy, the prosthetic valve clicks became clearly audible and his congestive symptoms were dramatically improved. Follow-up echocardiography no longer-showed significant mitral valve obstruction. A transient cerebral ischemic attack occurred at the end of thrombolytic therapy but there were no neurologic sequalae. The patient, on warfarin therapy, was well at follow-up 8 months after discharge. Surgical intervention has long been the standard therapy for patients with PHVT. Our case experience suggests that thrombolytic therapy may be considered as an effective alternative to surgical intervention for selected patients with PHVT. In this report, we also review the current literature regarding the indications, effectiveness and safety of thrombolytic therapy in PHVT.

Hepatitis C virus resistance to the new direct-acting antivirals.

PubMed

Esposito, Isabella; Trinks, Julieta; Soriano, Vicente

2016-10-01

The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

PubMed Central

Paini, Marina; Crippa, Stefano; Partelli, Stefano; Scopelliti, Filippo; Tamburrino, Domenico; Baldoni, Andrea; Falconi, Massimo

2014-01-01

Since the first description of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in the eighties, their identification has dramatically increased in the last decades, hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases. However, the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions. The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed. We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms, identifying some genes, molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy. The knowledge of molecular biology of IPMNs has impressively developed over the last few years. A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified, in pancreatic juice or in blood or in the samples from the pancreatic resections, but further researches are required to use these informations for clinical intent, in order to better define the natural history of these diseases and to improve their management. PMID:25110429

Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas.

PubMed

Paini, Marina; Crippa, Stefano; Partelli, Stefano; Scopelliti, Filippo; Tamburrino, Domenico; Baldoni, Andrea; Falconi, Massimo

2014-08-07

Since the first description of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in the eighties, their identification has dramatically increased in the last decades, hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases. However, the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions. The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed. We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms, identifying some genes, molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy. The knowledge of molecular biology of IPMNs has impressively developed over the last few years. A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified, in pancreatic juice or in blood or in the samples from the pancreatic resections, but further researches are required to use these informations for clinical intent, in order to better define the natural history of these diseases and to improve their management.

Analysis of the olfactory mucosa in chronic rhinosinusitis

PubMed Central

Yee, Karen K.; Pribitkin, Edmund A.; Cowart, Beverly J.; Rosen, David; Feng, Pu; Rawson, Nancy E

2009-01-01

The impact of chronic rhinosinusitis (CRS) on the olfactory mucosa (OM) is dramatic. Cellular profiles and epithelial integrity in OM biopsies were evaluated using histological and immunohistochemical methods to define a strategy for future histological studies of CRS. We have examined nasal biopsies of 54 CRS patients (18 - 63 years old) and have defined specific histopathological patterns of the OM: normal pseudostratified, goblet cell hyperplasia, squamous metaplasia and erosion. Goblet cell hyperplasia was most similar to a normal pseudostratified OM pattern but with goblet cells intermixed in the apical layers. Squamous metaplasia exhibited an absence of olfactory supporting cells and had olfactory sensory neurons that were morphologically abnormal. It is unknown if these neurons would be functional in this type of tissue transformation. The pattern of erosion exhibited a severe loss of epithelial layers and a higher prevalence of infiltrating inflammatory cells within the olfactory epithelium when compared to the other OM patterns. Although it is not known if the OM remodeling patterns we have noted correspond to specific stages or distinct pathways of the disease, the template proposed here can be used in further studies to understand how the histopathological progression of CRS relates to olfactory loss and the response to treatment. PMID:19686198

Green Roots: Photosynthesis and Photoautotrophy in an Underground Plant Organ.

PubMed Central

Flores, H. E.; Dai, Yr.; Cuello, J. L.; Maldonado-Mendoza, I. E.; Loyola-Vargas, V. M.

1993-01-01

The potential for photosynthetic and photoautotrophic growth was studied in hairy root cultures of Asteraceae and Solanaceae species. Upon transfer to light, initially heterotrophic root cultures of Acmella oppositifolia and Datura innoxia greened rapidly, differentiated chloroplasts, and developed light-dependent CO2 fixation in the cortical cells. Photosynthetic potential was expressed in root cultures of all the Asteraceae genera examined (Acmella, Artemisia, Rudbeckia, Stevia, and Tagetes). Hairy roots of A. oppositifolia and D. innoxia were further adapted to photoautotrophy by growing in the presence of light and added CO2 (1-5%) and by direct or sequential transfers into media containing progressively lower sugar concentrations. The transition to photoautotrophy was accompanied by an increase in CO2 fixation and in the specific activity of 1,5-ribulose-bisphosphate carboxylase/ oxygenase (Rubisco). During the adaptation of A. oppositifolia roots to photoautotrophy, the ratio of Rubisco to phosphoenolpyruvate carboxylase increased significantly, approaching that found in the leaves. The levels and patterns of alkaloids and polyacetylenes produced by Solanaceae and Asteraceae hairy roots, respectively, were dramatically altered in photomixotrophic and photoautotrophic cultures. Photoautotrophic roots of A. oppositifolia have been mainitained in vitro for over 2 years. PMID:12231691

Evaluating the federal role in financing health-related research

PubMed Central

Garber, Alan M.; Romer, Paul M.

1996-01-01

This paper considers the appropriate role for government in the support of scientific and technological progress in health care; the information the federal government needs to make well-informed decisions about its role; and the ways that federal policy toward research and development should respond to scientific advances, technology trends, and changes in the political and social environment. The principal justification for government support of research rests upon economic characteristics that lead private markets to provide inappropriate levels of research support or to supply inappropriate quantities of the products that result from research. The federal government has two basic tools for dealing with these problems: direct subsidies for research and strengthened property rights that can increase the revenues that companies receive for the products that result from research. In the coming years, the delivery system for health care will continue to undergo dramatic changes, new research opportunities will emerge at a rapid pace, and the pressure to limit discretionary federal spending will intensify. These forces make it increasingly important to improve the measurement of the costs and benefits of research and to recognize the tradeoffs among alternative policies for promoting innovation in health care. PMID:8917484

Peaceful Uses of Nuclear Energy: A Collection of Speeches

DOE R&D Accomplishments Database

Seaborg, Glenn T.

1970-07-01

It is now a quarter of a century since nuclear energy was introduced to the public. Its introduction was made in the most dramatic, but unfortunately in the most destructive way - through the use of a nuclear weapon. Since that introduction enormous strides have been made in developing the peaceful applications of this great and versatile force. Because these strides have always been overshadowed by the focusing of public attention on the military side of the atom, the public has never fully understood or appreciated the gains and status of the peaceful atom. This booklet is an attempt to correct, in some measure, this imbalance in public information and attitude. It is a compilation of remarks, and excerpts of remarks, that I [Seaborg] have made in recent years in an effort to bring to the public the story of the remarkable benefits the peaceful atom has to offer man. This is a story that grows with the development and progress of the peaceful atom. It must be told so that we can learn to use the power of nuclear energy wisely and through this use help to build a world in which the military applications of the atom will never again be a threat to mankind.

The evolution of phylogeographic data sets.

PubMed

Garrick, Ryan C; Bonatelli, Isabel A S; Hyseni, Chaz; Morales, Ariadna; Pelletier, Tara A; Perez, Manolo F; Rice, Edwin; Satler, Jordan D; Symula, Rebecca E; Thomé, Maria Tereza C; Carstens, Bryan C

2015-03-01

Empirical phylogeographic studies have progressively sampled greater numbers of loci over time, in part motivated by theoretical papers showing that estimates of key demographic parameters improve as the number of loci increases. Recently, next-generation sequencing has been applied to questions about organismal history, with the promise of revolutionizing the field. However, no systematic assessment of how phylogeographic data sets have changed over time with respect to overall size and information content has been performed. Here, we quantify the changing nature of these genetic data sets over the past 20 years, focusing on papers published in Molecular Ecology. We found that the number of independent loci, the total number of alleles sampled and the total number of single nucleotide polymorphisms (SNPs) per data set has improved over time, with particularly dramatic increases within the past 5 years. Interestingly, uniparentally inherited organellar markers (e.g. animal mitochondrial and plant chloroplast DNA) continue to represent an important component of phylogeographic data. Single-species studies (cf. comparative studies) that focus on vertebrates (particularly fish and to some extent, birds) represent the gold standard of phylogeographic data collection. Based on the current trajectory seen in our survey data, forecast modelling indicates that the median number of SNPs per data set for studies published by the end of the year 2016 may approach ~20,000. This survey provides baseline information for understanding the evolution of phylogeographic data sets and underscores the fact that development of analytical methods for handling very large genetic data sets will be critical for facilitating growth of the field. © 2015 John Wiley & Sons Ltd.

Dramatic weight loss associated with commencing clozapine.

PubMed

Lally, John; McDonald, Colm

2011-11-08

The authors report the case of a 44-year-old man with a long history of chronic enduring schizophrenia who experienced dramatic weight loss after commencing treatment with clozapine, an antipsychotic medication characteristically associated with the greatest degree of weight gain among medical treatments for schizophrenia. He was obese with a body mass index (BMI) of 41.5 kg/m(2), but after commencing clozapine therapy he experienced an improvement in psychotic symptoms and 40% loss of his body weight attained through an altered diet and exercise regime, which resulted in him attaining a normal BMI of 24.8 kg/m(2).

Evaluating Rifean Corridor Closure using Detrital Zircon Sediment Provenance of the Taza-Guercif Basin, Morocco

NASA Astrophysics Data System (ADS)

Pratt, J. R.; Barbeau, D. L.; Emran, A.

2013-12-01

In the late Miocene, the connection between the Mediterranean Sea and Atlantic Ocean was tectonically severed leading to severe evaporative draw down of Mediterranean sea level such that the entire basin was desiccated or near desiccated in an event from ~5.96-5.33 Ma known as the Messinian Salinity Crisis (MSC). The MSC sequestered 6% of global ocean salinity into evaporite deposits, created a deep, dry and hot basin that altered global atmospheric circulation, opened passageways for mammal migration between Europe, Africa and Arabia and ended in the largest flood observed in the geologic record. The combined effects of the Messinian Salinity Crisis make it the most important oceanic event in the last 20 million years, yet despite the dramatic ramifications of the MSC, the exact nature of its cause has remained both elusive and controversial. By examining the sedimentary provenance of Rifean Corridor, this research evaluates the progression of corridor closure and the tectonic context of the initiation of the Messinian Salinity Crisis. The difficulty in evaluating the progression of closure is due to the tectonic complexity of the Africa-Eurasia convergent plate boundary in north-central Morocco. The shortening associated with the tectonic convergence is accommodated by two genetically and tectonically distinct orogenic systems, the Rif and Atlas mountain belts, which lie in juxtaposition to the slab-rollback dominated Alboran Sea. The basins of the Rifean corridor lie between these two orogens and as such shortening and uplift associated with either or both ranges could be the cause of the corridor closure. Several hypotheses have been posited for the tectonic controls on basin emergence including slab-rollback related delamination on the Alboran margin, domal uplift of the Middle Atlas as well as a more traditional propagation of the Rifean orogenic wedge. This research provides the first quantitative provenance data for the Taza-Guercif basin in the form of LA-ICP-MS detrital zircon analysis of 10 samples from the basin-fill and 3 samples from two separate domains within the Rif. The new data reveal a lack of dramatic shifts in provenance within the basin-fill tied to corridor closure but instead reveal more subtle changes in peak zircon ages. Peak age shifts from 600 Ma to 700 Ma periodically within the strata in both open marine marls and within turbidites derived from the Middle Atlas in a pattern consistent with changes in basin bathymetry. Basin samples show an age-distribution consistent with the Rifean samples, which acquire an slight overprinting of Middle Atlas ages in the latter half of the succession. The data point to a progressive closure of the corridor through the advancement of the Rifean orogenic wedge with minor influence from uplift within the core of the Middle Atlas without a major shift in provenance during rapid basin emergence.

Frequency of Testing to Detect Visual Field Progression Derived Using a Longitudinal Cohort of Glaucoma Patients.

PubMed

Wu, Zhichao; Saunders, Luke J; Daga, Fábio B; Diniz-Filho, Alberto; Medeiros, Felipe A

2017-06-01

To determine the time required to detect statistically significant progression for different rates of visual field loss using standard automated perimetry (SAP) when considering different frequencies of testing using a follow-up scheme that resembles clinical practice. Observational cohort study. One thousand seventy-two eyes of 665 patients with glaucoma followed up over an average of 4.3±0.9 years. Participants with 5 or more visual field tests over a 2- to 5-year period were included to derive the longitudinal measurement variability of SAP mean deviation (MD) using linear regressions. Estimates of variability then were used to reconstruct real-world visual field data by computer simulation to evaluate the time required to detect progression for various rates of visual field loss and different frequencies of testing. The evaluation was performed using a follow-up scheme that resembled clinical practice by requiring a set of 2 baseline tests and a confirmatory test to identify progression. Time (in years) required to detect progression. The time required to detect a statistically significant negative MD slope decreased as the frequency of testing increased, albeit not proportionally. For example, 80% of eyes with an MD loss of -2 dB/year would be detected after 3.3, 2.4, and 2.1 years when testing is performed once, twice, and thrice per year, respectively. For eyes with an MD loss of -0.5 dB/year, progression can be detected with 80% power after 7.3, 5.7, and 5.0 years, respectively. This study provides information on the time required to detect progression using MD trend analysis in glaucoma eyes when different testing frequencies are used. The smaller gains in the time to detect progression when testing is increased from twice to thrice per year suggests that obtaining 2 reliable tests at baseline followed by semiannual testing and confirmation of progression through repeat testing in the initial years of follow-up may provide a good compromise for detecting progression, while minimizing the burden on health care resources in clinical practice. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Haemodynamic and anatomic progression of aortic stenosis.

PubMed

Nguyen, Virginia; Cimadevilla, Claire; Estellat, Candice; Codogno, Isabelle; Huart, Virginie; Benessiano, Joelle; Duval, Xavier; Pibarot, Philippe; Clavel, Marie Annick; Enriquez-Sarano, Maurice; Vahanian, Alec; Messika-Zeitoun, David

2015-06-01

Aortic valve stenosis (AS) is a progressive disease, but the impact of baseline AS haemodynamic or anatomic severity on AS progression remains unclear. In 149 patients (104 mild AS, 36 moderate AS and 9 severe AS) enrolled in 2 ongoing prospective cohorts (COFRASA/GENERAC), we evaluated AS haemodynamic severity at baseline and yearly, thereafter, using echocardiography (mean pressure gradient (MPG)) and AS anatomic severity using CT (degree of aortic valve calcification (AVC)). After a mean follow-up of 2.9±1.0 years, mean MGP increased from 22±11 to 30±16 mm Hg (+3±3 mm Hg/year), and mean AVC from 1108±891 to 1640±1251 AU (arbitrary units) (+188±176 AU/year). Progression of AS was strongly related to baseline haemodynamic severity (+2±3 mm Hg/year in mild AS, +4±3 mm Hg/year in moderate AS and +5±5 mm Hg/year in severe AS (p=0.01)), and baseline haemodynamic severity was an independent predictor of haemodynamic progression (p=0.0003). Annualised haemodynamic and anatomic progression rates were significantly correlated (r=0.55, p<0.0001), but AVC progression rate was also significantly associated with baseline haemodynamic severity (+141±133 AU/year in mild AS, +279±189 AU/year in moderate AS and +361±293 AU/year in severe AS, p<0.0001), and both baseline MPG and baseline AVC were independent determinants of AVC progression (p<0.0001). AS progressed faster with increasing haemodynamic or anatomic severity. Our results suggest that a medical strategy aimed at preventing AVC progression may be useful in all subsets of patients with AS including those with severe AS and support the recommended closer follow-up of patients with AS as AS severity increases. COFRASA (clinicalTrial.gov number NCT 00338676) and GENERAC (clinicalTrial.gov number NCT00647088). 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.

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.

The Sla1 adaptor-clathrin interaction regulates coat formation and progression of endocytosis.

PubMed

Tolsma, Thomas O; Cuevas, Lena M; Di Pietro, Santiago M

2018-06-01

Clathrin-mediated endocytosis is a fundamental transport pathway that depends on numerous protein-protein interactions. Testing the importance of the adaptor protein-clathrin interaction for coat formation and progression of endocytosis in vivo has been difficult due to experimental constrains. Here, we addressed this question using the yeast clathrin adaptor Sla1, which is unique in showing a cargo endocytosis defect upon substitution of 3 amino acids in its clathrin-binding motif (sla1 AAA ) that disrupt clathrin binding. Live-cell imaging showed an impaired Sla1-clathrin interaction causes reduced clathrin levels but increased Sla1 levels at endocytic sites. Moreover, the rate of Sla1 recruitment was reduced indicating proper dynamics of both clathrin and Sla1 depend on their interaction. sla1 AAA cells showed a delay in progression through the various stages of endocytosis. The Arp2/3-dependent actin polymerization machinery was present for significantly longer time before actin polymerization ensued, revealing a link between coat formation and activation of actin polymerization. Ultimately, in sla1 AAA cells a larger than normal actin network was formed, dramatically higher levels of various machinery proteins other than clathrin were recruited, and the membrane profile of endocytic invaginations was longer. Thus, the Sla1-clathrin interaction is important for coat formation, regulation of endocytic progression and membrane bending. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

TOPICAL REVIEW: Organic light-emitting devices (OLEDs) and OLED-based chemical and biological sensors: an overview

NASA Astrophysics Data System (ADS)

Shinar, Joseph; Shinar, Ruth

2008-07-01

The basic photophysics, transport properties, state of the art, and challenges in OLED science and technology, and the major developments in structurally integrated OLED-based luminescent chemical and biological sensors are reviewed briefly. The dramatic advances in OLED performance have resulted in devices with projected continuous operating lifetimes of ~2 × 105 h (~23 yr) at ~150 Cd m-2 (the typical brightness of a computer monitor or TV). Consequently, commercial products incorporating OLEDs, e.g., cell phones, MP3 players, and, most recently, OLED TVs, are rapidly proliferating. The progress in elucidating the photophysics and transport properties, occurring in tandem with the development of OLEDs, has been no less dramatic. It has resulted in a detailed understanding of the dynamics of trapped and mobile negative and positive polarons (to which the electrons and holes, respectively, relax upon injection), and of singlet and triplet excitons. It has also yielded a detailed understanding of the spin dynamics of polarons and triplet excitons, which affects their overall dynamics significantly. Despite the aforementioned progress, there are outstanding challenges in OLED science and technology, notably in improving the efficiency of the devices and their stability at high brightness (>1000 Cd m-2). One of the most recent emerging OLED-based technologies is that of structurally integrated photoluminescence-based chemical and biological sensors. This sensor platform, pioneered by the authors, yields uniquely simple and potentially very low-cost sensor (micro)arrays. The second part of this review describes the recent developments in implementing this platform for gas phase oxygen, dissolved oxygen (DO), anthrax lethal factor, and hydrazine sensors, and for a DO, glucose, lactate, and ethanol multianalyte sensor.

Recurrent craniopharyngioma after conformal radiation in children and the burden of treatment.

PubMed

Klimo, Paul; Venable, Garrett T; Boop, Frederick A; Merchant, Thomas E

2015-05-01

In this paper the authors present their experience treating children with recurrent craniopharyngioma who were initially managed with surgery followed by conformal radiation therapy (CRT). A departmental oncology information system was queried to identify all children (< 18 years old) who received CRT for a craniopharyngioma between 1998 and 2010 (inclusive) and specifically those who experienced tumor progression. For each patient, the authors recorded the type of recurrence (solid, cystic, or both), the time interval to first progression and each subsequent progression, the associated treatment complications, and disease status at last follow-up evaluation. Among the 97 patients that met criteria for entry into this study, 18 (18.6%) experienced tumor progression (9 cystic, 3 solid, 6 cystic and solid). The median time to first recurrence was 4.62 years (range 1.81-9.11 years). The subgroup included 6 female and 12 male patients with a median age of 7.54 years (range 3.61-13.83 years). Ten patients experienced first progression within 5 years of CRT. The 5- and 10-year treatment-free survival rates for the entire cohort were 89.0% (95% confidence interval [CI] 80.5%-93.9%) and 76.2% (95% CI 64%-85%), respectively. Seven patients had a single episode of progression and 11 had more than 1. The time interval between each subsequent progression was progressively shorter. The 18 patients underwent 38 procedures. The median follow-up duration for this group was 9.32 years (range 4.04-19.0 years). Three patients died, including 1 from perioperative complications. Craniopharyngioma progression after prior irradiation is exceedingly difficult to treat and local control is challenging despite repeated surgical procedures. Given our results, gross-total resection may need to be the surgical goal at the time of first recurrence, if possible. Decompressing new cyst formation alone has a low rate of long-term success.

The progression of myopia from its onset at age 8-12 to adulthood and the influence of heredity and external factors on myopic progression. A 23-year follow-up study.

PubMed

Pärssinen, Olavi; Kauppinen, Markku; Viljanen, Anne

2014-12-01

To examine myopic progression and factors connected with myopic progression. Myopic schoolchildren, with no previous spectacles, 119 boys and 121 girls, were recruited during 1983-1984 to a randomized 3-year clinical trial of bifocal treatment of myopia with a subsequent 20-year follow-up. Participants' mean age at Baseline was 10.9, ranging from 8.7 to 12.8 years. An ophthalmological examination was carried out annually for 3 years and twice thereafter at ca. 10-year intervals. Additional refraction values were received from prescriptions issued by different ophthalmologists and opticians. Altogether, 1915 refraction values were available. Reading distance and accommodation were measured at each control visit. Data on parents' myopia, daily time spent on reading and close work, outdoor activities and watching television were gathered with a structured questionnaire. Using bifocals (+1.75 add) or reading without glasses or accommodation stimulus during the 3-year period in childhood did not correlate with adulthood refraction. Short reading distance in childhood predicted higher adulthood myopia among females. The factors predicting faster myopic progression were parents' myopia and less time spent on sports and outdoor activities at childhood. Time spent on reading and close work in childhood was related to myopic progression during the first 3 years but did not predict adulthood myopia. Myopia throughout follow-up was higher among those who watched television <3 hr daily than those who spent more time watching television. Mean myopic progression 8 years after age 20-24 was -0.45 D ± 0.71 (SD), and in 45% of cases, progression was ≥0.5 D. In nearly half of the cases, myopia beginning at school continued to progress into adulthood. Higher adulthood myopia was mainly related to parents' myopia and less time spent on sports and outdoor activities in childhood. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Decoy receptor 3 inhibits renal mononuclear leukocyte infiltration and apoptosis and prevents progression of IgA nephropathy in mice.

PubMed

Ka, Shuk-Man; Hsieh, Tai-Tzu; Lin, Shih-Hua; Yang, Sung-Sen; Wu, Chin-Chen; Sytwu, Huey-Kang; Chen, Ann

2011-12-01

The progression of IgA nephropathy (IgAN), the most frequent type of primary glomerulonephritis, is associated with high levels of mononuclear leukocyte infiltration into the kidney. These cells consist mainly of T cells and macrophages. Our previous study showed that a decoy receptor 3 (DCR3) gene therapy can prevent the development of a mouse autoimmune glomerulonephritis model by its potent immune modulating effects (Ka SM, Sytwu HK, Chang DM, Hsieh SL, Tsai PY, Chen A. J Am Soc Nephrol 18: 2473-2485, 2007). Here, we tested the hypothesis that DCR3 might prevent the progression of IgAN, an immune complex-mediated primary glomerulonephritis, by inhibiting T cell activation, renal T cell/macrophage infiltration, and protecting the kidney from apoptosis. We used a progressive IgAN (Prg-IgAN) model in B cell-deficient mice, because the mice are characterized by a dramatic proliferation of activated T cells systemically and progressive NF-κB activation in the kidney. We treated the animals with short-term gene therapy with DCR3 plasmids by hydrodynamics-based gene delivery. When the mice were euthanized on day 21, we found that, compared with empty vector-treated (disease control) Prg-IgAN mice, DCR3 gene therapy resulted in 1) systemic inhibition of T cell activation and proliferation; 2) lower serum levels of proinflammatory cytokines; 3) improved proteinuria, renal function, and renal pathology (inhibiting the development of marked glomerular proliferation, crescent formation, glomerulosclerosis, and interstitial inflammation); 5) suppression of T cell and macrophage infiltration into the periglomerular interstitium of the kidney; and 5) a reduction in apoptotic figures in the kidney. On the basis of these findings, DCR3 might be useful therapeutically in preventing the progression of IgAN.

Future Educational Programs and Employment Prospects in Information Technology

ERIC Educational Resources Information Center

Pollack, Thomas A.

2005-01-01

Over the past several years, we have experienced a rather dramatic downward turn in demand for entry level information technology (IT) professionals. However, reports of trends at the end of 2004 indicated that job postings for IT workers reached their highest levels since 2001. This occurs at a time when the number of four year degree programs in…

Continuous Quality Improvement: A Roadmap for Rural School Improvement.

ERIC Educational Resources Information Center

Kilmer, Lloyd C.

A case study documented a continuous quality improvement approach to school improvement in a rural Nebraska high school over a 2-year period. Data gathered from surveys, portfolios, pilot results, and test scores indicated that the changes during the 2-year period were not dramatic, but significant and consistent with the Total Quality literature.…

International Association of Counseling Services: Standards for University and College Counseling Services

ERIC Educational Resources Information Center

Journal of College Student Psychotherapy, 2011

2011-01-01

University and college counseling services have played a vital role in higher education for many years. In the last 40 years, there has been a dramatic increase in the number of campus counseling services and the multiplicity of functions that are performed. Guidelines for university and college counseling services were first developed in 1970 by…

Learners' Preferences regarding Types of Language School: An Exploratory Market Research

ERIC Educational Resources Information Center

Cristobal, E.; Llurda, E.

2006-01-01

The use of multimedia technologies in language teaching and learning has become very popular in the last few years. In the case of countries like Spain, multimedia language schools have experienced a great boom and a dramatic fall in the last 10 years. This study applies marketing research techniques to the study of Catalan learners' preferences…

Back to School Blues: Seasonality of Youth Suicide and the Academic Calendar

ERIC Educational Resources Information Center

Hansen, Benjamin; Lang, Matthew

2011-01-01

Previous research has found evidence of academic benefits to longer school years. This paper investigates one of the many potential costs of increased school year length, documenting a dramatic decrease in youth suicide in months when school is not in session. A detailed analysis does not find that other potential explanations such as economic…

Willamette River Flow Sensitivity to Cascade Snowpack Variation: Insights from Water Stable Isotopes

EPA Science Inventory

Much of the water that people in Western Oregon rely on comes from snowpack in the Cascade Range, and this snowpack is expected to decrease in coming years. In fact, the past 7 years have shown dramatic variation in snowpack, from a high of 174% of normal in 2010-11 to a low of ...

Geothermal Technology: A Smart Way to Lower Energy Bills

ERIC Educational Resources Information Center

Calahan, Scott

2007-01-01

Heating costs for both natural gas and oil have risen dramatically in recent years--and will likely continue to do so. Consequently, it is important that students learn not only about traditional heating technology, but also about the alternative methods that will surely grow in use in the coming years. One such method is geothermal. In this…

Developing a Play-Based Communication Assessment through Collaborative Action Research with Teachers in Northern Canadian Indigenous Communities

ERIC Educational Resources Information Center

Stagg Peterson, Shelley

2017-01-01

With the goal of developing culturally appropriate approaches for assessing and supporting children's language use, teachers of 4-to 6-year-old children in northern Canadian rural and Indigenous communities are involved in a 6-year collaborative action research project. Teachers video record children's interactions during dramatic and construction…

Community College Estimated Growth: Fall 2010

ERIC Educational Resources Information Center

Phillippe, Kent; Mullin, Christopher M.

2011-01-01

A survey from the American Association of Community Colleges (AACC) found that enrollment growth in fall 2010 slowed its pace at community colleges, increasing 3.2% from the previous year. This contrasts with more dramatic increases in recent years: more than 11% between fall 2008 and fall 2009, and nearly 17% between fall 2007 and fall 2009,…

Matching University Graduates' Competences with Employers' Needs in Taiwan

ERIC Educational Resources Information Center

Ho, Hsuan-Fu

2015-01-01

The dramatic expansion of the number of higher educational institutions in Taiwan has contributed a great deal to the growing unemployment rate of university graduates. Given the accumulated number of students who graduated in previous years and failed to find a job, the pressure of finding a job is growing each year. On the other hand, however,…

Climate impacts on connectivity of snowmelt to flow in the Willamette River using water stable isotopes

EPA Science Inventory

Much of the water that people in Western Oregon rely on comes from snowpack in the Cascade Range, and this snowpack is expected to decrease in coming years with climate change. In fact, the past 6 years have shown dramatic variation in snowpack, from a high of 174% of normal in ...

Key Effectiveness Indicators (KEI Report): American River College Five-Year Profile, 1997-2002.

ERIC Educational Resources Information Center

Barr, Jim; Higgins, Jim; Grill, Cathie

This document addresses the key effectiveness indicators for American River College between 1997-2002. The figures are presented in table and graph format and some figures shown present detailed enrollment numbers for fall, spring, and summer while in other figures terms are collapsed into one full academic year. Dramatic enrollment gains were…

The Divorce Culture and Picture Books for Young Children

ERIC Educational Resources Information Center

Mo, Weimin

2007-01-01

In the past thirty years or so, divorce has been widespread in many countries. Globally the percentage of marriages that end up in divorce has increased dramatically even in countries where religious and legal impediments are strong. Divorce occurs most often within the first ten years of marriage. That means children of most couples who are…

NASA Multidisciplinary Design and Analysis Fellowship Program

NASA Technical Reports Server (NTRS)

1995-01-01

This report is a Year 1 interim report of the progress on the NASA multidisciplinary Design and Analysis Fellowship Program covering the period, January 1, 1995 through September 30, 1995. It summarizes progress in establishing the MDA Fellowship Program at Georgia Tech during the initial year. Progress in the advertisement of the program, recruiting results for the 1995-96 academic year, placement of the Fellows in industry during Summer 1995, program development at the M.S. and Ph.D. levels, and collaboration and dissemination of results are summarized in this report. Further details of the first year's progress will be included in the report from the Year 1 Workshop to be held at NASA Langley on December 7-8, 1995.

Radiographic progression of silicosis among Japanese tunnel workers in Kochi.

PubMed

Dumavibhat, Narongpon; Matsui, Tomomi; Hoshino, Eri; Rattanasiri, Sasivimol; Muntham, Dittapol; Hirota, Ryoji; Eitoku, Masamitsu; Imanaka, Momo; Muzembo, Basilua Andre; Ngatu, Nlandu Roger; Kondo, Shinichi; Hamada, Norihiko; Suganuma, Narufumi

2013-01-01

The aim of our study was to investigate the natural course of silicosis in terms of radiographic progression among Japanese tunnel workers. Tunnel workers with silicosis were included in our study between January 2008 and June 2011. We retrospectively assessed workers' radiographs from their first through last visits to see whether there was progression. All films were interpreted by two physicians, who had been specially trained in using the ILO (2000) International Classification of Radiographs of Pneumoconioses (ILO/ICRP). We classified the radiographic findings according to the ILO/ICRP. Survival analysis was performed and then presented as time to progression. Subgroup analysis among the progressed group was performed to demonstrate duration of progression. A total of 65 patients, who were no longer exposed to silica for the duration of the study, were included. The mean age at the first visit was 58.60 ± 7.10 years. The incidence rate of progression was 42 per 1,000 person-years with a median time to progression of 17 years. Progression was demonstrated among 33 cases (51%). The mean durations of progression from category 1 to category 4 and category 2 to category 4 were 14.55 and 10.65 years, respectively. Most patients (86%) had radiographic change from category 1 or 2 directly to category 4. Silicosis progressed at a relatively high rate among tunnel workers without further silica exposure. The high probability of progression directly from category 1 to category 4 may lead to further investigation for the improvement of disease prevention.

Different patterns of longitudinal brain and spinal cord changes and their associations with disability progression in NMO and MS.

PubMed

Liu, Yaou; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Liu, Zheng; Dong, Huiqing; Weiler, Florian; Hahn, Horst K; Shi, Fu-Dong; Butzkueven, Helmut; Barkhof, Frederik; Li, Kuncheng

2018-01-01

To investigate the longitudinal spinal cord and brain changes in neuromyelitis optica (NMO) and multiple sclerosis (MS) and their associations with disability progression. We recruited 28 NMO, 22 MS, and 20 healthy controls (HC), who underwent both spinal cord and brain MRI at baseline. Twenty-five NMO and 20 MS completed 1-year follow-up. Baseline spinal cord and brain lesion loads, mean upper cervical cord area (MUCCA), brain, and thalamus volume and their changes during a 1-year follow-up were measured and compared between groups. All the measurements were also compared between progressive and non-progressive groups in NMO and MS. MUCCA decreased significantly during the 1-year follow-up in NMO not in MS. Percentage brain volume changes (PBVC) and thalamus volume changes in MS were significantly higher than NMO. MUCCA changes were significantly different between progressive and non-progressive groups in NMO, while baseline brain lesion volume and PBVC were associated with disability progression in MS. MUCCA changes during 1-year follow-up showed association with clinical disability in NMO. Spinal cord atrophy changes were associated with disability progression in NMO, while baseline brain lesion load and whole brain atrophy changes were related to disability progression in MS. • Spinal cord atrophy progression was observed in NMO. • Spinal cord atrophy changes were associated with disability progression in NMO. • Brain lesion and atrophy were related to disability progression in MS.

A Small Disc Area Is a Risk Factor for Visual Field Loss Progression in Primary Open-Angle Glaucoma: The Glaucoma Stereo Analysis Study.

PubMed

Kitaoka, Yasushi; Tanito, Masaki; Yokoyama, Yu; Nitta, Koji; Katai, Maki; Omodaka, Kazuko; Nakazawa, Toru

2018-01-01

The Glaucoma Stereo Analysis Study, a cross-sectional multicenter collaborative study, used a stereo fundus camera (nonmyd WX) to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients. We compared the associations of each parameter between the visual field loss progression group and no-progression group. The study included 187 eyes of 187 patients with primary open-angle glaucoma or normal-tension glaucoma. We divided the mean deviation (MD) slope values of all patients into the progression group (<-0.3 dB/year) and no-progression group (≧-0.3 dB/year). ONH morphological parameters were calculated with prototype analysis software. The correlations between glaucomatous visual field progression and patient characteristics or each ONH parameter were analyzed with Spearman's rank correlation coefficient. The MD slope averages in the progression group and no-progression group were -0.58 ± 0.28 dB/year and 0.05 ± 0.26 dB/year, respectively. Among disc parameters, vertical disc width (diameter), disc area, cup area, and cup volume in the progression group were significantly less than those in the no-progression group. Logistic regression analysis revealed a significant association between the visual field progression and disc area (odds ratio 0.49/mm 2 disc area). A smaller disc area may be associated with more rapid glaucomatous visual field progression.

Progressive friction mobilization and enhanced Janssen's screening in confined granular rafts

NASA Astrophysics Data System (ADS)

Saavedra V., Oscar; Elettro, Hervé; Melo, Francisco

2018-04-01

Confined two-dimensional assemblies of floating particles, known as granular rafts, are prone to develop a highly nonlinear response under compression. Here we investigate the transition to the friction-dominated jammed state and map the gradual development of the internal stress profile with flexible pressure sensors distributed along the raft surface. Surprisingly, we observe that the surface stress screening builds up much more slowly than previously thought and that the typical screening distance later dramatically decreases. We explain this behavior in terms of progressive friction mobilization, where the full amplitude of the frictional forces is only reached after a macroscopic local displacement. At further stages of compression, rafts of large length-to-width aspect ratio experience much stronger screenings than the full mobilization limit described by the Janssen's model. We solve this paradox using a simple mathematical analysis and show that such enhanced screening can be attributed to a localized compaction front, essentially shielding the far field from compressive stresses.

Blockade of the SNARE Protein Syntaxin 1 Inhibits Glioblastoma Tumor Growth

PubMed Central

Ulloa, Fausto; Gonzàlez-Juncà, Alba; Meffre, Delphine; Barrecheguren, Pablo José; Martínez-Mármol, Ramón; Pazos, Irene; Olivé, Núria; Cotrufo, Tiziana; Seoane, Joan; Soriano, Eduardo

2015-01-01

Glioblastoma (GBM) is the most prevalent adult brain tumor, with virtually no cure, and with a median overall survival of 15 months from diagnosis despite of the treatment. SNARE proteins mediate membrane fusion events in cells and are essential for many cellular processes including exocytosis and neurotransmission, intracellular trafficking and cell migration. Here we show that the blockade of the SNARE protein Syntaxin 1 (Stx1) function impairs GBM cell proliferation. We show that Stx1 loss-of-function in GBM cells, through ShRNA lentiviral transduction, a Stx1 dominant negative and botulinum toxins, dramatically reduces the growth of GBM after grafting U373 cells into the brain of immune compromised mice. Interestingly, Stx1 role on GBM progression may not be restricted just to cell proliferation since the blockade of Stx1 also reduces in vitro GBM cell invasiveness suggesting a role in several processes relevant for tumor progression. Altogether, our findings indicate that the blockade of SNARE proteins may represent a novel therapeutic tool against GBM. PMID:25803850

CDK1 promotes nascent DNA synthesis and induces resistance of cancer cells to DNA-damaging therapeutic agents

PubMed Central

Liao, Hongwei; Ji, Fang; Geng, Xinwei; Xing, Meichun; Li, Wen; Chen, Zhihua; Shen, Huahao; Ying, Songmin

2017-01-01

Cyclin dependent kinase 1 (CDK1) is essential for cell viability and plays a vital role in many biological events including cell cycle control, DNA damage repair, and checkpoint activation. Here, we identify an unanticipated role for CDK1 in promoting nascent DNA synthesis during S-phase. We report that a short duration of CDK1 inhibition, which does not perturb cell cycle progression, triggers a replication-associated DNA damage response (DDR). This DDR is associated with a disruption of replication fork progression and leads to genome instability. Moreover, we show that compromised CDK1 activity dramatically increases the efficacy of chemotherapeutic agents that kill cancer cells through perturbing DNA replication, including Olaparib, an FDA approved PARP inhibitor. Our study has revealed an important role for CDK1 in the DNA replication program, and suggests that the therapeutic targeting CDK1 may be a novel approach for combination chemotherapy. PMID:29207595

Reduced cost alternatives to premise wiring using ATM and microcellular technologies

NASA Technical Reports Server (NTRS)

Gejji, Raghvendra R.

1993-01-01

The cost of premises wiring keeps increasing due to personnel moves, new equipment, capacity upgrades etc. It would be desirable to have a wireless interface from the workstations to the fixed network, so as to minimize the wiring changes needed. New technologies such as microcellular personal communication systems are promising to bring down the cost of wireless communication. Another promising technology is Code Division Multiple Access (CDMA), which could dramatically increase the bandwidth available for wireless connections. In addition, Asynchronous Transfer Mode (ATM) technology is emerging as a technique for integrated management of voice, data, and video traffic on a single network. The focus of this investigation will be to assess the future utility of these new technologies for reducing the premise wiring cost at KSC. One of the issues to be studied is the cost comparison of 'old' versus 'new,' especially as time and technology progress. An additional issue for closer study is a feasible time-line for progress in technological capability.